Insulin-like growth factor binding protein related protein 1 knockdown attenuates hepatic ?brosis via the regulation of MMPs/TIMPs in mice

Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue inhibitors of metalloproteinases(TIMP) play an essential role in hepatic fibrogenesis by regulating homeostasis and remodeling of the extracellular matrix(ECM). However, the interaction between IGFBPrP1 and MMP/TIMP is not clear. The present study was to knockdown IGFBPrP1 to investigate the correlation between IGFBPrP1 and MMP/TIMP in hepatic fibrosis. Methods: Hepatic fibrosis was induced by thioacetamide(TAA) in mice. Knockdown of IGFBPrP1 expression by ultrasound-targeted microbubble destruction-mediated CMB-shRNA-IGFBPrP1 delivery, or inhibition of the Hedgehog(Hh) pathway by cyclopamine treatment, was performed in TAA-induced liver fibrosis mice. Hepatic fibrosis was determined by hematoxylin and eosin and Sirius red staining. Hepatic expression of IGFBPrP1, α-smooth muscle actin( α-SMA), transforming growth factor β 1(TGF β1), collagen I, MMPs/TIMPs, Sonic Hedgehog(Shh), and glioblastoma family transcription factors(Gli1) were investigated by immunohistochemical staining and Western blotting analysis. Results: We found that hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I were increased longitudinally in mice with TAA-induced hepatic fibrosis, concomitant with MMP2/TIMP2 and MMP9/TIMP1 imbalance and Hh pathway activation. Knockdown of IGFBPrP1 expression, or inhibition of the Hh pathway, reduced the hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I and re-established MMP2/TIMP2 and MMP9/TIMP1 balance. Conclusions: Our findings suggest that IGFBPrP1 knockdown attenuates liver fibrosis by re-establishing MMP2/TIMP2 and MMP9/TIMP1 balance, concomitant with the inhibition of hepatic stellate cell activation, down-regulation of TGF β1 expression, and degradation of the ECM. Furthermore, the Hh pathway mediates IGFBPrP1 knockdown-induced attenuation of hepatic fibrosis through the regulation of MMPs/TIMPs balance.

Interaction between insulin-like growth factor binding protein-related protein 1 and transforming growth factor beta 1 in primary hepatic stellate cells

BACKGROUND: We previously showed that insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) is a novel mediator in liver fibrosis. Transforming growth factor beta 1 (TGF beta 1) is known as the strongest effector of liver fibrosis. Therefore, we aimed to investigate the detailed interaction between IGFBPrP1 and TGF beta 1 in primary hepatic stellate cells (HSCs). METHODS: We overexpressed TGF beta 1 or IGFBPrP1 and inhibited TGF beta 1 expression in primary HSCs for 6, 12, 24, 48, 72, and 96 hours to investigate their interaction and observe the accompanying expressions of a-smooth muscle actin (alpha-SMA), collagen I, fibronectin, and phosphorylated-mothers against decapentaplegic homolog 2/3 (p-Smad2/3). RESULTS: We found that the adenovirus vector encoding the TGF beta 1 gene (AdTGF beta 1) induced IGFBPrP1 expression while that of alpha-SMA, collagen I, fibronectin, and TGF beta 1 increased gradually. Concomitantly, AdIGFBPrP1 upregulated TGF beta 1, alpha-SMA, collagen I, fibronectin, and p-Smad2/3 in a time-dependent manner while IGFBPrP1 expression was decreased at 96 hours. Inhibition of TGF beta 1 expression reduced the IGFBPrP1-stimulated expression of alpha-SMA, collagen I, fibronectin, and p-Smad2/3. CONCLUSIONS: These findings for the first time suggest the existence of a possible mutually regulation between IGFBPrP1 and TGF beta 1, which likely accelerates liver fibrosis progression. Furthermore, IGFBPrP1 likely participates in liver fibrosis in a TGF beta 1-depedent manner, and may act as an upstream regulatory factor of TGF beta 1 in the Smad pathway.

Insulin-like growth factor 2 mRNA-binding protein 1 promotes cell proliferation via activation of AKT and is directly targeted by microRNA-494 in pancreatic cancer

BACKGROUND Studies have shown that insulin-like growth factor 2 mRNA-binding protein 1(IGF2BP1)plays critical roles in the genesis and development of human cancers.AIM To investigate the clinical significance and role of IGF2BP1 in pancreatic cancer.METHODS Expression levels of IGF2BP1 and microRNA-494(miR-494)were mined based on Gene Expression Omnibus datasets and validated in both clinical samples and cell lines by quantitative real-time polymerase chain reaction and Western blot.The relationship between IGF2BP1 expression and clinicopathological factors of pancreatic cancer patients was analyzed.The effect and mechanism of IGF2BP1 on pancreatic cancer cell proliferation were investigated in vitro and in vivo.Analyses were performed to explore underlying mechanisms of IGF2BP1 upregulation in pancreatic cancer and assays were carried out to verify the posttranscriptional regulation of IGF2BP1 by miR-494.RESULTS We found that IGF2BP1 was upregulated and associated with a poor prognosis in pancreatic cancer patients.We showed that downregulation of IGF2BP1 inhibited pancreatic cancer cell growth in vitro and in vivo via the AKT signaling pathway.Mechanistically,we showed that the frequent upregulation of IGF2BP1 was attributed to the downregulation of miR-494 expression in pancreatic cancer.Furthermore,we discovered that reexpression of miR-494 could partially abrogate the oncogenic role of IGF2BP1.CONCLUSION Our results revealed that upregulated IGF2BP1 promotes the proliferation of pancreatic cancer cells via the AKT signaling pathway and confirmed that the activation of IGF2BP1 is partly due to the silencing of miR-494.

