Risk factors for infant hearing loss: a meta-analysis.

Hearing loss is a common disability in infants that significantly impacts their cognitive, language, and literacy development. This study aimed to systematically assess the risk factors for the early identification and intervention in infant hearing loss. Databases were searched for meta-analyses of observational studies until November 2023. The quality assessment was performed using the Cochrane risk of bias tool, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of the evidence. A meta-analysis identified 14 risk factors significantly associated with infant hearing loss. According to the GRADE approach, there were four factors with moderate-certainty evidence (low birth weight(LBW), congenital anomalies, craniofacial anomalies, intracranial hemorrhages), seven factors with low-certainty evidence (ototoxic medications, family history of hearing loss, mechanical ventilation > 5 days, intrauterine infection, admission to neonatal intensive care unit (NICU) > 5 days, mechanical ventilation and asphyxia) and six with extremely-low-certainty evidence (very low birth weight < 1500 g (VLBW), hyperbilirubinemia, sepsis or meningitis, male sex, premature birth, small for gestational age (SGA)). Nevertheless, no significant association was found between infant hearing loss and factors such as small for gestational age (SGA), male sex, and premature birth (P > 0.05).  Conclusion: The identification of these 14 interrelated risk factors can prove advantageous in clinical practice, as these findings could guide hearing screening and parental counseling. Furthermore, prospective research could be conducted to develop risk-based scoring systems based on these factors. What is Known: • Infant hearing loss is a worldwide issue. • Risk factors for this condition are debated. What is New: • This is the first meta-analysis to comprehensively evaluate perinatal and postnatal risk factors for hearing loss in infants. • Intracranial hemorrhage, mechanical ventilation, and low birth weight are associated with infant hearing loss. However, no evidence of an association was found between premature birth, being small for gestational age, or male sex and hearing loss.

Association between high-mobility group box 1 levels and febrile seizures in children: a systematic review and meta-analysis.

The relationship between High-mobility group box 1 (HMGB1) and febrile seizures (FS) in children remains unclear. This study aimed to apply meta-analysis to reveal the correlation between HMGB1 levels and FS in children. Databases including PubMed, EMBASE, Web of science, Cochrane library, CNKI, SinoMed and WanFangData were searched for relevant studies. Pooled standard mean deviation and 95% confidence interval were calculated as effect size since the random-effects model was used when I2 > 50%. Meanwhile, between-study heterogeneity was determined by performing subgroup and sensitivity analyses. A total of 9 studies were finally included. Meta-analysis showed that the children with FS had significantly higher HMGB1 levels compared with healthy children and children with fever but no seizures (P<0.05). Additionally, subgroup analysis showed that the HMGB1 level in children with complex FS was higher than those with simple FS (P<0.05), and children with duration >15 min were higher than those with duration ≤15min (P<0.05). There were no statistical differences between children with or without a family history of FS (P>0.05). Finally, children with FS who converted to epilepsy exhibited higher HMGB1 levels than those who did not convert to epilepsy (P<0.05). The level of HMGB1 may be implicated in the prolongation, recurrence and development of FS in children. Thus, it was necessary to evaluate the precise concentrations of HMGB1 in FS patients and to further determine the various activities of HMGB1 during FS by well-designed, large-scale, and case-controlled trials.

A novel manganese dioxide-based drug delivery strategy via in situ coating γ-polyglutamic acid/cisplatin for intelligent anticancer therapy.

Cisplatin (CDDP) is one of the most frequently used chemotherapeutic drugs due to its broad-spectrum and potent antitumor activity. Unfortunately, inactivation due to glutathione (GSH) substances and insufficient cellular uptake of CDDP greatly hinder its clinical applications. Herein, manganese dioxide (MnO2) was reported as an efficient glutathione (GSH) consumption material for promoting the accumulation and preventing premature leakage of CDDP in tumor cells. In this work, γ-polyglutamic acid/cisplatin (PGA/CDDP) conjugates and PGA/CDDP nanoparticles (NPs) were respectively constructed via the ligand exchange reaction and electrostatic interaction. Furthermore, PGA/CDDP NPs were in situ coated with MnO2 (PGA/CDDP@MnO2 NPs) through the redox reaction of the residual carboxyl group (-COOH) and potassium permanganate (KMnO4). As a result, the PGA/CDDP@MnO2 NPs achieved a satisfactory drug-loading efficiency (ca. 37.26%) and multi-responsive controlled drug release. Remarkably, the MnO2 shells exhibited excellent performance for efficient glutathione (GSH) consumption and significantly enhanced the killing effect (ca. 2-3 times) in human lung cancer cells (A549) compared with pure CDDP. Moreover, it was observed that PGA/CDDP@MnO2 NPs could also inhibit the migration and invasion of A549 cells. Overall, these remarkable performances of PGA/CDDP@MnO2 NPs make MnO2 promising for controlled drug release and intelligent anticancer therapy.

