Preliminary investigation into the genetic etiology of short stature in children through whole exon sequencing of the core family.

A comprehensive survey was carried out to investigate the genetic etiology of short stature in children by whole exon sequencing of a core family cohort to find and study mutations in multiple genes to assess their potential correlations to low height in children. The study included 56 pediatric patients from the Department of Pediatrics at the Zhangzhou Affiliated Hospital of Fujian Medical University. The participants met strict inclusion criteria, including age, Han Chinese ethnicity, low height standard deviation score, and the absence of known causes for short stature. Core pedigrees were identified using exome sequencing. After sequencing, variations were categorized and interpreted according to a variety of factors, including inheritance, location, type, and disease-causing gene databases. Variants were verified by Sanger sequencing. Most of the 97 gene mutations were missense. ACAN, PHEX, and COL2A1 were the most common gene mutations. Copy number variations were identified, particularly associated with the PHEX gene. Protein functional studies revealed that the mutations had a considerable influence on disease-promoting damage. The chromosomal locations with the highest enrichment of these genes were chr12, chr5, and chr2. In conclusion, the study revealed numerous genetic changes that may substantially impact physiological processes and disease. These findings establish the basis for further investigations into their diagnostic and therapeutic capabilities.

Rapamycin Plays an Anti-Epileptic Role by Restoring Blood-Brain Barrier Dysfunction, Balancing T Cell Subsets and Inhibiting Neuronal Apoptosis.

BACKGROUND: Rapamycin (RAP), as a Mammalian Target of Rapamycin (mTOR) inhibitor, has a certain antiepileptic effect. The blood-brain barrier (BBB), neuroinflammation, lymphocyte immune cells, and neuronal apoptosis play an obligatory role in the course of a seizure. The aim of this study is to probe whether the antiepileptic mechanism of RAP involves the blood-brain barrier, neuroinflammation, lymphocytes, and neuronal apoptosis. METHODS: First, we established a rat epilepsy model by injecting lithium chloride and pilocarpine into the rats (intraperitoneal injection). Then the epileptic rats were treated with different doses of RAP (1 mg/kg.d, 2 mg/kg.d, 4 mg/kg.d). Peripheral blood, brain tissue, and temporal lobe tissue were collected. The levels of blood-brain barrier-related proteins and inflammatory cytokines in the peripheral blood of rats were measured by enzyme-linked immunosorbent assay (ELISA). The effect of RAP on T cell subsets in epileptic rats was analyzed by flow cytometry. The apoptosis of neurons and glial cells in the temporal lobe of rats was analyzed by immunohistochemistry. RESULTS: This study found that RAP reduces the levels of BBB-interrelated proteins (matrix metallopeptidase 9 (MMP-9), MMP-2, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2) and inflammatory cytokines (interleukin-2 (IL-2), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α)) in epileptic rats compared to the model group (p < 0.05). RAP increases the level of total T cells (CD3+CD45+) and T helper cells (CD3+CD4+), decreases the level of cytotoxic T lymphocytes (CD3+CD8+), and inhibits the apoptosis of neurons and glial cells in the temporal lobe compared to the model group (p < 0.05). CONCLUSIONS: The antiepileptic mechanism of RAP may be to restore BBB dysfunction, reduce the inflammatory response, balance T cell subsets, and inhibit neuronal and glial cell apoptosis in temporal lobe epilepsy lesions.

An Automated TW3-RUS Bone Age Assessment Method with Ordinal Regression-Based Determination of Skeletal Maturity.

The assessment of bone age is important for evaluating child development, optimizing the treatment for endocrine diseases, etc. And the well-known Tanner-Whitehouse (TW) clinical method improves the quantitative description of skeletal development based on setting up a series of distinguishable stages for each bone individually. However, the assessment is affected by rater variability, which makes the assessment result not reliable enough in clinical practice. The main goal of this work is to achieve a reliable and accurate skeletal maturity determination by proposing an automated bone age assessment method called PEARLS, which is based on the TW3-RUS system (analysis of the radius, ulna, phalanges, and metacarpal bones). The proposed method comprises the point estimation of anchor (PEA) module for accurately localizing specific bones, the ranking learning (RL) module for producing a continuous stage representation of each bone by encoding the ordinal relationship between stage labels into the learning process, and the scoring (S) module for outputting the bone age directly based on two standard transform curves. The development of each module in PEARLS is based on different datasets. Finally, corresponding results are presented to evaluate the system performance in localizing specific bones, determining the skeletal maturity stage, and assessing the bone age. The mean average precision of point estimation is 86.29%, the average stage determination precision is 97.33% overall bones, and the average bone age assessment accuracy is 96.8% within 1 year for the female and male cohorts.