Preparatory training attenuates drastic response of the insulin-like growth factor binding protein 1 at the point of maximal oxygen consumption in handball players

Background:Intensive exercise changes physiological need for glucose and several biochemical pathways responsible for its metabolism response.Among them are those which involve insulin,insulin-like growth factor(IGF-1),and IGF-binding proteins(IGFBPs).Different types and degrees of exercise,as well as an athlete's fitness,may induce a range of responses regarding concentrations and time needed for the alteration.The idea of the work was to find out whether and how insulin/IGF axis responds to additional physical activity in the already trained subjects and if so,is the adaptation potentially beneficial from the aspect of metabolic control.Methods:The effect of 4-week intensive training on campus(preparatory training) on the levels of insulin,IGF-1,and IGFBPs during maximal progressive exercise test(MPET) on a treadmill was compared to the results obtained during MPET conducted after a regular training season of a female elite handball team(n = 17,age:17 ± 1 years,height:171 ± 8 cm,weight:65 ± 8 kg,body mass index:22 ± 1 kg/m^2 at the beginning of the study;there were no significant changes at the end).Serum samples were obtained from players immediately before the test(basal),at the end of the test after reaching the point of maximal oxygen consumption(VO_(2max)),and after recovery.Results:The concentration of insulin decreased at VO_(2max),but remained higher in players after preparatory training(12.2 ± 2.5 m U/L vs.8.9 ± 4.4 m U/L,p = 0.049).The level of IGFBP-1 decreased in players at VO_(2max) in either case of training,but it remained much higher in tests performed after the preparatory regime than before(p = 0.029).Concentrations of IGF-1,IGFBP-2,-3,and-4 did not change significantly.Conclusion:The inverse relation between insulin and IGFBP-1 was lost during MPET,as these 2 molecules changed in the same direction.The results obtained suggest less severe stress-induced depression of insulin and IGFBP-1 after preparatory training.But another metabolic mechanism cannot be excluded,and that is potentially impaired insulin sensitivity resulting in higher level of IGFBP-1.

Insulin-like growth factor-binding protein-3 inhibits IGF-1-induced proliferation of human hepatocellular carcinoma cells

OBJECTIVE Basic fibroblast growth factor(b FGF)and platelet-derived growth factor(PDGF)produced by hepatocellular carcinoma(HCC)cells are responsible for the cell growth.Accumulating evidence shows that insulin-like growth factor-binding protein-3(IGFBP-3)suppresses HCC cell proliferation in both IGF-dependent and independent manners.The present study is to investigate whether treatment with exogenous IGFBP-3 inhibits bF GF and PDGF production and the cell proliferation of HCC cells.METHODS Cell Counting Kit 8 assay were designed to detect HCC cell proliferation,transcription factor early growth response-1(EGR1)involving in IGFBP-3 regulation of b FGF and PDGF were detected by RT-PCR and Western blot assays.Western blot assay was adopted to detect the IGFBP-3 regulating insulin-like growth factor 1 receptor(IGF-1R)signaling pathway.RESULTS The present study demonstrates that IGFBP-3 suppressed IGF-1-induced b FGF and PDGF expression while it does not affect their expression in the absence of IGF-1.To delineate the underlying mechanism,Western-blot and RT-PCR assays confirmed that the transcription factor early growth response protein 1(EGR1)is involved in IGFBP-3 regulation of b FGF and PDGF.IGFBP-3 inhibition of type 1 insulin-like growth factor receptor(IGF1R),ERK and AKT activation is IGF-1-dependent.Furthermore,transient transfection with constitutively activated AKT or MEK partially blocks the IGFBP-3 inhibition of EGR1,b FGF and PDGF expression.CONCLUSION In conclusion,these findings suggest that IGFBP-3suppresses transcription of EGR1 and its target genes b FGF and PDGF through inhibiting IGF-1-dependent ERK and AKT activation.It demonstrates the importance of IGFBP-3 in the regulation of HCC cell proliferation,suggesting that IGFBP-3 could be a target for the treatment of HCC.