New Insights into Mechanisms of Ferroptosis Associated with Immune Infiltration in Neonatal Hypoxic-Ischemic Brain Damage.

BACKGROUND: The mechanisms underlying ferroptosis in neonatal hypoxic-ischemic brain damage (HIBD) remain unclear. METHOD: Four microarray datasets were collected from the GEO database (three mRNA datasets GSE23317, GSE144456, and GSE112137, and one miRNA microarray dataset GSE184939). Weighted gene co-expression network analysis (WGCNA) was used to identify modules of HIBD-related genes. The ferroptosis-related genes were extracted from FerrDb, of which closely correlated to HIBD were obtained after the intersection with existing HIBD's DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as protein-protein interaction (PPI) network analysis were subsequently conducted. Cytoscape was used to identify central genes. Immune cell infiltration analysis was performed by the CIBERSORT algorithm. RESULT: Fifty-six ferroptosis-related differentially expressed genes (FRDEGs) were screened, mainly related to ferroptosis, autophagy, hypoxia response, metabolic pathways, and immune inflammation. The seven optimal hub FRDEGs were obtained by intersecting with key modules of WGCNA. Then, the expression levels of the seven optimal hub FRDEGs were validated in the GSE144456 and GSE112137 datasets, and the ferroptosis-related mRNA-miRNA network was established. In addition, this study revealed immune cell infiltration in the HIBD cerebral cortex and the interaction between immune cells. Moreover, notably, specific FRDEGs were strongly positively correlated with immune function. CONCLUSIONS: The mechanism of ferroptosis is intricate and closely related to neonatal HIBD. Therefore, targeting ferroptosis-related gene therapy and immunotherapy may have therapeutic prospects for neonatal HIBD.

Risk factors for metabolic bone disease of prematurity: A meta-analysis.

OBJECTIVE: To investigate the risk factors for metabolic bone disease of prematurity (MBDP), and to provide a reference for the prevention of MBDP. METHODS: The databases including China Biomedical Literature Service System, China National Knowledge Infrastructure, Wanfang Data, and Weipu Periodical Database, PubMed, Web of Science, Embase, Cochrane Library and other databases were searched for studies on the risk factors for MBDP published up to June 18, 2021. RevMan 5.3 and Stata 14.1 software were used to perform a Meta analysis. RESULTS: A total of 15 articles were included, including 13 case-control studies, 1 current investigation, and 1 retrospective cohort study. There were 1,435 cases in the case group and 2,057 cases in the control group, with a total sample size of 3,492 cases. Meta analysis showed that risk factors for MBDP include birth weight <1000g (OR = 6.62, 95%CI: 2.28-19.25), gestational age <32 weeks (OR = 2.73, 95%CI: 1.07-6.95), septicemia (OR = 2.53, 95%CI: 1.69-3.79), parenteral nutrition time (OR = 4.04, 95%CI: 1.72-9.49), cholestasis (OR = 3.50, 95%CI: 1.49-8.23), intrauterine growth retardation (OR = 6.89, 95%CI: 3.81-12.44), while the birth weight(OR = 0.44, 95%CI: 0.21-0.90) and gestational age (OR = 0.57, 95%CI: 0.44-0.73)are the protective factors of MBDP. CONCLUSION: Factors like birth weight <1000g, gestational age <32 weeks, septicemia, parenteral nutrition time, cholestasis, and intrauterine growth retardation may increase the risk of metabolic bone disease of prematurity.

Mechanisms of Vitamin C Regulating Immune and Inflammation Associated with Neonatal Hypoxic-Ischemic Encephalopathy Based on Network Pharmacology and Molecular Simulation Technology.