Correlation of serum levels of LH, IGF-1 and leptin in girls with the development of idiopathic central precocious puberty.

BACKGROUND: This paper aims to investigate the correlation between serum levels of luteinizing hormone (LH), insulin-like growth factor-1 (IGF-1) and leptin and the incidence of idiopathic central precocious puberty (ICPP) in girls, and to explore the clinical values in the diagnosis of ICPP. METHODS: A total of 48 girls with ICPP were selected in our hospital from March 2014 to March 2015 to serve as ICPP group. At the same time, 48 girls with the same age distribution were selected as control group. Bone age, body weight, Body Mass Index (BMI) and gender development index of girls in each group were recorded. Levels of LH, IGF-1 and leptin in serum were measured by chemiluminescence immunoassay. The correlations within levels of LH, IGF-1 and leptin, and the correlations between levels of LH, IGF-1 and leptin and body height, body weight and gender development index were analyzed. RESULTS: Levels of LH, IGF-1 and leptin in ICPP group were significantly higher than those in control group (P<0.01). Body weight and BMI of ICPP group were significantly higher than those of control group (P<0.01), and were positively correlated with the expression level of leptin; ovarian volume and thickness of breast of ICPP group were significantly higher than those of control group (P<0.01), and were positively correlated with serum level of LH; serum level of IGF-1 was positively correlated with bone age. Levels of LH, IGF-1 and leptin in serum of ICPP girls were all increased compared with control group. CONCLUSIONS: LH peak value and levels of IGF-1 and leptin in serum can be used as diagnostic indexes of ICPP.

Effect of miR-19b on the protective effect of Exendin-4 on islet cells in non-obese diabetic mice.

This study analyzed the effect of miR-19b on the protective effect of Exendin-4 on islet cells in non-obese diabetic (NOD) mice. Twenty-four NOD/LT mice were randomized, according to the random number table, into a control group (4 µg/kg•day), a low-dose group (2 µg/kg•day Exendin-4), a medium-dose group (4 µg/kg•day Exendin-4) and a high-dose group (8 µg/kg•day Exendin-4) (n=6), with miR-19b expression interfered (an interference group) except for the control group. RT-qPCR was used to detect interference results and different doses of Exendin-4 were given for 8 weeks of intervention after the interference. CD4+ and CD8+ cell levels were detected by flow cytometry, IL-2 and IL-10 levels in the peripheral blood by enzyme-linked immunosorbent assay, and the apoptosis rate of islet cells in the pancreatic tissue by TUNEL. After 4 and 8 weeks of Exendin-4 intervention, mice in the high-dose group had lower blood glucose level than the medium-dose group (P<0.05). The medium-dose group had lower CD4+ cell level than the high-dose group (P<0.05), while the medium-dose group had higher CD8+ cell level than the high-dose group (P<0.05). After 8 weeks of intervention, compared with the medium-dose group, the high-dose group had lower IL-2 level (P<0.05), but higher IL-10 level (P<0.05). After 8 weeks of intervention, the medium-dose group had a higher apoptosis rate than the high-dose group (P<0.05). In conclusion, the decrease in miR-19b expression can improve the therapeutic effect of Exendin-4 on NOD, control blood glucose effectively and improve inflammatory response and immune function, as well as reduce islet cell injury. The increase in the dose of Exendin-4 can further improve its therapeutic effect on NOD.

Exendin-4 prevented pancreatic beta cells from apoptosis in (Type I) diabetic mouse via keap1-Nrf2 signaling.

IMPACT STATEMENT: Nrf2 is an essential part of the defense mechanism of vertebrates and protects them from surrounding stress via participation in stimulated expression of detoxification as well as antioxidant enzymes. It also exerts a role in defending hosts from different stress in the environment, including reactive oxygen species. Our study investigates the role of exendin-4 on Nrf2 pathway as well as cell death in pancreatic ß-cell and in non-obese diabetic mice. Result of study indicates exendin-4 mediates activation of Keap1-Nrf2-ARE pathway and may serve as a potential agent to treat type I diabetes mellitus. In our research, we observed excessive reactive oxygen species production, low level of cell death, and PKC phosphorylation on exendine-4 treatment. Nrf2 knockdown led to suppression of reactive oxygen species generation as well as increasing apoptosis. Moreover, siRNA-mediated Nrf2 down-regulation attenuated the suppressive effect of exendin-4 in pancreatic ß-cell viability, via modulating apoptosis promoting- and counteracting-proteins, Bax, and Bcl-2.

