Background: Liver transplantation remains the main curative treatment option for hepatocellular carcinoma(HCC) patients. In the Eurotransplant area Milan criteria are used to assign priority extra points(exceptional M...Background: Liver transplantation remains the main curative treatment option for hepatocellular carcinoma(HCC) patients. In the Eurotransplant area Milan criteria are used to assign priority extra points(exceptional MELD, ex MELD) for patients on the waiting list. To prevent patients from tumor progression, loco-regional(neoadjuvant) treatment(LRT) is used. For patients unlikely to timely receive an organ via primary allocation,“extended critera donor(ECD) organs” are used. The present study aimed to investigate the survival after LT with a strategy of minimizing waiting list dropouts by using LRT for bridging and transplanting ECD organs if possible and necessary. Methods: Between October 2010 and May 2015, 50 liver transplants for HCC were included in this retrospective study. Of those, 42(84%) met the Milan criteria according to the preoperative radiological examination. Forty-one patients(82%) received LRT. The waiting time was analyzed according to LRT. Kaplan-Meier curves with log-rank statistics were used for survival analyses. Results: One-and five-year overall survival within Milan criteria was 94.3% and 83.7% compared with 91.7% and 67.9% beyond Milan criteria, though statistical significance was not reached( P = 0.487). LRT had no impact on overall survival( P = 0.629). Median waiting time was shorter if no LRT was performed(4.6 months vs. 1.5 months, P = 0.006) and there were no cases of waiting list dropouts. Using ECD organs had no impact on overall survival( P = 0.663). Conclusions: Patients with an expected waiting time to transplantation of > 6 months could be successfully treated with LRT as a bridge to transplant. Overall and disease-free survival for patients within and beyond Milan criteria was comparable and the use of ECD organs in this cohort of HCC patients proved to be a safe option.展开更多
Objective: The study aims to elucidate the association of host-related factors on systemic inflammation in COPD patients. Methods: In 295 clinically stable and optimally treated COPD patients from 39 outpatient center...Objective: The study aims to elucidate the association of host-related factors on systemic inflammation in COPD patients. Methods: In 295 clinically stable and optimally treated COPD patients from 39 outpatient centers, age, gender, and body composition (body mass index, BMI;fat-free mass index, FFMI;fat mass index, FMI) were related to inflammatory biomarkers: CRP, fibrinogen, TNFα, and its soluble receptors (s)TNFαR1 and sTNFαR2. Furthermore, forced expiratory volume in the first second (FEV1), BMI, FFMI, and FMI were stratified by quartiles to elucidate the influence on inflammatory biomarkers. Monovariate and multivariate regression analyses were performed for associations between inflammatory biomarkers. Results: Positive correlations were found for FFMI with sTNFαR1, FMI with CRP and age with TNFα, sTNFαR1 and sTNFαR2 (p < 0.01). FEV1 was not correlated with body composition and inflammatory markers. Mono- and multivariate analysis showed weak correlations between the acute phase markers and the TNFα system after correcting for multiple co-variants. Conclusions: This study highlights the modest role of age and body composition on levels of systemic inflammatory biomarkers in COPD. Results show the degree of airflow limitation does not affect systemic inflammation. Last, a weak relationship between acute phase markers and markers of the TNFα system is present in COPD.展开更多
Background Retinopathy of prematurity(ROP)is generally considered to be more frequent in males than in females.However,it is not known whether sex differences in ROP affect all degrees of the condition,are global and ...Background Retinopathy of prematurity(ROP)is generally considered to be more frequent in males than in females.However,it is not known whether sex differences in ROP affect all degrees of the condition,are global and have changed as neonatology has developed.We aimed to conduct a systematic review and meta-analysis of studies addressing sex differences in the risk of developing ROP.Methods PubMed/MEDLINE and Embase databases were searched.The frequentist,random-effects risk ratio(RR)and 95%confidence interval(CI)were calculated.Bayesian model averaged(BMA)meta-analysis was used to calculate the Bayes factors(BFs).The BF10 is the ratio of the probability of the data under the alternative hypothesis(H1)over the probability of the data under the null hypothesis(H0).Results We included 205 studies(867,252 infants).Frequentist meta-analysis showed a positive association between male sex and severe ROP(113 studies,RR=1.14,95%CI=1.07–1.22)but no association with any ROP(144 studies,RR=1.00,95%CI=0.96–1.03).BMA showed extreme evidence in favor of H1 for severe ROP(BF10=71,174)and strong evidence in favor of H0 for any ROP(BF10=0.05).The association between male sex and severe ROP remained stable over time and was present only in cohorts from countries with a high or high-middle sociodemographic index.Conclusions Our study confirms the presence of a male disadvantage in severe ROP but not in less severe forms of the disease.There are variations in the sex differences in ROP,depending on geographical location and sociodemographic level of the countries.展开更多
