Interplay between micro RNA-17-5p, insulin-like growth factor-Ⅱ through binding protein-3 in hepatocellular carcinoma

AIM: To investigate the effect of microR NA on insulinlike growth factor binding protein-3(IGFBP-3) and hence on insulin-like growth factor-Ⅱ(IGF-Ⅱ) bioavailability in hepatocellular carcinoma(HCC).METHODS: Bioinformatic analysis was performed using microrna.org, DIANA lab and Segal lab softwares. Total RNA was extracted from 23 HCC and 10 healthy liver tissues using mir Vana mi RNA Isolation Kit. microR NA-17-5p(miR-17-5p) expression was mimicked and antagonized in Hu H-7 cell lines using Hi Per Fect Transfection Reagent, then total RNA was extracted using Biozol reagent then reverse transcribed into cD NA followed by quantification of mi R-17-5p and IGFBP-3 expression using Taq Man real-time quantitative PCR. Luciferase reporter assay was performed to validate the binding of miR-17-5p to the 3'UTR of IGFBP-3. Free IGF-Ⅱ protein was measured in transfected Hu H-7 cells using IGF-Ⅱ ELISA kit. RESULTS: Bioinformatic analysis revealed IGFBP-3 as a potential target for miR-17-5p. Screening of miR-17-5p and IGFBP-3 revealed a moderate negative correlation in HCC patients, where mi R-17-5p was extensively underexpressed in HCC tissues(P = 0.0012), while IGFBP-3 showed significant upregulation in the same set of patients(P = 0.0041) compared to healthy donors. Forcing mi R-17-5p expression in Hu H-7 cell lines showed a significant downregulation of IGFBP-3 mR NA expression(P = 0.0267) and a significant increase in free IGF-Ⅱ protein(P = 0.0339) compared to mock untransfected cells using unpaired t-test. Luciferase assay validated IGFBP-3 as a direct target of mi R-17-5p; luciferase activity was inhibited by 27.5% in cells co-transfected with miR-17-5p mimics and the construct harboring the wild-type binding region 2 of IGFBP-3 compared to cells transfected with this construct alone(P = 0.0474).CONCLUSION: These data suggest that regulating IGF-Ⅱ bioavailability and hence HCC progression can be achieved through targeting IGFBP-3 via manipulating the expression of miR NAs.

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.

Serum measurements of testosterone, insulin-like growth factor 1, and insulin-like growth factor binding protein-3 in the diagnosis of prostate cancer among Korean men

Aim： To investigate the relationships of serum testosterone, insulin-like growth factor （IGF）- 1 and IGF-binding protein （IGFBP）-3 levels with prostate cancer risk and also with known prognostic parameters of prostate cancer in Korean men who received radical retropubic prostatectomy （RRP） for clinically-localized prostate cancer. Methods： Serum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 were determined in 592 patients who subsequently received prostate biopsy. Results were compared between patients who eventually received RRP for prostate cancer （n = 159） and those who were not diagnosed with prostate cancer from biopsy （control group, n = 433）. Among the prostate cancer only patients, serum hormonal levels obtained were analyzed in relation to serum prostate specific antigen （PSA）, pathological T stage and pathological Gleason score. Results： Prostate cancer patients and the control group demon- strated no significant differences regarding serum levels of total testosterone, free testosterone, IGF-I and IGFBP-3 across the different age groups. Among the cancer only patients, no significant associations were observed for serum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 levels with pathological T stage, pathological Oleason score and preoperative PSA. Conclusion： Our data indicate that simple quantifications of serum testosterone and IGF-1 along with IGFBP-3 levels might not provide useful clinical information in the diagnosis of clinically localized prostate cancer in Korean men. Also, our results suggest that serum levels of testosterone, IGF-1 and IGFBP-3 might not be significantly associated with known prognostic factors of clinically localized prostate cancer in Korean men. （Asian J Androl 2008 Mar; 10： 207-213）

Increased expression of insulin-like growth factor-binding protein-3 is implicated in erectile dysfunction in two-kidney one-clip hypertensive rats after propranolol treatment

