AIM: To investigate the prognostic significance of insulin-like growth factor-binding protein 3(IGFBP-3) in patients with cirrhosis.METHODS: Prospective study that included two cohorts: outpatients with stable cirrhos...AIM: To investigate the prognostic significance of insulin-like growth factor-binding protein 3(IGFBP-3) in patients with cirrhosis.METHODS: Prospective study that included two cohorts: outpatients with stable cirrhosis(n = 138) and patients hospitalized for acute decompensation(n = 189). Development of complications, mortality or liver transplantation was assessed by periodical phone calls and during outpatient visits. The cohort of stable cirrhosis also underwent clinical and laboratory evaluation yearly(2013 and 2014) in predefined study visits. In patients with stable cirrhosis, IGFBP-3 levels were measured at baseline(2012) and at second re-evaluation(2014). In hospitalized subjects, IGFBP-3 levels were measured in serum samples collected in the first and in the third day after admission and stored at-80 ℃. IGFBP-3 levels were measured by immunochemiluminescence.RESULTS: IGFBP-3 levels were lower in hospitalized patients as compared to outpatients(0.94 mcg/mL vs 1.69 mcg/m L, P < 0.001) and increased after liver transplantation(3.81 mcg/m L vs 1.33 mcg/mL, P = 0.008). During the follow-up of the stable cohort, 17 patients died and 11 received liver transplantation. Bivariate analysis showed that death or transplant was associated with lower IGFBP-3 levels(1.44 mcg/mL vs 1.74 mcg/m L, P = 0.027). The Kaplan-Meier transplant-free survival probability was 88.6% in patients with IGFBP-3 ≥ 1.67 mcg/mL and 72.1% for those with IGFBP3 < 1.67 mcg/mL(P = 0.015). In the hospitalized cohort, 30-d mortality was 24.3% and was independently associated with creatinine, INR, SpO_2/FiO_2 ratio and IGFBP-3 levels in the logistic regression. The 90-d transplant-free survival probability was 80.4% in patients with IGFBP-3 ≥ 0.86 mcg/mL and 56.1% for those with IGFBP3 < 0.86 mcg/mL(P < 0.001). CONCLUSION: Lower IGFBP-3 levels were associated with worse outcomes in patients with cirrhosis, and might represent a promising prognostic tool that can be incorporated in clinical practice.展开更多
BACKGROUND Atrial fibrillation(AF)is one of the most common persistent arrhythmias among adult cardiovascular diseases.It is important to identify potential risk factors for AF.Members of the insulin-like growth facto...BACKGROUND Atrial fibrillation(AF)is one of the most common persistent arrhythmias among adult cardiovascular diseases.It is important to identify potential risk factors for AF.Members of the insulin-like growth factor(IGF)family exert a variety of effects on various cell types in the context of the pathogenesis of cardiovascular diseases,and previous population-based studies indicate associations between IGF family members and AF.However,the causal effects of IGF family members in AF have not been evaluated.assess genetic relationships between IGF family members and AF.METHODS MR was performed based on genome-wide association study(GWAS)datasets,and concentration levels of 14 IGF family members were retrieved.An initial MR analysis was conducted to identify single nucleotide polymorphisms potentially associated with IGF serum concentrations.A GWAS meta-analysis including 60620 AF cases and 970216 control participants of European ancestry was then conducted to identify AF