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.

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.

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.

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.

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.

N6-甲基腺苷甲基化相关基因IGF2BP3在肾透明细胞癌的作用研究

目的筛选肾透明细胞癌(ccRCC)中的关键N6-甲基腺苷(m^(6)A)甲基化相关基因,并研究其与ccRCC预后、ccRCC细胞的迁移和侵袭的关系。方法从癌症基因组图谱(TCGA)和基因型组织表达(GTEx)数据库中下载ccRCC和癌旁组织的RNA测序数据和临床数据,采用R4.1.1分析表达谱和预后,并筛选关键基因。收集10例ccRCC手术临床标本,采用定量PCR(qPCR)和免疫组织化学法分别检测基因mRNA和蛋白表达。在人ccRCC细胞系RCC23中,通过SiRNA敲减关键基因,并用CCK-8检测细胞的存活率,采用划痕试验和Transwell试验分别检测细胞的迁移和侵袭。结果19个m^(6)A甲基化相关基因中仅有胰岛素样生长因子ⅡmRNA结合蛋白3(IGF2BP3)在ccRCC组织中高表达,且IGF2BP3高表达与ccRCC患者预后不良呈正相关。通过qPCR和免疫组织化学法在临床标本中验证了IGF2BP3的高表达。通过小干扰RNA(siRNA)将IGF2BP3敲减后发现,RCC23细胞的存活率明显下降,且细胞的迁移和侵袭能力下降。结论IGF2BP3可能是预测ccRCC患者预后的生物标志物和潜在的药物治疗靶点。

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.

输尿管软镜钬激光碎石术后尿路感染患者血清sTREM-1、RBP4、HBD-3水平变化及检测意义

目的:探讨输尿管软镜钬激光碎石术(FURL)后尿路感染(UTI)患者血清可溶性髓样细胞触发受体-1(sTREM-1)、视黄醇结合蛋白4(RBP4)、人β-防御素-3(HBD-3)水平变化及检测意义。方法:选取行FURL患者183例,根据患者术后是否发生UTI分为UTI组(98例)和非UTI组(85例)。比较两组临床资料及血清sTREM-1、RBP4、HBD-3水平。采用多因素Logistic回归分析患者FURL术后发生UTI的影响因素。分析血清sTREM-1、RBP4、HBD-3对患者FURL术后发生UTI的预测价值。结果:UTI组有泌尿道手术史、导尿管留置时间≥7 d、抗菌药物种类>3种患者比例高于非UTI组(均P<0.05)。UTI组血清sTREM-1、RBP4、HBD-3水平高于非UTI组(均P<0.05)。泌尿道手术史、导尿管留置时间、抗菌药物种类及血清sTREM-1、RBP4、HBD-3是患者FURL术后发生UTI的影响因素(均P<0.05)。血清sTREM-1、RBP4、HBD-3水平与患者泌尿道手术史、导尿管留置时间及抗菌药物种类呈正相关(均P<0.05)。血清sTREM-1、RBP4、HBD-3联合预测患者FURL术后发生UTI的曲线下面积(AUC)为0.894,高于三者独立预测的AUC(均P<0.05)。结论:FURL术后UTI患者血清sTREM-1、RBP4、HBD-3水平升高,三者联合对FURL术后发生UTI具有较高的预测价值。

