Dose pulmonary hemorrhage increase the risk of bronchopulmonary dysplasia in very low birth weight infants?

OBJECTIVE: To evaluate the association between pulmonary hemorrhage and bronchopulmonary dysplasia (BPD) in very low birth weight infants (VLBWIs). METHODS: The study participants were all VLBW newborns admitted from January 1, 2019 to December 31, 2021. The BPD subjects finally included were VLBWIs who survived until the diagnosis was established. This study was divided into pulmonary hemorrhage group (PH group, n = 35) and non-pulmonary hemorrhage group (Non-PH group, n = 190). RESULTS: By univariate analysis it was found that premature rupture of membranes, tracheal intubation in the delivery room, duration of mechanical ventilation, course of invasive ventilation (≥3 courses), pulmonary surfactant (>1 dose), medically and surgically treated patent ductus arteriosus, grade III-IV RDS, early onset sepsis, BPD and moderate to severe BPD showed significant differences between groups (p < .05). By Multivariate analysis, pulmonary hemorrhage did not increase the risks of BPD and moderate to severe BPD (adjusted OR for BPD = 1.710, 95% CI 0.581-5.039; adjusted OR for moderate to severe BPD = 2.401, 95% CI 0.736-7.834). CONCLUSION: It suggests that pulmonary hemorrhage is not associated with the development of BPD and moderate to severe BPD in VLBWIs.

RNA sequencing and bioinformatics analysis of circular RNAs in asphyxial newborns with acute kidney injury.

As one kind of novel noncoding RNA, circular RNAs (circRNAs) are involved in different biological processes. Although growing evidences have supported the important role of circRNAs in renal diseases, the mechanism remains unclear in neonatal acute kidney injury (AKI). High-throughput sequencing analysis was used to investigate the expression of circRNAs between hypoxia-induced AKI neonates and controls. Bioinformatics analysis was conducted to predict the function of differentially expressed circRNAs. Finally, the differentially expressed circRNAs were screened and determined by quantitative real-time PCR (qPCR). (1) A total of 296 differentially expressed circRNAs were identified (Fold change >2 and p < 0.05). Of them, 184 circRNAs were markedly upregulated, and 112 were significantly downregulated in the AKI group. (2) The pathway analysis showed that ubiquitin-mediated proteolysis, renal cell carcinoma, Jak-STAT, and HIF-1 signaling pathways participated in AKI. (3) Top five upregulated and five downregulated circRNAs with higher fold changes were selected for qPCR validation. Hsa_circ_0008898 (Fold Change = 5.48, p = 0.0376) and hsa_circ_0005519 (Fold Change = 4.65, p = 0.0071) were significantly upregulated, while hsa_circ_0132279 (Fold Change = -4.47, p = 0.0008), hsa_circ_0112327 (Fold Change = -4.26, p = 0.0048), and hsa_circ_0017647 (Fold Change = -4.15, p = 0.0313) were significantly downregulated in asphyxia-induced AKI group compared with the control group. This study could contribute to future research on neonatal AKI and facilitate the identification of novel therapeutic targets.

Frequency-following response among neonates with progressive moderate hyperbilirubinemia.

OBJECTIVE: To evaluate the feasibility of auditory monitoring of neurophysiological status using frequency-following response (FFR) in neonates with progressive moderate hyperbilirubinemia, measured by transcutaneous (TcB) levels. STUDY DESIGN: ABR and FFR measures were compared and correlated with TcB levels across three groups. Group I was a healthy cohort (n = 13). Group II (n = 28) consisted of neonates with progressive, moderate hyperbilirubinemia and Group III consisted of the same neonates, post physician-ordered phototherapy. RESULT: FFR amplitudes in Group I controls (TcB = 83.1 ± 32.5µmol/L; 4.9 ± 1.9 mg/dL) were greater than Group II (TcB = 209.3 ± 48.0µmol/L; 12.1 ± 2.8 mg/dL). After TcB was lowered by phototherapy, FFR amplitudes in Group III were similar to controls. Lower TcB levels correlated with larger FFR amplitudes (r = -0.291, p = 0.015), but not with ABR wave amplitude or latencies. CONCLUSION: The FFR is a promising measure of the dynamic neurophysiological status in neonates, and may be useful in tracking neurotoxicity in infants with hyperbilirubinemia.