KEAP1/NRF2 axis regulates H2O2-induced apoptosis of pancreatic ß-cells.

In human pancreatic ß-cells, oxidative stress and cellular injures can be induced by H2O2 treatment. The KEAP1/NRF2 axis is a key antioxidant signaling pathway. The present study attempted to elucidate the mechanism by which the KEAP1/NRF2 axis mediates oxidative stress-induced death in pancreatic ß-cells. Our data showed that H2O2 treatment obviously induced the apoptosis of ß-cells. Further experiments demonstrated that KEAP1 expression was downregulated in H2O2-treated pancreatic ß-cells and this change correlated with increase in the cellular abundance and nuclear translocation of NRF2. The restoration of KEAP1 expression in cells resulted in a recovery of cell proliferation and inhibition of apoptosis. Furthermore, we found that KEAP1 overexpression negatively regulated the abundance of NRF2, subsequently causing decreased antioxidant response element activation. This led to HO-1 protein downregulation in H2O2-treated human pancreatic ß-cells, which was also observed in NRF2-silenced ß-cells. Conversely, the silencing of KEAP1 led to NRF2 upregulation and inhibited ARE and HO-1 signaling in pancreatic ß-cells. The increase in the abundance of NRF2 following treatment with H2O2 drastically elevated the production of BAX, FAS, FAS-L, CASP-3, and CASP-9, and this change was reversed by KEAP1 overexpression or NRF2 silencing. Taken together, H2O2 treatment activated KEAP1/NRF2 signaling to promote the production of pro-apoptotic factors and consequently led to the apoptosis of human pancreatic ß-cells.

The influence of exendin-4 intervention on -obese diabetic mouse blood and the pancreatic tissue immune microenvironment.

The aim of the study was to determine the influence of exendin-4 intervention on non-obese diabetic (NOD) mouse blood and the pancreatic tissue immune microenvironment. A total of 40 clean NOD mice were used in the study and randomly divided into 4 groups (n=10/group). The first group was blank control group D with normal saline intervention, and with different doses of exendin, i.e.,-4 2, 4 and 8 µg/kg/day. The three remaining groups were: i) Low-dose group A; ii) medium-dose group B; and iii) high-dose group C. Mice in the four groups went through intervention for 8 weeks. Their mass and blood glucose levels were tested each week. After 8 weeks, the mice were sacrificed, and mouse serum samples were reserved. The ELISA method was used to test peripheral blood (PB), IL-2, IFN-γ and IL-10 levels. Pancreatic samples were created. Immunohistochemistry was used to observe the infiltration degree of mouse pancreatitis and the local expression state of pancreatic IL-10. Mouse pancreatic tissues were suspended in pancreatic cell suspension. Flow cytometry was used to test the state of T-cell subsets CD4 and CD25. Mouse pancreatitis in control group D was mainly at grade 2and 3. Under a light microscope, it was observed that pancreatic cell morphology was in disorder, and the size and quantity of the pancreas was small. Mouse pancreatitis in the exendin-4 low-dose group A, medium-dose group B and high-dose group C was mainly at grade 0 and 1. Under a light microscope, it was observed that pancreatic cell morphology improved, the infiltration degree of lymphocyte was improved and pancreatic islet size was restored somewhat. Additionally, a few brownish granules were identified within the pancreatic sample cells in control group D. There were many brownish granules with deep color within the pancreatic sample cells in exendin-4 low-dose group A, medium-dose group B and high-dose group C. IL-10 immunohistochemistry scores in the low-dose group A, medium-dose group B and high-dose group C were 3.82±0.72, 4.34±0.86 and 4.81±0.94, respectively, and were higher than the score of 2.25±0.63 in control group D. CD4+CD25+T-cell proportions in mouse pancreatic tissues of low-dose group A, medium-dose group B and high-dose group C were 5.31, 5.53 and 5.74%, respectively, which were higher than that of the CD4+CD25+T-cell proportion (1.62% in control group D). The CD4+CD25high T-cell proportion in CD4+T-cells in group A, B and C increased. Compared with control group D, serum IL-10 levels in the exendin-4 low-dose group A, medium-dose group B and high-dose group C increased (P<0.05), while levels of IL-2 and IFN-γ decreased (P<0.05). Additionally, the difference of serum IL-10, IL-2 and IFN-γ levels in the low-dose group A, medium-dose group B and high-dose group C was of statistical significance (P<0.05). Exendin-4 intervention can increase quantities of CD4 and CD8+T cells in NOD mouse pancreases, with PB IL-10 expression and local expression of IL-10 in pancreatic tissues. It also can inhibit the expression of serum IL-2 and IFN-γ, regulate the organism immune microenvironment and prevent diabetes. CD4+CD25high T cells increase in NOD tumor infiltration lymphocytes mediated by exendin-4 intervention, which may be related to the fact that exendin-4 inhibits the lethal effect of CD8+T cells through contact among cells and eventually exerts immunosuppressive effect.