Vascular endothelial growth factor(VEGF)plays a vital role in promoting attachment and proliferation of endothelial cells,and induces angiogenesis.In recent years,much research has been conducted on the functionalizat...Vascular endothelial growth factor(VEGF)plays a vital role in promoting attachment and proliferation of endothelial cells,and induces angiogenesis.In recent years,much research has been conducted on the functionalization of tissue engineering scaffolds with VEGF or a VEGF-mimetic peptide to promote angiogenesis.However,most chemical reactions are nonspecific and require organic solvents,which can compromise control over functionalization and alter peptide/protein activity.An attractive alternative is the fabrication of functionalizable electrospun fibers,which can overcome these hurdles.In this study,we used thiol-ene chemistry for the conjugation of a VEGF-mimetic peptide to the surface of poly(ε-caprolactone)(PCL)fibrous scaffolds with varying amounts of a functional PCL-diacrylate(PCL-DA)polymer.30%PCL-DA was selected due to homogeneous fiber morphology.A VEGF-mimetic peptide was then immobilized on PCL-DA fibrous scaffolds by a light-initiated thiol-ene reaction.7-Mercapto-4-methylcoumarin,RGD-FITC peptide and VEGF-TAMRA mimetic peptide were used to validate the thiol-ene reaction on the fibrous scaffolds.Tensile strength and elastic modulus of the 30%PCL-DA fibrous scaffolds were significantly increased after the reaction.Conjugation of the 30%PCL-DA fibrous scaffolds with the VEGF peptide increased the surface water wettability of the scaffolds.Patterned structures could be obtained after using a photomask on the fibrous film.Moreover,in vitro studies indicated that scaffolds functionalized with the VEGF-mimetic peptide were able to induce phosphorylation of the VEGF receptor and enhanced HUVECs survival,proliferation and adhesion.A chick chorioallantoic membrane(CAM)assay further indicated that the VEGF peptide functionalized scaffolds were able to promote angiogenesis in vivo.These results show that scaffold functionalization can be controlled via a simple polymer mixing approach,and that the functionalized VEGF peptide-scaffolds have potential for vascular tissue regeneration.展开更多
文摘Background: Liver transplantation remains the main curative treatment option for hepatocellular carcinoma(HCC) patients. In the Eurotransplant area Milan criteria are used to assign priority extra points(exceptional MELD, ex MELD) for patients on the waiting list. To prevent patients from tumor progression, loco-regional(neoadjuvant) treatment(LRT) is used. For patients unlikely to timely receive an organ via primary allocation,“extended critera donor(ECD) organs” are used. The present study aimed to investigate the survival after LT with a strategy of minimizing waiting list dropouts by using LRT for bridging and transplanting ECD organs if possible and necessary. Methods: Between October 2010 and May 2015, 50 liver transplants for HCC were included in this retrospective study. Of those, 42(84%) met the Milan criteria according to the preoperative radiological examination. Forty-one patients(82%) received LRT. The waiting time was analyzed according to LRT. Kaplan-Meier curves with log-rank statistics were used for survival analyses. Results: One-and five-year overall survival within Milan criteria was 94.3% and 83.7% compared with 91.7% and 67.9% beyond Milan criteria, though statistical significance was not reached( P = 0.487). LRT had no impact on overall survival( P = 0.629). Median waiting time was shorter if no LRT was performed(4.6 months vs. 1.5 months, P = 0.006) and there were no cases of waiting list dropouts. Using ECD organs had no impact on overall survival( P = 0.663). Conclusions: Patients with an expected waiting time to transplantation of > 6 months could be successfully treated with LRT as a bridge to transplant. Overall and disease-free survival for patients within and beyond Milan criteria was comparable and the use of ECD organs in this cohort of HCC patients proved to be a safe option.
