Background: Inclusion body myositis (IBM) is a unique idiopathic inflammatory myopathy with unclear pathogenesis and poor prognosis. Although previous publications have identified some molecular biomarkers, the value of these biomarkers is unknown. Objective: To identify hub genes and signaling pathways related to IBM for understanding the IBM-related mechanisms and providing guidance for therapy development. Methods: Two microarray datasets (GSE3112 and GSE128470) were downloaded from the Gene Expression Omnibus (GEO) database. GEO2R was used to detect differentially expressed genes (DEGs) between IBM and normal muscle tissues. The hub genes were determined using protein-protein interaction (PPI) network in Cytoscape. The specific signaling pathways and biological functions of IBM were identified using GO, KEGG, and GSEA enrichment analyses. Moreover, CIBERSORT was applied to estimate the expression level of 22 immune cell types in IBM and normal muscle tissue. The relationship between the immune cell types and hub genes was then explored. Results: A total of 219 DEGs and 10 hub genes were identified. Enrichment analyses revealed that the chemokine signaling pathway, cellular response to interferon-gamma, and P53 pathway have crucial roles in IBM. Immune infiltration analyses showed that IBM was associated with high level of CD8 T cells, Tregs, and macrophages. Finally, five potential drugs were predicted for IBM patients through CMap (connectivity map) database. Conclusion:In this study, the underlying molecular mechanisms and immunological landscape of IBM were investigated, and thus may provide new directions for future research on IBM pathogenesis.

Aims: To evaluate the clinical, pathological, and genetic features of patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD). Methods: Thirty-one patients with RR-MADD admitted to our hospital from January 2005 to November 2020 were enrolled, and their clinical data were collected. Pathological characteristics of the muscle tissue and possible pathogenic gene mutations were analyzed. Results: The most common clinical features in all patients were symmetrical proximal muscle weakness. Laboratory examination revealed elevated levels of creatine kinase, homocysteine, and uric acid, acylcarnitines, and organic acid. The muscle biopsy revealed typical pathological changes like lipid deposition. Genetic analysis identified ETFDH mutations in 29 patients, among which one had homozygotes, 19 had compound heterozygotes, 7 had heterozygous mutations, and 2 had heterozygous mutations of both ETFDH and ETFA. Two patients had no pathogenic gene mutations. All patients were treated with riboflavin, and their symptoms improved, which was consistent with the diagnosis of RR-MADD. Conclusion: The clinical manifestations and genetic test results of patients with RR-MADD are heterogeneous. Therefore, a comprehensive analysis of clinical, pathological, and genetic testing is essential for the early diagnosis of RR-MADD.

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Reversible splenial lesion syndrome (RESLES) is a rare clinical imaging syndrome that is characterized by magnetic resonance imaging (MRI) findings of reversible abnormal signals in the splenium of the corpus callosum (SCC). There are a variety of pathogenic causes, including infection, metabolic disturbances, and antiepileptic drug use. Moreover, the disease is clinically rare and easily misdiagnosed. Here, we report a unique case of a 32-year-old man with Fanconi syndrome who had an intensified signal in the SCC and diffuse white matter swelling on MRI. We believe this to be the first adult case of RESLES as a manifestation of Fanconi syndrome, which further expands the disease spectrum leading to RESLES. The imaging features of this case included extensive lesions, symmetrical diffuse restricted signals, and reversibility. The identification of these features improves our understanding of the imaging characteristics of RESLES, thus enabling clinicians to better understand this disease, correctly establish its diagnosis, and improve its prognosis in this kind of patient.

We report a family with riboflavin-reactive multiple acyl-CoA dehydrogenase deficiency (RR-MADD) partially caused by a novel mutation in the electron transfer flavoprotein dehydrogenase gene (ETFDH). The RR-MADD family was identified by physical examination, electromyography, and muscle biopsy of the proband. Laboratory examination and electromyography suggested a muscle disease of the lipid storage myopathies. This was confirmed by a muscle biopsy that revealed lipid deposition in the muscle fibers. The proband’s sister previously had a similar disease, so the family underwent genetic testing. This revealed complex heterozygous ETFDH mutations c.389A > T (p. D130V) and c.1123C > A (p. P375T) in the proband and her sister, of which c.1123C > A (p. P375T) is a novel pathogenic mutation. The proband was treated with riboflavin and changes in physical symptoms and laboratory tests were evaluated before and after treatment. The discovery of a novel locus further expands the ETFDH mutation spectrum and suggests that genotyping is vital for early detection of RR-MADD as it can greatly improve the prognosis.