“温阳补气”针法对EAMG大鼠神经肌肉接头处AchR蛋白表达的影响

目的: 探讨"温阳补气"针法对实验性自身免疫性重症肌无力(EAMG)大鼠腓肠肌神经肌肉接头(NMJ)处乙酰胆碱受体(AchR)蛋白表达水平的影响,阐明针灸治疗重症肌无力(MG)的作用机制。方法: 采用AchR α1129-145多肽片段免疫接种Lewis雌性大鼠,建立EAMG大鼠模型。在建模成功的EAMG大鼠中随机选取30只,分为模型对照组10只、药物对照组10只和针刺治疗组10只,并将同期购进的未建模的10只大鼠设为空白对照组。药物对照组大鼠予以18.5 mg·kg^-1·d^-1溴吡斯的明灌胃治疗;针刺治疗组大鼠予以"温阳补气"针法治疗;其余2组不予任何处置作为对照。记录治疗前后各组大鼠Lennon症状评分。治疗结束后,取4组大鼠腓肠肌NMJ处组织,采用Western blotting法检测各组大鼠NMJ处AchR蛋白表达水平。结果: 与空白对照组比较,建模成功后治疗前模型对照组、药物对照组和针刺治疗组大鼠Lennon症状评分明显升高(P<0.01);与模型对照组比较,经过2个疗程治疗后药物对照组和针刺治疗组大鼠Lennon症状评分均明显降低(P<0.01);与空白对照组比较,模型对照组大鼠腓肠肌NMJ处AchR蛋白表达水平明显降低(P<0.01);与模型对照组比较,治疗后针刺治疗组和药物对照组EAMG大鼠腓肠肌NMJ处AchR蛋白表达水平明显升高(P<0.01)。结论: "温阳补气"针法可以提高EAMG大鼠NMJ处AchR蛋白表达水平,发挥治疗EAMG的作用。     

电视胸腔镜与传统开胸手术治疗I型重症肌无力疗效比较

目的：探讨电视胸腔镜手术治疗Ⅰ型重症肌无力患者的疗效。方法回顾分析海南医学院附属医院2011年3月至2015年8月期间行胸腺切除手术的82例Ⅰ型重症肌无力患者的临床资料,其中胸腔镜组38例,开胸组44例。比较两组患者的一般情况、免疫指标、应激反应、并发症及临床疗效。结果胸腔镜组在手术时间、术中出血量、切口长度、总住院时间、带管时间分别为(90.2±22.7) min、(50.4±28.1) mL、(3.0±0.5) cm、(2.1±1.1) d、(7.0±2.6) d,低于开胸组的(100.6±22.3) min、(150.6±50.1) mL、(13.0±5.1) cm、(7.2±2.8) d、(9.3±2.8) d,差异均有统计学意义(P<0.05);术毕,胸腔镜组的CD4、CD8值分别为(39.74±6.48)、(31.76±3.42),高于开胸组的(35.62±5.61)、(30.94±5.42);术后24 h胸腔镜组的CD3值为(50.08±3.33),高于开胸组的(45.55±3.84);术后48 h胸腔镜组的CD8、HLA-DR分别为(30.6±8.49)、(69.10±8.44),高于开胸组的(28.11±4.65)、(61.03±6.50);术后24 h、48 h胸腔镜组去甲肾上腺素(NE)浓度分别为(360.71±25.08)、(284.66±25.08),低于开胸组的(406.88±32.75)、(360.67±30.25),差异均有统计学意义(P<0.05);胸腔镜组术后并发症发生率为26.3%(10/38),低于开胸组的63.6%(28/44),差异有统计学意义(P<0.05)。结论电视胸腔镜手术治疗Ⅰ型重症肌无力疗效优于开胸组,其具有免疫功能抑制轻、应激反应小的特点,术后并发症发生率更低,是治疗Ⅰ型重症肌无力的较好选择。     

