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Objective To retrospectively analyze the clinical sign and symptom, pathological and genetic characteristics of a case of hereditary myopathy with early respiratory failure (HMERF). Methods and Results A 26‑year‑old female patient presented with muscle weakness (including the proximal and distal arms and lower legs) and myalgia, typical daytime and nighttime respiratory failure symptoms. The serum creatine kinase (CK, 258 U/L) and creatine kinase isoenzyme (CK ‑ MB, 17.80 ng/ml) levels were increased. The EMG showed myogenic changes, and thigh muscle MRI showed selective semitendinous muscle involvement. The skeletal muscle biopsy showed the formation of cytoplasm arranged in the submuscular membrane like a "necklace". Gene test revealed a mutation of TTN gene with c.90211T > C (p. Cys30071Arg). The final diagnosis was HMERF. Conclusions The possibility of HMERF should be considered in patients with unexplained respiratory failure, especially with muscle weakness. Skeletal muscle biopsy and genetic test can make a definitive diagnosis.

Immune checkpoint inhibitors (ICIs) have been widely used in tumor treatment. Immune⁃related adverse events (irAEs) are common in skin, endocrine, gastrointestinal tract, liver and cardiovascular system symptoms. Nervous system adverse events are relatively rare, but the clinical presentations are various and difficult to identify. Neurologists should strengthen their understanding of neurologic immune⁃related adverse events (NirAEs), so as to enable the events to be identified in time, intervene as early as possible, and closely monitor the events, in order to improve the disease prognosis.

The pathophysiological process of ischemic stroke is a complex inflammatory process involving multiple factors (genetic factors, immune factors, etc.). Its inflammatory response is multiphasic, with both pro⁃inflammatory and anti⁃inflammatory reactions. Moreover, the changes and effects of inflammatory cells and cytokines are time⁃dependent, thus exerting neurodestruction or neuroprotection. This article reviews the research progress of ischemic stroke⁃related immunology in recent years.

CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining immune homeostasis in multiple sclerosis (MS). Hence, we aimed to explore the therapeutic efficacy and safety of adoptive cell therapy (ACT) utilizing induced antigen-specific Tregs in an animal model of MS, that is, in an experimental autoimmune encephalomyelitis (EAE) model. B cells from EAE model that were activated with soluble CD40L were used as antigen-presenting cells (APCs) to induce the differentiation of antigen-specific Tregs from naïve CD4 precursors, and then, a stepwise isolation of CD4+CD25highCD127low Tregs was performed using a flow sorter. All EAE mice were divided into Treg-treated group (2 × 104 cells in 0.2 mL per mouse, n = 14) and sham-treated group (0.2 mL normal saline (NS), n = 20), which were observed daily for clinical assessment, and for abnormal appearance for 6 weeks. Afterward, histological analysis, immunofluorescence and real-time PCR were performed. Compared to sham-treated mice, Treg-treated mice exhibited a significant decrease in disease severity scores and reduced inflammatory infiltration and demyelination in the spinal cord. Additionally, Tregs-treated mice demonstrated higher CCN3 protein and mRNA levels than sham-treated mice. The results of this preclinical study further support the therapeutic potential of this ACT approach in the treatment of MS. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory demyelinating disorders of the central nervous system (CNS). Various genetic and environmental factors have been identified to contribute to etiology of MS and NMO. Aquaporin 4 (AQP4), is the most abundant water channel in CNS. AQP4 is expressed in astrocytes of the brain, spinal cord, optic nerve and supportive cells in sensory organs. In contrast to MS, immunoreactivity of AQP4 is abolished in NMO lesions. However, conflicting results have been reported regarding the association between AQP4 polymorphisms and demyelinating disorders. Considering the ethnic differences of genetic variations, replications in other cohorts are required. In this study, single nucleotide polymorphisms (SNPs) of AQP4 gene in patients with NMO/neuromyelitis optica spectrum disorders (NMOSD), and MS in the Northern Han Chinese population were examined. Six selected AQP4 SNPs were genotyped by high-resolution melting (HRM) method. Compared with healthy control (HC), there was no significant difference of AQP4 allele and genotype frequency in MS or NMO/NMOSD group. This study showed no significant association of common AQP4 SNPs with MS or NMO/NMOSD, strongly suggesting that polymorphisms of AQP4 gene are unlikely to confer MS or NMO/NMOSD susceptibility, at least in Northern Han Chinese population.