Partial Deletion of the Long Arm of Chromosome 7: A Case Report.

Study advances with a childhood case of partial deletion of the long arm of chromosome 7. The patient is a 36-month-old girl with growth retardation, mild mental retardation and delayed bone age. She showed no signs of hypotelorism, upslanting palpebral fissures, epicanthal folds, low-set ears, or flat and broad nasal bridge. Microarray testing using the Affymetrix CytoScan HD array revealed an approximately 58 kb deletion at 7q31.1 in the girl and her father, suggesting paternal origin. As the patient had no characteristic facial features, 7q deletions had not been considered. This case broadens the range of case presentations for microdeletions of chromosome 7.

The 5th national survey on the physical growth and development of children in the nine cities of China: Anthropometric measurements of Chinese children under 7 years in 2015.

OBJECTIVES: To describe the physical growth of healthy children under 7 years in China based on the latest national survey and provide more data for revising growth reference and monitoring the impact of social development on children's health and growth. METHODS: In the cross-sectional survey, 161,774 healthy children under 7 years were selected by multistage stratified cluster sampling method in nine cities of China. According to the geographical location, the nine cities were divided into northern, central and southern regions, and each city included urban and suburban areas. Anthropometric measurements were obtained on the spots and other related information was collected with questionnaires. RESULTS: There were slight urban-suburban difference and obvious regional difference in anthropometric measurements in China. Comparison with the 4th NSPGDC in 2005, measurements increased 0.1-1.1 kg in weight, 0.5-1.8 cm in height in urban areas (except children under 3 years) and 0.1-2.5 kg in weight, 0.2-3.8 cm in height in suburban areas. The urban-suburban difference of those measurements became smaller than 10 years ago, but their regional difference persistently exist. Chinese children were 0.36 SD in weight, 0.43 SD in height in urban areas and 0.30 SD in weight, 0.30 SD in height in suburban areas higher than WHO standards. CONCLUSIONS: Physical growth of children under 7 years old was undergoing a slowly positive secular trend during the latest decade in more economically developed regions of China. Urban-suburban difference of those measurements became smaller, while their regional difference persistently exist. Chinese healthy children under 7 years in nine cities was taller and heavier than WHO standards.

The role of Homer 1a in increasing locomotor activity and non-selective attention, and impairing learning and memory abilities.

The current study aimed to investigate the possible role of Homer 1a in the etiology and pathogenesis of attention deficit hyperactivity disorder (ADHD). We divided 32 rats into four groups. The rats in the RNAi-MPH group were given the lentiviral vector containing Homer 1a-specific miRNA (Homer 1a-RNAi-LV) by intracerebroventricular injection, and 7 days later they were given three daily doses of methylphenidate (MPH) by intragastric gavage. The RNAi-SAL group was given Homer 1a-RNAi-LV and saline later. The NC-MPH group was given the negative control lentiviral vector (NC-LV) and MPH later. The NC-SAL group was given NC-LV and saline later. Rats that were given Homer 1a RNAi exhibited increased locomotor activity and non-selective attention, and impaired learning and memory abilities, which is in line with the behavioral findings of animal models of ADHD. However, MPH ameliorated these abnormal behaviors. All findings indicated that Homer 1a may play an important role in the etiology and pathogenesis of ADHD.

Increased locomotor activity and non-selective attention and impaired learning ability in SD rats after lentiviral vector-mediated RNA interference of Homer 1a in the brain.