This study aimed to investigate the role of insulin-like growth factor-binding protein-3 （IGFBP-3） in erectUe dysfunction （ED） in two-kidney one-clip （2K-1C） hypertensive rats treated with the β-blocking agent propranolol. Adult male Wistar rats were randomly divided into three groups： a normal control group, a hypertensive control group and a propranolol treatment group （n=9）. After 4 weeks of propranolol treatment, intracavemous pressure （ICP） responses to electrical stimulation of the cavernous nerves were evaluated. The expression of IGFBP-3 and insulin-like growth factor-1 （IGF-1） mRNA and protein in the rat cavernous tissue were detected by quantitative real-time PCR and Western blot, respectively. The concentration of cyclic guanosine monophosphate （cGMP） in the cavernous tissue was determined by enzyme-linked immunosorbent assay （ELISA）. Cavernosal pressure in response to cavernous nerve stimulation was decreased 4 weeks after propranolol treatment （P〈0.01, compared to the hypertensive control group）. IGFBP-3 mRNA and protein expression was increased in the propranolol treatment group compared to the hypertensive control group （P〈O.01）, whereas IGF-1 expression was decreased in the propranolol treatment group compared to the hypertensive control group （P〈0.01）. In addition, cavernous cGMP concentration was decreased in the prepranolol treatment group compared to the hypertensive control group （P〈0.01）. Taken together, these results suggest that the upregulation of IGFBP-3 may play a role in the development of ED in hypertensive rats.

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.

Changes of insulin-like growth factor-Ⅱ and insulin-like growth factor binding protein-3 in cerebrospinal fluid of children with tuberculous meningitis

BACKGROUND： Recent studies have found that insulin-like growth factors （IGFs） and insulin-like growth factor binding protein-3 （IGFBP-3） have stronger neurotrophic and neuroprotective effects. But whether their levels in cerebrospinal fluid could be used as an auxiliary indicator in differentially diagnosing tuberculous meningitis and viral encephalitis is not yet clear. OBJECTIVE： To explore the changes of insulin-like growth factor-Ⅱ （IGF-Ⅱ ） and IGFBP-3 in cerebrospinal fluid （CSF） of children with tuberculous meningitis and the significance of the changes. DESIGN： A non-randomized concurrent controlled study. SETTING： Department of Pediatric Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College. PARTICIPANTS： Thirty children with tuberculous meningitis （14 males and 16 females） were selected from the Department of Pediatric Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College from January 2005 to December 2006. Tuberculous meningitis was diagnosed according to their clinical manifestations, the history of close contact with tuberculosis, typical cerebrospinal fluid changes of tuberculous meningitis, positive tuberculosis antibody and effective antituberculosis treatment. There were 30 children （13 males and 17 females） with viral encephalitis, and viral encephalitis was diagnosed according to epidemiological history, clinical manifestations, conventional and biochemical changes of cerebrospinal fluid, and negative bacteriology judgment. Meanwhile, 30 children （13 males and 17 females） without infectious and central nervous system disease were selected as the control group. Informed consent was obtained from the parents of all the enrolled children. METHODS： ①The lumbar puncture operation was implemented immediately to obtain cerebrospinal fluid （3 mL）. The contents of IGF-Ⅱ and IGFBP-3 were detected with immunoradiometric assay. The concentrations of glucose and protein in cerebrospinal fluid were determined with a dry-chemical method. The number of white blood cells was counted by Fushi Method. ②The Pearson correlation analysis was used to analyze the correlation of the contents of IGF-Ⅱ and IGFBP-3 in cerebrospinal fluid with the leucocyte counting and the concentrations of glucose and protein in cerebrospinal fluid. MAIN OUTCOME MEASURES： The contents of IGF- Ⅱ and IGFBP-3 in cerebrospinal fluid, and their correlation with the leucocyte counting and the concentrations of glucose and protein in cerebrospinal fluid. RESULTS： ①Contents of IGF-Ⅱ and IGFBP-3 in cerebrospinal fluid： The contents of IGF-Ⅱ and IGFBP-3 in cerebrospinal fluid in the tuberculous meningitis group were significantly higher than those in the encephalitis virus group and control group （P 〈 0.05）. There was no significant difference in the contents of IGF- Ⅱ and IGFBP-3 in cerebrospinal fluid between the viral encephalitis group and control group （P 〉 0.05）. ②Correlation： The IGF- Ⅱ and IGFBP-3 contents in cerebrospinal fluid were positively correlated with the protein concentration in cerebrospinal fluid （r =0.821, 0.855, P 〈 0.01）, but negatively with the glucose （r =0.742, - 0.605, P 〈 0.01）. CONCLUSION- ①IGFs and IGVBPs are involved in the pathophysiological process of tuberculous meningitis, as well as the glucose and protein metabolism in cerebrospinal fluid. ②The IGF-Ⅱ and IGFBP-3 contents in cerebrospinal fluid can be used as the auxiliary indicators to differentially diagnose tuberculous meningitis and viral enceohalitis.

