Effects of ADAM12 abnormal expression on chondrocyte injury and IGFBP-related genes in patients with Kashin-Beck disease / 中华地方病学杂志

Objective:To investigate the role of a disintegrin and metalloprotease 12 (ADAM12) gene in chondrocyte injury in patients with Kashin-Beck disease (KBD) and its impact on genes related to insulin-like growth factor binding protein (IGFBP).Methods:Articular cartilage samples were obtained from 5 patients with KBD and 5 control subjects admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University. Chondrocytes were extracted and cultured in vitro. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to detect the expression levels of ADAM12 mRNA and protein in chondrocytes of patients with KBD and control subjects, respectively. Subsequently, ADAM12 gene overexpression was performed using lentivirus in chondrocytes of patients with KBD. MTT assay was used to detect changes in cell viability after ADAM12 gene overexpression, and qRT-PCR was used to detect the mRNA expression levels of chondrocyte differentiation related genes SRY-box transcription factor 9 (SOX9) and type Ⅱ collagen (COLⅡ), apoptosis-related gene B-cell lymphoma/leukaemia-2-associated X protein (BAX), and anabolic related genes IGFBP3 and IGFBP5. Results:The expression levels of ADAM12 mRNA and protein in chondrocytes of patients with KBD (0.57 ± 0.05, 0.81 ± 0.07) were significantly lower than those of control subjects (1.00 ± 0.00, 1.00 ± 0.00), and the differences were statistically significant ( t = - 24.50, - 3.61, P < 0.05). The results of MTT assay showed that the cell viability of chondrocytes in ADAM12 overexpression group (1.09 ± 0.05) was higher than that in empty vector control group (1.00 ± 0.08), and the difference was statistically significant ( t = 4.12, P = 0.031). The results of qRT-PCR showed that compared with empty vector control group, the mRNA expression levels of IGFBP3 (2.35 ± 0.79 vs 0.96 ± 0.25), IGFBP5 (2.13 ± 0.30 vs 0.98 ± 0.34), SOX9 (2.92 ± 0.51 vs 0.94 ± 0.36) and COLⅡ (6.45 ± 2.81 vs 0.87 ± 0.19) in ADAM12 overexpression group were significantly increased, and the differences were statistically significant ( t = 3.19, 5.16, 6.27, 4.10, P < 0.05); while the expression level of BAX mRNA (0.31 ± 0.06 vs 1.02 ± 0.22) was significantly decreased, and the difference was statistically significant ( t = - 11.16, P < 0.001). Conclusion:The ADAM12 gene may have a role in inhibiting apoptosis and promoting differentiation in chondrocyte injury in patients with KBD, and its overexpression can increase expression of IGFBP3 and IGFBP5.

Therapeutic effect of recombinant human growth hormone on children with growth hormone deficiency and different pituitary developmental conditions: a prospective study / 中国当代儿科杂志

OBJECTIVES@#To investigate the therapeutic effect of recombinant human growth hormone (rhGH) on children with growth hormone deficiency (GHD) and different pituitary developmental conditions.@*METHODS@#A prospective study was performed on 90 children with GHD who were admitted to Xuchang Maternity and Child Health Hospital from June 2020 to December 2021. According to pituitary height on the median sagittal plane, they were divided into three groups: pituitary dysplasia group (n=45), normal pituitary group (n=31), and enlarged pituitary growth group (n=14). The changes in body height, growth velocity, height standard deviation score and serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) were examined after treatment in the above three groups, and the differences of the above indices before and after treatment were compared among the three groups.@*RESULTS@#After treatment, all three groups had significant increases in body height, growth velocity, height standard deviation score, and the serum levels of IGFBP-3 and IGF-1 (P<0.05). Compared with the normal pituitary group, the pituitary dysplasia group and the enlarged pituitary growth group had significantly higher values in terms of the differences in body height, growth velocity, height standard deviation score, IGF-1, and IGFBP-3 before and after treatment (P<0.05). There was no significant difference in the incidence rate of adverse reactions among the three groups (P>0.05).@*CONCLUSIONS@#In GHD children with different pituitary developmental conditions, rhGH can promote bone growth and increase body height, especially in children with pituitary dysplasia and pituitary hyperplasia, with good safety.

Advances in the clinical value of tissue inhibitors of metalloproteinase-2 and insulin-like growth factor binding protein 7 in sepsis associated-acute kidney injury / 中华危重病急救医学

Sepsis is an important cause of acute kidney injury (AKI). About 60% of sepsis patients will develop AKI. At present, the standard of clinical diagnosis of AKI is still based on the changes in serum creatinine and urine volume. Because of its lag in time, it may lead to delay in treatment and increase the mortality. To find a new biomarker similar to "troponin" for the diagnosis of AKI, and to achieve the early diagnosis and prevention of AKI, is of great significance to reduce the mortality of AKI. In recent years, it has been found that tissue inhibitors of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) can be used for early diagnosis of sepsis associated-acute kidney injury (SA-AKI). They also have important values in risk stratification, prognosis judgment, intervention and other aspects of SA-AKI. In this paper, the research progress of the application of TIMP-2 and IGFBP7 in SA-AKI is reviewed.