Our previous studies found that Homer 1a, a scaffolding protein localized at the post-synaptic density (PSD) of glutamatergic excitatory synapses, is significantly down-regulated in the brain of spontaneous hypertensive rats (SHR), an animal model of attention deficit hyperactivity disorder (ADHD). Furthermore, a first-line treatment drug for ADHD, methylphenidate, can up-regulate the expression of Homer 1a. To investigate the possible role of Homer 1a in the etiology and pathogenesis of ADHD, a lentiviral vector containing miRNA specific for Homer 1a was constructed in this study. Intracerebroventricular injection of this vector into the brain of Sprague Dawley (SD) rats significantly decreased Homer 1a mRNA and protein expression levels. Compared to their negative controls, these rats displayed a range of abnormal behaviors, including increased locomotor activity and non-selective attention and impaired learning ability. Our results indicated that Homer 1a down-regulation results in deficits in control over behavioral output and learning similar to ADHD.

An evaluation of a web-based diabetes education program designed to enhance self-management among patients living with diabetes.

Diabetes is a global public health problem. Maintaining optimal glycemic control is critical for minimizing associated long-term complications and achieving better quality of life. Effective diabetes self-management education is one key component to enhance diabetes clients' self-management capabilities. The research team established a "Caring for Yourself-Managing Your Diabetes" Web site, which contained 35 video clips about diabetes management. The aim of this study was to evaluate user satisfaction with the Web-based diabetes self-management education program. A convenience sample of 100 diabetes clients (mean age, 61.5 [SD, 10.7] years) was invited to view one of the video clips via a laptop computer. A modified version of the Computer-Aided Learning Evaluation Questionnaire and the End-User Computing Satisfaction Questionnaire was used to evaluate participants' satisfaction with the program. The results indicate that participants were satisfied with the format, content, and accuracy of the Web-based diabetes education program. Some participants suggested adding different types of exercises that are specific to the needs of client groups and more explanation of diabetes medications. The results of this study support the use of computer-assisted learning as a promising method for delivering diabetes self-management education, which is satisfactory to diabetes clients.

Knockdown of NYGGF4 increases glucose transport in C2C12 mice skeletal myocytes by activation IRS-1/PI3K/AKT insulin pathway.

NYGGF4, an obesity-related gene, is proposed to be involved in the development of insulin resistance. Skeletal muscle is a primary target organ for insulin and NYGGF4 showed a relatively high expression level in skeletal muscle. Therefore, this study aimed to explore the effect of NYGGF4 on insulin sensitivity of skeletal muscle cells. RNA interference (RNAi) was adopted to silence NYGGF4 expression in mice C2C12 skeletal myocytes. A remarkably increased insulin-stimulated glucose uptake and GLUT4 translocation was observed in NYGGF4 silencing C2C12 cells. Importantly, the enhanced glucose uptake induced by NYGGF4 silencing could be abrogated by the PI3K inhibitor LY294002. In addition, the crucial molecules involved in PI3K insulin signaling pathway were detected by western blotting. The results showed that NYGGF4 knockdown dramatically activate the insulin-stimulated phosphorylation of IRS-1 and AKT. Taken together, these data demonstrate that NYGGF4 knockdown increases glucose transport in myocytes by activation of the IRS-1/PI3K/AKT insulin pathway.

Genomic DNA methylation changes in NYGGF4-overexpression 3T3-L1 adipocytes.

NYGGF4, an obesity-related gene, is proposed to be involved in the development of insulin resistance; however, the underlying molecular mechanisms remain unclear. In the present analysis, NimbleGen tiling arrays were used to determine the patterns of genomic DNA methylation at CpG islands and promoters in NYGGF4-overexpression adipocytes. A total of 2352 CpG dinucleotides in 2018 genes and 3490 CpG dinucleotides in 3064 genes were found to be hypermethylated or hypomethylated, respectively, in NYGGF4-overexpression adipocytes. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis revealed enrichment of biological processes associated with energy metabolism and signal transduction events, including the peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathway, and mitogen-activated protein kinases(MAPK) and Ras homolog gene family, member A (RhoA) signaling. These data demonstrate that differentially methylated genes are significantly overrepresented in NYGGF4-overexpression adipocytes, providing valuable clues for further exploration of the role of NYGGF4 in insulin sensitivity regulation.

Effects of embryonic exposure to polychlorinated biphenyls on zebrafish (Danio rerio) retinal development.