Effects of transfected adenovirus-mediated transcription factor X-box binding protein 1 on hippocampal-derived neural stem cell proliferation and apoptosis under hypoxia

BACKGROUND： Neural stem cell （NSC） survival is closely associated with cell apoptosis in ischemic-hypoxic regions following transplantation. Numerous studies have revealed that X-box binding protein 1 （XBP1） is a transcription factor during endoplasmic reticulum unfolded protein response and is essential for cell survival, differentiation, and anti-apoptotic effects. OBJECTIVE： To determine the effects of the XBP1 gene on NSC proliferation and apoptosis under hypoxic conditions following XBP1 gene transfection into rat embryonic hippocampal NSCs using recombinant adenovirus vector. DESIGN, TIME AND SETTING： In vitro experiments were performed at the Laboratory of Cell Biology of Jilin University and Laboratory of Proteomics, Department of Neurology, Jilin University China from September 2008 to November 2009. MATERIALS： Recombinant adenovirus package XBP1 gene and Ad-XBPl-enhanced green fluorescent protein plasmid （Guangzhou Easywin BioMed Technology, China）, rabbit anti-XBP1 and its target gene estrogen receptor degradation-enhancing a-mannosidase-like protein （EDEM） glucose-regulated protein 78 （GRP78）, anti-apoptotic molecule Bcl-2 and proapoptotic molecule Bax polyclonal antibody （Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA）, and COCI2 （Sigma, St. Louis, MO, USA） were used in the present study. METHODS： Hippocampi from embryonic, Sprague Dawley rats on gestational day 16 were harvested for NSC isolation and cloning, followed by immunofluorescence for Nestin and sub-culturing. The recombinant adenovirus Ad-XBPl-enhanced green fluorescent protein plasmid was transfected into rat embryonic hippocampal NSCs, and then CoCl2 was applied to induce hypoxia. MAIN OUTCOME MEASURES： Cell quantification and 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide colorimetric assay were utilized to detect proliferation in XBPl-transfected NSCs for 7 consecutive days. Western blot assay was utilized to quantify XBP1 GRP78, EDEM, Bcl-2, and Bax expression. Flow cytometry was used to measure apoptosis. RESULTS： NSC proliferation was significantly enhanced following XBP1 gene transfection （P 〈 0.05）. Under hypoxic conditions, GRP78, EDEM, and Bcl-2 levels increased, but Bax levels decreased. In addition, NSC apoptosis decreased following transfection （P 〈 0.05）. CONCLUSION： The XBP1 gene was successfully transfected into rat embryonic hippocampal NSCs using a recombinant adenovirus vector. NSC proliferation following transfection, as well as anti-apoptotic effects under hypoxia, was significantly increased.

DIAGNOSTIC VALUE OF SERUM INSULIN- LIKE GROWTH FACTOR BINDING PROTEIN- 3 IN CHILDREN WITH OR WITHOUT GROWTH HORMONE DEFICIENCY

OBJECTIVE: To study the value of serum insulin-like growth factor binding protein-3 (IGFBP-3) levels in differential diagnosis of growth hormone deficiency (GHD). METHODS: To measure serum IGFBP-3 levels by RIA in normal children and adolescents, GHD children and short-stature children without GHD. RESULTS: Serum level of IGFBP-3 in 129 children with untreated GHD and with no pubertal development was 1.6 +/- 0.9 mg/L, which was less than that in normal group of the same age, but overlapped with the normal children in Tanner stage I. After six-month treatment with recombinant human growth hormone (rhGH), serum level of IGFBP-3 in 59 GHD significantly increased from 1.3 +/- 0.7 mg/L to 2.7 +/- 0.9 mg/L, accompanied by an increase of body heights, growth velocities and serum level of IGF-1. Serum level of IGFBP-3 in 55 short-stature children without GHD was 3.3 +/- 2.2 mg/L, which was not significantly different from that in normal group. CONCLUSION: Serum IGFBP-3 level can reflect the status of GH secretion in children with GHD and is a useful marker for differential diagnosis of GHD.

Tribulus terrestris extracts alleviate muscle damage and promote anaerobic performance of trained male boxers and its mechanisms： Roles of androgen, IGF-1, and IGF binding protein-3

Purpose: To investigate the effects of Tribulus terrestris(TT) extracts on muscle mass, muscle damage, and anaerobic performances of trained male boxers and its mechanisms: roles of plasma androgen, insulin growth factor 1(IGF-1), and IGF-1 binding protein-3(IGFBP-3).Methods: Fifteen male boxers were divided into exercise group(E, n = 7) and exercise plus TT group(E + TT, n = 8). The 2 groups both undertook3-week high-intensity and 3-week high-volume trainings separated by a 4-week rest. TT extracts(1250 mg/day) were orally administered by boxers in E + TT group. TT extract compositions were detected by UHPLC–Q-TOF/MS. Before and at the end of the 2 trainings, muscle mass, anaerobic performance, and blood indicators were explored.Results: Compared with E group, decreases of plasma CK(1591.5 ± 909.6 U/L vs. 2719.9 ± 832.5 U/L) and IGFBP-3(3075.5 ± 1072.5 ng/m L vs. 3950.8 ± 479.3 ng/m L) as well as increases of mean power(MP, 459.4 ± 122.3 W vs. 434.6 ± 69.5 W) and MP/body weight(MP/BW, 7.5 ± 0.9 W/kg vs. 7.1 ± 1.1 W/kg) were detected in E + TT group after a high-intensity training. For high-volume training, reduction of IGFBP-3(2946.4 ± 974.1 ng/m L vs. 3632.7 ± 470.1 ng/m L) and increases of MP(508.7 ± 103.2 W vs. 477.8 ± 49.9 W) and MP/BW(8.2 ± 0.3 W/kg vs.7.5 ± 0.9 W/kg) were detected in E + TT group, compared with E group. Muscle mass, blood levels of testosterone, dihydrotestosterone(DHT),and IGF-1 were not signifiantly changed between the 2 groups.Conclusion: Taking 1250 mg capsules containing TT extracts did not change muscle mass and plasma levels of testosterone, DHT, and IGF-1 but significantly alleviated muscle damage and promoted anaerobic performance of trained male boxers, which may be related to the decrease of plasma IGFBP-3 rather than androgen in plasma.

