A novel mutation in ryanodine receptor 2 (RYR2) genes at c.12670G>T associated with focal epilepsy in a 3-year-old child.

Background: Ryanodine receptor 2 (RYR2) encodes a component of a calcium channel. RYR2 variants were well-reported to be associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), but rarely reported in epilepsy cases. Here, we present a novel heterozygous mutation of RYR2 in a child with focal epilepsy. Methods: At the age of 2 years and 7 months, the patient experienced seizures, such as eye closure, tooth clenching, clonic jerking and hemifacial spasm, as well as abnormal electroencephalogram (EEG). Then, he was analyzed by whole-exome sequencing (WES). The mutations of both the proband and his parents were further confirmed by Sanger sequencing. The pathogenicity of the variant was further assessed by population-based variant frequency screening, evolutionary conservation comparison, and American Association for Medical Genetics and Genomics (ACMG) scoring. Results: WES sequencing revealed a novel heterozygous truncating mutation [c.12670G > T, p.(Glu4224*), NM_001035.3] in RYR2 gene of the proband. Sanger sequencing confirmed that this mutation was inherited from his mother. This novel variant was predicted to be damaging by different bioinformatics methods. Cardiac investigation showed that the proband had no structural abnormalities, but sinus tachycardia. Conclusion: We proposed that RYR2 is a potential candidate gene for focal epilepsy, and epilepsy patients carried with RYR2 variants should be given more attention, even if they do not show cardiac abnormalities.

Correlation analysis between characteristics under gastroscope and image information of tongue in patients with chronic gastriti.

OBJECTIVE: To explore the correlation between diagnostic information of tongue and gastroscopy results of patients with chronic gastritis. METHODS: Frequent pattern growth (FP-Growth), SPSS Modeler was used to analyze the correlation rules between the image information of tongue parameters and the characteristics of the stomach and duodenum seen under gastroscopy. RESULTS: Ranking in order of confidence: cyanotic tongue, slippery fur, yellow fur and spotted tongue were sequently associated with both gastric antrum mucosal hyperemia or edema and gastric antrum mucosal erythema/macula. L, one value of tongue coating color, which counted among (30, 60), tooth-marked tongue and b, one value of tongue coating color, which counted in the range of (5, 20) were sequently associated with gastric antrum mucosal erythema /macula. A, one value of tongue body color, which counted in the range of (0, 20), was related to both gastric antrum mucosal hyperemia or edema and gastric antrum mucosal erythema /macula. a, one value of tongue coating color, which counted in the range of (15, 35), was associated with gastric antrum mucosal erythema / macula. There are a total of 9 strong correlation rules. CONCLUSIONS: Cyanotic tongue, slippery fur, yellow fur, the CIE Lab value of tongue coating, a, the value of tongue body color, spotted tongue, and tooth-marked tongue are all related to the gastric antrum mucosal hyperemia or edema and gastric antrum mucosal erythema / macula. The conditions of gastric mucosa could be predicted by the examination of the above related image information of tongue.

Aerobic exercise promotes the expression of ATGL and attenuates inflammation to improve hepatic steatosis via lncRNA SRA.

The role of aerobic exercise in preventing and improving non-alcoholic fatty liver has been widely established. SRA is a long non-coding RNA, which has received increasing attention due to its important role in lipid metabolism. However, it is unclear whether aerobic exercise can prevent and treat hepatic lipid accumulation via SRA. The mice were randomly divided into four groups as follows, normal control group, normal aerobic exercise group, high-fat diet group (HFD), and high-fat diet plus aerobic exercise (8 weeks, 6 days/week, 18 m/min for 50 min, 6% slope) group (HAE). After 8 weeks, the mice in the HAE group showed significant improvement in hepatic steatosis. Body weight as well as blood TC, LDL-C, and liver TG levels were significantly lower in the HAE group than in the HFD group. Compared with the HFD group, the expression of SRA was markedly suppressed and the expression of ATGL was significantly increased in the HAE group. Additionally, the JNK/P38 signaling was inhibited, the pro-inflammatory factors were down-regulated, and the anti-inflammatory factor was increased. In addition to this, the same results were shown in experiments with overexpression of SRA. The results of this study provided new support for aerobic exercise to improve hepatic lipid metabolism via lncRNA.

Identification of two rare NPRL3 variants in two Chinese families with familial focal epilepsy with variable foci 3: NGS analysis with literature review.

Background: The GAP Activity Towards Rags 1 (GATOR1) complex, which includes DEPDC5, NPRL2, and NPRL3, plays a key role in epilepsy. It has been reported that focal epilepsy is associated with mutations in the NPRL3 gene in some cases. We report two rare mutations in the NPRL3 gene in two unrelated Chinese families with focal epilepsy in this study. Methods: The proband and her brother in family E1 first experienced seizures at 1.5 and 6 years of age, respectively. Despite resection of epileptogenic foci, she still suffered recurrent seizures. The first seizure of a 20-year-old male proband in family E2 occurred when he was 2 years old. To identify pathogenic variants in these families, whole-exome sequencing (WES) was performed on genomic DNA from peripheral blood. Results: In family E1, the trio-WES analysis of the proband and her brother without apparent structural brain abnormalities identified a heterozygous variant in the NPRL3 gene (c.954C>A, p.Y318*, NM_001077350.3). In family E2, the proband carried a heterozygous NPRL3 mutation (c.1545-1G>C, NM_001077350.3). Surprisingly, the mothers of the two probands each carried the variants, but neither had an attack. Bioinformatics analysis predicted that the mutation (c.954C>A) was in the highly conserved amino acid residues of NPRL3, which affected the α-helix of NPRL3 protein, leading to a truncated protein. The splice variant (c.1545-1G>C) resulted in the loss of the last exon of the NPRL3 gene. Conclusion: The results of this study provide a foundation for diagnosing NPRL3-related epilepsy by enriching their genotypes and phenotypes and help us identify the genetic etiologies of epilepsy in these two families.

Improvement of hyperlipidemia by aerobic exercise in mice through a regulatory effect of miR-21a-5p on its target genes.

Hyperlipidemia is a risk factor for cardiovascular disease, and miR-21a-5p plays an important role in the occurrence and progression of hyperlipidemia. Here, we aimed to investigate the mechanism of aerobic exercise improved hyperlipidemia through enhancing miR-21a-5p expression. In this study, high-fat/high-cholesterol diet mice received 8 weeks of aerobic exercise intervention, then we collected plasma and liver samples, we found that there had a notable improvement in weight gain, blood lipid level, and liver steatosis in hyperlipidemia mice after 8 weeks of aerobic exercise intervention. Besides, aerobic exercise significantly up-regulated the expression of miR-21a-5p and provoked favorable changes in the expression of target genes. Knockdown of miR-21a-5p resulted in dysregulation of lipid metabolism and increased expression of FABP7, HMGCR, ACAT1, and OLR1. While aerobic exercise could alleviate miR-21a-5p knock-down induced lipid metabolism disorder. Taken together, these results demonstrated that aerobic exercise improved hyperlipidemia through miR-21a-5p-induced inhibition of target genes FABP7, HMGCR, ACAT1, and OLR1.