Chondrogenesis of periodontal ligament stem cells by transforming growth factor-β3 and bone morphogenetic protein-6 in a normal healthy impacted third molar

The periodontal ligament-derived mesenchymal stem cell is regarded as a source of adult stem cells due to its multipotency.However, the proof of chondrogenic potential of the cells is scarce.Therefore,we investigated the chondrogenic differentiation capacity of periodontal ligament derived mesenchymal stem cells induced by transforming growth factor(TGF)-p3 and bone morphogenetic protein(BMP)-6.After isolation of periodontal ligament stem cells(PDLSCs) from human periodontal ligament,the cells were cultured in Dulbecco’s modified Eagle’s medium(DMEM) with 20%fetal bovine serum(FBS).A mechanical force initiated chondrogenic differentiation of the cells.For chondrogenic differentiation,10μg·LTGF-β3 or 100μg·LBMP-6 and the combination treating group for synergistic effect of the growth factors.We analyzed the PDLSCs by fluorescence-activated cell sorting and chondrogenesis were evaluated by glycosaminoglycans assay,histology,immunohistochemistry and genetic analysis.PDLSCs showed mesenchymal stem cell properties proved by FACS analysis.Glycosaminoglycans contents were increased 217%by TGF-β3 and 220%by BMP-6. The synergetic effect of TGF-β3 and BMP-6 were shown up to 281%compared to control.The combination treatment increased Sox9, aggrecan and collagen II expression compared with not only controls,but also TGF-P3 or BMP-6 single treatment dramatically.The histological analysis also indicated the chondrogenic differentiation of PDLSCs in our conditions.The results of the present study demonstrate the potential of the dental stem cell as a valuable cell source for chondrogenesis,which may be applicable for regeneration of cartilage and bone fracture in the field of cell therapy.

食管鳞癌中microRNA let-7a-3甲基化与IGF-Ⅱ的相关性

目的探讨食管鳞癌组织中microRNA let-7a-3甲基化状态与血浆中类胰岛素样生长因子2(Insulin like growth factor 2,IGF-Ⅱ)表达的相关性。方法采用甲基化特异性PCR法(Methylation specific PCR,qMSP)检测83例食管癌及相对应的癌旁正常组织中let-7a-3甲基化状态,采用酶联免疫吸附试验(Enzyme linked immunosorbent assay,ELISA)检测血浆中IGF-Ⅱ的表达水平。结果83例食管鳞癌患者癌组织中的microRNA let-7a-3甲基化程度显著高于癌旁正常组织(P<0.001)。83例食管鳞癌患者血浆中IGF-Ⅱ的表达水平与let-7a-3基因的甲基化程度总体上呈正相关,具有统计学意义(r=0.600,P<0.001)。结论microRNA let-7a-3可能通过对下游分子的甲基化调控参与食管鳞癌的发生发展,这对了解食管鳞癌形成的机制具有重要意义,可为食管鳞癌的诊断和预后提供依据。