The Relationship Between Gene Polymorphism of Leptin and Leptin Receptor and Growth Hormone Deficiency.

BACKGROUND Growth hormone deficiency (GHD) is a major cause of congenital short stature. GHD patients have significantly decreased serum leptin levels, which are regulated by gene polymorphism of leptin and leptin receptor. This study thus investigated the relationship between gene polymorphism and susceptibility to GHD. MATERIAL AND METHODS A case-control study was performed using 180 GHD children in addition to 160 healthy controls. After the extraction of whole genomic DNA, the genotypes of leptin and leptin receptor gene loci were analyzed by sequencing for single-nucleotide polymorphism. RESULTS The frequency distribution of all alleles identified in leptin gene (loci rs7799039) and leptin receptor gene (loci rs1137100 and rs1137101) fit Hardy-Weinberg equilibrium. There was a significant difference in allele frequency at loci rs7799039 or rs1137101, as individuals with heterozygous GA allele had lower (rs7799039) or higher (rs1137101) GHD risk. No significant difference in allele frequency was discovered at loci rs1137100 (p>0.05), which was unrelated to GHD susceptibility. CONCLUSIONS Gene polymorphism of leptin (loci rs7799039) and leptin receptor (loci rs1137101) are correlated with GHD susceptibility.

[Distribution of HOMA-IR among children and adolescent in Zhangzhou and Zhongshan cities].

OBJECTIVE: To investigate the distribution of the homeostasis model assessment of insulin resistance (HOMA-IR) among children and adolescent in Zhangzhou city and Zhongshan city. METHODS: Total of 3102 children and adolescent aged 6 to 18-year-old were recruited, which were enrolled in a population-based cross-sectional study. Anthropometric and biochemical parameters were measured. RESULTS: A total of 1528 (49.26%) girls and 1574 (50.74%) boys were included in this study. The concentrations of insulin and fasting glucose gradually increased from 6 to 18 years of age, there was no statistical difference between boys ang girls. The mean values for the BMI were similar in age-matched boys and girls from 6 to 18-year-old ,but for 12 to 15-year-old children was significantly higher in the girls compared with the boys and conversely for 16 to 18-year-old (P < 0.05). The HOMA-IR gradually increased with age and reached a plateau at 12 years of age and there was no markedly differential in gender. CONCLUSION: The glucose levels, insulin concentrations and HOMA-IR exhibited a gradual increase with age. It was suggested that the evaluation of IR in children should be based on percentiles of the HOMA-IR rather than a dichotomous value derived from a single cutoff point.

Specific Inhibition of ß-Catenin in Jeko-1 Mantle Cell Lymphoma Cell Line Decreases Proliferation and Induces Apoptosis.

BACKGROUND: The canonical Wnt signaling pathway has been considered as a potent oncogenic signaling in the initiation and progression of hematological malignancies. As a key regulator of the Wnt signaling pathway, the role of ß-catenin in mantle cell lymphoma (MCL) pathogenesis and progression was investigated in this study. MATERIAL AND METHODS: A total of 30 MCL samples were collected from patients and were examined for the expression of ß-catenin and p-GSK3ß using immunohistochemical (IHC) staining. Further in vitro studies employed MTT and Western blot assays detecting proliferation and apoptosis-related proteins in MCL cell line Jeko-1, which were transfected with ß-catenin shRNA or specific inhibitor XAV939. RESULTS: Expression of ß-catenin and phosphorylated glycogen synthase kinase-3 beta (p-GSK3ß) in MCL was significantly higher than those in controlled samples. In vitro studies indicated that ß-catenin knockdown significantly inhibited cell proliferation and induced apoptosis in Jeko-1 cells. Furthermore, XAV939 induced apoptosis and growth arrest in Jeko-1 cells. Both inhibitory agents increased Bax and caspase 3 proteins, and decreased Bcl-2, c-Myc, and Cyclin D1 proteins. CONCLUSIONS: The specific inhibition of ß-catenin induces apoptosis and growth arrest, making it a potential therapeutic target against MCL.

