Charcot-Marie-Tooth (CMT) disease represents a clinically and genetically heterogeneous group of inherited neuropathies. Here, we report a five-generation family of eight affected individuals with CMT disease type 2, CMT2. Genome-wide linkage analysis showed that the disease phenotype is closely linked to chromosomal region 10p13-14, which spans 5.41 Mb between D10S585 and D10S1477. DNA-sequencing analysis revealed a nonsense mutation, c.1455T>G (p.Tyr485(∗)), in exon 8 of dehydrogenase E1 and transketolase domain-containing 1 (DHTKD1) in all eight affected individuals, but not in other unaffected individuals in this family or in 250 unrelated normal persons. DHTKD1 mRNA expression levels in peripheral blood of affected persons were observed to be half of those in unaffected individuals. In vitro studies have shown that, compared to wild-type mRNA and DHTKD1, mutant mRNA and truncated DHTKD1 are significantly decreased by rapid mRNA decay in transfected cells. Inhibition of nonsense-mediated mRNA decay by UPF1 silencing effectively rescued the decreased levels of mutant mRNA and protein. More importantly, DHTKD1 silencing was found to lead to impaired energy production, evidenced by decreased ATP, total NAD(+) and NADH, and NADH levels. In conclusion, our data demonstrate that the heterozygous nonsense mutation in DHTKD1 is one of CMT2-causative genetic alterations, implicating an important role for DHTKD1 in mitochondrial energy production and neurological development.
Cervical cancer is a common malignant neoplasm in women, and its incidence is increasing year by year. This study explored the effects of traditional Chinese medicine combined with recombinant human interferon α2b in cervical cancer patients. 178 cervical intraepithelial neoplasias (CIN) combined with high-risk HPV-positive patients from June 2017 to August 2020 were divided into the study group (n = 89 cases) and the control group (n = 89 cases) by the random number table method. Patients in the control group were treated with recombinant human interferon α2b, and the study group was treated with traditional Chinese medicine (TCM) on the basis of the control group. After treatment, the recurrence rate in the study group was significantly decreased while the human papillomavirus (HPV) negative conversion rate was significantly increased. 3 months after treatment, the TCM symptom scores in the study group were lower than in the control group. Moreover, serum levels of inflammatory factors decreased in both groups, and the decrease was more significant in the study group. After treatment, the ultrasound parameters were significantly decreased in the study group than in the control group. In conclusion, traditional Chinese medicine combined with recombinant human interferon α2b in cervical cancer patients could effectively improve the negative conversion rate of HPV infection, the level of inflammatory factors, reduce the degree of cervical erosion, and enhance the immunity of patients with high safety and significantly improve the quality of life.
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