2型糖尿病合并甲状腺功能亢进患者血清Sema 5A、IGFBP-3水平与糖代谢指标的相关性分析

目的分析2型糖尿病合并甲状腺功能亢进(以下简称甲亢)患者血清信号素5A(Sema 5A)、胰岛素样生长因子结合蛋白-3(IGFBP-3)水平与糖代谢指标的相关性。方法选取2021年6月至2022年6月邯郸市中心医院收治的73例2型糖尿病合并甲亢患者作为合并组,56例单纯2型糖尿病患者作为糖尿病组,另选取同期在邯郸市中心医院体检的68例健康者作为对照组。比较对照组、糖尿病组、合并组血清Sema 5A、IGFBP-3水平,比较糖尿病组、合并组临床资料[体质量指数、糖尿病病程、空腹血糖(FBG)、餐后2 h血糖(2 h PG)、胰岛素(FIN)、甘油三酯、总胆固醇、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、糖化血红蛋白(HbA1c)、三碘甲腺原氨酸(T_(3))、甲状腺素(T_(4))、游离三碘甲腺原氨酸(FT_(3))、游离甲状腺素(FT_(4))、促甲状腺素(TSH)、促甲状腺激素受体抗体(TRAB)及甲状腺过氧化物酶抗体(TPOAB)、胰岛素抵抗指数(HOMA-IR)]。采用多因素Logisitic回归分析2型糖尿病并发甲亢的危险因素,采用Pearson相关分析2型糖尿病合并甲亢患者血清Sema 5A、IGFBP-3水平与糖代谢指标的相关性,绘制受试者工作特征(ROC)曲线分析血清Sema 5A、IGFBP-3对2型糖尿病合并甲亢的诊断价值。结果合并组血清Sema 5A、IGFBP-3水平高于对照组和糖尿病组,且糖尿病组高于对照组,差异均有统计学意义(P<0.05)。合并组糖尿病病程长于糖尿病组,血清HOMA-IR、FIN、HbA1c、T_(3)、T_(4)、FT_(3)、FT_(4)、TRAB、TPOAB水平高于糖尿病组,TSH水平低于糖尿病组,差异均有统计学意义(P<0.05)。多因素Logisitic回归分析结果显示,HOMA-IR、TPOAB、Sema 5A、IGFBP-3水平升高,TSH水平降低为2型糖尿病并发甲亢的危险因素(P<0.05)。Pearson相关分析结果显示,2型糖尿病并发甲亢患者血清Sema 5A、IGFBP-3水平与HOMA-IR、FBG、2 h PG、FIN、HbA1c、HDL-C水平均呈正相关(P<0.05)。2型糖尿病并发甲亢患者血清Sema 5A、IGFBP-3水平与LDL-C水平呈负相关(P<0.05)。ROC曲线分析结果显示,血清Sema 5A、IGFBP-3诊断2型糖尿病合并甲亢的曲线下面积(AUC)分别为0.854、0.804,2项指标联合诊断的AUC为0.900,且2项指标联合诊断的AUC高于Sema 5A、IGFBP-3单独诊断的AUC(Z联合-Sema 5A=2.156,P=0.043;Z联合-IGFBP-3=2.873,P=0.004)。结论2型糖尿病合并甲亢患者血清Sema 5A、IGFBP-3水平升高,且二者与糖代谢指标密切相关。

高危儿体格发育情况影响因素分析及胰岛素样生长因子1和胰岛素样生长因子结合蛋白3对高危儿体格发育的预测价值

目的 分析高危儿体格发育情况的影响因素及胰岛素样生长因子1(IGF-1)、胰岛素样生长因子结合蛋白3(IGFBP-3)对高危儿体格发育的预测价值。方法 选取2021年10月—2022年8月北京大学第一医院宁夏妇女儿童医院产科出生的105例高危儿为研究对象,统计高危儿体格发育情况,检测高危儿IGF-1、IGFBP-3水平。结果 105例高危儿中,74例体格发育正常,占70.48%。单因素分析显示:与体格发育正常高危儿相比,体格发育不良高危儿出生体质量<1.5 kg(35.14%vs.74.19%)、出生身长<47 cm(39.19%vs.77.42%)、未添加营养补充剂(28.38%vs.58.06%)、母乳喂养(24.32%vs.41.94%)、人工喂养(18.92%vs.38.71%)、母亲文化程度高中及以下(33.78%vs.61.29%)、无多个看护人(36.49%vs.64.52%)、IGF-1<200 ng/ml(29.73%vs.74.19%)、IGFBP-3<5.0μg/ml(33.78%vs.70.97%)比例较高(均P<0.05)。多因素logistic回归分析结果显示:出生体质量、出生身长、是否添加营养补充剂、喂养方式、母亲文化程度、多个看护人、IGF-1、IGFBP-3为影响高危儿体格发育情况的主要因素(均P<0.05)。与IGF-1、IGFBP-3单项诊断相比,两项联合预测高危儿体格发育不良的灵敏度(58.06%vs.77.42%vs.93.55%)、准确度(72.38%vs.64.76%vs.90.48%)较高(均P<0.05)。结论 出生体质量、出生身长、是否添加营养补充剂、喂养方式、母亲文化程度、多个看护人、IGF-1、IGFBP-3为高危儿体格发育情况的影响因素,IGF-1、IGFBP-3联合检测对高危儿体格发育不良的预测价值较高。

