胰岛素样生长因子对克罗恩病患者的临床意义

目的:研究我国克罗恩病(CD)患者胰岛素样生长因子水平(IGF)的变化及临床意义.方法:收集54例CD患者的临床资料,并根据临床严重程度分为轻(20例)、中(18例)、重(16例)3组.采用酶标化学发光免疫分析的方法分别检测轻、中、重各组CD患者规范性治疗前后的外周血IGF-I和胰岛素样生长因子结合蛋白-3(IGFBP3)的结果,50例健康人群作为对照组,分析外周血IGF-I和IGFBP3对CD的临床意义.结果:(1)中重度CD患者外周血IGF-I值分别为104.78μg/L±16.28μg/L和77.50μg/L±12.46μg/L,IGFBP3值分别为2.83mg/L±1.02mg/L和1.93mg/L±0.65mg/L,均较正常对照组明显减低,并随着病情加重呈进行性下降(均P<0.05).轻度组IGF-I及IGFBP3值较对照组也有所下降,但无统计学差异;(2)中重度CD经治疗有效后IGF-I值分别为122.75μg/L±27.14μg/L和102.31μg/L±29.24μg/L,IGFBP3值分别为3.85mg/L±0.92mg/L和3.35mg/L±1.35mg/L,均较治疗前明显升高(P<0.0...     

Fibroblast growth factor signaling in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis:Paving the way to hepatocellular carcinoma

Metabolic disorders are increasingly leading to non-alcoholic fatty liver disease,subsequent steatohepatitis,cirrhosis and hepatocellular carcinoma.Fibroblast growth factors and their receptors play an important role in maintaining metabolic homeostasis also in the liver and disorders in signaling have been identified to contribute to those pathophysiologic conditions leading to hepatic lipid accumulation and chronic inflammation.While specific and well tolerated inhibitors of fibroblast growth factor receptor activity are currently developed for(non-liver)cancer therapy,treatment of non-alcoholic fatty liver disease and nonalcoholic steatohepatitis is still limited.Fibroblast growth factor-mimicking or restoring approaches have recently evolved as a novel therapeutic option and the impact of such interactions with the fibroblast growth factor receptor signaling network during non-alcoholic fatty liver disease/non-alcoholic steatohepatitis development is reviewed here.     

Circulating insulin-like growth factor-binding protein 3 as prognostic biomarker in liver cirrhosis

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.     

非酒精性脂肪性肝病在心血管疾病发生发展中的作用

随着经济水平的提高、饮食结构和生活方式的改变,非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的发病率不断上升,逐渐成为全球慢性肝病的主要病因.心血管疾病(cardiovascular disease,CVD)作为NAFLD患者的主要死亡原因,越来越多的研究发现两者之间存在相关性;NAFLD患者CVD发生发展的风险更大,其机制可能与血管和内皮细胞功能障碍、胆汁酸代谢、氧化应激、全身炎症反应和肾素-血管紧张素系统的激活等相关.其中,代谢综合征在两者联系中发挥了重要的作用.因此,早期识别NAFLD患者心血管疾病相关危险因素,进而减少心血管相关并发症,对于改善该类患者的预后至关重要.     