重症肌无力患者血清Titin抗体和RyR抗体的临床研究

目的探讨重症肌无力（MG）患者血清Titin抗体和Ryanodine受体（RyR）抗体的临床意义。方法采用ELISA法检测61例MG患者和35例健康体验者（正常对照组）的血清Titin抗体、RyR抗体、AChR抗体。结果MG组Titin抗体和RyR抗体阳性率均显著高于对照组（均P＜0.001）;合并胸腺瘤MG（MGT）组患者Titin抗体阳性率明显高于未合并胸腺瘤MG（NTMG）组（P＜0.01）;MGT组和NTMG组患者RyR抗体阳性率差异无统计学意义（P＞0.05）;晚发型MG患者中Titin抗体和RyR抗体阳性率均明显高于早发型MG患者（均P＜0.05）;全身型或重症型（ⅡA、ⅡB、Ⅲ、Ⅳ型）Titin抗体阳性率显著高于眼肌型（Ⅰ型）（P＜0.01）,而两组间RyR抗体阳性率未见统计学差异（P＞0.05）;MG患者Titin抗体和RyR抗体水平与肌无力严重程度相关分析呈正相关（r=0.520、0.487,均P＜0.01）。结论Titin抗体和RyR抗体检测有助于MG的诊断,且Titin抗体有助于鉴别MG患者是否伴随胸腺瘤及进行Osserman分型。Titin抗体与RyR抗体水平还与MG患者病情的严重程度相关,可应用于评估MG患者的病情与预后。     

External treatment of traditional Chinese medicine for myasthenia gravis: A protocol for systematic review and meta-analysis

Background:Myasthenia gravis (MG) is an archetypal autoimmune disorder. The conventional treatments for this disease are drugs, plasma exchange, surgical, and so on. However, this disease is difficult to cure. A mass of studies revealed that the external treatment of traditional Chinese medicine (TCM) for MG is a safe and economical approach. The present study conducted a meta-analysis to compare TCM external treatment combined with modern medicine with modern medicine for MG, in order to determine which TCM external treatment intervention has the best relative efficacy, safety, and provide the best evidence for clinical practice.Methods:PubMed, Cochrane Library, EMBASE, Web of Science, Springer, China National Knowledge Infrastructure (CNKI), Wan-fang database, VIP Chinese Science and Technique Journals Database, the Chinese Bio Medical Database (CBM), and Baidu Scholar were searched. The time of publication was limited from inception to February 28, 2021. Two reviewers independently searched for the selected articles and extract the data. The RevMan V.5.3 statistical software (Cochrane Collaboration) and Stata V.16.0 software were used to conduct the meta-analysis.Results:The results of the systematic review and meta-analysis will be published in a peer-reviewed journal.Conclusion:The present study provides a protocol that can be used in the systematic review and meta-analysis, with the intent to inform professionals on the external treatment of TCM for MG. These would lead to investigations on the use of the most external treatment of TCM for MG.Trial registration number:INPLASY202110083     

Postoperative survival for patients with thymoma complicating myasthenia gravis—preliminary retrospective results of the ChART database

Background

It is so far not clear that how myasthenia gravis (MG) affected the prognosis of thymoma patients. The aim of this assay is to compare the postoperative survival between patients with thymoma only and those with both thymoma and MG.

Methods

The Chinese Alliance for Research in Thymomas (ChART) registry recruited patients with thymoma from 18 centers over the country on an intention to treat basis from 1992 to 2012. Two groups were formed according to whether the patient complicated MG. Demographic and clinical data were reviewed, patients were followed and their survival status were analyzed.

Results

There were 1,850 patients included in this study, including 421 with and 1,429 without MG. Complete thymectomy were done in 91.2% patients in MG group and 71.0% in non-MG group (P<0.05). There were more percentage of patients with the histology of thymoma AB, B1, or B2 (P<0.05) in MG group, and more percentage of patients with MG were in Masaoka stage I and II. The 5- and 10-year overall survival (OS) rates were both higher in MG group (93% vs. 88%; 83% vs. 81%, P=0.034) respectively. The survival rate was significantly higher in patients with MG when the Masaoka staging was 3/4 (P=0.003). Among patients with advanced stage thymoma (stage 3, 4a, 4b), the constituent ratios of 3, 4a, 4b were similar between MG and non-MG group. Histologically, however, there were significantly more proportion of AB/B1/B2/B3 in the MG group while there were more C in the non-MG group (P=0.000). Univariate analyses for all patients showed that MG, WHO classification, Masaoka stage, surgical approach, chemotherapy and radiotherapy and resectability were significant factors, and multivariate analysis showed WHO classification, Masaoka stage, and resectability were strong independent prognostic indicators.