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。

血清IGFBP-3、Gd-IgA1在儿童紫癜性肾炎早期诊断中的应用价值

目的 探索血清胰岛素样生长因子结合蛋白-3(IGFBP-3)及半乳糖缺乏免疫球蛋白A1(Gd-IgA1)联合检测在儿童紫癜性肾炎(HSPN)早期诊断中的应用价值。方法 选取2021年6月至2023年4月在该院确诊的105例首发过敏性紫癜(HSP)患儿作为研究对象,在入院后按照HSP是否累及肾脏将患儿分为HSPN组及无肾炎组(HSP组),同期选择在该院体检的52例健康儿童作为对照组(NC组)。收集3组临床资料,采用酶联免疫吸附试验(ELISA)对血清及尿液中IGFBP-3、Gd-IgA1表达水平进行检测,受试者工作特征(ROC)曲线分析血清IGFBP-3、Gd-IgA1对HSPN的早期诊断价值,多因素Logistic回归分析HSPN早期发生的影响因素。结果 与NC组相比,HSPN组及HSP组的IgA、IgG、补体C3、IgA/C3、白细胞计数(WBC)、红细胞计数(RBC)、血小板计数(PLT)及血清光抑素C(CysC)、血肌酐(sCr)水平显著升高(P<0.05),但HSPN组与HSP组的临床资料差异无统计学意义(P>0.05);HSPN组及HSP组血清IGFBP-3、Gd-IgA1及尿液IGFBP-3/尿肌酐(uCr)、Gd-IgA1/uCr表达水平较NC组显著升高(P<0.05),并且,与HSP组相比,HSPN组血清IGFBP-3、Gd-IgA1及尿液Gd-IgA1/uCr表达水平进一步升高(P<0.05);ROC曲线分析显示,联合IGFBP-3、Gd-IgA1诊断HSPN的曲线下面积(AUC)显著大于IGFBP-3单独诊断的AUC(Z=3.629,P<0.001)和Gd-IgA1单独诊断的AUC(Z=2.274,P=0.023);多因素Logistic回归分析显示,血清CysC、IGFBP-3、Gd-IgA1、尿液Gd-IgA1/uCr是HSPN早期发生的影响因素(P<0.05)。结论 HSPN患儿血清IGFBP-3、Gd-IgA1的表达水平均显著上升,二者是HSPN早期发生的影响因素,血清IGFBP-3、Gd-IgA1水平联合检测对HSPN的早期诊断具有较高的应用价值。

3D打印技术用于经鼻蝶窦入路垂体腺瘤切除术应用效果及对血清MMP-9和IGF-1水平的影响

目的:探究3D打印技术在经鼻蝶窦入路垂体腺瘤(PA)切除术的应用效果及对血清基质金属蛋白酶-9(MMP-9)和胰岛素样生长因子-1(IGF-1)水平的影响。方法:选取2020年5月至2022年5月秦皇岛市第一医院收治的84例PA患者,按照随机数表法将其分为观察组和对照组,每组42例。对照组行经鼻蝶窦入路垂体腺瘤切除术,观察组行经鼻蝶窦入路垂体腺瘤切除术联合应用3D打印技术,比较两组肿瘤切除效果、围术期指标、视力改善情况、MMP-9和IGF-1水平,以及鼻腔功能的鼻气道阻力(NAR)、T&T嗅觉测试评分及并发症。结果:观察组肿瘤切除效果优于对照组,差异有统计学意义(U=2.286,P<0.05);观察组手术时间、术中出血量及住院时间均少于对照组,差异有统计学意义(t=4.780、11.438、11.842,P<0.05);术后3 d、7 d时观察组血清MMP-9和IGF-1水平低于对照组,差异有统计学意义(F=7.526、4.985,P<0.05);术后1个月、3个月时观察组NAR及T&T嗅觉测试评分低于对照组,差异有统计学意义(F=6.359、8.436,P<0.05);两组视力视野改善情况及并发症发生率比较,差异无统计学意义(P>0.05)。结论:3D打印技术用于经鼻蝶窦入路垂体腺瘤切除术可提高肿瘤切除效果,优化手术操作,减少创伤,有利于减轻疼痛,改善嗅觉功能与视力视野,并能降低血清MMP-9、IGF-1水平,且安全性较高。