特发性中枢性性早熟女童IGF-1、IGFBP-3与Tanner分期的关系

目的:分析特发性中枢性性早熟(ICPP)女童血清胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)与Tanner分期的关系。方法:回顾性分析2022年11月—2023年11月抚州市第一人民医院收治的80例ICPP女童的临床资料。根据ICPP女童乳房发育情况(Tanner分期)分为B2组(n=18)、B3组(n=39)、B4组(n=15)、B5组(n=8),比较四组IGF-1、IGFBP-3水平,使用Spearman相关性模型分析ICPP女童IGF-1、IGFBP-3水平与Tanner分期的相关性。同期纳入本院收治的40例单纯乳房早发育(SPT)女童,比较ICPP女童和SPT女童的IGF-1、IGFBP-3水平。以受试者操作特征(ROC)曲线评估IGF-1、IGFBP-3水平诊断ICPP的价值。结果:不同Tanner分期ICPP女童IGF-1、IGFBP-3水平比较,差异均有统计学意义(P<0.05);B2组IGF-1、IGFBP-3水平均低于B3组,B3组均低于B4组,B4组均低于B5组,差异均有统计学意义(P<0.05)。经Spearman相关性模型分析,IGF-1、IGFBP-3水平与Tanner分期均呈正相关(P<0.05)。ICPP女童IGF-1、IGFBP-3水平均高于SPT女童,差异均有统计学意义(P<0.05)。ROC曲线显示,IGF-1、IGFBP-3水平诊断ICPP的曲线下面积(AUC)分别为0.939、0.797,敏感度分别为90.00%、88.75%,特异度分别为85.00%、60.00%。结论:IGF-1、IGFBP-3水平诊断ICPP有较高价值,且与Tanner分期密切相关。

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。

附子理中汤联合骨髓间充质干细胞调控变应性鼻炎大鼠鼻黏膜T-bet和GATA3 mRNA表达的研究

目的研究附子理中汤联合骨髓间充质干细胞(MSCs)对变应性鼻炎大鼠鼻黏膜T盒转录因子(T-bet)、锌指蛋白3(GATA3)mRNA表达的影响。方法将40只雄性SD大鼠随机分为5组,每组8只。对照组大鼠不造模、不干预;模型组、MSCs组、附子理中汤组、附子理中汤+MSCs组大鼠均进行变应性鼻炎造模,其中模型组造模后不治疗,MSCs组造模后给予骨髓MSCs尾静脉注射1次,附子理中汤组造模后给予附子理中汤连续灌胃14 d,附子理中汤+MSCs组造模后给予骨髓MSCs尾静脉注射1次和附子理中汤连续灌胃14 d。比较各组大鼠干预前后的行为学积分;干预结束后ELISA法检测鼻腔灌洗液中白细胞介素-4(IL-4)、白细胞介素-13(IL-13)、干扰素-γ(IFN-γ)水平,qRT-PCR法检测鼻黏膜组织中T-bet和GATA3 mRNA表达情况。结果MSCs组、附子理中汤组和附子理中汤+MSCs组大鼠干预后行为学积分均明显低于干预前及模型组(P均<0.05),且附子理中汤+MSCs组大鼠干预后行为学积分均明显低于MSCs组和附子理中汤组(P均<0.05)。与对照组比较,模型组大鼠鼻腔灌洗液中IL-4、IL-13水平和鼻黏膜组织中GATA3 mRNA相对表达量均明显升高(P均<0.05),鼻腔灌洗液中IFN-γ水平和鼻黏膜组织中T-bet mRNA相对表达量均明显降低(P均<0.05)。与模型组比较,MSCs组、附子理中汤组和附子理中汤+MSCs组大鼠鼻腔灌洗液中IL-4、IL-13水平和鼻黏膜组织中GATA3 mRNA相对表达量均明显降低(P均<0.05),附子理中汤组和附子理中汤+MSCs组大鼠鼻腔灌洗液中IFN-γ水平和鼻黏膜组织中T-bet mRNA相对表达量均明显升高(P均<0.05),MSCs组大鼠鼻腔灌洗液中IFN-γ水平和鼻黏膜组织中T-bet mRNA相对表达量均无明显变化(P均>0.05);且附子理中汤+MSCs组大鼠鼻腔灌洗液中IL-4、IL-13水平和鼻黏膜组织中GATA3 mRNA相对表达量均明显低于MSCs组(P均<0.05),鼻腔灌洗液中IFN-γ水平和鼻黏膜组织中T-bet mRNA相对表达量均明显高于MSCs组(P均<0.05)。结论附子理中汤联合骨髓MSCs能上调T-bet mRNA和下调GATA3 mRNA表达,进而调节Th1/Th2细胞的平衡,抑制炎症反应,改善变应性鼻炎症状。