Serum levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in children with autism spectrum disorder / 中国当代儿科杂志

OBJECTIVES@#To study the serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in children with autism spectrum disorder (ASD) and their association with the core symptoms of ASD.@*METHODS@#A total of 150 ASD children aged 2-7 years (ASD group) and 165 healthy children matched for age and sex (control group) who were recruited at the outpatient service of Chongqing Health Center for Women and Children were enrolled as subjects. Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to evaluate the core symptoms of the ASD children. Chemiluminescence was used to measure the serum levels of IGF-1 and IGFBP-3 in both groups.@*RESULTS@#The ASD group had a significantly lower serum level of IGF-1 than the control group (P<0.05). The children with severe ASD had significantly lower serum levels of IGF-1 and IGFBP-3 than those with mild-to-moderate ASD (P<0.001). For the children aged 2-3 years, the ASD group had a significantly lower serum level of IGF-1 than the control group (P<0.05). Boys had a significantly lower serum level of IGF-1 than girls in both ASD and control groups (P<0.05). The serum levels of IGF-1 and IGFBP-3 were negatively correlated with the total score of CARS (r=-0.32 and -0.40 respectively, P<0.001).@*CONCLUSIONS@#The reduction in serum IGF-1 level in early childhood may be associated with the development of ASD, and the serum levels of IGF-1 and IGFBP-3 are associated with the core symptoms of ASD children.

Insulin-like growth factor-binding protein-7 combined with sequential organ failure assessment can early predict sepsis associated acute kidney injury / 中华检验医学杂志

Objective:To explore the predictive value of serum tissue inhibitor of metalloproteinases-2(TIMP-2), insulin-like growth factor-binding protein-7 (IGFBP-7), angiopoietin-2 (Ang-2) and laboratory examination indicators in patients with sepsis associated acute kidney injury (SAKI).Methods:Present study included 69 patients with sepsis, who were admitted to the emergency department of Peking University Third Hospital from April 2017 to August 2018. Within 72 hours of admission, 28 cases developed SAKI. General clinical features including sequential organ failure assessment (SOFA), acute physiological and chronic health status score Ⅱ (APACHE Ⅱ) and laboratory examination indicators including white blood cells (WBC), neutrophil/lymphocyte ratio (NLR), procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), D-dimer, fibrinogen (Fib), urea, uric acid (UA) were analyzed and serum samples were obtained to detect the levels of biomarkers TIMP-2, IGFBP-7, and Ang-2. Multivariate logistic regression analysis was performed to determine independent risk factors of SAKI, and the receiver operating characteristic (ROC) area under the curve (AUC) was used to assess the early predictive value of biomarkers and laboratory examination indicators for SAKI.Results:Compared with the non-SAKI group, patients in the SAKI group had higher SOFA score, higher incidence of septic shock, higher NLR, PCT, CRP, D-dimer, and UA levels (all P<0.05). The levels of TIMP-2, IGFBP-7, TIMP-2×IGFBP-7 and Ang-2 in the SAKI group were 23.5 (17.3, 30.3)ng/ml, (185.6±47.2)ng/ml, 3.98(2.89, 6.00) (ng/ml) 2/1 000, 1 953 (950, 2 239) pg/ml respectively, which were significantly higher than those in the non-SAKI group (16.4[13.5, 22.4] ng/ml, [139.4±34.7]ng/ml, 2.28[1.57, 4.03](ng/ml) 2/1 000, 576[334, 1 076] pg/ml, respectively, all P<0.05). Logistic regression analysis showed that IGFBP-7 ( OR=1.039, 95%CI 1.000-1.079, P<0.05) and SOFA ( OR=1.521, 95%CI 1.144-2.022, P<0.05) are independent risk factors of SAKI. ROC curve analysis showed that the AUC of IGFBP-7 and SOFA scores for early prediction of SAKI was 0.805 (sensitivity 78.6%,specificity 78.3%), 0.832 (sensitivity 67.9%,specificity 82.9%) respectively. Combined both biomarkers, the AUC increased to 0.893 (sensitivity 82.1%, specificity 87.8%), the diagnostic performance was superior to IGFBP-7 or SOFA alone ( P<0.05). Conclusion:Elevated IGFBP-7 and SOFA are independent risk factors for sepsis associated acute kidney injury, and combined assessment with IGFBP-7 and SOFA can increase the diagnostic performance on the early detection of high-risk patients with SAKI.

Effect of miR-539-5p on ARN-509 sensitivity and malignant phenotype of androgen independent prostate cancer cells and its mechanism / 中华内分泌外科杂志