IGF-1、IGFBP-3在非小细胞肺癌患者血清中的表达及其临床意义

目的探讨胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)在非小细胞肺癌(NSCLC)患者血清中的表达及其临床意义。方法选择84例NSCLC患者作为肺癌组,84例肺部良性疾病患者作为对照组。采集所有患者入院第2 d时空腹静脉血4 ml,应用全自动化学发光免疫分析仪检测血清IGF-1、IGFBP-3含量。对比两组受检者血清IGF-1、IGFBP-3差异,分析血清IGF-1、IGFBP-3表达与NSCLC患者临床病理特征的关系。结果肺癌组血清IGF-1水平高于对照组,IGFBP-3水平低于对照组,有统计学差异(P<0.05);不同年龄、性别、肿瘤部位、肿瘤最大直径、病理类型、分化程度NSCLC患者血清IGF-1、IGFBP-3水平比较,无统计学差异(P<0.05);局部侵犯T_(1)~T_(2)、Ⅰ~Ⅱ期NSCLC患者血清IGF-1水平低于T_(3)~T_(4)、Ⅲ期者,IGFBP-3水平高于T_(3)~T_(4)、Ⅲ期者,有淋巴结转移者血清IGF-1水平高于T_(3)~T_(4)者,IGFBP-3水平低于T_(3)~T_(4)者,有统计学差异(P<0.05)。Pearson分析显示,血清IGF-1水平与NSCLC患者局部侵犯程度、TNM分期、淋巴结转移呈正相关(P<0.05),血清IGFBP-3-水平与NSCLC患者局部侵犯程度、TNM分期、淋巴结转移呈负相关(P<0.05)。结论NSCLC患者血清IGF-1、IGFBP-3水平表达异常,其水平高低与患者局部侵犯程度、TNM分期、淋巴结转移有关。

危重患者血浆IGF-1和IGFBP-3水平对预测ARDS和预后判断的临床价值

目的探讨危重患者血浆胰岛素样生长因子(insulin-like growth factor,IGF)-1和胰岛素样生长因子结合蛋白(insulin-like growth factor binding protein,IGFBP)-3水平对预测急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)和预后判断的临床价值。方法回顾性分析131例在温州医科大学附属第一医院重症监护室住院的危重患者,检测入组患者血浆IGF-1、IGFBP-3水平和血生化、降钙素原(procalcitonin,PCT)、乳酸(lactic acid,LAC)、血白蛋白等。计算入组患者60d病死率。比较ARDS患者和对照组患者及60d死亡患者和生存患者的差异。结果ARDS组患者血浆IGF-1、IGFBP-3明显低于对照组,而PCT高于对照组。死亡组患者血浆IGF-1、IGFBP-3水平明显低于存活组。多因素Logistic回归分析和受试者操作特征曲线结果显示IGF-1曲线下面积(area under the curve,AUC)为0.770、序贯器官衰竭评分(sequential organ failure assessment,SOFA)评分(AUC=0.692)和PCT(AUC=0.710)是危重患者发生ARDS的独立危险因素,IGF-1(AUC=0.807)、IGFBP-3(AUC=0.759)和SOFA评分(AUC=0.859)是危重患者死亡发生的独立危险因素。结论危重患者血浆IGF-1、IGFBP-3水平明显降低,血浆IGF-1和IGFBP-3水平降低是危重患者可能发生ARDS和死亡的重要因素。

安图A2000全自动化学发光分析仪检测IGFBP3的性能验证及与IGF-1相关性研究

目的:对安图A2000全自动化学发光仪检测血清胰岛素样生长因子结合蛋白3(IGFBP3)的性能进行评价,并探讨其在矮小症、性早熟及垂体性病变中与IGF-1的相关性。方法:对安图A2000系统检测IGFBP3的精密度(CV)、线性范围、可报告范围、参考区间进行验证。选取2023年1月-2023年9月在本院诊断或治疗的矮小症21例、性早熟10例、垂体性病变19例,回顾性分析其胰岛素生长因子-Ⅰ(IGF-1)和IGHBP3水平,并进行Spearman相关性分析。结果:IGFBP3高低水平质控品批内CV为2.019%、2.931%,批间CV为3.818%、4.137%;测定结果在0.3~16.0μg/mL范围内呈线性,线性回归方程为Y=0.9995X~0.0213,R2=0.9974;临床可报告范围为0.3~32.0μg/mL;18~70岁和>70岁健康体检者检测结果均在厂家提供的参考区间内;IGFBP3和IGF-1在矮小症、性早熟和垂体性病变患者中具有较好的相关性(r=0.81,P<0.0001)。结论:安图A2000检测血清IGFBP3的性能能够满足实验室质量要求,且与IGF-1具有较好的相关性。