[Expression Changes of ß-catenin and P-GSK-3ß in Patients with Mantle Cell Lymphoma].

OBJECTIVE: This study was purposed to detect the expressions of ß-catenin and P-GSK-3 ß in Wnt signaling pathway of patients with mantle cell lymphoma(MCL), and investigate its relationship with the pathogenesis of MCL. METHODS: The expression levels of ß -catenin protein and P-GSK-3 protein in mantle cell lymphoma and hyperplastic lymphadenitis were detected by using anti-ß-catenin, P-GSK-3ß polyclonal antibody and S-P staining technique. RESULTS: The abnormal expression of ß-catenin protein(73.33%) in mantle cell lymphoma group was significantly higher than that (6.7%) in reactive lymph node hyperplasia group (P<0.05); and the positive rate of P-GSK-3 ß(66.67%) in mantle cell lymphoma group was significantly higher than that (16.67%) in reactive hyperplasia of lymph node group (P<0.05). Spearman correlation analysis showed that there was obvious positive correlation (R=0.852, P<0.01). CONCLUSION: The abnormal high expressions of ß-catenin and P-GSK-3 ß protein have been confirmed to appeare in mantle cell lymphoma.

[Antiproliferative Effect of Specific Inhibitor XAV939 for ß-catenin on MCL Jeko-1 Cells].

OBJECTIVE: To investigate the effect of short hairpin RNA (shRNA) and XAV939, a specific inhibitor for ß-catenin, on growth and apoptosis of mantle cell lymphoma(MCL) Jeko-1 cell line. METHODS: ß-catenin shRNA eukaryotic expression vector was transfected into Jeko-1 cells, the antiproliferative effect of shRNA on Jeko-1 cells was detected by RT-PCR and Western blot. The proliferation inhibitory rate of Jeko-1 cells treated by different doses of XAV939 was assayed by MTT method; the level of apoptosis of Jeko-1 cells was detected by flow cytometry; the expression levels of apoptosis-related protein BCL-2, BAX, CyclinD1, C-MYC and Caspase-3 in Jeko-1 cells were determined by Western blot. RESULTS: The expression of ß-catenin mRNA and growth of Jeko-1 cell line were inhibited by shRNA; after Jeko-1 cells treated with 0,2 and 8 µmol/L XAV939 for 48 hours, the cell proliferation rate decreased, while the cell apoptosis rate increased, the expressions of apoptosis-related protein BCL-2, CyclinD1 and C-MYC were down-regulated, on the contrary, the expression of BAX and caspase-3 were up-regulated. CONCLUSION: The specific inhibition of ß-catenin can inhibit Jeko-1 cell proliferation and promote the cell apoptosis.

Effect of CXCL10 receptor antagonist on islet cell apoptosis in a type I diabetes rat model.

In recent years, the incidence of type 1 diabetes mellitus (T1DM) has been increasing. The role of CXCL10 and its receptor, CXCR3, in the occurrence of T1DM has drawn lots of research interests, as the disease incidence was correlated with their expression levels. We thus used an antagonist of CXCR3, NBI-74330, to block the specific binding, for further observation of islet cell apoptosis in a T1MD rat model. A total of 80 SD rats were given STZ intraperitoneally for generating T1DM model. Different concentrations of NBI-74330 were then applied, followed by the collection of blood and pancreatic tissue samples. CXCL10 and CXCR3 levels were detected by enzyme linked immunosorbent assay (ELISA), followed by expressional assays in pancreatic tissues by real-time PCR, Western blotting and flow cytometry. Compared to control group, model rats had significantly elevated blood glucose level (>16.7 mmol/L), with depressed CXCL10 and CXCR3 levels compared to model group (P<0.05). After NBI-74330 treatment, mRNA and protein levels of CXCL10 and CXCR3 were significantly lowered, with significantly decreased apoptotic cell ratios compared to model group (P<0.05). CXCL10 receptor antagonist NBI-74330 can inhibit the apoptosis of pancreatic islet cells in T1DM rats.

miR-218 expression in osteosarcoma tissues and its effect on cell growth in osteosarcoma cells.