Objective:To study the effect of miR-539-5p on apalutamide (ARN-509) sensitivity and malignant phenotype of androgen independent prostate cancer cell line C4-2B and related mechanisms.Methods:Castrated resistant prostate cancer, castrated sensitive prostate cancer and benign prostate tissue were obtained. C4-2B cell lines were divided into blank group, transfection group (miR-539-5p plasmid) and control group (control plasmid). qPCR was used to detect the expression of miR-539-5p, androgen receptor (AR) and HSBP1 in the tissues and 3 group of cells. The protein expressions of AR and HSBP1 were detected by western blot. Transwell assay was used to detect the invasion and migration ability of three groups of cells. CCK-8 assay was used to detect the proliferation ability and semi-inhibitory concentration (IC50) of AR antagonist ARN-509. The colony forming ability of the three groups of cells was detected by plate cloning experiment.Results:Tissue-qPCR indicated that, in the benign prostate tissue, tumor tissue of castration sensitive patients and tumor tissue of castration resistant patients, the expressions of miR-539-5p were 0.29 ± 0.04, 0.17 ± 0.02 and 0.07 ± 0.01, the expressions of AR were 0.13 ± 0.02, 0.28 ± 0.04 and 0.79 ± 0.11, and the expressions of HSBP1 were 0.20 ± 0.03, 0.38 ± 0.04 and 0.72 ± 0.11, respectively. Compared with benign prostate tissue and prostate cancer tissue, the expression of AR and HSBP1 gene was higher in prostate cancer tissues with castration resistance, and the expression of miR-539-5p was lower. Cell-qPCR demonstrated that the expressions of miR-539-5p in blank group, control group and transfection group were 1.00±0.09, 1.07±0.11 and 7.19±0.51, the expressions of AR were 1.00±0.10, 1.03±0.14 and 0.51±0.08, and the expressions of HSBP1 were 1.00±0.10, 0.96±0.12 and 0.97±0.11. The expression of miR-539-5p in the transfection cells was significantly higher than that in the control group and the blank group, the expression of AR gene was significantly lower than that in the control group and the blank group, and there was no significant difference in the expression of HSBP1. Western blot showed that, in blank group, control group and transfection group, the protein expressions of AR were 1.00±0.10, 1.12±0.22 and 0.72±0.16, and the expressions of HSBP1 were 1.00±0.10, 0.94±0.18 and 0.48±0.11. The protein expression of AR and HSBP1 in the transfection group was significantly lower than that in the control group and the blank group. Transwell experiment showed that the invasion and migration of cells in the transfection group were significantly lower than that in the control group and the blank group. CCK-8 assay and plate cloning experiment showed that the proliferative capacity and the number of clone formation in the transfection group were significantly lower than those in the control group and the blank group, and the expression of AR and HSBP1 in the transfection group was significantly lower than that in the control group and blank group. Compared with the control group and blank group, the IC50 value of ARN-509 decreased significantly in the transfection group.Conclusion:miR-539-5p may inhibit the malignant phenotype and castration resistance of cells via interfering with the translation level of HSBP1.

Level and diagnostic value of serum insulin-like growth factor binding protein 7 in patients with gastric cancer / 国际肿瘤学杂志

Objective:To investigate the serum level of insulin-like growth factor binding protein 7 (IGFBP7) in patients with gastric cancer and its diagnostic significance.Methods:A total of 100 gastric cancer patients (gastric cancer group) including 49 patients with early gastric cancer (early gastric cancer group) , who were hospitalized in Sun Yat-sen University Cancer Center from May to December 2019 were selected as the research subjects, and 94 physical examination subjects during the same period were selected as the normal control group. The levels of serum IGFBP7 were detected by enzyme-linked immunosorbent assay. At the same time, the laboratory carcinoembryonic antigen (CEA) test results were collected. The relationships between the level of serum IGFBP7 and the clinicopathological features of gastric cancer patients were analyzed. The diagnostic value was evaluated by receiver operating characteristic (ROC) curve.Results:The level of serum IGFBP7 in the gastric cancer group was (1.595±0.159) ng/ml, and that in the normal control group was (1.850±0.328) ng/ml, with a statistically significant difference ( t=-0.26, P<0.001) , and among them, the level of serum IGFBP7 in the early gastric cancer group was (1.601±0.153) ng/ml, and there was a statistically significant difference compared with the normal control group ( t=-0.26, P<0.001) . The level of serum CEA in the gastric cancer group was 2.230 (2.043) ng/ml, and that in the normal control group was 1.805 (1.020) ng/ml, with a statistically significant difference ( U=0.45, P=0.004) , and among them, the level of serum CEA in the early gastric cancer group was 2.220 (1.780) ng/ml, and there was a statistically significant difference compared with the normal control group ( U=0.53, P=0.002) . There were no significant correlations between IGFBP7 and CEA level ( χ2=0.36, P=0.547) , age ( χ2=0.16, P=0.688) , gender ( χ2=0.97, P=0.326) , depth of invasion ( χ2=0.30, P=0.585) , lymph node metastasis ( χ2=0.17, P=0.684) , distant metastasis ( χ2=0.09, P=0.767) and TNM stage ( χ2=0.38, P=0.537) . ROC curve analysis showed that the area under the curve (AUC) of IGFBP7 for gastric cancer diagnosis was 0.84 (95% CI: 0.78-0.89) , the AUC of CEA for gastric cancer diagnosis was 0.62 (95% CI: 0.54-0.70) , and there was a statistically significant difference ( Z=4.33, P<0.001) . The AUC of IGFBP7 combined with CEA for gastric cancer diagnosis was 0.85 (95% CI: 0.79-0.90) . Compared with CEA alone, there was a statistically significant difference ( Z=4.97, P<0.001) . Compared with IGFBP7 alone, there was no statistically significant difference ( Z=1.41, P=0.159) . The AUC of IGFBP7 in the diagnosis of early gastric cancer was 0.84 (95% CI: 0.78-0.91) , the AUC of CEA in the diagnosis of early gastric cancer was 0.66 (95% CI: 0.56-0.75) , and there was a statistically significant difference ( Z=3.11, P=0.002) . The AUC of IGFBP7 combined with CEA in the diagnosis of early gastric cancer was 0.85 (95% CI: 0.78-0.91) . Compared with CEA alone, there was a statistically significant difference ( Z=3.54, P<0.001) . Compared with IGFBP7 alone, there was no statistically significant difference ( Z=1.19, P=0.232) . Conclusion:The serum IGFBP7 level of gastric cancer patients is lower than that of normal controls. Compared with CEA, serum IGFBP7 has better diagnostic value for gastric cancer.

