Objective To identify a new genetic cause in patients segregating distal hereditary motor neuropathy (dHMN) with an autosomal recessive pattern. Methods Whole‐exome sequencing was conducted in two siblings and was combined with segregation analysis. Additionally, 83 unrelated dHMN patients with unknown genetic cause were screened. RNA analysis was performed using blood lymphocytes and HEK293 cells transfected with mutant plasmids. Immunohistochemistry and Western blot analysis was applied to the nerve tissue. The enzymatic activities of mutant proteins were measured in the cultured cells to verify the pathogenicity of variants. Results The clinical features of the patients showed late‐onset phenotype of distal motor neuropathy without sensory involvement. We identified that compound heterozygous variants of c.1342C>T and c.2071_2072delGCinsTT in the membrane metalloendopeptidase (MME) gene co‐segregated with the phenotype in a dHMN family. In an additional group of 83 patients with dHMN, compound heterozygous variants of c.1416+2T>C and c.2027C>T in MME were identified in one patient. The splice site variant c.1416+2T>C results in skipping of exon 13. The stop variant c.1342C>T induces mRNA degradation via nonsense‐mediated mRNA decay. Transcript levels of MME in the lymphocytes showed no significant differences between the patients and controls. We also identified that MME variants were associated with mild decrease in protein expression in the sural nerve and significant impairments of enzymatic activity. Interpretation Variants in the MME gene were associated with not only a Charcot‐Marie‐Tooth neuropathy phenotype but also with an autosomal‐recessive dHMN phenotype. Loss of function may play a role in the pathogenesis of dHMN.

Transcranial magnetic stimulation (TMS) is a noninvasive neurophysiologic technique that can stimulate the human brain. Positioning of the coil was often performed based merely on external landmarks on the head, meaning that the anatomical target in the cortex remains inaccurate. Navigated transcranial magnetic stimulation (nTMS) combines a frameless stereotactic navigational system and TMS coil and can provide a highly accurate delivery of TMS pulses with the guidance of imaging. Therefore, many novel utilities for TMS could be explored due to the ability of precise localization. Many studies have been published, which indicate nTMS enables presurgical functional mapping. This review aimed to provide a comprehensive literature review on nTMS, especially the principles and clinical applications of nTMS. All articles in PubMed with keywords of "motor mapping," "presurgical mapping," "navigated transcranial magnetic stimulation," and "language mapping" published from 2000 to 2018 were included in the study. Frequently cited publications before 2000 were also included. The most valuable published original and review articles related to our objective were selected. Motor mapping of nTMS is validated to be a trustful tool to recognize functional areas belonging to both normal and lesioned primary motor cortex. It can offer reliable mapping of speech and motor regions at cortex prior to operation and has comparable accuracy as direct electrical cortical stimulation. nTMS is a powerful tool for mapping of motor and linguistic function prior to operation, has high application value in neurosurgery and the treatment of neurological and psychiatric diseases, and has gained increasing acceptance in neurosurgical centers across the world.

Background: With the acceleration of population aging, sarcopenia will place a heavy burden on families and society. Thus, effective treatments urgently need to be developed to slow down the development of sarcopenia. This study adopted a network pharmacological approach to explore the possible mechanisms of puerarin in treating sarcopenia. Methods:The potential therapeutic targets of puerarin were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, while the targets of sarcopenia were obtained from the GeneCards, DisGeNET, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD) databases. The protein-protein interaction (PPI) network was generated by BisoGenet, and core targets were identified by a topological analysis. To determine the potential targeting pathways, the core targets were further imported into the Metascape platform for the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The results were visualized using an online bioinformatics tool.Results: We identified 53 targets for puerarin and 129 targets for sarcopenia. A total of 206 core targets, which were considered potential therapeutic targets, were identified from the merged PPI network. Further, the GO and KEGG analyses revealed that the functions of the core targets and related pathways were mainly associated with the cell cycle, apoptosis, protein synthesis, and proteolysis.Conclusions: Puerarin has the potential to treat sarcopenia through the regulation of the cell cycle, apoptosis, and protein homeostasis. Our study has laid a foundation for further studies on drug development and pharmacological experiments in the treatment of sarcopenia.