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。

血清GDF-15、chemerin、PTX3水平与2型糖尿病患者肥胖、胰岛素抵抗及炎症的关系及其预测效能的构建与评价

目的探讨血清生长分化因子-15(GDF-15)、趋化素(chemerin)、正五聚蛋白3(PTX3)水平与2型糖尿病(T2DM)患者肥胖、胰岛素抵抗及炎症因子的关系,并进行预测效能的构建及评价。方法选取2020年2月至2022年9月该院收治的T2DM患者231例作为T2DM组。另选取同期来该院体检的健康者100例作为对照组。采用酶联免疫吸附试验法检测并比较两组血清GDF-15、chemerin、PTX3水平,收集两组临床资料并进行比较。采用Pearson相关性分析及多元线性回归分析血清GDF-15、chemerin、PTX3水平与肥胖、胰岛素抵抗及炎症指标的关系。采用多因素Logistic回归评估T2DM发生的独立危险因素,并构建血清GDF-15、chemerin、PTX3联合预测模型,绘制受试者工作特征(ROC)曲线评价其对T2DM发生的预测效能。结果与对照组比较,T2DM组体重指数(BMI)、腰臀比(WHR)、收缩压、总胆固醇、甘油三酯、空腹血糖、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、白细胞介素(IL)-1β、IL-6、GDF-15、chemerin、PTX3均升高,差异有统计学意义(P<0.05)。Pearson相关性分析显示,T2DM组血清GDF-15、chemerin、PTX3水平与BMI、WHR、FINS、HOMA-IR、IL-1β、IL-6呈正相关(P<0.05)。多元线性回归分析显示,BMI、FINS、HOMA-IR、IL-1β、IL-6与血清GDF-15、chemerin、PTX3水平呈正相关(P<0.05)。多因素Logistic回归分析结果发现,血清GDF-15、chemerin、PTX3水平升高是影响T2DM发生的独立危险因素(P<0.05)。ROC曲线分析结果显示,血清GDF-15、chemerin、PTX3联合预测模型预测效能较好,其曲线下面积及灵敏度、特异度、准确度均高于各指标单独应用。结论T2DM患者血清GDF-15、chemerin、PTX3水平升高,且其水平随着T2DM患者肥胖、胰岛素抵抗及炎症反应程度的加重而增加,该研究所构建的联合预测模型预测效能较好,对T2DM发生具有较高的预测价值。

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。

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.

Insulin-like growth factor-I receptor in proliferation and motility of pancreatic cancer