磁共振SWI序列联合血清Id1、IGFBP-3对脑胶质瘤术前分级的评估价值

目的分析磁共振磁敏感加权成像(SWI)序列联合血清分化抑制因子1(Id1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)对脑胶质瘤术前分级的评估价值。方法选取2019年12月至2022年6月我院收治的脑胶质瘤患者98例作为此次研究对象,根据恶化情况分为低级别组(世界卫生组织Ⅰ级和Ⅱ级)46例,高级别组(世界卫生组织Ⅲ级和Ⅳ级)52例;入选患者均进行磁共振SWI序列检查;采用酶联免疫吸附(ELISA)法检测血清Id1、IGFBP-3水平;采用Pearson法分析血清Id1、IGFBP-3水平的相关性;受试者工作特征(ROC)曲线分析Id1、IGFBP-3水平对脑胶质瘤术前分级的临界诊断点;采用四格表分析磁共振SWI序列联合血清Id1、IGFBP-3对脑胶质瘤术前高低级别的诊断价值。结果高级别组ITSS分级显著高于低级别组(P>0.05)。高级别组Id1、IGFBP-3水平均显著高于低级别组(P>0.05)。根据pearson相关性分析得知,脑胶质瘤患者血清Id1、IGFBP-3水平呈正相关(r=0.486,P<0.05)。根据ROC曲线得知,Id1、IGFBP-3诊断脑胶质瘤术前分级的曲线下面积(AUC)分别为0.837、0.861,二者联合诊断脑胶质瘤术前分级的AUC为0.908。磁共振SWI序列在脑胶质瘤术前分级诊断中准确度为83.67%,灵敏度为84.62%,特异度为82.61%;Id1在脑胶质瘤术前分级诊断中准确度为79.59%,灵敏度为80.77%,特异度为78.26%;IGFBP-3在脑胶质瘤术前分级诊断中准确度为81.63%,灵敏度为82.69%,特异度为80.43%;三者联合检测在脑胶质瘤术前分级诊断中准确度为91.84%,灵敏度为92.31%,特异度为91.30%。结论Id1、IGFBP-3在脑胶质瘤患者血清中显著升高,磁共振SWI序列联合血清Id1、IGFBP-3可以提高对脑胶质瘤术前分级的评估价值。

探讨脾虚汤联合生长激素治疗特发性矮小症的临床疗效及其对血清IGFBP-3、IGF-1表达的影响

目的 探讨脾虚汤联合生长激素治疗特发性矮小症的临床疗效及其对血清胰岛素样生长因子结合蛋白-3(IGFBP-3)、胰岛素样生长因子-1(IGF-1)表达的影响。方法 70例特发性矮小症患儿,以随机数字表法分为对照组和观察组,各35例。对照组采用生长激素治疗,观察组在对照组基础上联合脾虚汤治疗。对比两组患儿治疗6、12个月后的身高增长量,治疗前后血清IGFBP-3、IGF-1指标改善情况。结果 观察组治疗6、12个月的身高增长量(5.3±0.6)、(11.2±0.8)cm均高于对照组的(4.1±1.0)、(8.9±0.9)cm,差异有统计学意义(P<0.05);观察组治疗后的血清IGFBP-3(6.8±1.2)mg/L、IGF-1(452.0±14.1)ng/ml均高于对照组的(6.0±0.9)mg/L、(388.5±17.1)ng/ml,差异有统计学意义(P<0.05)。结论 特发性矮小症采用脾虚汤联合生长激素治疗,可有效改善患儿的血清IGFBP-3、IGF-1,促使身高增长,应用效果显著。