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that affect embryonic development. The purpose of this study was to examine the effects of embryonic exposure to PCBs on early retinal development in zebrafish, Danio rerio. Zebrafish embryos were immediately exposed to different concentrations (0, 0.125, 0.25, 0.5, 1.0 and 2.0 mg) of PCBs per liter of medium at 28.5 °C. Embryos were assessed at 30, 48, 72 and 96 h post-fertilization (hpf) for changes in embryonic survival rate, development, larval retinal morphology and ultrastructure of the retina. The results show that PCB exposure decreased the survival rate of embryos in a time- and dose-dependent manner. Embryos exposed to the higher concentrations of PCBs (0.5, 1.0 and 2.0 mg l(-1) ) displayed obvious gross morphological deformities. At 72 hpf, the retinal layer development of zebrafish was delayed at higher PCB concentrations (1.0 mg l(-1) ). At 96 hpf, irregularity of photoreceptor cells arrangement and thickening of photoreceptor and ganglionic layers were observed in PCB-treated larvae at concentrations of 0.25-1 mg l(-1) . Ultrastructural examination showed signs of growth inhibition of the photoreceptor outer segment at 0.25-1 mg l(-1) PCB exposure at 72 hpf, as well as the appearance of massive vacuoles and holes inside the outer segments in the PCB exposure group at 96 hpf. These results suggest that embryonic exposure to moderate and high levels of PCBs induced developmental deficits in zebrafish retinas, particularly in photoreceptor cells.

Homer expression in the hippocampus of an animal model of attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a pervasive neurobehavioral disorder. We previously demonstrated differential expression of some isoforms of Homer, a family of scaffolding proteins localized to the postsynaptic density of glutamatergic excitatory synapses, in the spontaneous hypertensive rat (SHR), which is the most frequently used animal model of ADHD. Since these changes were observed in the prefrontal cortex (PFC), a critical structure in ADHD, it was hypothesized that these Homer isoforms may play a role in ADHD. The present study aimed to extend these findings to the hippocampus, which has direct connections to the PFC and subserves attention and cognition, two functions that are disturbed in ADHD. Hippocampal mRNA and protein expression of several Homer isoforms were investigated in both SHR and control Wistar-Kyoto (WKY) rats using reverse transcription-polymerase chain reaction and Western blotting, respectively. Both mRNA and protein for Homer 1a and Homer 2a/b, but not Homer 1b/c, were expressed at significantly lower levels in the hippocampus of SHR compared to WKY rats. The effects of methylphenidate (MPH) on spatial learning and memory in SHRs were also examined using the Morris water maze and on hippocampal expression of Homer isoforms. MPH improved spatial learning and memory and up-regulated hippocampal expression of Homer 1a and Homer 2a/b, but not Homer 1b/c, in SHRs. The animal model of ADHD may have altered expression of Homer 1a and Homer 2a/b in the hippocampus, in addition to the PFC. Future studies will focus on elucidating the specific mechanisms of Homer 1a and Homer 2a/b in ADHD.

[Longitudinal study of the physical catch-up growth in 84 preterm appropriate for gestational age infants].

OBJECTIVE: To study the growth rhythm of preterm appropriate for gestational age (AGA) infants by investigating their physical catch-up growth characteristics. METHODS: Eighty-four preterm AGA newborns (44 males and 40 females) with gestational ages between 28-36 weeks were enrolled. The weight, length and head circumference were evaluated by Z score according to the criterions of actual and corrected ages. RESULTS: The preterm infants had the catch-up growth in weight, length and head circumference in the first year of life. The growth velocity within the first three months was the highest. The velocity in the weight catch-up was higher than that in the length. CONCLUSIONS: The fastest growing period is the early three month of life in preterm AGA infants. The catch-up growth in weight and length is unbalanced.

Effects of NYGGF4 knockdown on insulin sensitivity and mitochondrial function in 3T3-L1 adipocytes.