causal effects.Two-sample MR packages were used to perform MR analysis in R.MR-Egger,weighted median(WM),and inverse va-riance weighted(IVW)methods were used.RESULTS Core Tip:Due to the high prevalence of atrial fibrillation(AF),and adverse outcomes related to it,it is important to identify risk factors associated with development of the condition.Insulin-like growth factor(IGF)family members exert a variety of effects on various cell types in the context of the pathogenesis of cardiovascular diseases,and previous population-based studies indicate associations between IGF family members and AF.However,the causal effects of IGF family members in AF have not been evaluated.The results of the current study provide novel insights on the pathogenesis of AF,and implic-ations of serum IGF family member concentrations when assessing the risk of AF.The study generated evidence on the potential roles of developmental pathological effects in the pathogenesis of AF.Further observational and experimental studies are critically needed.展开更多
Background Insulin-like growth factor binding protein-related protein 1 （IGFBPrP1） can activate hepatic stellate cells and increase extracellular matrix （ECM） in vitro. However, the effects of IGFBPrP1 in mice wit...Background Insulin-like growth factor binding protein-related protein 1 （IGFBPrP1） can activate hepatic stellate cells and increase extracellular matrix （ECM） in vitro. However, the effects of IGFBPrP1 in mice with hepatic fibrosis, and the mechanisms of these effects, are currently unknown. We aim to address these issues in this study. Methods Intraperitoneal injection of thioacetamide （TAA） is a classic method for establishing a mouse model of hepatic fibrosis. Using this model, we administered anti-IGFBPrP1 antibody, again via intraperitoneal injection. The morphological changes of liver fibrosis were observed with both HE and Masson stainning. The immunohistochemical assays and Western blotting were used to measure changes in IGFBPrP1, a-smooth muscle actin （a-SMA） and ECM in liver tissues, and the expression of transforming growth factor-β1 （TGF-β1） and Smad3. Data were statistically analyzed using one-way analysis of variance （ANOVA）, the SNK-q test for inter-group differences. Results The Masson staining analysis showed that compared with normal control group, content of collagen fiber in TAA5w group was significantly increased （P 〈0.01）, and it was significantly decreased in TAA5w/alGFBPrP1 group compared with in TAA5w group （P 〈0.01）. The expression of hepatic IGFBPrP1, a-SMA, TGF-β1, Smad3, collagen 1 and fibronectin （FN） was significantly up-regulated in the TAA5w group （P 〈0.01）. Anti-IGFBPrP1 treatment reversed these changes （P 〈0.01）. Conclusions IGFBPrP1 plays an important role in the development of hepatic fibrosis. Anti-IGFBPrP1 prevents fibrosis in mice by suppressing the activation of hepatic stellate cells, inhibiting the synthesis of major components of the ECM （namely, collagen I and FN）. The mechanism for this suppression of fibrosis is associated with the TGF-β1/Smad3 signaling pathways.展开更多