雷公藤多苷联合他克莫司及激素治疗难治性肾病综合征的效果及对血清sTNF-R1、IGFBP-2、CFH水平的影响

目的 探讨雷公藤多苷联合他克莫司及激素治疗难治性肾病综合征(RNS)的疗效对血清可溶性肿瘤坏死因子受体1(s TNF-R1)、胰岛素样生长因子结合蛋白-2(IGFBP-2)、补体因子H(CFH)水平的影响。方法 研究对象为2018年8月至2021年8月于江南大学附属医院治疗的RNS患者102例,以随机数字表法分为对照组(n=51,采取甲泼尼龙片加他克莫司胶囊治疗)和观察组(n=51,在对照组基础上给予雷公藤多苷片治疗)。评估两组的治疗效果、血清相关指标,统计两组的不良反应。结果 观察组治疗总有效率(96.08%)高于对照组(80.39%)(χ^(2)=6.044,P=0.014);治疗后,观察组患者血清白蛋白、CFH水平[分别为(36.54±8.11) g·L^(-1)、(586.20±100.72)μg·m L^(-1)],高于对照组[分别为(32.58±6.12) g·L^(-1)、(540.11±100.47)μg·m L^(-1)],差异均有统计学意义(t=2.783,P=0.006;t=2.314,P=0.023);观察组患者24 h尿蛋白、肌酐、s TNF-R1、IGFBP-2水平[分别为(2.67±0.69) g、(82.25±16.13)μmol·L^(-1)、(1.56±0.45) ng·m L^(-1)、(51.34±10.44) ng·m L^(-1)],低于对照组[分别为(3.24±1.02) g、(92.68±17.35)μmol·L^(-1)、(1.91±0.58) ng·m L^(-1)、(57.79±12.58) ng·m L^(-1)],差异均有统计学意义(t=3.306,P=0.001;t=3.135,P=0.002;t=3.405,P=0.001;t=2.820,P=0.005);观察组复发率(1.96%)低于对照组(13.73%)(χ^(2)=4.883,P=0.027)。结论 公藤多苷联合他克莫司及激素治疗RNS效果佳,降低复发率,改善肾功能,减轻炎症,有望作为辅助治疗RNS的药物。

血清IGFBP-1、IGFBP-7与SiewertⅡ、Ⅲ型食管胃结合部腺癌患者临床病理参数和预后的关系

目的分析血清胰岛素生长因子结合蛋白(IGFBP)-1、IGFBP-7与SiewertⅡ、Ⅲ型食管胃结合部腺癌(AEG)患者临床病理参数和预后的关系。方法选取2019年1月至2020年11月山东省聊城市第二人民医院收治的264例SiewertⅡ、Ⅲ型AEG患者作为AEG组,另选取同期在山东省聊城市第二人民医院体检中心体检的112例健康志愿者作为对照组。检测所有研究对象的血清IGFBP-1、IGFBP-7水平并统计AEG患者的临床病理参数。随访患者3年生存情况,根据生存情况将患者分为死亡组和存活组。以IGFBP-1、IGFBP-7的均值界限将患者分为高水平IGFBP-1组、低水平IGFBP-1组、高水平IGFBP-7组、低水平IGFBP-7组。采用Kaplan-Meier生存曲线分析IGFBP-1、IGFBP-7水平与SiewertⅡ、Ⅲ型AEG患者预后的关系。采用多因素Logistic回归分析SiewertⅡ、Ⅲ型AEG患者死亡的危险因素。绘制受试者工作特征(ROC)曲线分析血清IGFBP-1、IGFBP-7对SiewertⅡ、Ⅲ型AEG患者死亡的预测价值。结果AEG组血清IGFBP-1、IGFBP-7水平低于对照组,差异均有统计学意义(P<0.05)。肿瘤最大径≥4 cm、低中分化患者血清IGFBP-1、IGFBP-7水平分别低于肿瘤最大径<4 cm、高分化患者,差异均有统计学意义(P<0.05)。随访期间死亡75例,存活189例。高水平IGFBP-1组、低水平IGFBP-1组、高水平IGFBP-7组、低水平IGFBP-7组患者分别有129、135、136、128例。低水平IGFBP-1组3年生存率为59.26%,低于高水平IGFBP-1组的81.40%(P=0.017)。低水平IGFBP-7组3年生存率为57.81%,低于高水平IGFBP-7组的81.26%(P=0.011)。死亡组低中分化、淋巴管侵犯、壁外血管侵犯患者比例高于存活组,血清IGFBP-1、IGFBP-7水平低于存活组,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,低中分化程度、淋巴管侵犯、IGFBP-1水平降低、IGFBP-7水平降低是SiewertⅡ、Ⅲ型AEG患者死亡的危险因素(P<0.05)。ROC曲线分析结果显示,IGFBP-1、IGFBP-7单独及2项指标联合预测SiewertⅡ、Ⅲ型AEG患者死亡的曲线下面积分别为0.741、0.722、0.786。结论SiewertⅡ、Ⅲ型AEG患者血清IGFBP-1、IGFBP-7水平显著降低,与肿瘤最大径、分化程度有关。低水平IGFBP-1、IGFBP-7与SiewertⅡ、Ⅲ型AEG患者死亡有关。血清IGFBP-1联合IGFBP-7对SiewertⅡ、Ⅲ型AEG患者死亡的预测价值较高。