OBJECTIVE: To investigate the expression of miR-218 and its clinical significance in osteosarcoma tissues and explore its effect on proliferation and apoptosis in osteosarcoma cells. METHODS: miR-218 expression was detected in 76 samples of surgically resected osteosarcoma and matched normal tumor-adjacent tissues using quantitative reverse transcription polymerase chain reaction (qRT-PCR). MiR-218 was over-expressed by exogenous miR-218 plasmids in Saos-2 cells, and then BrdU cell proliferation assay and flow cytometry were used to determine cell proliferation and apoptosis. RESULTS: The expression of miR-218 in osteosarcoma tissues was significantly lower than those in normal tumor-adjacent tissues (t=8.735, P<0.001). MiR-218 expression in tumor tissues was significantly correlated with tumor size (χ(2)=5.380, P=0.020), clinical stage (χ(2)=6.692, P=0.010) and distant metastasis (χ(2)=4.180, P=0.041). MiR-218 was obviously over-expressed by exogenous miR-218 plasmids (t=19.42, P<0.001), and miR-218 overexpression significantly reduced cell proliferation (t=9.045, P<0.001) and induced apoptosis (t=12.38, P<0.001) in Saos-2 cells. CONCLUSIONS: The low-expression of miR-218 is correlated with the poor clinicopathological features in osteosarcoma. Moreover, miR-218 overexpression reduces cancer cell proliferation and induces apoptosis in Saos-2 cells, suggesting that miR-218 may play a key role in the progression of human osteosarcoma.

Role of immune dysfunction in pathogenesis of type 1 diabetes mellitus in children.

OBJECTIVES: To investigate the function of cytokines, chemokines, and regulatory T cells (Tregs) in the pathogenesis of type 1 diabetes mellitus (T1DM) in children. METHODS: A total of 35 children with T1DM and 30 healthy controls were enrolled in this study. Levels of serum cytokines (IL-1α, IL-6, IL-10, IL-12, and TNF-α) and chemokines (MIP-1α, MIP-1α and MCP-1) were detected by enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells (PBMCs) were isolated and culture supernatant of phytohaemagglutinin (PHA)-stimulated PBMCs was subjected to ELISA for levels of cytokines (IL-1α, IL-6, IL-10, IL-12 and TNF-α) in T1DM and control group. Furthermore, flow cytometry was used to determine the percentage of Tregs in PBMCs of two groups. RESULTS: Levels of serum cytokines including IL-1α, IL-6, IL-10 and TNF-α as well as chemokines, such as MIP-1α and MIP-1α in children with T1DM children were significantly higher than those in healthy controls (P<0.05, respectively). PBMCs with PHA stimulation in T1DM group secreted more IL-1α and TNF-α (P<0.05, respectively), but less IL-10 (P<0.05), as compared with control group. Furthermore, the proportion of CD4(+), CD25(+), Foxp3(+), Tregs in PBMCs isolated from children with T1DM was obviously lower than those in healthy controls (P<0.05). CONCLUSIONS: Immune dysfunction, with upregulation of inflammatory factors such as IL-1α, IL-6, TNF-α and MIP-1α, downregulation of IL-10 and Tregs, plays an important role in the pathogenesis of T1DM in children.

[Early use of recombinant human erythropoietin promotes neurobehavioral development in preterm infants].

OBJECTIVE: To evaluate the effect of the early use of recombinant human erythropoietin (rhu-EPO) on neurobehavioral development in preterm infants. METHODS: Forty-four preterm infants (30 males and 14 females) were randomly divided into two groups: Rhu-EPO treatment and untreated control (n=22 each). From postnatal day 7, the Rhu-EPO treatment group received intravenous rhu-EPO (250 IU/kg3 times weekly) for 4 weeks. A Neonatal Behavioral Neurological Assessment (NBNA) was performed at 40 weeks of corrected gestational age. A Gesell Development Schedule was used to evaluate neurological development 6 and 12 months after birth. RESULTS: The NBNA score in the rhu-EPO treatment group (36.20+/-0.75) was significantly higher than that in the control group (34.40+/-1.05) at 40 weeks of corrected gestational age (P<0.05). The developmental quotient of fine motor in the rhu-EPO treatment group was significantly higher than that in the control group 6 months after birth (P<0.05). By 12 months after birth, the developmental quotient of gross motor, fine motor and language in the rhu-EPO treatment group was significantly higher than that in the control group (P<0.05). CONCLUSIONS: Early use of Rhu-EPO can promote neurobehavioral development in preterm infants.