目的:分析肝癌患者血清胰岛素样生长因子ⅡmRNA结合蛋白3(insulin-like growth factorⅡmRNA binding protein 3,IMP3)水平,并揭示其用于肝癌早期诊断和评价肝癌进展的临床价值.方法:选择2011-12/2013-11确诊为肝癌的患者120例为观察组...目的:分析肝癌患者血清胰岛素样生长因子ⅡmRNA结合蛋白3(insulin-like growth factorⅡmRNA binding protein 3,IMP3)水平,并揭示其用于肝癌早期诊断和评价肝癌进展的临床价值.方法:选择2011-12/2013-11确诊为肝癌的患者120例为观察组,同时纳入30例健康志愿者作为对照组.按照肝癌的严重程度将观察组分成Ⅰ期、Ⅱ期和Ⅲ期.采用RT-PCR检测观察组、对照组、Ⅰ期、Ⅱ期和Ⅲ期组IMP3的mRNA转录量,使用ELISA检测方法检测观察组、对照组、Ⅰ期、Ⅱ期和Ⅲ期组患者血清IMP3浓度.结果:Ⅰ期组IMP3 mRNA转录量显著高于对照组(t=19.72,P=0.000),Ⅱ期组IMP3mRNA转录量显著高于Ⅰ期组(t=9.67,P=0.000),Ⅲ期组I M P3 m R N A转录量显著高于Ⅱ期组(t=23.34,P=0.000).观察组血清IMP3平均浓度为134.25 ng/mL±19.33 ng/mL,显著高于对照组(9.37 ng/mL±1.23 ng/mL)(t=70.22,P=0.000).Ⅰ期组血清IMP3平均浓度为48.35 ng/mL±12.03 ng/mL,显著高于对照组(t=19.84,P=0.000).Ⅱ期组血清IMP3平均浓度为95.36 ng/mL±9.25 ng/mL,显著高于Ⅰ期组(t=19.67,P=0.000).Ⅲ期组血清IMP3平均浓度为214.23 ng/mL±23.64 ng/mL,显著高于Ⅱ期组(t=28.83,P=0.000).结论:随着肝癌的进展血清IMP3浓度显著上升,血清IMP3检测具有肝癌早期诊断和肝癌进展评价的潜在价值.展开更多
目的:探究Snail2、胰岛素样生长因子II mRNA结合蛋白3(insulin-like growth factor II mRNA-binding protein 3,IMP3)和Wnt通路抑制因子1(Wnt inhibitory factor-1,Wif-1)在食管胃交界处的腺癌(adenocarcinoma of the esophagogastric j...目的:探究Snail2、胰岛素样生长因子II mRNA结合蛋白3(insulin-like growth factor II mRNA-binding protein 3,IMP3)和Wnt通路抑制因子1(Wnt inhibitory factor-1,Wif-1)在食管胃交界处的腺癌(adenocarcinoma of the esophagogastric junction,AEG)中的表达特点及临床意义。方法:随机选择2017年3月至2019年3月间的AEG患者90例作为AEG组,收集同期正常胃组织50例作为健康组。患者经过手术或全身PET-CT检测AEG转移情况。通过免疫组化染色和Western blot检测组织中Snail2、Wif-1、IMP3的表达情况。结果:免疫组化研究结果显示Snail2主要表达于细胞核和细胞质,IMP3主要表达于细胞质,AEG组中Snail2和IMP3的表达水平显著升高。Wif-1在健康组中呈阳性表达,但是在AEG组中表达水平降低。性别、年龄以及肿瘤大小对AEG组织中Snail2、IMP3和Wif-1的影响不大(P>0.05),III/IV分期、出现淋巴转移和远端转移的患者的AEG组织中Snail2、IMP3水平显著增高(P<0.05)。III/IV分期、出现淋巴转移和远端转移的患者的AEG组织中Wif-1水平显著降低(P<0.05)。结论:Snail2和IMP3在AEG中过表达,而Wif-1低表达,并且高水平的Snail2、IMP3和低水平的Wif-1与AEG的恶性特征有关,可作为预测AEG转移、预后和复发的生物标志因子。展开更多
文摘AIM: To investigate the prognostic significance of insulin-like growth factor-binding protein 3(IGFBP-3) in patients with cirrhosis.METHODS: Prospective study that included two cohorts: outpatients with stable cirrhosis(n = 138) and patients hospitalized for acute decompensation(n = 189). Development of complications, mortality or liver transplantation was assessed by periodical phone calls and during outpatient visits. The cohort of stable cirrhosis also underwent clinical and laboratory evaluation yearly(2013 and 2014) in predefined study visits. In patients with stable cirrhosis, IGFBP-3 levels were measured at baseline(2012) and at second re-evaluation(2014). In hospitalized subjects, IGFBP-3 levels were measured in serum samples collected in the first and in the third day after admission and stored at-80 ℃. IGFBP-3 levels were measured by immunochemiluminescence.RESULTS: IGFBP-3 levels were lower in hospitalized patients as compared to outpatients(0.94 mcg/mL vs 1.69 mcg/m L, P < 0.001) and increased after liver transplantation(3.81 mcg/m L vs 1.33 mcg/mL, P = 0.008). During the follow-up of the stable cohort, 17 patients died and 11 received liver transplantation. Bivariate analysis showed that death or transplant was associated with lower IGFBP-3 levels(1.44 mcg/mL vs 1.74 mcg/m L, P = 0.027). The Kaplan-Meier transplant-free survival probability was 88.6% in patients with IGFBP-3 ≥ 1.67 mcg/mL and 72.1% for those with IGFBP3 < 1.67 mcg/mL(P = 0.015). In the hospitalized cohort, 30-d mortality was 24.3% and was independently associated with creatinine, INR, SpO_2/FiO_2 ratio and IGFBP-3 levels in the logistic regression. The 90-d transplant-free survival probability was 80.4% in patients with IGFBP-3 ≥ 0.86 mcg/mL and 56.1% for those with IGFBP3 < 0.86 mcg/mL(P < 0.001). CONCLUSION: Lower IGFBP-3 levels were associated with worse outcomes in patients with cirrhosis, and might represent a promising prognostic tool that can be incorporated in clinical practice.