过敏性紫癜患儿血清胰岛素样生长因子及胰岛素样生长因子结合蛋白-3的变化

目的 探讨胰岛素样生长因子(IGF)-1及胰岛素样生长因子结合蛋白(IGFBP)-3在过敏性紫癜(HSP)中的作用.方法 采用放射免疫法方法测定45例HSP患儿不同时期的血清IGF-1及IGFBP-3、C反应蛋白(CRP)水平.采用t检验和直线相关关系.结果 HSP急性发作组血清IGF-1[(452±183)μg/L]、IGFBP-3[(13 897±3124)μg/L]及CRP[(20±8)mg/L]水平升高,与健康对照组和缓解组比较,差异均有统计学意义(t值分别为3.42、4.10、11.17、11.63、8.59、9.86.P均<0.01);HSP缓解组血清IGF-1、IGFBP-3及CRP与健康对照组比较,差异无统计学意义(t=0.3,4、0.34、0.52,P均>0.05).HSP急性期并发肾损害组血清IGF-1[(621±253)μg/L]、IGFBP-3[(18 763±3173)μg/L]水平升高,与无肾损害组比较,差异有统计学意义(t值分别为4.21、7.26,P均<0.01),有胃肠道症组血清IGF-1[(479±192)μg/L]、IGFBP-3[(13 986±3162)μg/L]水平与无胃肠道症状组比较,差异无统计学意义(t值分别为0.83、0.16,P均>0.05);血清CRP水平在肾损害组与非肾损害组及胃肠道症组与无胃肠道症状组问差异均无统计学意义(t值分别为0.56、0.32.P均>0.05).HSP急性期患儿血IGF-1、IGFBP-3与CRP浓度之间呈直线正相关(r值分别为0.624,0.672,JP均<0.01).结论 IGF-1、IGFBP-3参与了HSP疾病的病理生理过程,血清IGF-1、IGFBP-3测定对紫癜性肾损害的诊断、病情监测及预后判断有一定帮助.

Abstract：

Objecfive To investigate the role of serum Insulin-like growth factor(IGF)-1,insulinlike growth factor-binding potein(IGFBP)-3 in children with Henoch-Schonlein purpura(HSP).Methods The serum concentration of IGF-1,1GFBP-3 was measured by enzyme-linked immunosorbent assay(ELISA)method in 45 acute SHP patients,40 recoverv patients and 30 healthy controls.Results The serum levels of IGF-1 [(452±183)μg/L],IGFBP-3 [(13 897±3124)μg/L] and C-reactive protein(CRP)[(20±8)mg/L]in acute phase were significantly higher than those in healthy controls(P<0.0 1)and higher than those during recovery period.The serum level of IGF-1,IGFBP-3 for the HSP patients dropped back slowly and their levels during recovery period were the same as those in healthy controls(P>0.05).The serum levels of IGF-1[(621±253)μg/L] and IGFBP-3[(18 763±3173)μg/L] were higher in the renal damage group than in the non-renal damage group(P<0.01).and the same in patients with gastrointestinal symptoms group as in patients without gastrointestinal symptoms group(P>0.05).whereas the serum level of CRP was not significantly different(P>0.05).The serum levels of IGF-1,IGFBP-3 showed positive correlation with the level of CRP(r=0.624,0.672,P<0.01).Conclusion The IGF-1 and IGFBP-3 may play an important role in the pathological mechanism of HSP.The level of IGF-1 may be used as an indicator for HSP disease activity and progression.IGF-1 mav have a close relation with the damage"of renaJ system in HSP.     

Role of cytokines and chemokines in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat content within the liver. The accumulation/deposition of fat within the liver is essential for diagnosis of NAFLD and might be associated with alterations in the hepatic and systemic inflammatory state. Although it is still unclear if each histological entity represents a different disease or rather steps of the same disease, inflammatory processes in NAFLD might influence its pathophysiology and prognosis. In particular, non-alcoholic steatohepatitis (the most inflamed condition in NAFLDs, which more frequently evolves towards chronic and serious liver diseases) is characterized by a marked activation of inflammatory cells and the upregulation of several soluble inflammatory mediators. Among several mediators, cytokines and chemokines might play a pivotal active role in NAFLD and are considered as potential therapeutic targets. In this review, we will update evidence from both basic research and clinical studies on the potential role of cytokines and chemokines in the pathophysiology of NAFLD.     