Research progress of urine TIMP-2×IGFBP-7 in early diagnosis, risk stratification and prognosis of acute kidney injury / 中华检验医学杂志

Acute kidney injury (AKI) is a common complication in critically ill patients with complex etiology and high morbidity, which is closely related to the patient's mortality rate, hospital stay and long-term poor outcomes. Therefore, timely detection of AKI in the early reversible stage is particularly important to prevent its progression to renal failure and initiating renal replacement therapy. Therefore, exploring the relevant biomarkers in the occurrence and development of acute kidney injury has important clinical significance for the diagnosis and treatment of the disease. Tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein-7 (IGFBP-7) are used as cell cycle arrest proteins, which has shown certain advantages in the early diagnosis, risk stratification, prognosis judgment, and treatment effect of acute kidney injury. Cell cycle arrest protein [TIMP-2]×[IGFBP-7] plays a role in acute kidney injury caused by various reasons and can be used as a reference index for disease prognosis.

The predictive value of TIMP-2 and IGFBP7 in delayed renal function recovery after DCD renal transplantation / 中华泌尿外科杂志

Objective:This study is to investigate the predictive value of serum levels of TIMP-2 and insulin-like growth factor-binding protein 7(IGFBP7) in patients with DCD(donation after cardiac death) kidney transplantation.Methods:A prospective research design was used to select DCD kidney transplant patients admitted to the Li Huili Hospital of Ningbo University from January 2018 to October 2020.Inclusion criteria: ①Complete data; ②There were no serious complications affecting the function of the transplanted kidney in the early postoperative period.Exclusion criteria: ①Incomplete data; ②Patients were unable or unwilling to cooperate with the study; ③Severe complications affecting the function of the transplanted kidney occurred early after the operation.The ELASE method was used to quantitatively detect the serum TIMP-2 and IGFBP7 levels at 6, 12, 24, 48, 72 hours and 7 days after renal transplantation, and monitor the serum creatinine values during the same period and 21 days after the operation. According to the occurrence of DGF, the measured values of TIMP-2 and IGFBP7 at different time points and their product's ability to predict the occurrence of DGF after kidney transplantation were analyzed. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic efficacy of TIMP-2 and IGFBP7 for DGF.Results:A total of 33 patients were enrolled, 7 patients (21.2%) in the DGF group and 26 patients (78.8%) in the non-DGF group. Between the two groups, the donor glomerular filtration rate were [98.5(15.8-132.5)ml/(min·1.73m 2) and 79.1(60.6-102.5)ml/(min·1.73m 2)], recipient gender (male/female: 3/4 cases and 10/16 cases), recipient age [48(34-56) Years old and 45(23-61) years old], the recipient's preoperative creatinine [1114.0(731.4-1293.0)μmol/L and 858.4(657.6-1051.9)μmol/L], the recipient's preoperative urea nitrogen [15.0(13.2-19.6)mmol/L and 17.3(13.6-20.9)mmol/L], receptor preoperative albumin [43.5(38.5-45.3)mmol/L and 41.2(37.5-46.1) mmol/L], recipient dialysis method [hemodialysis/peritoneal dialysis: 3/4 cases and 9/17 cases], warm ischemia time [6(5-7) and 5(4-6) min, there was no statistically significant difference] ( P>0.05). The values of serum IGFBP7 and TIMP-2×IGFBP7 in the DGF group were higher than those in the non-DGF group at all time points ( F=15.753, P=0.040; F=13.000, P=0.024), while serum TIMP-2 was not significant between the two groups difference ( F=1.157, P=0.075). For the diagnostic value of DGF, the AUC of serum IGFBP7 at 48 h after surgery was 0.863 (95% CI 0.696-1.000, P=0.004). When 5.97 ng/ml was used as the cut-off value, the sensitivity was 85.7% and the specificity was 80.8 %. The AUC of TIMP-2×IGFBP7 at 48 hours after surgery was 0.819 (95% CI 0.641-0.996, P=0.011). When 62.06(ng/ml) 2 was used as the cutoff value, the sensitivity was 71.4% and the specificity was 80.8%.There was no statistical difference in the area under the curve between the two ( P>0.05). There were differences in the dynamic trend of serum IGFBP7 and creatinine in the DGF group. Serum IGFBP7 at 7 days after surgery was positively correlated with creatinine at 21 days after surgery. Conclusion:Serum IGFBP7 and TIMP-2×IGFBP7 could predict the occurrence of DGF after DCD donor kidney surgery. The predictive value changes with time. Among them, 48h and 7d after surgery are the most valuable. However, serum TIMP-2 has not been found to have predictive value in this study.