Objective To investigate the clinical features of multiple sclerosis (MS) patients with positive serum aquaporin 4 (AQP4) antibody. Methods A total of 18 MS patients who had been diagnosed in accord with McDonald Criteria (2010) were enrolled and were divided into AQP4 positive group (N = 5) and AQP4 negative group (N = 13). In combination with accessory examination, clinical features and laboratory data of MS patients were correlatively studied between 2 groups in association with follow-up study in Outpatient Clinic. Results Five seropositive patients, including 2 men and 3 women, were collected. The median age of onset was 43 years and the median clinical course was 4 months. Compared with patients with negative AQP4 antibody, MS patients with positive AQP4 antibody demonstrated increased spinal cord lesions and optic nerve involvement. MRI revealed multiple abnormal long T1 and long T2 signals in brain and cervicothoracic spinal cord (3/5), and multiple abnormal long T1 and long T2 signals in cervicothoracic spinal cord (2/5) in seropositive group. Relatively more patients in seropositive group had increased cerebral spinal fluid (CSF) IgG index (4/4) and 24 h intrathecal IgG synthesis rate (3/4), and positive oligoclonal bands (OBs, 3/4). Two patients presented with positive anti- nuclear antibody (ANA) and one Sjögren's syndrome (SS) in seropositive group. Conclusions There were some differences in clinical features between AQP4 antibody positive MS and classical MS, suggesting distinctive pathogenesis may exist between these two entities, which need to be emphasized and treated accordingly from the diagnostic and therapeutic points of view. [ABSTRACT FROM AUTHOR]

Objective To investigate the immunological abnormalities beyond central nervous system (CNS) associated with neuromyelitis optica spectrum disorders (NMOSDs). Methods Clinical data of 56 patients with NMOSDs from January 2010 to December 2013 enrolled in Department of Neurology at Peking University People's Hospital were analyzed retrospectively. All patients were divided into 2 groups: neuromyelitis optica (N = 33) and non - neuromyelitis optica (N = 23). Each patient underwent detailed physical examination including internal medicine and nervous system. Records of complicated autoimmune diseases as well as scoring of Expanded Disability Status Scale (EDSS) were used to evaluate disease severity. Part of patients received detection of multiple immunological indicators. Results In all patients with NMOSDs, there were 3 cases with Hashimoto thyroiditis, one case with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS), asthma, hyperthyroidism, rheumatoid arthritis and iridocyclitis, respectively. In patients whose immunological indices were available, the first three abnormal immunological changes were abnormal thyroid function (10/17), positive anti-nuclear antibody (14/28) and positive complement 3 (8/19). In addition, NMOSDs got worsen in 2 cases after delivery. Conclusions NMOSDs coexist with many kinds of autoimmune diseases and multiple autoantibodies. The above - mentioned autoimmunity may be related to the pathogenesis of NMOSDs. Besides, pregnancy or delivery may aggravate the disease severity of NMOSDs. [ABSTRACT FROM AUTHOR]

Objective: Norcantharidin (NCTD) is a new small molecule with anticarcinogen activity, which was extracted from Chinese cantharides. ABT-737 is another small molecule with anticarcinogen activity in lower dose by inhibiting BCL-2. This study was designed to explore the effect of NCTD combined with ABT-737 on the in vitro proliferation and apoptosis of cervical cancer cells. Methods: HeLa and SiHa cell lines were cultured in vitro. NCTD alone or in combination with ABT-737 was used to treat cells. MTT assay was used to determine the viability of cells. The flow cytometry was used to detect apoptosis. Results: NCTD alone could significantly inhibit the proliferation of HeLa and SiHa in a dose -dependent manner. NCTD combined with ABT-737 could significantly enhance the effect of NCTD. The apoptosis rates of HeLa in the ABT-737 (1 µmol/L) group and the NCTD (60 µmol/L) group were (31.65±7.75)% and (40.34±14.52)%, while this rate was (63.03±10.90)% in the NCTD combined ABT-737 group. The apoptosis rates of SiHa in the ABT-737 group and the NCTD group were (9.76±0.04)% and (22.04±3.03)%, respectively; while the rate in the NCTD combined ABT-737 group was (58.36±2.31)%. Effect of the combined two drugs on apoptosis was significantly stronger than that of any single drug (P<0.05). Conclusions: NCTD shows the in vitro anti-proliferation effect on the HeLa and SiHa cell lines and the effects of both inhibiting proliferation and inducing apoptosis when combined with ABT-737. [ABSTRACT FROM AUTHOR]