非酒精性脂肪肝与生长激素相关性研究

目的 探讨非酒精性脂肪肝（NAFLD）与生长激素（GH）的关系。方法入选NAFLD组38例,非NAFLD组42例．测定GH、腰围（Wc）、空腹血糖（FPG）、空腹胰岛素（Fins）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL—C）、低密度脂蛋白胆固醇（LDL—C）、高敏c反应蛋白（hs—CRP）,谷氨酸氨基转移酶（AIJrr）、γ-谷氨酰转肽酶（GGT）水平,计算体质量指数（BMI）、胰岛素抵抗指数（HOMA—IR）。结果NAFLD组GH、HDL—C水平显著低于非NAFLD组（P〈0．05）;NAFLD组BMI、WC、FPG、Fins、HOMA—IR、TG、hsCRP、AIJT、GGT水平显著高于非NAFLD组（P〈0．05）。GH、HDL—C与NAFLD呈负相关,WC、BMI、FPG、Fins、HOMA—IR、TG、hsCRP、ALT、GGT与NAFLD呈正相关。结论GH与NAFLD密切相关,低水平CH可能是NAFLD危险因素,与肥胖、胰岛素抵抗、血脂紊乱等共同参与了NAFLD的发生与发展。     

胰高血糖素样肽-1改善非酒精性脂肪性肝病作用机制研究进展*

近期研究表明,胰高血糖素样肽-1受体激动剂可从改善肝细胞脂质代谢、抑制炎症反应、调节细胞自噬等多个环节减轻非酒精性脂肪性肝病（NAFLD）患者肝脏脂质沉积,改善组织学损伤,有望成为治疗NAFLD药物的新选择。     

肺癌患者胰岛素样生长因子1和胰岛素样生长因子结合蛋白3的表达及其临床意义

目的 分析肺癌患者血清和支气管肺泡灌洗液（BALF）中胰岛素样生长因子1（IGF-1）、胰岛素样生长因子结合蛋白3（IGFBP-3）的表达,探讨其在肺癌诊断和预后中的临床意义.方法 运用免疫放射法检测80例非小细胞肺癌患者和14名健康者（对照组）外周血血清与BALF中IGF-1、IGFBP-3的水平.结果 肺癌组血清和BALF中IGF-1表达显著高于对照组（P＜0.01）,IGFBP-3的表达显著低于对照组（P＜0.05）,同时IGF-1/IGFBP-3升高（P＜0.01）.IGF-1、IGF-1/IGFBP-3在有淋巴结转移、远处转移和TNMⅢ～Ⅳ的肺癌患者血清、BALF中明显高于无转移者和TNMⅠ～Ⅱ期者（P＜0.05）,而IGFBP3下降明显高于无转移者及TNMⅠ～Ⅱ期者（P＜0.05）.肺癌组血清IGF-1、IGFBP-3浓度与BALF中的浓度呈正相关（P ＜0.01）;患者血清BALF中IGF-1与IGFBP-3浓度呈负相关（P＜0.05）.结论 非小细胞肺癌患者血清和支气管肺泡灌洗液中IGF-1、IGFBP-3的表达对肺癌的诊断、判断预后有重要临床意义.     

脂肪因子与非酒精性脂肪肝

非酒精性脂肪性肝病的发病机制目前尚不十分清楚,脂代谢异常(尤其是TG)与胰岛素抵抗(IR)可能是其病因的关键环节,瘦素、脂联素、抵抗素、肿瘤坏死因子等多种脂肪因子在非酒精性脂肪肝的形成、炎性改变及纤维化的过程中发挥了重要作用.     

非酒精性脂肪性肝病治疗进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)已成为目前全球最主要的慢性肝病病因,是当前研究的热点问题,其预防和治疗也成了研究的重点和难点,目前尚无批准上市的特异性药物及明确的治疗方案,本文针对NAFLD的相关治疗及新兴靶向药物作一概述,给临床医师提供参考。     

Glycosyltransferases and non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD) is the most common form of chronic liver disease and its incidence is increasing worldwide. However, the underlying mechanisms leading to the development of NAFLD are still not fully understood. Glycosyltransferases(GTs) are a diverse class of enzymes involved in catalyzing the transfer of one or multiple sugar residues to a wide range of acceptor molecules. GTs mediate a wide range of functions from structure and storage to signaling, and play a key role in many fundamental biological processes. Therefore, it is anticipated that GTs have a role in the pathogenesis of NAFLD. In this article, we present an overview of the basic information on NAFLD, particularly GTs and glycosylation modification of certain molecules and their association with NAFLD pathogenesis. In addition, the effects and mechanisms of some GTs in the development of NAFLD are summarized.     

