OBJECTIVE: To explore the role of IL-21 in the pathogenesis of myasthenia gravis (MG) and its influence on the the class switch of anti-AChR antibodies. METHODS: Blood was taken from 26 patients and 18 healthy controls, and the expression of IL-21R mRNA in peripheral blood mononuclear cells (PBMCs) was detected by RT-PCR. The expression of IL-21R on B lymphocytes was measured by flow cytometry, while the concentrations of serum IL-21 and the levels of anti-AChR-IgG and its isotype IgG(1), IgG(2), and IgG(3) were tested by ELISA. RESULTS: The serum concentration of IL-21 in the MG group was higher than that in the control group (31.686±8.499 pg/mL, 15.147±6.366 pg/mL) and the difference was significant (P<0.01). IL-21R mRNA expressed on PBMCs in the MG group was higher than that in the control group (0.139±0.052, 0.101±0.022), and the difference was significant (P<0.05). There was no difference between ocular MG and generalized MG subgroup (P>0.05). Compared with the control group, the expression of IL-21R on B lymphocytes also increased in the MG group (P<0.05). In the anti-AChR-Ab positive MG group, the serum concentration of IL-21 showed positive correlation with anti-AChR-IgG(P<0.05),but no correlation with its isotype IgG(1), IgG(2), and IgG(3), respectively(P>0.05). Expression of IL-21R mRNA in the PBMCs showed no correlation with the level of serum anti-AChR-IgG and its isotype IgG(1), IgG(2), and IgG(3), respectively(P>0.05); however the expression of IL-21R in B lymphocytes showed positive correlation with anti-AChR-IgG and it's isotype IgG(1) and IgG(3) (P<0.05,P<0.01,P<0.05), but no correlation with IgG(2) (P>0.05). CONCLUSION IL-21 might induce the class switch of anti-AChR antibodies to IgG(1) and IgG(3) isotype through IL-21R on B lymphocytes which promotes the pathogenesis of the MG.
Adolescent ; Adult ; Autoantibodies ; classification ; immunology ; Female ; Humans ; Immunoglobulin Class Switching ; immunology ; Immunoglobulin G ; classification ; Interleukins ; blood ; genetics ; Male ; Middle Aged ; Myasthenia Gravis ; blood ; immunology ; RNA, Messenger ; blood ; genetics ; Receptors, Cholinergic ; immunology ; Receptors, Interleukin-21 ; blood ; genetics ; Young Adult

Objective:To evaluate the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in striatum in paclitaxel-induced neuropathic pain and the relationship with GABA B receptors in rats. Methods:Healthy clean-grade male Sprague-Dawley rats, aged 6-9 weeks, weighing 180-220 g, were used in this study.The neuropathic pain model was established by intraperitoneal injection of paclitaxel 2 mg/kg once every 2 days for 7 consecutive days in anesthetized rats, and then intrathecal catheterization was performed.Fifty rats in which intrathecal catheters were successfully implanted were divided into 5 groups ( n=10 each) using a random number table method: paclitaxel group (P group), paclitaxel plus normal saline group(N group), paclitaxel plus lentivirus empty vector group (BV group), paclitaxel plus HCN4 channel lentivirus group (H group), and paclitaxel plus HCN channel inhibitor ZD7288 group (I group). Ten rats of the same age were selected as the blank control group (C group). At 15 days after intraperitoneal injection of paclitaxel, normal saline 20 μl was intrathecally injected in group N, group BV received intrathecal injection of HCN4 channel lentivirus empty vector 1×10 8 TU/ml, 20 μl, group H received intrathecal injection of HCN4 channel lentivirus 1×10 8 TU/ml, 20 μl, and group I received intrathecal injection of ZD728830 μg, 20 μl.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before paclitaxel injection and 14 and 21 days after injection.The cerebral striatum tissues were obtained at T 2, and the expression of HCN4 channel and GABA B receptors was determined by immunohistochemistry and Western blot. Results:Compared with group C, the MWT was significantly decreased, HCN4 channel expression was up-regulated, and GABA B receptor expression was down-regulated in group P ( P<0.05). Compared with group P, the MWT was significantly increased, HCN4 channel expression was down-regulated, and GABA B receptor expression was up-regulated in group H and group I ( P<0.05), and no significant change was found in the parameters mentioned above in group N and group BV ( P>0.05). Conclusion:Up-regulation of expression of HCN4 channels in striatum can induce down-regulation of GABA B receptor expression, which is involved in the pathophysiological mechanism of paclitaxel-induced neuropathic pain in rats.

The Chinese Guidelines on Diagnosis and Management of Atrial Fibrillation, jointly formulated by the Chinese Society of Cardiology, Chinese Medical Association and the Heart Rhythm Committee of Chinese Society of Biomedical Engineering, was first released on June 15, 2023. The guidelines elaborate the various aspects of atrial fibrillation management, in which emergency management of atrial fibrillation is also an integral part. This article interpreted the emergency management part in the guidelines in detail by reviewing relevant literature.

The World Health Organization (WHO) released the “Global report on hypertension” on September 19, 2023. This report systematically summarizes the prevalence, mortality, diagnosis and treatment of hypertension in various countries, and elucidates the current situation of hypertension management, and gives a series of suggestions on how to manage hypertension, providing new thinking and inspiration for countries to optimize hypertension management. Through the summary of relevant studies and reports, this paper further reviews the present situation, early identification and management of hypertension.

COVID-19 ; Coronavirus Nucleocapsid Proteins ; Humans ; Nucleocapsid Proteins ; Phosphoproteins ; SARS-CoV-2