NYGGF4 is a recently discovered gene that is involved in obesity-associated insulin resistance. It has been suggested that mitochondrial dysfunction might be responsible for the development of insulin resistance induced by NYGGF4 overexpression. In the present study, we aimed to define the impact of down-regulating NYGGF4 expression by RNA interference (RNAi) on the insulin sensitivity and mitochondrial function of 3T3-L1 adipocytes. The results revealed that NYGGF4 knockdown enhanced the glucose uptake of adipocytes, which reconfirmed the regulatory function of NYGGF4 in adipocyte insulin sensitivity. However, an unexpected observation was that knockdown of NYGGF4 reduced intracellular ATP concentration and promoted an increase in mitochondrial transmembrane potential (ΔΨm) and reactive oxygen species (ROS) level without affecting mitochondrial morphology or mtDNA. Therefore, the role of NYGGF4 in mitochondrial function remains unclear, and further animal studies are needed to explore the biological function of this gene.

TNF-alpha induces mitochondrial dysfunction in 3T3-L1 adipocytes.

TNF-alpha was the first proinflammatory cytokine identified linking obesity, insulin resistance and chronic inflammation. However, the mechanism of TNF-alpha in the etiology of insulin resistance is still far from clear. Because the mitochondria play an important role in energy metabolism, we investigated whether mitochondrial dysfunction is involved in pathogenesis of TNF-alpha-mediated insulin resistance. First, a fully differentiated insulin-resistant 3T3-L1 adipocyte model was established by incubating with 4 ng/ml TNF-alpha for 4 d, and then the mitochondrial morphology and functions were observed. TNF-alpha treatment induced pronounced morphological changes in the mitochondria, which became smaller and condensed, and some appeared hollow and absent of cristae. Mitochondrial dynamics changes were observed as increased mitofusion protein mfn1 and mitofission protein Drp1 levels compared with controls. No obvious effects on mitochondrial biogenesis were found. PGC-1alpha levels decreased, but no significant changes were found in mtTFA mRNA expression, NRF1mRNA expression and mitochondrial DNA (mtDNA). TNFalpha treatment also led to decreased mitochondrial membrane potential and reduced production of intracellular ATP, as well as accumulation of significant amounts of reactive oxygen species (ROS). Further research is required to determine if mitochondrial dysfunction is involved in the inflammatory mechanism of insulin resistance and may be a potential target for the treatment of insulin resistance.

Short report: Tissue-specific expression profiles of the uncoupling protein family in normal control mice and genetically ob/ob mice.

Uncoupling proteins (UCPs) located in the inner mitochondrial membrane are involved in the regulation of energy balance. Thus far, 5 UCP isoforms have been identified, but controversies exist in the research focused on the function of the UCPs (except UCP1) in the pathogenesis of obesity. Because of the known cross-reactivity of the antibodies presently available for the detection of UCP proteins, this study systematically analyzed the differential tissue expression profiles of the 5 UCP isoforms in lean control mice and ob/ob mice by using real-time polymerase chain reaction (PCR) analysis. The results show that the tissue-specific expression patterns of individual isoforms in normal and ob/ob mice are considerably different; this will provide new insights into the functions of UCPs in the pathogenesis of genetic obesity.

Mitochondrial dysfunction is induced by high levels of glucose and free fatty acids in 3T3-L1 adipocytes.

Hyperglycemia and high free fatty acids (FFAs) are two well-known characteristics of type 2 diabetes, and are also implicated in the etiology of insulin resistance. However, their roles in mitochondrial dysfunction of white adipocytes are not well-studied. In this study, we investigated the effects of high glucose (25 mM), high free fatty acids (FFAs, 1mM), or a combination of both high glucose+high FFAs on mitochondrial function in differentiated 3T3-L1 adipocytes after 48 h of treatment. We found that high glucose, high FFAs, or high glucose+high FFAs reduced insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes. In addition, the mitochondria became smaller and more compact. Levels of the mitofusion protein mfn1 decreased and levels of the mitofission protein Drp1 increased as compared to controls. NRF1 was downregulated, and PGC-1 beta levels were diminished in the high glucose and high glucose+high FFAs conditions. Levels of PGC-1 alpha and mtTFA mRNA were greatly downregulated. No difference was found in the mitochondrial DNA (mtDNA) and intracellular ATP levels of treated cells compared to control cells. Cells treated with high glucose or high FFAs accumulated significant amounts of reactive oxygen species (ROS) and displayed a loss of the mitochondrial membrane potential. High glucose and high glucose+high FFAs led to similar decreases in intramitochondrial calcium concentration, although high FFAs had no effect. Therefore, high glucose and high FFAs can regulate insulin sensitivity, and mitochondrial dysfunction may occur in this process.