文摘Objective: The study aims to elucidate the association of host-related factors on systemic inflammation in COPD patients. Methods: In 295 clinically stable and optimally treated COPD patients from 39 outpatient centers, age, gender, and body composition (body mass index, BMI;fat-free mass index, FFMI;fat mass index, FMI) were related to inflammatory biomarkers: CRP, fibrinogen, TNFα, and its soluble receptors (s)TNFαR1 and sTNFαR2. Furthermore, forced expiratory volume in the first second (FEV1), BMI, FFMI, and FMI were stratified by quartiles to elucidate the influence on inflammatory biomarkers. Monovariate and multivariate regression analyses were performed for associations between inflammatory biomarkers. Results: Positive correlations were found for FFMI with sTNFαR1, FMI with CRP and age with TNFα, sTNFαR1 and sTNFαR2 (p < 0.01). FEV1 was not correlated with body composition and inflammatory markers. Mono- and multivariate analysis showed weak correlations between the acute phase markers and the TNFα system after correcting for multiple co-variants. Conclusions: This study highlights the modest role of age and body composition on levels of systemic inflammatory biomarkers in COPD. Results show the degree of airflow limitation does not affect systemic inflammation. Last, a weak relationship between acute phase markers and markers of the TNFα system is present in COPD.
文摘Background Retinopathy of prematurity(ROP)is generally considered to be more frequent in males than in females.However,it is not known whether sex differences in ROP affect all degrees of the condition,are global and have changed as neonatology has developed.We aimed to conduct a systematic review and meta-analysis of studies addressing sex differences in the risk of developing ROP.Methods PubMed/MEDLINE and Embase databases were searched.The frequentist,random-effects risk ratio(RR)and 95%confidence interval(CI)were calculated.Bayesian model averaged(BMA)meta-analysis was used to calculate the Bayes factors(BFs).The BF10 is the ratio of the probability of the data under the alternative hypothesis(H1)over the probability of the data under the null hypothesis(H0).Results We included 205 studies(867,252 infants).Frequentist meta-analysis showed a positive association between male sex and severe ROP(113 studies,RR=1.14,95%CI=1.07–1.22)but no association with any ROP(144 studies,RR=1.00,95%CI=0.96–1.03).BMA showed extreme evidence in favor of H1 for severe ROP(BF10=71,174)and strong evidence in favor of H0 for any ROP(BF10=0.05).The association between male sex and severe ROP remained stable over time and was present only in cohorts from countries with a high or high-middle sociodemographic index.Conclusions Our study confirms the presence of a male disadvantage in severe ROP but not in less severe forms of the disease.There are variations in the sex differences in ROP,depending on geographical location and sociodemographic level of the countries.
基金supported in part by China Scholarship Council(No.201508610081 to T.Y.)by the National Natural Science Foundation of China(No.32071360,No.31900976 to H.C.)。
文摘Vascular endothelial growth factor(VEGF)plays a vital role in promoting attachment and proliferation of endothelial cells,and induces angiogenesis.In recent years,much research has been conducted on the functionalization of tissue engineering scaffolds with VEGF or a VEGF-mimetic peptide to promote angiogenesis.However,most chemical reactions are nonspecific and require organic solvents,which can compromise control over functionalization and alter peptide/protein activity.An attractive alternative is the fabrication of functionalizable electrospun fibers,which can overcome these hurdles.In this study,we used thiol-ene chemistry for the conjugation of a VEGF-mimetic peptide to the surface of poly(ε-caprolactone)(PCL)fibrous scaffolds with varying amounts of a functional PCL-diacrylate(PCL-DA)polymer.30%PCL-DA was selected due to homogeneous fiber morphology.A VEGF-mimetic peptide was then immobilized on PCL-DA fibrous scaffolds by a light-initiated thiol-ene reaction.7-Mercapto-4-methylcoumarin,RGD-FITC peptide and VEGF-TAMRA mimetic peptide were used to validate the thiol-ene reaction on the fibrous scaffolds.Tensile strength and elastic modulus of the 30%PCL-DA fibrous scaffolds were significantly increased after the reaction.Conjugation of the 30%PCL-DA fibrous scaffolds with the VEGF peptide increased the surface water wettability of the scaffolds.Patterned structures could be obtained after using a photomask on the fibrous film.Moreover,in vitro studies indicated that scaffolds functionalized with the VEGF-mimetic peptide were able to induce phosphorylation of the VEGF receptor and enhanced HUVECs survival,proliferation and adhesion.A chick chorioallantoic membrane(CAM)assay further indicated that the VEGF peptide functionalized scaffolds were able to promote angiogenesis in vivo.These results show that scaffold functionalization can be controlled via a simple polymer mixing approach,and that the functionalized VEGF peptide-scaffolds have potential for vascular tissue regeneration.
