Wilson's disease (WD) is an autosomal recessive inheritance disorder of copper metabolism due to mutations in the ATP7B gene. The distribution of ATP7B gene mutations is diverse in different population. This study aimed to examine the genotypes of the ATP7B mutant alleles in WD patients from Southern China. Genomic DNA was extracted from 103 WD patients and 60 healthy patients. Mutations were screened and detected by DNA sequencing. A total of 51 different ATP7B mutations were identified in WD patients, including six homozygous, 51 compound heterozygous, and 39 single heterozygotes. Three mutations were found to be novel, including one missense mutation (c.2549C>T) and two frameshift mutations (c.3851_3876del and c.1057delC). The most frequent mutations are Arg778Leu (18.93%), Ile1148Thr (8.74%), and Pro992Leu (4.37%). Different from the published results of early studies, Ile1148Thr was found to be the second common mutation in our cohort. The highest mutation detection rate was on exon 8 (43.69%), followed by exon 16 (24.27%), and exon 12 (17.48%). The total mutation detection rate on exon 8, 12, and 16 was 85.44%. No ATP7B gene mutation was found in healthy patients. In conclusion, we identified three novel mutations and Ile1148Thr as another hotspot mutation in WD patients from Southern China. Most of the mutations can be detected by screening exon 8, 12, and 16. Our research has further enriched the mutation spectrum of the ATP7B gene in Chinese and may help to develop genetic screening strategies of WD.

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Based on investigation dada on Petroleum Hydrocarbon (PHC) in April, August

Objective: To investigate whether a super-high dose (SHD) of methylprednisolone (MP) improves its efficacy or induces glucocorticoid (GC) resistance, and to explore the potential mechanisms of GC resistance in experimental allergic encephalomyelitis (EAE). Methods: The therapeutic effects of SHD and low-dose MP were evaluated in EAE by analyzing clinical scores, pathological changes and cytokine production. Immunohistochemistry and RT-PCR were used to investigate the expression of GC receptor (GR) isoforms and splicing factor SRp30c. Results: Both MP doses had similar therapeutic effects. The ratio of GRα to GRβ was positively correlated with clinical score changes. However, there was no difference in the GRα/GRβ ratio between SHD and low-dose MP groups. SRp30c mRNA was correlated with GRβ expression. Conclusion: This study indicates that the GRα/GRβ ratio is associated with GC sensitivity, and SRp30c may play an important role in promoting alternative splicing of GR pre-mRNA to generate GRβ in EAE rats. Compared with low-dose MP, SHD MP does not improve efficacy or induce GC resistance.