文摘BACKGROUND Atrial fibrillation(AF)is one of the most common persistent arrhythmias among adult cardiovascular diseases.It is important to identify potential risk factors for AF.Members of the insulin-like growth factor(IGF)family exert a variety of effects on various cell types in the context of the pathogenesis of cardiovascular diseases,and previous population-based studies indicate associations between IGF family members and AF.However,the causal effects of IGF family members in AF have not been evaluated.assess genetic relationships between IGF family members and AF.METHODS MR was performed based on genome-wide association study(GWAS)datasets,and concentration levels of 14 IGF family members were retrieved.An initial MR analysis was conducted to identify single nucleotide polymorphisms potentially associated with IGF serum concentrations.A GWAS meta-analysis including 60620 AF cases and 970216 control participants of European ancestry was then conducted to identify AF causal effects.Two-sample MR packages were used to perform MR analysis in R.MR-Egger,weighted median(WM),and inverse va-riance weighted(IVW)methods were used.RESULTS Core Tip:Due to the high prevalence of atrial fibrillation(AF),and adverse outcomes related to it,it is important to identify risk factors associated with development of the condition.Insulin-like growth factor(IGF)family members exert a variety of effects on various cell types in the context of the pathogenesis of cardiovascular diseases,and previous population-based studies indicate associations between IGF family members and AF.However,the causal effects of IGF family members in AF have not been evaluated.The results of the current study provide novel insights on the pathogenesis of AF,and implic-ations of serum IGF family member concentrations when assessing the risk of AF.The study generated evidence on the potential roles of developmental pathological effects in the pathogenesis of AF.Further observational and experimental studies are critically needed.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 30871146）, and the New Century Excellent Talent of the Ministry of Education of China （No. NCET-06-0264）.
文摘Background Insulin-like growth factor binding protein-related protein 1 （IGFBPrP1） can activate hepatic stellate cells and increase extracellular matrix （ECM） in vitro. However, the effects of IGFBPrP1 in mice with hepatic fibrosis, and the mechanisms of these effects, are currently unknown. We aim to address these issues in this study. Methods Intraperitoneal injection of thioacetamide （TAA） is a classic method for establishing a mouse model of hepatic fibrosis. Using this model, we administered anti-IGFBPrP1 antibody, again via intraperitoneal injection. The morphological changes of liver fibrosis were observed with both HE and Masson stainning. The immunohistochemical assays and Western blotting were used to measure changes in IGFBPrP1, a-smooth muscle actin （a-SMA） and ECM in liver tissues, and the expression of transforming growth factor-β1 （TGF-β1） and Smad3. Data were statistically analyzed using one-way analysis of variance （ANOVA）, the SNK-q test for inter-group differences. Results The Masson staining analysis showed that compared with normal control group, content of collagen fiber in TAA5w group was significantly increased （P 〈0.01）, and it was significantly decreased in TAA5w/alGFBPrP1 group compared with in TAA5w group （P 〈0.01）. The expression of hepatic IGFBPrP1, a-SMA, TGF-β1, Smad3, collagen 1 and fibronectin （FN） was significantly up-regulated in the TAA5w group （P 〈0.01）. Anti-IGFBPrP1 treatment reversed these changes （P 〈0.01）. Conclusions IGFBPrP1 plays an important role in the development of hepatic fibrosis. Anti-IGFBPrP1 prevents fibrosis in mice by suppressing the activation of hepatic stellate cells, inhibiting the synthesis of major components of the ECM （namely, collagen I and FN）. The mechanism for this suppression of fibrosis is associated with the TGF-β1/Smad3 signaling pathways.
