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Calsequestrin 1 (CASQ1) is the most crucial Ca2+ binding protein localized in the sarcoplasmic reticulum (SR) of skeletal muscle. With high capacity and low affinity for Ca2+, CASQ1 plays a significant role in maintaining a large amount of Ca2+ necessary for muscle contraction. However, only five mutations in CASQ1 have been identified to date. Here, we report a 42‐year‐old Chinese female patient who presented with a 12 years history of slowly progressive upper limb weakness, predominantly affecting distal muscles, which was uncommon comparing to other CASQ1‐related patients. Next‐generation sequencing (NGS) analysis revealed a novel heterozygous mutation (c.766G > A, p.Val256Met) in CASQ1. Functional studies confirmed the likely pathogenicity of this variant. Muscle histopathology revealed rare optically empty vacuoles in myofibers and atypical eosinophilic granules in the cytoplasm, which has not been observed before. We also performed a literature review on all the pathogenic mutations in CASQ1 and summarized their genetic and clinical characteristics. This is the first report on CASQ1‐related myopathy from China, further expanding the mutation spectrum of CASQ1 gene and provides new insights into the function of CASQ1. [ABSTRACT FROM AUTHOR]

Congenital myasthenic syndrome (CMS) encompasses a heterogeneous group of inherited disorders affecting nerve transmission across the neuromuscular junction. The aim of this study was to characterize the clinical, physiological, pathohistological and genetic features of nine unrelated Chinese patients with CMS from a single neuromuscular centre. A total of nine patients aged from neonates to 34 years were enrolled who exhibited initial symptoms. Physical examinations revealed that all patients exhibited muscle weakness. Muscle biopsies demonstrated multiple myopathological changes, including increased fibre size variation, myofibrillar network disarray, necrosis, myofiber grouping, regeneration, fibre atrophy and angular fibres. Genetic testing revealed six different mutated genes, including AGRN (2/9), CHRNE (1/9), GFPT1 (1/9), GMPPB (1/9), PLEC (3/9) and SCN4A (1/9). In addition, patients exhibited differential responses to pharmacological treatment. Prompt utilization of genetic testing will identify novel variants and expand our understanding of the phenotype of this rare syndrome. Our findings contribute to the clinical, pathohistological and genetic spectrum of congenital myasthenic syndrome in China. [ABSTRACT FROM AUTHOR]

Background: Direct moxibustion (DM) is reported to be useful for cervical spondylotic radiculopathy (CSR), but the analgesic mechanism remains unknown. Autophagy plays a protective role in neuronal apoptosis, Act A/Smads signaling pathway has been confirmed to be associated with the activation of autophagy. The study aimed to explore the effect of DM on autophagy in rats with CSR and the involvement of Act A/Smads signaling pathway. Methods: Rats were randomly divided into Sham, CSR, CSR + DM, CSR + DM + 3‐MA (PI3K inhibitor), and CSR + DM + SB (Act A inhibitor) group. Three days after establishment of CSR model with a fish line inserted under the axilla of the nerve roots, DM at Dazhui (GV14) was performed six times once for seven consecutive days. Western blot and immunofluorescence staining were used to observe the expression of the neuronal autophagy molecule LC3II/I, Atg7, and Act A/Smads signaling molecule Act A, p‐Smad2, and p‐Smad3. Bcl‐2/Bax mRNA expression was measured by real time PCR. Results: DM improved the pain threshold and motor function of CSR rats and promoted the expression of Act A, p‐Smad2, p‐Smad3, LC3II/I, and Atg7 in the entrapped‐nerve root spinal dorsal horn. DM reduced the expression of Bax mRNA and decreased the number of apoptotic neurons. 3‐MA and Act A inhibitor SB suppressed the expression of above‐mentioned proteins and reduced the protective effect of DM on apoptotic neurons. Conclusion: DM exerts analgesic effects by regulating the autophagy to reduce cell apoptosis and repair nerve injury, and this feature may be related to the Act A/Smads signaling pathway. [ABSTRACT FROM AUTHOR]

GNE myopathy is a heterogeneous group of ultrarare neuromuscular disorders caused by mutations in the GNE gene. An estimated prevalence of 1~21/1,000,000 leads to a deficiency of data and a lack of availability of samples to conduct clinical research on this neuromuscular disorder. Although GNE, which is the mutated gene responsible for the disease, is well known as the key enzyme in the biosynthesis pathway of sialic acid, the clinicopathological‐genetic spectrum of GNE mutant patients is still unclear and expanding. This study presents ten unrelated patients with GNE myopathy, discovering five novel missense mutations. Clinical, electrophysiological, imaging, pathological and genetic data are presented in a retrospective manner. Interestingly, several patients in the cohort were found to have peripheral neuropathy and inflammatory cell infiltration in muscle biopsies, which have seldom been reported. This study, conducted by a neuromuscular centre in China, is the first attempt to highlight these abnormal clinicopathological features and associate them with genetic mutations in GNE myopathy. [ABSTRACT FROM AUTHOR]

Acquired lymphedema is a complex disease caused by cancer treatment or parasitic infection and few effective treatments are available for lymphedema.1-3 It is urgently needed to develop new experimental approaches and therapeutic strategies.3 In this study, we address a new role and mechanism of MSC-ex (human umbilical cord Wharton's jelly mesenchymal stem cells derived exosome) in lymphedema treatment. MSC-ex treatment promoted lymphatic drainage in lymphedema mice as injected methylene blue across the site of incision at week 6, which was not found in PBS treated mice (Figure 1J). As lymphangiogenesis is crucial in lymphedema development after lymphatic ablation,4,5 we analyzed the lymphatic anatomy and lymphangiogenesis in MSC-ex treated animals. [Extracted from the article]

Objectives: Long noncoding RNAs (lncRNAs) play important roles in cancer development and progression. The deregulated expression of LINC00978 has been reported in human cancers. However, the expression pattern and biological roles of LINC00978 in gastric cancer (GC) remain unclear. In this study, we investigated the potential roles and clinical value of LINC00978 in gastric cancer. Materials and methods: QRT-PCR was performed to investigate the expression of LINC00978 in gastric cancer cell lines, tissues and serum samples. Cell counting, colony formation, transwell migration and matrigel invasion assays were performed to determine the effects of shRNA-mediated knockdown of LINC00978 on gastric cancer cell functions. In vivo tumour growth assay was also conducted. Flow cytometry, immunohistochemistry, western blot and qRT-PCR were used for potential mechanism study. Results: LINC00978 expression level was elevated in GC tumour tissues, serum samples and cell lines. The expression level of LINC00978 was significantly correlated with tumour size (P = 0.02), lymphatic metastasis (P = 0.009) and TNM stage (P = 0.009). LINC00978 knockdown inhibited the proliferation of GC cells by suppressing cell cycle progression and inducing apoptosis. LINC00978 knockdown also inhibited the migration and invasion of GC cells. In addition, LINC00978 knockdown inhibited the activation of TGF-β/ SMAD signalling pathway and the process of epithelial-mesenchymal transition (EMT) in GC cells. Moreover, the in vivo tumorigenicity of LINC00978 knockdown GC cells in mice was significantly decreased. Conclusions: LINC00978 promotes gastric cancer progression and may serve as a potential biomarker for GC. [ABSTRACT FROM AUTHOR]