Prevalence of hypothyroidism and effect of thyroid hormone replacement therapy in patients with non-alcoholic fatty liver disease: A population-based study

BACKGROUNDNon-alcoholic fatty liver disease (NAFLD) is currently considered as the most common cause of chronic liver disease worldwide. Risk factors for NAFLD have been well-described, including obesity, type 2 diabetes mellites (T2DM), dyslipidemia (DLP) and metabolic syndrome. Hypothyroidism has been identified as an independent risk factor for the development of NAFLD, although the literature is inconsistentAIMTo evaluate the prevalence of hypothyroidism in patients with NAFLD, assess if it is an independent risk factor and explore the effect of thyroxine replacement therapy.METHODSOur cohort’s data was obtained using a validated, large, multicenter database (Explorys Inc, Cleveland, OH, United States) aggregated from pooled outpatient and inpatient records of 26 different healthcare systems, consisting of a total of 360 hospitals in the United States, and utilizing Systematized Nomenclature of Medicine-Clinical Terms for coding. We evaluated a cohort of patients with hypothyroidism and NAFLD. Multivariate analysis was performed to adjust for confounding risk factors including hypertension (HTN), T2DM, DLP, obesity and metabolic syndrome. SPSS version 25, IBM Corp was used for statistical analysis, and for all analyses, a 2-sided P value of < 0.05 was considered statistically significant. Exclusion criteria were limited to age < 18 years.RESULTSAmong the 37648180 included individuals in this database who are above the age of 18 years, there were a total of 2320 patients with NAFLD (6.16 per 100000) in the last five years (2015-2020), amongst which 520 patients (22.4%) had hypothyroidism. Baseline characteristics of patients in this database are described in Table ​Table1.1. Patients with NAFLD were also more likely to have obesity, T2DM, DLP, HTN, and metabolic syndrome (Table ​(Table2).2). While males and females were equally affected, patients in the age group 18-65 years as well as Caucasians seem to be at a higher risk. There was an increased risk of NAFLD among patients with hypothyroidism (OR = 1.587). Furthermore, thyroid hormone replacement was not associated with a decreased risk for developing NAFLD (OR = 1.106, C = 0.952-1.285, P = 0.303).Table 1Baseline characteristics of patients with hypothyroidism in explorys database

非酒精性脂肪性肝病患者甲状腺激素水平变化及其临床意义

目的探讨非酒精性脂肪性肝病（NAFLD）患者血清甲状腺激素水平变化及其临床意义。方法采用放射免疫法检测123例NAFLD患者及56例对照组的血清甲状腺激素（TT3、TT4、TSH）及透明质酸（HA）、层粘连蛋白（LN）、Ⅲ型前胶原氨基末端肽（PⅢNP）、Ⅳ型胶原（CⅣ）等反映肝纤维化的血清学指标。结果 非酒精性脂肪性肝炎（NASH）组血清TT3浓度低于对照组及非酒精性单纯性脂肪肝（NASFL）组（P〈0.05）;三组间血清TT4、TSH浓度比较无显著差异（P〉0.05）;NASFL组患者血清HA、PⅢNP浓度高于对照组（P〈0.05）,CⅣ、LN浓度与对照组比较无显著差异（P〉0.05）;NASH组血清HA、PⅢNP、CⅣ、LN浓度均高于对照组及NASFL组（P〈0.05）;中、重脂肪肝组TT3浓度低于对照组（P〈0.05）,HA、PⅢNP、CⅣ、LN浓度高于对照组（P〈0.05）;轻度脂肪肝组TT3、HA、PⅢNP、CⅣ、LN浓度与对照组比较无显著差异（P〉0.05）。NASFL患者血清TT3水平与HA、PⅢNP呈负相关（P〈0.05）;NASH组患者血清TT3水平与HA、PⅢNP、CⅣ、LN均呈负相关（P〈0.05）。结论 NAFLD患者存在血清TT3水平降低,且下降程度与临床分型、超声分度及肝纤维化严重程度一致,检测NAFLD患者血清TT3浓度变化对判断病情及预后有一定的临床意义。     