Gene expression profiles in the prefrontal cortex of SHR rats by cDNA microarrays.

We have undertaken cDNA microarrays to identify differentially expressed genes in the prefrontal cortex (PFC) of spontaneously hypertensive-rat (SHR), a rodent model of attention deficit hyperactivity disorder (ADHD) versus control Wistar-Kyoto (WKY) rats. The analysis of the gene expression profiles indicated that 57 genes were up-regulated and 97 genes were down-regulated in the PFC of SHR. These predominately expressed genes included genes involved in neural development, immunity, transcription factor, monoamine neurotransmitter, metabolism, signal transduction, apoptosis and so on. Although more detailed analyses are necessary, it is anticipated that further study of genes identified will provide insights into their specific roles in the etiology of ADHD.

Prefrontal cortex Homer expression in an animal model of attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a pervasive neurobehavioral disorder affecting approximately 5% of children and adolescents and 3% of adults, and the prefrontal cortex (PFC) may play the most critical role in the expression of ADHD. Converging previous studies indicate a potential role of Homer--a scaffolding protein family localized at the postsynaptic density (PSD) of glutamatergic excitatory synapses--in behavioral pathologies associated with neuropsychiatric disorders. Accordingly, we speculate that these Homer isoforms might contribute to the etiology and development of ADHD. METHOD: We investigated the differential mRNA and protein expressions of several Homer isoforms in the PFC of the spontaneous hypertensive rat/Wistar-Kyoto rats (SHR/WKY), the most frequently used animal model of ADHD, using RT-PCR and western blotting. Furthermore, we examined the effects of methylphenidate (MPH) exposure on the behaviors and the expression of different Homer isoforms in the PFC of SHR, using Làt maze, RT-PCR and western blotting, respectively. RESULTS: Homer 1a and Homer 2a/b, but not Homer 1b/c, were expressed at a significantly lower levels in the PFC of SHR compared with WKY. MPH exposure decreased the locomotor activity and non-selective attention of SHR, and it up regulated the expression of Homer 1a and Homer 2a/b, but not Homer 1b/c, in the PFC of SHR. CONCLUSION: It is plausible that Homer 1a and Homer 2a/b may be involved in the etiology and pathogenesis of ADHD. Future work will focus on elucidating the specific mechanisms of Homer 1a and Homer 2a/b in ADHD.

LYRM1, a novel gene promotes proliferation and inhibits apoptosis of preadipocytes.

OBJECTIVE: To characterize a novel gene, Homo sapiens LYR motif containing 1 (LYRM1), that is highly expressed in omental adipose tissue of obese subjects. METHODS AND RESULTS: RT-PCR and western blot analysis confirmed that both mRNA and protein levels of LYRM1 were higher in omental adipose tissue of obese subjects than in normal weight subjects. RT-PCR analysis demonstrated that LYRM1 expression is widely distributed, with the highest levels of expression occurring in adipose tissue. A fusion protein of LYRM1 and green fluorescent protein as well as western blot analysis were used to identify the subcellular localization of LYRM1 in the nucleus. Based on Oil red O staining and the expression profile of specific differentiation markers, ectopic LYRM1 expression was not found to significantly affect adipogenesis. MTT assays and cell cycle analysis showed that LYRM1 promotes preadipocyte proliferation, and data from annexin V-FITC and caspase-3 activity assays further determined that LYRM1 can inhibit apoptosis of preadipocytes. CONCLUSIONS: By increasing cell proliferation and lowering the rate of apoptosis, LYRM1 has the potential to modulate the size of the preadipocyte pool and influence adipose tissue homeostasis.