Gallbladder cancer-associated fibroblasts promote the migration of lymphatic endothelial cells via releasing IGFBP3 / 西安交通大学学报(医学版)

【Objective】 To investigate the effects of gallbladder cancer-associated fibroblasts (CAFs) on the migration of lymphatic endothelial cells (LECs) so as to elucidate the molecular mechanisms involved. 【Methods】 The CAFs and normal fibroblasts (NFs) were extracted by enzymatic digestion, and the supernatant (CM) of CAFs and NFs was collected. The levels of IL-6, IGFBP3 and other related cytokines were detected by semi-quantitative protein factor microarray and ELISA. The expressions of α-SMA (CAFs maker) and IGFBP3 in gallbladder cancer and para-cancer tissues were detected by immunohistochemistry, and the correlation of α-SMA and IGFBP3 expressions with clinicopathological characteristics were analyzed. LECs were cultured and divided into serum-free medium group (control group), CAF-CM co-culture group, NF-CM co-culture group, IGFBP3 group, and CAF-CM+IGFBP3 inhibitor (2-Deoxy-D-glucose, 2-DG) group according to different treatment. Transwell migration assays and wound healing assays were applied to analyze the migration ability of LECs under different treatment. The expressions of E-cadherin, N-cadherin and Vimentin were detected by Western blotting. 【Results】 Protein factor microarray and ELISA showed that the concentration of IGFBP3 in CAF-CM was significantly increased, and the expression of α-SMA was significantly related to lymph node metastasis, advanced TNM stage and expression of IGFBP3. IGFBP3 secreted from CAF-CM significantly promoted LECs migration, up-regulated the expression of N-cadherin and Vimentin, and down-regulated the expression of E-cadherin. Treatment with IGFBP3 inhibitor 2-DG could reverse the effect of CAF-CM on migration of LECs and related protein expressions. 【Conclusion】 Gallbladder CAFs promote the migration of LECs via releasing IGFBP3, which affects EMT transformation.

Influencing factors of serum insulin-like growth factor binding protein-3 level in radiological workers in medical institutions / 中华放射医学与防护杂志

Objective:To investigate the influence of low-dose ionizing radiation on the expression level of serum insulin-like growth factor binding protein-3 (IGFBP-3) in radiation workers in hospitals.Methods:183 radiation workers were randomly selected and grouped by work type including interventional radiology ( n=37), nuclear medicine ( n=43), radiotherapy ( n=48), and diagnostic radiology ( n=55). The content of IGFBP-3 in the serum of radiation workers was detected by ELISA assay. Results:It was observed that the expression level of serum IGFBP-3 in the four groups had significant differences ( F=6.056, P<0.05), and the content of serum IGFBP-3 in the interventional radiology group was significantly higher than that of nuclear medicine, radiotherapy, and diagnostic radiology groups ( t= 2.815, 3.611, 3.936, P<0.05). The concentration of IGFBP-3 in the serum of radiation workers among different annual effective dose groups was statistically different ( F=8.380, P<0.05), which gradually increased with the increase of annual effective dose and length of service ( rs=0.202, 0.151, P<0.05). Conclusions:The expression level of serum IGFBP-3 has the potential to be used as a biomarker to reflect the cumulative exposure of long-term chronic low-dose ionizing radiation.

Cardiovascular disease risk markers in children under 10 years of age and their relationship with serum concentrations of IGF-1, IGFBP-1, IGFBP-2 and IGFBP-3 / Marcadores de riesgo cardiovascular en niños menores de 10 años y su relación con niveles séricos de IGF-1, IGFBP-1, IG-FBP-2 e IGFBP-3

Abstract Introduction: Any type of nutritional imbalance experienced during childhood will affect the health of an individual, both in their childhood and their adulthood. Several studies have proved that there is an association between cardiovascular disease (CVD) risk and endocrine and lipid markers at early stages of life. Objective: To establish the relationship between nutritional status (IGF-1 and serum levels of its binding proteins IGFBP-1, IGFBP-2 and IGFBP-3), and CVD risk markers in students aged 7 to 9 years. Materials and methods: Cross-sectional observational study conducted in 84 children attending two schools from Bogotá D.C. and Soacha, Colombia, to identify the relationship between possible variations in CVD risk markers and nutritional status. Sexual development stage, lipid profile, anthropometric data, blood sugar levels and IGF-1 and IGFBP serum levels of all participants were measured. Statistical analysis was conducted using the Pearson's correlation coefficient, the analysis of variance (ANOVA), and the Kruskall-Wallis, Games-Howell and Dunnett's tests. The confidence interval and statistical significance were 95% and p<0.05, respectively. Results: IGFBP-1 and IGFBP-2 levels proportionally decreased as weight increased. An inverse correlation between both proteins and triglyceride levels was found, as well as a direct correlation with HDL cholesterol levels. Conclusions: Alterations in CVD risk markers can be identified during childhood. If said alterations are timely detected, it is possible to adopt preventive and therapeutic actions such as the promotion of public policies aimed at preventing childhood overweight and obesity, which in turn will reduce the risk of developing cardiovascular disease in adulthood.

Resumen Introducción. Los desequilibrios nutricionales en la infancia afectan la salud tanto en la niñez como en la adultez. Estudios previos demuestran la asociación de marcadores endocrinos y lipídicos con riesgo cardiovascular (RCV) desde edades tempranas. Objetivo. Establecer la relación entre estado nutricional (niveles séricos de IGF-1 y sus proteínas enlazantes IGFBP-1, IGFBP-2 e IGFBP-3) y marcadores de RCV en estudiantes de 7 a 9 años. Materiales y métodos. Estudio observacional comparativo transversal realizado en 84 niños de 2 colegios de Bogotá D.C. y Soacha, Colombia, para identificar la relación entre posibles variaciones de marcadores de RCV y estado nutricional. Se midieron los niveles de glucemia y niveles séricos de IGF-1 e IGFBP, el nivel de desarrollo sexual, el perfil lipídico y los valores antropométricos. Para el análisis estadístico se utilizaron el coeficiente de correlación de Pearson, un análisis de varianza (ANOVA) y las pruebas de Kruskal Wallis, Games-Howell y Dunnett. El intervalo de confianza fue del 95% y la significancia estadística, de p<0.05. Resultados. La reducción en los niveles de IGFB-1 e IGFBP-2 fue directamente proporcional al aumento de peso. Por otra parte, se observó una correlación inversa entre ambas proteínas y concentraciones de triglicéridos, y una directa con los niveles colesterol HDL. Conclusiones. Las alteraciones de marcadores de RCV se pueden identificar en la infancia. Si estas son detectadas a tiempo es posible adoptar medidas preventivas y terapéuticas como la promoción de políticas públicas dirigidas prevenir el sobrepeso infantil, lo que a su vez reducirá el riesgo de padecer enfermedades cardiovasculares en edades adultas.