BACKGROUND: There are still controversies about the curative effect of vitamin C in treating HIE, and its mechanism of action is not entirely clear. This study is designed to explore the potential molecular mechanism of vitamin C in treating neonatal hypoxic ischemic encephalopathy (HIE). METHODS: The effect targets of vitamin C and the pathogenic targets of neonatal HIE were obtained via retrieval of public databases to screen out the molecular targets of vitamin C acting on neonatal HIE. Gene Ontology (GO) functional annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the main targets. Vitamin C and the optimum target structural components are subjected to molecular docking and molecular dynamics simulation analysis via computer software so as to verify their binding activity and stability. RESULT: Based on 16 overlapping targets of vitamin C and HIE, seven main targets were identified in this study. According to GO and KEGG analysis, molecular functions (top 25 items) and signal pathways (21 items) related to inflammatory reaction, immune response, and cell transcriptional control may be potential pathways for vitamin C to treat neonatal HIE. Molecular docking and molecular dynamics simulation were adopted to definitively determine the 4 optimum core target spots. CONCLUSION: The efficacy of vitamin C on HIE is involved in the immunoregulation and inflammation-related functional processes and signal pathways. These molecular mechanisms, including core targets, will contribute to the clinical practice of neonatal HIE in the future.

No association between children's febrile seizures and S100B protein levels: A meta-analysis.

BACKGROUND: In recent years, studies have examined the relationship between febrile seizures in children and S100B protein with contradictory results. We systematically evaluated the relationship between children's febrile seizures and S100B protein levels. METHODS: We used Stata 11.0 software to conduct a meta-analysis of the included studies published in The China National Knowledge Infrastructure, VIP, Wanfang, Chinese Biology Medicine Disc, PubMed, Web of Science, Cochrane Library, and EMBASE databases as well as clinical trial registries in China, Europe, and the United States. RESULTS: Six case-control studies were finally included in the meta-analysis. The results of the meta-analysis showed that the serum S100B protein level of children with febrile seizures was 0.72 higher than the serum S100B protein level of healthy children (Z=6.85, 95% CI 0.52∼0.93, P<0.05). There was no difference in the serum S100B protein level between the children with febrile seizures and children with fever but without seizures (Z=0.70, 95% CI -0.20∼0.41, P>0.05). CONCLUSION: The level of serum S100B protein in children with febrile seizures was higher than that of healthy children and was statistically significant, whereas the increase in children with higher fever without seizures was not statistically significant. Because there was only a difference in serum S100B protein levels between children with febrile seizures and healthy children but not in febrile children without seizures as the strongest confounding factors for the results, febrile seizures do not elevate the level of S100B protein levels any more than fever.

Correlation between neonatal hyperbilirubinemia and vitamin D levels: A meta-analysis.

OBJECTIVE: Hyperbilirubinemia is a common disease in the neonatal period, and hyperbilirubinemia may cause brain damage. Therefore, prevention and diagnosis and management of hyperbilirubinemia is very important, and vitamin D may affect bilirubin levels. To evaluate the relationship between neonatal hyperbilirubinemia and vitamin D levels. METHOD: The China National Knowledge Infrastructure, VIP, Wanfang, Chinese Biology Medicine Disc, PubMed, Web of Science, Cochrane Library, and Embase databases as well as clinical trial registries in China and the United States were searched for relevant studies from inception to September 2020 without restrictions on language, population, or year. The studies was screened by two reviewers independently, the data were extracted, and the risk of bias of the included studies was evaluated using the NOS. A meta-analysis was conducted on the included studies using Stata11 software. RESULTS: Six case-control studies were included, and the methodological quality of the studies was high (grade A). The studies included 690 newborns; more than 409 were diagnosed with hyperbilirubinemia. The means and standard deviations were calculated. Meta-analysis results showed that neonatal vitamin D levels were 7.1 ng/ml lower among infants with hyperbilirubinemia than among healthy newborn levels (z = 6.95, 95% CI 9.10 ~ 5.09, P < 0.05). Subgroup analysis was conducted based on whether the bilirubin levels were concentrated in the 15 to 20 mg/dl range. Vitamin D level of infants with hyperbilirubinemia (the bilirubin levels were concentrated in the 15 to 20 mg/dl range) was 9.52 ng/ml (Z = 15.55, 95% CI-10.72~-8.32, P<0.05) lower than that of healthy infants. The bilirubin levels in four cases were not concentrated in the 15-20 mg/dl range. The results showed that the vitamin D level of hyperbilirubinemia (The bilirubin levels were not concentrated in the 15-20 mg/dl range) neonates were 5.35 ng/ml lower than that of healthy neonates (Z = 6.43, 95% CI-6.98~-3.72, P<0.05). CONCLUSION: Vitamin D levels were observed to be lower in neonates with hyperbilirubinemia as compared to term neonates without hyperbilirubinemia in this study. This can possibly suggest that neonates with lower vitamin D levels are at higher risk for developing hyperbilirubinemia.