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。

胃癌患者癌组织LDOC1、GNL3L表达及其与病理特征、预后的关系

目的探讨胃癌患者癌组织中亮氨酸拉链下调因子1(LDOC1)、鸟嘌呤核苷酸结合蛋白样3-样蛋白(GNL3L)表达水平及与患者病理特征、预后的关系。方法收集2019年12月至2022年12月新乡市中心医院收治的65例胃癌患者癌组织标本(胃癌组)及对应癌旁组织标本(癌旁组)。采用免疫组化法检测组织中LDOC1、GNL3L表达水平。采用χ^(2)检验分析LDOC1、GNL3L表达与胃癌患者临床病理特征的关系,多因素Cox回归分析探讨影响胃癌患者预后的相关因素。结果胃癌组LDOC1阳性表达率(30.76%)低于癌旁组(61.52%),GNL3L阳性表达率(72.31%)高于癌旁组(43.07%)(χ^(2)=12.381、11.377,P<0.05)。低分化、肿瘤直径>3 cm、TNM分期Ⅲ/Ⅳ期、淋巴结转移的胃癌患者LDOC1阴性率、GNL3L阳性率高于中/高分化、肿瘤直径≤3 cm、TNM分期Ⅰ/Ⅱ期、无淋巴结转移患者(P<0.05)。LDOC1阳性表达患者3 a生存率(85.00%)高于LDOC1阴性表达患者(37.77%),GNL3L阳性表达患者3 a生存率(36.17%)低于GNL3L阴性表达患者(94.44%)(P<0.05)。低分化、TNM分期Ⅲ/Ⅳ期、淋巴结转移胃癌患者的3 a生存率低于中/高分化、TNM分期Ⅰ/Ⅱ期、无淋巴结转移患者(P<0.05)。多因素Cox回归分析显示,TNM分期Ⅲ~Ⅳ期(HR=2.113,95%CI:1.425~3.133)、淋巴结转移(HR=2.625,95%CI:1.564~4.404)、LDOC1阴性表达(HR=5.607,95%CI:3.408~9.224)、GNL3L阳性表达(HR=2.930,95%CI:1.716~5.003)是胃癌患者预后的危险因素(P<0.05)。结论LDOC1在胃癌患者中呈低表达,GNL3L在胃癌患者中呈高表达,二者均与患者临床病理特征、预后有关。

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。

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。

GATA3通过调控LIFR抑制人乳腺癌细胞的迁移能力

目的探究GATA结合蛋白3(GATA binding protein 3,GATA3)对乳腺癌细胞迁移能力的影响。方法在MCF7细胞中利用慢病毒载体介导的基因干涉技术敲低GATA3基因,使用实时定量荧光PCR(qRT-PCR)和蛋白质印迹检测GATA3和LIFR的mRNA和蛋白表达水平,Transwell实验检测MCF7细胞的迁移能力。在MCF7和T47D细胞中用染色质免疫沉淀(ChIP-qPCR)实验检测GATA3在LIFR的启动子区的结合位点。在敲低GATA3基因的MCF7细胞中回补LIFR,通过细胞划痕实验和Transwell实验检测MCF7细胞的迁移能力。结果与对照组相比,敲低GATA3基因的MCF7细胞的迁移能力增强(P_(均)<0.05)。与对照组相比,敲低GATA3基因的MCF7细胞的LIFR表达水平降低(P_(均)<0.05)。乳腺癌细胞MCF7与T47D中GATA3在LIFR的启动子区有结合(P_(均)<0.05)。在敲低GATA3基因的MCF7细胞中稳定过表达LIFR可以部分挽救GATA3基因敲低引起的细胞迁移能力的增强(P_(均)<0.05)。结论GATA3通过转录激活LIFR抑制乳腺癌细胞MCF7的迁移。

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。