Role of ezetimibe in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to steatohepatitis,advanced fibrosis and inflammatory changes.Ezetimibe inhibits cholesterol absorption from the intestinal lumen into enterocytes.The molecular target of ezetimibe is the sterol transporter Niemann-Pick C1-like 1 protein (NPC1L1).Human NPC1L1 is abundantly expressed in the liver and may facilitate the hepatic accumulation of cholesterol.Ezetimibe ex-erts beneficial effects on several metabolic variables.Ezetimibe treatment attenuates hepatic steatosis and is beneficial in terms of NAFLD biochemical markers.The combination of ezetimibe with other interventions may also be beneficial in NAFLD patients.Our group inves-tigated the ezetimibe-orlistat combination treatment in overweight and obese patients with hypercholeste-rolemia,with beneficial effects on NAFLD biochemical markers.These results are promising for patients with NAFLD,who usually have increased cardiovascular disease risk and need a multifactorial treatment.How-ever,it should be mentioned that most results are from animal studies and,although modest elevation of liver function tests may raise the suspicion of NAFLD,none of these tests are sensitive to establish the diagnosis of NAFLD with great accuracy.     

早发冠心病患者合并非乙醇性脂肪性肝病的发生率及危险因素

目的 :探讨早发冠心病患者非乙醇性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的患病率和危险因素。方法:冠状动脉造影诊断为早发冠心病的748例患者,入院期间进行空腹肝胆超声检查。结果:NAFLD患者发生率为49.6%(371/748)。NAFLD组糖尿病,血清总胆固醇,三酰甘油,血清丙氨酸转氨酶及天冬氨酸转氨酶高于非NAFLD组,差异有统计学意义(P<0.05)。NAFLD组多支病变比率明显高于非NAFLF组(χ2=4.455,P=0.04)。多因素Logistic回归分析中,只有糖尿病和冠心病左主干病变是NAFLD的危险因素。结论:早发冠心病患者中NAFLD发生率高达50%,其中冠状动脉多支病变和糖尿病与NAFLD的发生密切相关。     

抵抗素与非酒精性脂肪性肝病

抵抗素是存在于血浆中的富含半胱氨酸的分泌性蛋白,属于抵抗素样分子家族,又称脂肪组织特异性分泌因子.其与胰岛素抵抗及炎症等关系密切.非酒精性脂肪性肝病(NAFLD)代表了一组以甘油三酯在肝内过度贮积而引起的临床病理综合征,目前认为其属于代谢综合征的范畴,胰岛素抵抗及炎症因子的参与是其发病的重要环节.深入研究抵抗素与胰岛素抵抗及炎症的关系将有助于进一步了解NAFLD的发病机制,为寻求合理的治疗方案提供理论依据.     

非酒精性脂肪性肝病与代谢综合征的相关性研究

目的分析非酒精性脂肪性肝病（NAFLD）与代谢综合征（MS）的关系。方法10357例在我院体检的普通人群入选本研究,检测人体学参数、生化指标及肝脏彩超,分析该人群NAFLD和MS的患病率,探讨MS组分与NAFLD的关系。结果10357例体检者中NAFLD的患病率为31．1％,MS患病率为23．6％,NAFLD合并MS患病率为15．5％。经年龄标化后NAFLD和MS患病率男性仍明显高于女性。将全部受试者按BM1分组后,各组间NAFLD、MS及NAFLD合并MS患病率差异均有统计学意义（P〈0．01）。选择同期体检无NAFLD的个体（非NAFLD组）,经性别、年龄、BMI与NAFLD组相匹配后,NAFLD组MS患病率明显高于非NAFLD组（59．8％VS5．2％,P〈0．01）。多因素Logistic回归分析表明：NAFI。D危险因素的前五位为TG、BMI、FPG、LDL-C和吸烟。结论即使排除BMI因素的影响,NAFLD患者MS的患病率仍然明显增高。NAFLD危险因素由高到低依次为TG、BMI、FPG、LDL-C、吸烟、TC、性别、血压、SUA及ALT。HDL-C为NAFLD保护性因素。