肝癌患者血清IGFBP1的表达及其临床意义

目的探究肝癌患者血清胰岛素生长因子结合蛋白1(insulin growth factor binding protein 1,IGFBP1)的表达变化及其临床意义。方法回顾性选取于武汉大学中南医院就诊的体检正常对照个体(CTL组,n=32)、慢性乙型肝炎患者(CHB组,n=32)和肝癌患者(HCC组,n=64)。采用-80℃冻存上述研究对象的血清标本,酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测血清中IGFBP1的水平,3组间差异比较采用单因素方差分析,事后两两比较采用LSD-t检验;不符合正态分布的计量资料多组间差异比较采用Kruskal-Wallis H检验,并一步两两比较;计数资料组间差异比较采用Fisher确切概率法;相关性分析采用Spearman法,受试者工作特征(receiver operating characteristic,ROC)曲线用于评价血清IGFBP1的诊断效能,二元Logistic回归分析用于血清IGFBP1水平对肝癌的风险评估。结果HCC组患者的血清IGFBP1表达水平明显高于CTL组和CHB组,差异有统计学意义(H=29.427,P<0.001);乙型肝炎病毒(hepatitis B virus,HBV)感染不影响血清IGFBP1水平。血清IGFBP1水平与经典的肝癌血清蛋白标志物甲胎蛋白(alpha fetoprotein,AFP)存在较强的正相关关系(r=0.484,P<0.001),其诊断效能为(AUC=0.773,95%CI:0.693~0.852,P<0.001)。二元Logistic回归分析结果显示,血清IGFBP1升高是肝癌的风险因子(OR=1.049,95%CI:1.014~1.084,P=0.005)。结论肝癌患者血清中IGFBP1水平升高是肝癌的风险因素,对肝癌的诊断具有一定的临床价值。

CXCR1、ESM-1及IGFBP-2与COPD合并肺部感染患者疾病严重程度、预后的关系

目的 分析血清趋化因子受体1(CXCR1)、内皮细胞特异性分子-1(ESM-1)、胰岛素样生长因子结合蛋白2(IGFBP-2)水平与慢性阻塞性肺疾病(COPD)合并肺部感染患者疾病严重程度、预后的关系。方法 选取2021年1月至2023年1月于阜阳市人民医院就诊的COPD患者325例,根据肺部感染情况分为感染组及未感染组。比较两组入院时的血清CXCR1、ESM-1、IGFBP-2水平及常规感染指标[C-反应蛋白(CRP)、降钙素原(PCT)]水平,采用Pearson相关分析感染组上述指标的关系。比较不同病情严重程度COPD合并肺部感染患者入院时的CXCR1、ESM-1、IGFBP-2水平。对感染组患者跟踪随访6个月或死亡止,根据预后情况分为存活亚组及死亡亚组,比较两亚组患者入院时的血清CXCR1、ESM-1、IGFBP-2水平;采用受试者工作曲线(ROC)分析上述指标对COPD合并肺部感染患者死亡的预测价值。结果 325例COPD患者包括感染组109例及未感染组216例。感染组患者入院时的血清CXCR1、ESM-1、IGFBP-2、CRP、PCT水平高于未感染组,差异有统计学意义(P<0.05)。不同病情严重程度COPD合并肺部感染患者入院时的血清CXCR1、ESM-1、IGFBP-2水平比较差异有统计学意义(P<0.05)。Pearson相关分析显示,感染组入院时的血清CRP水平与CXCR1、ESM-1水平呈正相关(P<0.05)。随访期间感染组死亡19例(17.43%),存活90例(82.57%),死亡亚组入院时的血清CXCR1、ESM-1、IGFBP-2水平高于存活亚组,差异有统计学意义(P<0.05)。ROC结果显示,血清CXCR1、IGFBP-2水平预测COPD合并肺部感染患者死亡具有一定局限性(AUC=0.636、0.769),ESM-1的预测效能较好(AUC=0.827),CXCR1+ESM-1+IGFBP-2三项联合诊断的预测效能最佳(AUC=0.904)。结论 血清CXCR1、ESM-1、IGFBP-2水平在COPD合并肺部感染患者的疾病严重程度及预后评估方面具有一定指导意义。

2型糖尿病患者血清IGF-1、IGFBP-3表达与甲状腺功能减退的相关性

目的探讨2型糖尿病(T2DM)患者胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)表达与甲状腺功能减退的相关性。方法选取2022年1月-2023年3月在本院就诊的单纯T2DM患者63例为T2DM组,并选取同期T2DM伴甲状腺功能减退患者60例为研究组以及健康体检者60例为健康组。收集受试者一般资料和生化指标,酶联免疫吸附法检测血清IGF-1、IGFBP-3水平,化学发光法检测游离三碘甲状腺原氨酸(FT 3)、游离甲状腺素(FT 4)、促甲状腺激素(TSH)、甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TgAb)。采用Pearson相关系数分析IGF-1、IGFBP-3与其他指标相关性;采用Logistic回归分析T2DM患者甲状腺功能减退的影响因素。结果研究组、T2DM组BMI、空腹血糖(FPG)、餐后两小时血糖(2 h PG)、空腹胰岛素(FINS)、糖化血红蛋白(HbAlc)、TC、TG、LDL、Cr、BUN、血尿酸(UA)、TSH、甲状腺过氧化物酶抗体(TPOAb)、抗甲状腺球蛋白抗体(TgAb)显著高于健康组,HDL、FT 3、FT 4、IGF-1、IGFBP-3低于健康组(均P<0.05);研究组FPG、HbAlc、TC、TG、LDL、Cr、UA、TSH、TPOAb、TgAb显著高于T2DM组,HDL、FT 3、FT 4、IGF-1、IGFBP-3低于T2DM组(均P<0.05)。研究组血清IGF-1、IGFBP-3与FPG、FINS、HbAlc、TC、TSH、TgAb呈负相关(P<0.05)。FPG、HbAlc、TC、TSH、IGF-1、IGFBP-3是T2DM患者甲状腺功能减退发生的影响因素(P<0.05)。结论T2DM伴甲状腺功能减退患者血清IGF-1、IGFBP-3水平异常降低,二者与甲状腺功能减退的发生密切相关。