AIM:To develop a molecular therapy for pancreatic cancer, the insulin-like growth factor-I (IGF-I) signaling pathway was analyzed.METHODS: Pancreatic cancer cell lines (MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4) were cultured in media with 10 mL/L fetal bovine serum. Western blotting analysis was performed to clarify the expression of IGF-I receptor (IGF-IR). Picropodophyllin (PPP), a specific inhibitor of IGF-IR, LY294002, a specific inhibitor of phosphatidylinositol3 kinase (PI3K), and PD98059, a specific inhibitor of mitogen-activated protein kinase, were added to the media. After 72 h, a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay was performed to analyze cell proliferation. A wound assay was performed to analyze cell motility with hematoxylin and eosin (HE) staining 48 h after addition of each inhibitor. RESULTS: All cell lines clearly expressed not only IGF-IR but also phosphorylated IGF-IR. PPP significantly suppressed proliferation of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 36.9% ± 2.4% (mean ± SD), 30.9% ± 5.5%, 23.8% ± 3.9%, 37.1% ± 5.3%, 10.4% ± 4.5%, 52.5% ± 4.5% and 22.6% ± 0.4%, at 2 μmol/L, respectively (P < 0.05). LY294002 significantly suppressed proliferation of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 44.4% ± 7.6%, 32.9% ± 8.2%, 53.9% ± 8.0%, 52.8% ± 4.0%, 32.3% ± 4.2%, 51.8% ± 4.5%, and 30.6% ± 9.4%, at 50 μmol/L, respectively (P < 0.05). PD98059 did not significantly suppress cell proliferation. PPP at 2 μmol/L suppressed motility of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 3.0% ± 0.2%, 0%, 0%, 2.0% ± 0.1%, 5.0% ± 0.2%, 3.0% ± 0.1%, and 5.0% ± 0.2%, respectively (P < 0.05). LY294002 at 50 μmol/L suppressed motility of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 to 3.0% ± 0.2%, 0%, 3.0% ± 0.2%, 0%, 0%, 0% and 3% ± 0.1%, respectively (P < 0.05). PD980509 at 20 μmol/L did not suppress motility. Cells were observed by microscopy to analyze the morphological changes induced by the inhibitors. Cells in medium treated with 2 μmol/L PPP or 50 μmol/L LY294002 had pyknotic nuclei, whereas those in medium with 20 μmol/L PD98059 did not show apoptosis.CONCLUSION: IGF-IR and PI3K are good candidates for molecular therapy of pancreatic cancer.

血清LH、IGF-ⅠSDS、IGF-bp3诊断女童快速进展型中枢性性早熟的价值研究

目的分析血清黄体生成素(LH)、胰岛素样生长因子Ⅰ标准差积分(IGF-ⅠSDS)及胰岛素样生长因子结合蛋白3(IGF-bp3)在早期识别快速进展型中枢性性早熟(RP-CPP)和缓慢进展型中枢性性早熟(SP-CPP)患儿中的有效性,为临床进一步提高对女童RP-CPP的诊疗水平提供参考资料。方法回顾性分析2021年4月至2023年6月西安交通大学附属儿童医院收治的120例中枢性性早熟(CPP)女童患儿的临床资料,将其纳入研究组,按照线性生长或骨龄成熟加速等条件,将其分为RP-CPP组(71例),SP-CPP组(49例);纳入同期在院体检的青春期发育正常女童64例为对照组。比较不同人群LH、IGF-ⅠSDS及IGF-bp3水平的变化情况,采用多元Logistic回归分析影响儿童RP-CPP的相关危险因素,采用受试者工作特征(ROC)曲线评估LH、IGF-ⅠSDS及IGF-bp3预测RP-CPP的效能。结果研究组的LH、IGF-ⅠSDS、IGF-bp3及骨龄均明显高于对照组,经比较差异均有统计学意义(t值分别为26.256、47.930、20.390、14.008,P<0.05)。LH、IGF-ⅠSDS、IGF-bp3与骨龄均呈正相关(r值分别为0.435、0.502、0.397,P<0.05)。RP-CPP组的LH、IGF-ⅠSDS水平均明显高于SP-CPP组,经比较差异均有统计学意义(t值分别为7.867、33.943,P<0.05),但RP-CPP组与SP-CPP组的IGF-bp3水平比较,差异无统计学意义(P>0.05)。经多元Logistic回归分析显示,LH[OR(95%CI):1.962(1.172~3.285)]、IGF-ⅠSDS[OR(95%CI):1.707(1.142~2.552)]及IGF-bp3[OR(95%CI):2.314(1.221~4.384)]均是影响RP-CPP发生的危险因素(P<0.01)。经ROC曲线分析显示,LH、IGF-ⅠSDS及IGF-bp3单独预测RP-CPP的曲线下面积(AUC)从高到低依次为0.799、0.762、0.714,三者联合预测RP-CPP的AUC为0.864,其明显高于各指标单独预测的结果(P<0.001)。结论CPP女童的血清LH、IGF-ⅠSDS及IGF-bp3水平均存在异常,通过检测患儿的上述指标变化,可有效地预测病情的进展,LH、IGF-ⅠSDS及IGF-bp3水平较高者发生RP-CPP的风险相对较大。