Protective effect of cardiomyopeptide on doxorubicin induced cell injury in H9c2 cardiomyocytes / 中国药理学通报

Aim To investigate the effect of cardio-myopeptide on doxorubicin-induced toxicity on H9c2 cardiomyoblasts and its related mechanism. Methods H9c2 cells were respectively pretreated with different concentrations(0, 10, 20, 40 mg ∗ L-1) of cardio-myopeptide for 6 h,8 h, 12 h. Cell viability was determined by MTT assay. The protein expression of caspase-3, Bcl-2, Bax, IGF-1R and IGFBP-3 were detected by Western blot. Results Cardiomyopeptide protected H9c2 cardiomyocytes from doxorubicin induced apoptosis in a dose-and time-dependent manner. The half maximal inhibitory concentration (IC50) was shifted from(1.2 ±0.4) umol • L-1 to(2.3 ±0.2) jimol • L-1 The expression of Bcl-2, IGF-1R was up-regulated , and Bax, IGFBP-3 and caspase-3 decreased in H9c2 cells. Conclusions Cardiomyopeptide could prevent from apoptosis induced by doxorubicin in H9c2 cells via increasing expression of IGF-1R, thus up-reg-ulation of the antiapoptotic protein Bcl-2 and inhibiting caspase-3 activity.

Expression and significance of insulin-like growth factor binding protein-related protein 1 in pancreatic neoplasms and its relationship with tumor microenvironment / 中华消化杂志

Objective To observe the expression of insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) in human pancreatic tumor tissues and investigate its significance and relationship with clinic pathological characteristics and tumor microenvironment of the pancreatic neoplasms.Methods A total of 236 patients with surgically resected pancreatic tissue from January 2007 to December 2017 were selected from the First Hospital of Shanxi Medical University.Totally 236 patients were divided into paracancer control group (normal pancreatic tissue adjacent to the tumor,n =111),benign group (benign or low-grade malignant tumor such as solid pseudopapillary tumor,n =37),and malignant group (malignant tumors such as pancreatic ductal adenocarcinoma,n =88).The histomorphology and collagen deposition were observed using hematoxylin-eosin (H-E) staining and Sirius red staining in the three groups.The expressions of IGFBPrP1,transforming growth factor β1 (TGFβ1),α-smooth muscle actin (α-SMA)and collagen type Ⅰ of pancreatic tissues in the three groups were detected by immunohistochemical staining.The relationship between IGFBPrP1 and TGFβ1,α-SMA or collagen type Ⅰ,and the relathionship between IGFBPrP1 and clinicopathological features of the pancreatic neoplasms were analyzed.T test and one-way analysis of variance were used for statistical analysis,and Spearman rank correlation test was used for correlation analysis.Results In benign group and malignant group,there were obvious cell atypia,and the cell atypia of malignant group was more significant than benign group.The contents of collagen fibers in benign group and malignant group were significantly higher than that in paracancer control group.IGFBPrP1,TGFβ1,α-SMA and collagen type Ⅰ were highly expressed in the endochylema of the tumor cells and (or) the myofibroblast.The expression level of IGFBPrP1 in highly differentiated ductal adenocarcinoma was significantly higher than that in moderately and poorly differentiated ductal adenocarcinoma ((9.46 ± 2.10) × 104 vs.(6.48 ± 1.38) × 104 and (6.07 ± 1.29) × 104);t =7.430 and 6.767,both P ＜ 0.05).The expression of IGFBPrP1 in human pancreatic neoplasms was positively correlated with TGFβ1,α-SMA and collagen type Ⅰ (r=0.530,0.619,0.625;all P ＜0.05).Conclusions IGFBPrP1 is highly expressed in pancreatic tumor tissue and its expression level may correlate with the histological grade of pancreatic neoplasms.The expression of IGFBPrP1 in human pancreatic tumor tissues may be accompanied by the activation of pancreatic stellate cells and the generation of cancer-related fibroblasts,and IGFBPrP1 may involve in the formation of tumor by changing the tumor microenvironment.