文摘目的:分析肝癌患者血清胰岛素样生长因子ⅡmRNA结合蛋白3(insulin-like growth factorⅡmRNA binding protein 3,IMP3)水平,并揭示其用于肝癌早期诊断和评价肝癌进展的临床价值.方法:选择2011-12/2013-11确诊为肝癌的患者120例为观察组,同时纳入30例健康志愿者作为对照组.按照肝癌的严重程度将观察组分成Ⅰ期、Ⅱ期和Ⅲ期.采用RT-PCR检测观察组、对照组、Ⅰ期、Ⅱ期和Ⅲ期组IMP3的mRNA转录量,使用ELISA检测方法检测观察组、对照组、Ⅰ期、Ⅱ期和Ⅲ期组患者血清IMP3浓度.结果:Ⅰ期组IMP3 mRNA转录量显著高于对照组(t=19.72,P=0.000),Ⅱ期组IMP3mRNA转录量显著高于Ⅰ期组(t=9.67,P=0.000),Ⅲ期组I M P3 m R N A转录量显著高于Ⅱ期组(t=23.34,P=0.000).观察组血清IMP3平均浓度为134.25 ng/mL±19.33 ng/mL,显著高于对照组(9.37 ng/mL±1.23 ng/mL)(t=70.22,P=0.000).Ⅰ期组血清IMP3平均浓度为48.35 ng/mL±12.03 ng/mL,显著高于对照组(t=19.84,P=0.000).Ⅱ期组血清IMP3平均浓度为95.36 ng/mL±9.25 ng/mL,显著高于Ⅰ期组(t=19.67,P=0.000).Ⅲ期组血清IMP3平均浓度为214.23 ng/mL±23.64 ng/mL,显著高于Ⅱ期组(t=28.83,P=0.000).结论:随着肝癌的进展血清IMP3浓度显著上升,血清IMP3检测具有肝癌早期诊断和肝癌进展评价的潜在价值.
文摘目的:探究Snail2、胰岛素样生长因子II mRNA结合蛋白3(insulin-like growth factor II mRNA-binding protein 3,IMP3)和Wnt通路抑制因子1(Wnt inhibitory factor-1,Wif-1)在食管胃交界处的腺癌(adenocarcinoma of the esophagogastric junction,AEG)中的表达特点及临床意义。方法:随机选择2017年3月至2019年3月间的AEG患者90例作为AEG组,收集同期正常胃组织50例作为健康组。患者经过手术或全身PET-CT检测AEG转移情况。通过免疫组化染色和Western blot检测组织中Snail2、Wif-1、IMP3的表达情况。结果:免疫组化研究结果显示Snail2主要表达于细胞核和细胞质,IMP3主要表达于细胞质,AEG组中Snail2和IMP3的表达水平显著升高。Wif-1在健康组中呈阳性表达,但是在AEG组中表达水平降低。性别、年龄以及肿瘤大小对AEG组织中Snail2、IMP3和Wif-1的影响不大(P>0.05),III/IV分期、出现淋巴转移和远端转移的患者的AEG组织中Snail2、IMP3水平显著增高(P<0.05)。III/IV分期、出现淋巴转移和远端转移的患者的AEG组织中Wif-1水平显著降低(P<0.05)。结论:Snail2和IMP3在AEG中过表达,而Wif-1低表达,并且高水平的Snail2、IMP3和低水平的Wif-1与AEG的恶性特征有关,可作为预测AEG转移、预后和复发的生物标志因子。
