Prevalence of cerebral palsy comorbidities in China: a systematic review and meta-analysis.

Objectives: This systematic review aimed to comprehensively understand the comorbidity of cerebral palsy (CP) in China. Methods: We searched through databases in both Chinese and English until December 2022 to gather cross-sectional studies on the comorbidity of CP in China. After two reviewers independently screened the articles, collected the data, and assessed the bias risk, a meta-analysis was conducted using the Stata 17.0 software. Results: A total of 73 articles were included. Of these, 16 articles reported total comorbidity, with a prevalence of 79.7% (95% CI: 73.8-85.7%); 56 articles reported epilepsy, with a prevalence of 17.9% (95% CI: 15.4-20.4%); 48 articles reported intellectual disability, with a prevalence of 58.0% (95% CI: 51.8-64.3%); 32 articles reported speech disorders, with a prevalence of 48.0% (95% CI: 41.6-54.4%); 41 articles reported hearing disorders, with a prevalence of 17.2% (95% CI: 13.0-21.4%); and 35 articles reported vision disorders, with a prevalence of 23.1% (95% CI: 16.3-29.8%). The topographical type of CP was the primary source of heterogeneity in the prevalence of epilepsy. Diagnostic criteria for CP, clinical type of CP, GMFCS, publishing time, and topographical type of CP were the primary sources of heterogeneity in the prevalence of intellectual disability. Clinical type of CP and topographical type were the primary sources of heterogeneity in the prevalence of speech disorders. Finally, the region was the primary source of heterogeneity in the prevalence of hearing disorders. Conclusion: The prevalence of comorbidities in CP is high in China. Comorbidities are related to the characteristics, severity, and risk factors of brain insult and have a particular relationship with regional economic development and medical and health levels.

Characterization of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD)-induced cardiotoxicity in larval zebrafish (Danio rerio).

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) is a type of p-phenylenediamine (PPD), which is widely used in the manufacture of rubber tires owing to its excellent antiozonant properties. In this study, the developmental cardiotoxicity of 6PPD was evaluated in zebrafish larvae, and the LC50 was approximately 737 µg/L for the larvae at 96 h post fertilization (hpf). In the 6PPD treatment of 100 µg/L, the accumulation concentrations of 6PPD were up to 2658 ng/g in zebrafish larvae, and 6PPD induced significant oxidative stress and cell apoptosis in the early developmental stages of zebrafish. Transcriptome analysis showed that 6PPD exposure could potentially cause cardiotoxicity in larval zebrafish by affecting the transcription of the genes related to the calcium signal pathway and cardiac muscle contraction. The genes related to calcium signaling pathway (slc8a2b, cacna1ab, cacna1da, and pln) were verified by qRT-PCR, which were significantly downregulated in larval zebrafish after exposing to 100 µg/L of 6PPD. Simultaneously, the mRNA levels of the genes related to cardiac functions (myl7, sox9, bmp10, and myh71) also respond accordingly. H&E staining and heart morphology investigation indicated that cardiac malformation occurred in zebrafish larvae exposed to 100 µg/L of 6PPD. Furthermore, the phenotypic observation of transgenic Tg (myl7: EGFP) zebrafish also confirmed that 100 µg/L of 6PPD exposure could change the distance of atria and ventricles of the heart and inhibit some key genes (cacnb3a, ATP2a1l, ryr1b) related to cardiac function in larval zebrafish. These results revealed the toxic effects of 6PPD on the cardiac system of zebrafish larvae.

Oral exposure to tire rubber-derived contaminant 6PPD and 6PPD-quinone induce hepatotoxicity in mice.

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) is a widely used additive for protecting various rubber products, and its product of oxidation N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPDQ) has attracted extensive attention in aquatic toxicity. However, the toxicity of 6PPD and 6PPDQ in mammals has not been reported yet. In this study, the effects of 6PPD and 6PPDQ on the liver of C57BL/6 mice were assessed by orally administering different doses of 6PPD and 6PPDQ (10, 30, and 100 mg/kg) in mice for 6 weeks. 6PPD and 6PPDQ were found to bioaccumulate in the liver in a dose-dependent manner. Moreover, a high dose of 6PPD and 6PPDQ exposure increased not only the liver weights but also liver triglyceride levels, indicating that 6PPD and 6PPDQ exposure induced hepatotoxicity in mice. Furthermore, transcriptomic analysis revealed that 6PPD and 6PPDQ induced differential expression of genes mainly enriched in glycolipid metabolism, immune-related, and glutathione metabolism pathways. Therefore, 6PPD and 6PPDQ altered hepatic metabolism in mice. Furthermore, 6PPDQ could induce an immune response by upregulating the transcription of immune-related genes and promoting macrophage infiltration in the liver. In conclusion, our study revealed the toxic effects of 6PPD and 6PPDQ exposure on multi-endpoints in the liver of mice and improve our understanding of the health risks of 6PPD and 6PPDQ to mammals. The findings of our study may help formulate better safety regulations for the use and disposal of rubber products.