Utilidad de la proteína de unión al factor de crecimiento similar a la insulina tipo 1 en la ruptura prematura de membrana / Utility of insulin-like growth factor-binding protein type 1 in premature membrane rupture

Introducción: Fercuentemente no disponemos de una clara evidencia de la pérdida de líquido amniótico observado por examen con espéculo, por lo que el diagnóstico de rotura prematura de membranas puede ser con frecuencia incierto, por lo que se necesitan pruebas de diagnóstico apropiadas y complementarias para la toma de decisiones. Objetivo: conocer la precisión diagnóstica de la proteína-1 de unión al factor de crecimiento similar a la insulina (IGFBP-1) en la rotura prematura de membranas al compararla con la medición del bolsilla mayor por ecografía y el Test de de Ferning. Material y métodos: 102 gestantes de 24 a 37 semanas con signos y/o síntomas de rotura de membranas fueron elegibles, fueron evaluadas con las pruebas IGFBP-1, ecografía y Test de Ferning. Resultados: Para el IGFBP-1 se obtuvo 95% de sensibilidad (S), 95% de especificidad (E), 95% de valor predictivo positivo (VPP) y 96% de valor predictivo negativo (VPN). Par el Test de Fernig se obtuvieron valores de 85%, 25%, 25% y 83% respectivamente. En tanto que para la ecografía los hallazgos fueron de 81%, 29%, 56% y 58% respectivamente. Conclusión: el ensayo IGFBP-1 fue el método más preciso para diagnosticar la ruptura prematura de membranas con la mayor sensibilidad, especificidad, valor predictivo positivo y valor predictivo negativo.

Introduction: We do not have clear evidence of the loss of amniotic fluid observed by speculum examination, so the diagnosis of premature rupture of membranes can often be uncertain and appropriate and complementary diagnostic tests are needed for decision making. Objective: to know the diagnostic accuracy of insulin-like growth factor-binding protein-1 (IGFBP-1) in the premature rupture of membranes when compared with the measurement of the greater pocket by ultrasound and the Ferning test. Material and methods: 102 pregnant women from 24 to 37 weeks with signs and / or symptoms of rupture of membranes were eligible, which were evaluated with the IGFBP-1, ultrasound and Ferning Test. Results: For IGFBP-1 95% sensitivity (S), 95% specificity (E), 95% positive predictive value (PPV) and 96% negative predictive value (NPV) were obtained. For the Ferning Test values of 85%, 25%, 25% and 83% respectively were obtained. While for ultrasound the findings were 81%, 29%, 56% and 58% respectively. Conclusion: the IGFBP-1 assay was the most accurate method to diagnose the premature rupture of membranes with the highest sensitivity, specificity, positive predictive value and negative predictive value.

Porcine transcription factor AP-2δ promotes porcine circovirus type 2 replication through enhancing the activity of the rep gene promoter / 生物工程学报

Several putative transcription factor binding sites (TFBSs) exist in the PCV2 rep gene promoter. To explore if porcine circovirus type 2 (PCV2) could regulate the viral replication by using these TFBSs, we conducted electrophoretic mobility shift assay (EMSA), DNA-pull down and liquid chromatography-tandem mass spectrometric (LC-MS/MS) assays. EMSA confirmed the binding activity of the rep gene promoter with nuclear proteins of host cells. DNA-pull down and LC-MS/MS identified the porcine transcription factor AP-2δ (poTFAP2δ) could bind the PCV2 rep gene promoter. Dual-luciferase reporter assay, quantitative real-time PCR, Western blotting and indirect immunofluorescent assay demonstrated that poTFAP2δ could not only promote the activity of the rep gene promoter, but also enhance the transcription/translation activity of the rep/cap gene and the virus titer of PCV2 during the entire life cycle of PCV2 infection. This study revealed the molecular mechanism of PCV2 using host proteins to enhance the viral replication, provided a new perspective for studying the pathogenic mechanism of PCV2 from virus and host interactions, and provided a theoretical basis for developing highly effective PCV2 vaccines.

Effects of insulin-like growth factor binding protein 7 gene on the biological characteristics of colorectal cancer / 中国现代普通外科进展

Objective:To investigate the effects of insulin-like growth factor binding protein 7 gene on the biological characteristics of colorectal cancer.methods:human colorectal cancer SW480 cells were cultured.According to the different transfectants,the cells were divided into IGFBP7 plasmid group,blank plasmid group and control group.The expression of IGFBP7 gene was detected by RT-PCR.MTT assay was used to detect cell proliferation.Flow cytometry was used to detect the apoptotic rate.Transwell chamber was used to detect cell migration and cell invasion.Results:The relative expression levels of IGFBP7 mRNA in IGFBP7 plasmid group was higher than which in the blank plasmid group and the control group,the difference was statistically significant (P＜0.05).Compared with the blank plasmid group and the control group,the A values at 24h,48h,72h and 96h in the IGFBP7 plasmid group were decreased,the differences were statistically significant(P＜0.05).Compared with the blank plasmid group and the control group,the apoptosis rate in the IGFBP7 plasmid group was increased,the difference was statistically significant (P＜0.05).The number of migrating cells and the number of invasive cells in IGFBP7 plasmid group were lower than those in the blank plasmid group and the control group,the differences were statistically significant (P＜0.05).Conclusion:Overexpression of IGFBP7 gene could inhibit proliferation of colorectal cancer cells,accelerate cell apoptosis,reduce cell migration and cell invasion.