基于维生素K2、IGFBP-3、Omentin-1构建特发性矮小症儿童疗效预测模型的研究

目的探讨维生素K_(2)、胰岛素样生长因子结合蛋白3(IGFBP-3)、网膜素(Omentin-1)与特发性矮小症(ISS)儿童疗效的关系,并以此构建预测模型。方法选取2019-2021年济南市第二妇幼保健院收治的242例ISS儿童,均接受重组人生长激素(rhGH)治疗,根据治疗12个月后的疗效分为有效组和无效组。统计两组一般资料及维生素K2、IGFBP-3、Omentin-1水平,采用Logistic回归模型、决策树模型分析ISS儿童治疗疗效的影响因素,采用受试者工作特征(ROC)曲线分析两种模型预测效能。结果两组25-羟维生素D[25(OH)D]、甲状旁腺激素(PTH)、促甲状腺激素(TSH)、维生素K2、IGFBP-3、Omentin-1、rhGH剂量、每周户外运动时间比较,差异有统计学意义(P<0.05);PTH(OR=7.011,95%CI:2.456~20.014)、维生素K2(OR=0.605,95%CI:0.465~0.788)、IGFBP-3(OR=0.458,95%CI:0.321~0.654)、Omentin-1(OR=0.514,95%CI:0.389~0.679)、rhGH剂量(OR=0.563,95%CI:0.445~0.712)是ISS儿童治疗无效的影响因素(P<0.05);决策树模型显示,维生素K2、IGFBP-3、Omentin-1是ISS治疗疗效的影响因素,其中IGFBP-3的影响最为显著;ROC曲线结果显示,决策树模型、Logistic回归模型对预测ISS治疗无效的曲线下面积分别为0.922、0.908,模型分类效果均良好。结论ISS儿童的治疗疗效受维生素K2、IGFBP-3、Omentin-1等因素影响,且IGFBP-3影响最为显著,Logistic回归模型、决策树模型可互为补充,从不同方面为改善ISS儿童治疗疗效提供参考。

血清Nesfatin-1、IGFBP-3、FGF-21联合检测对特发性矮小症的诊断价值

目的探究血清摄食抑制因子(Nesfatin-1)、类胰岛素生长因子结合蛋白3(IGFBP-3)、成纤维细胞生长因子21(FGF-21)联合检测对特发性矮小症(ISS)的诊断价值。方法本研究选取2022年6月至2023年6月期间在本院诊治的85例ISS患儿记为ISS组,另选74例在本院体检的儿童记为对照组,记录两组儿童一般资料并进行比较分析。酶联免疫吸附实验(ELISA)检测受试者血清Nesfatin-1、IGFBP-3、FGF-21;使用原子吸收光谱仪测定受试者血清营养元素钙(Ca)、镁(Mg)、铜(Cu)、铁(Fe)、锌(Zn)的水平。X线骨密度仪检查受试者骨龄(BA)。Pearson相关性分析ISS患儿血清Nesfatin-1、IGFBP-3、FGF-21水平的相关性;多因素Logistic回归分析影响儿童发生ISS的影响因素;受试者工作特征(ROC)曲线分析Nesfatin-1、IGFBP-3、FGF-21水平对ISS的诊断价值;通过Z检验比较曲线下面积(AUC)的差异。结果与对照组相比,ISS组BA、身高、体重、BMI以及IGFBP-3、FGF-21水平较低,Nesfatin-1水平、性发育状态I级人数较高(P<0.05);ISS组患儿Nesfatin-1与IGFBP-3、FGF-21水平呈负相关(r_(Nesfatin-1 vs IGFBP-3)=-0.469,r_(Nesfatin-1 vs FGF-21)=-0.483),IGFBP-3与FGF-21水平呈正相关(r_(IGFBP-3 vs FGF-21)=0.456)(P<0.05);BA、性发育状态、IGFBP-3、FGF-21是儿童发生ISS的独立保护因素,而Nesfatin-1是儿童发生ISS的独立危险因素(P<0.05);Nesfatin-1、IGFBP-3、FGF-21单独诊断ISS的AUC分别为0.831、0.836、0.823,3者联合诊断ISS的AUC为0.928,优于单独及两两联合诊断(P<0.05)。结论ISS患儿血清中Nesfatin-1水平较高,IGFBP-3、FGF-21水平较低,3者是儿童发生ISS的影响因素,联合诊断ISS具有较高价值。