[Correlation between clinical manifestation, prognosis and antibody in anti-muscle-specific tyrosine kinase antibody positive myasthenia gravis].

Objective: To determine the correlation between the titer of anti-muscle-specific tyrosine kinase (anti-MuSK) antibodies (Abs) and the severity and prognosis of Musk-associated myasthenia gravis (Musk-MG). Methods: A total of 33 MuSK-MG patients diagnosed at Department of Neurology, Peking Union Medical College Hospital from May 2018 to June 2020 were prospectively included. Patients were divided into different groups according to immune state, and the immune naive patients were further divided by the Myasthenia Gravis Foundation of America (MGFA) classification. There were 28 Musk-MG patients who completed the follow-up and subdivided into different groups according to post-intervention status (PIS). Twenty-five patients who received immunotherapy were divided into corticosteroid monotherapy group (n=17) and corticosteroid combined with immunosuppressant group (n=8). The comparison of Ab titers between different MGFA groups and PIS groups was determined by Kruskal-Wallis method, and the comparison of Ab titers between different time points was analyzed by Mann-Whitney U method. Results: There were 11 males and 22 females included in the study, with an onset age of 48 (18, 73) years, of which 16 cases were immune naive and 17 cases were treated with corticosteroids or immunosuppressant at least once. In immune naive population, a significant difference of Ab titers among different MGFA phenotypes was detected (P=0.04). Ab titers were reduced by immunosuppression therapy (the median value decreased from 1.20 to 0.87, P=0.01). Twenty-four (85.7%) MuSK-MG patients achieved a good prognosis (PIS-PR/MM), 1 (3.6%) case achieved improvement (PIS-I), and 3 (10.7%) patients' condition worsened (PIS-W), there was no significant difference of Ab titers among the three groups (P=0.21). Meanwhile, there was no significant difference of Ab titers between different treatment groups (P=0.95). Conclusions: In the immune naive state, the concentration of MuSK-Ab is consistent with the severity of the disease, and the Ab titers decrease after immunotherapy. Change of Ab titers is related to the daily dosage of corticosteroid and is not consistent with PIS grades.

MiR-223-5p inhibitor suppresses microglia inflammation and promotes Nrg-1 in rats of spinal cord injury.

OBJECTIVE: The aim of this study was to investigate the role of microRNA-233-5p (miR-233-5p) in spinal cord injury (SCI), and to explore the possible underlying mechanism. MATERIALS AND METHODS: Microglia were first isolated from neonate rats and cultured in a suitable environment in vitro. Lipopolysaccharide (LPS) and interleukin-4 (IL-4) were used to activate microglia. The expressions of miR-223-5p, inducible nitric oxide synthase (iNOS) and arginase 1 (Arg-1) were measured by qRT-PCR, respectively. After transfection of miR-233-5p inhibitor, the expression levels of miR-223-5p, iNOS and Arg-1 in cells were detected as well. A moderate SCI model was successfully established in rats (10 g fallen on T10 spinal cord at the height of 5 cm). Subsequently, inflammation indexes at miR-223-5p peak moment were observed. Meanwhile, its neuro-protective effect at 28 days after SCI was estimated. Finally, Basso, Beattie, and Bresnahan (BBB) rating scale was applied to evaluate the hindlimb locomotor function of rats at 1, 3, 7, 14, 21, 28 days after SCI. RESULTS: MiR-223-5p inhibitor significantly promoted M2 microglia expression and degenerated M1 microglia expression in vitro. SCI elevated the level of miR-223-5p in injured spinal cord tissues within one week, which reached a peak at 5 days after injury. Meanwhile, miR-223-5p inhibitor remarkably reduced the expressions of inflammatory factors, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) at 3 days after SCI, as well as increased neuregulin1 (NRG-1) expression. However, miR-223-5p inhibitor significantly declined the levels of apoptosis key enzyme-caspase-3 and glia reaction marker-glial fibrillary acidic protein (GFAP) at 7 and 28 days after SCI, respectively. As a result, BBB rating scale demonstrated that hindlimb locomotor function was significantly recovered in miR-223-5p injection group. CONCLUSIONS: MiR-223-5p was up-regulated in M1 microglia, whereas down-regulated in M2 microglia. MiR-223-5p inhibitor could significantly increase M2 microglia expression, while decrease M1 microglia expression in vitro. In vivo, miR-223-5p inhibitor suppressed the inflammatory response and reinforced NRG-1 level to reduce glia reaction and neuron apoptosis. Thereby, its treatment promoted the hindlimb locomotor function of rats.

[Glucose and lipid metabolic disorders in myasthenia gravis patients and its mechanisms].

Objective: To investigate the glucose and lipid metabolic disorders in patients with myasthenia gravis (MG) without glucocorticoid therapy, and the relationships between insulin, insulin resistance, muscle strength, serum levels of osteocalcin, 25-hydroxy vitamin D (25OHD) and glucose and lipid metabolism. Methods: A total of 102 MG patients [(40±11) years old, 43 males and 59 females] without glucocorticoid treatment were enrolled in this cross-sectional study. Height, weight and the handgrip of dominant hands were measured. Serum levels of fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PBG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), 2-hour postprandial insulin (2 h PINS), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and osteocalcin, 25OHD were detected. Insulin resistance was assessed using homeostasis model assessment of insulin resistance (HOMA-IR). Results: The proportion of impaired fasting glucose or impaired glucose tolerance, type 2 diabetes, dyslipidemia, hyperinsulinemia in male and female were 30.0%, 10.0%, 50.0%, 33.3% and 17.5%, 3.5%, 27.7%, 7.1%, respectively. Serum osteocalcin levels in male and female were 2.8 (1.7, 4.4) µg/L and 2.3 (1.3, 3.9) µg/L, respectively. And 25OHD levels in male and female were (93.5±34.9) nmol/L and (81.0±30.5) nmol/L, respectively. Handgrip of male and female was (37.0±9.4) kg and (20.5±6.3) kg. After adjusted for age, FINS (r=0.619, P<0.001), 2 h PINS (r=0.640, P<0.001), HOMA-IR (r=0.534, P<0.001) were positively correlated with 2 h PBG, and the handgrip was negatively correlated with TC (r=-0.486, P=0.026), LDL-C (r=-0.485, P=0.026) in male. FINS (r=0.352, P=0.008; r=0.300, P=0.026; r=0.646, P<0.001) and 2 h PINS (r=0.278, P=0.040; r=0.518, P<0.001; r=0.382, P=0.006) and HOMA-IR (r=0.695, P<0.001; r=0.583, P<0.001; r=0.818, P<0.001) were positively correlated with FBG, 2 h PBG, HbA1c, and the handgrip were negatively correlated with FBG (r=-0.424, P=0.016), 2 h PINS (r=-0.345, P=0.034) and positively correlated with HDL-C (r=0.389, P=0.037) in female. There was no association between osteocalcin, 25OHD and glucose and lipid metabolism. Multivariate linear regression analysis also found that there were significant relationships between handgrip, insulin, insulin resistance levels and glucose and lipid metabolic disorders. Conclusion: There was a high proportion of glucose and lipid metabolic disorders in MG patients without glucocorticoid treatment, and the mechanism may be related to insulin resistance induced by muscle weakness.