Accuracy of different biomarkers for early diagnosis of acute kidney injury in patients undergoing cardiovascular surgery under cardiopulmonary bypass / 中华麻醉学杂志

Objective To evaluate the accuracy of different biomarkers for early diagnosis of acute kidney injury ( AKI ) in the patients undergoing cardiovascular surgery under cardiopulmonary bypass ( CPB) . Methods A total of 200 patients, aged 22-86 yr, weighing 46-87 kg, scheduled for elective cardiovascular surgery under CPB, were enrolled in this study. The concentration of serum creatinine was determined at 1 day before operation and 1-7 days after operation. At 1 day before operation and 0, 2, 6 and 12 h after operation, the concentrations of urine neutrophil gelatinase-associated lipocalin (NGAL), cystatin C ( Cys C) , tissue inhibitor of matrix metalloproteinase type 2 ( TIMP-2) and insulin-like growth factor binding protein-7 ( IGFBP-7) were determined. The TIMP-2 and IGFBP-7 product ( TI) was calcu-lated. AKI was diagnosed after surgery according to Kidney Disease Improving Global Outcomes criteria. The receiver operating characteristic curve was plotted, and the area under receiver operating characteristic curve ( AUC) was calculated. Results The incidence of AKI was 20. 5％. The AUC of AKI diagnosed by the concentration of urine NGAL was 0. 689, 0. 709, 0. 713 and 0. 803 at 0, 2, 6 and 12 h after opera-tion, respectively ( P<0. 05) . The AUC of AKI diagnosed by the concentration of urine Cys C was 0. 639, 0. 762, 0. 774 and 0. 812 at 0, 2, 6 and 12 h after operation, respectively ( P<0. 05) . The AUC of AKIdiagnosed by TI was 0. 687, 0. 721, 0. 740 and 0. 779 at 0, 2, 6 and 12 h after operation, respectively ( P<0. 05) . The AUC of AKI diagnosed by combined three indices the parallel test was 0. 694, 0. 773 and 0. 794 at 0, 2 and 6 h after operation, respectively ( P<0. 05) . The AUC of AKI diagnosed by the serial test was 0. 610, 0. 631 and 0. 667 at 0, 2 and 6 h after operation, respectively. Conclusion Urine NGAL or Cys C concentrations or TI single detection and parallel test have a certain accuracy for early diag-nosis of AKI in the patients undergoing cardiovascular surgery under CPB.

Changes in Serum Concentrations of Insulin-like Growth Factor Binding Protein-3 after General Anesthesia Using Propofol or Isoflurane / 이화의대지

OBJECTIVES: The insulin-like growth factor binding proteins (IGFBP) regulate the bioavailability and bioactivity of insulin-like growth factor. We aimed to evaluate whether the IGFBP-3 level undergo major changes during perioperative periods according to the different kind of anesthetic agents. METHODS: Eighteen adults scheduled for elective total abdominal hysterectomy were enrolled. The patients were randomly assigned to have either propofol or isoflurane for maintenance of general anesthesia. A venous sample was taken for analysis of IGFBP-3 at the following time points: before induction, at the time of peritoneal closure, 1 hour after extubation at recovery room, and 2 and 5 postoperative days. The samples were analyzed by enzyme linked immunosolvent assay. RESULTS: Demographic data were similar between groups. In the both groups, the IGFBP-3 concentration decreased after anesthesia induction, reaching a nadir at the time of peritoneal closure without a significant difference between groups. In analysis between groups, the IGFBP-3 concentration in the isoflurane group on the postoperative 5th day was recovered to preoperative value and significantly higher than that in the propofol group (P < 0.05). CONCLUSION: This is the first study to show that the anesthetics used for general anesthesia affect the IGFBP-3 level during perioperative periods. The decrease of IGFBP-3 level following anesthesia induction in the isoflurane group was recovered to preoperative value, whereas that observed in the propofol group was not recovered on the postoperative 5th day. Further study is needed to establish the definitive effect of general anesthetics on IGFBP-3 and provide a comprehensive interpretation.

Study on feasibility of urinary TIMP-2 and IGFBP-7 for predicting acute kidney injury in pediatric patients with sepsis / 重庆医学

Objective To explore the feasibility and accuracy of urinary tissue inhibitor of metalloproteinase-2(TIMP-2) and insulin-like growth factor binding protein-7(IGFBP-7) for predicting acute kidney injury(AKI) occurrence in pediatric patients with sepsis.Methods A total of 174 pediatric patients with sepsis in PICU of Chengdu Municipal Women and Children Central Hospital and 30 healthy control children(control group) from March 2014 to March 2017 were included.Fasting venous blood was collected at 8:00 every morning during 7 d before admitting to PICU for detecting serum SCr level;fresh urine sample was taken at 8:00 am and 20:00 pm.for detecting TIMP-2 and IGFBP-7 levels.The AKI was diagnosed according to KDIGO criteria in 2012.Thus the septic children patients were divided into the AKI group and non-AKI group.The receiver operating characteristic(ROC) curve and the area under the curve(AUC) were adopted to analyze the predictive value of TIMP-2 and IGFBP-7 at 12,24,36,48 h before diagnosis for AKI.Results Within 7 d in 174 children cases admitting to PICU,52 cases(29.89％) were diagnosed as AKI.The TIMP-2 and IGFBP-7 levels had no statistical difference between the non-AKI group and control group(P＞0.05).Urinary TIMP-2 and IGFBP-7 levels at 12,24,36 h before diagnosing AKI were significantly increased compared with those at admitting to PICU(P＜0.01);AUC of urinary TIMP-2 and IGFBP-7 levels for predicting AKI occurrence within following 12,24,36 h were 0.967 (95 ％CI:0.946-0.989),0.898(95％CI:0.844-0.951) and 0.748(95％CI:0.669-0.827) respectively,the difference was statistically significant(P＜0.01).Conclusion The urinary TIMP-2 and IGFBP-7 increase can more accurately predict AKI occurrence in pediatric patients with sepsis.