Conclusions

Although MG is not an independent prognostic factor, the survival of patients with thymoma was superior when MG was present, especially in late Masaoka stage patients. Possible reasons included early diagnosis of the tumor, better histologic types, an overall higher R0 resection and less recurrence.     

In vitro characterization of an acetylcholine receptor–transferrin fusion protein for the treatment of myasthenia gravis

SHG2210, a fusion protein containing the N-terminus of human nicotinic acetylcholine receptor α (AchR-α; aa1-210) and human transferrin (TF), was characterized as a potential therapeutic for myasthenia gravis (MG) caused predominately by α subunit autoantibodies. SHG2210 was shown to be able to bind to α subunit autoantibodies and the TF receptor (TFR). SHG2210 and SHG2210–anti-AchR antibody complex are internalized through TFR-mediated endocytosis. The SHG2210 and SHG2210–anti-AchR antibody complex is present in Lamp1-positive lysosomal compartments after internalization; however, neither SHG2210 nor SHG2210–antibody complex is present in Rab11-positive recycling endosomes. SHG2210 bound to α subunit of AChR autoantibodies may be cleared by the lysosome, resulting in short cellular half-life relative to SHG2210. SHG2210 is shown to have a protective effect on antigenic modulation of the AChR induced by serum from select patients with MG, suggesting that a fusion protein approach may be an effective therapeutic for treating MG.     

Clinical aspects of myasthenia explained

Myasthenia gravis and myasthenic syndromes are diseases of the neuromuscular junction. Autoantibodies and toxins to or mutations in one of the synaptic proteins are the main causes of dysfunction. Myasthenic phenotypes can be classified according to the basic aetiological mechanisms or divided depending on the clinical phenotype.     

A review of the current literature and a guide to the early diagnosis of autoimmune disorders associated with neuromyelitis optica

Abstract

Neuromyelitis optica (NMO) is an immune-mediated neurological disorder characterised by recurrent episodes of optic neuritis and longitudinally extensive transverse myelitis. A serum biomarker, aquaporin-4 IgG, the autoantibody against aquaporin-4 water channel, has been specifically associated with NMO and has assisted early recognition and prediction of relapses. Less commonly, a monophasic course, associated with antibodies to myelin oligodendrocyte glycoprotein has been reported. Specific diagnostic criteria have been defined; however, some cases that do not fulfil these criteria (but are nevertheless associated with aquaporin-4 IgG) are classified as NMO spectrum disorder and follow the same relapsing course. An ever-growing list of autoimmune disorders, both organ-specific and non-organ-specific, have been associated in up to 20–30% of patients with NMO. These disorders, which may become symptomatic before or after the development of NMO, are often diagnosed long after the diagnosis of NMO, as symptoms may be wrongly attributed to NMO, its residual effects or medication side effects. In addition, autoantibodies can be found in patients with NMO without coexisting disease (up to 40% in some series) and maybe suggestive of a heightened humoral immune response. We present a comprehensive review of the current literature on autoimmune disorders co-existing with NMO and identified 22 autoimmune conditions (myasthenia gravis, coeliac disease, ulcerative colitis, sclerosing cholangitis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid antibody syndrome, Sjogren’s syndrome, autoimmune hypothyroidism, immune thrombocytopenic purpura, pernicious anaemia, narcolepsy, pemphigus foliaceus, alopecia areata, psoriasis, scleroderma, dermatitis herpetiformis, polymyositis, chronic inflammatory demyelinating polyneuropathy, paraneoplastic disorders, insulin dependent diabetes mellitus and autoimmune encephalitis).     

Initial Repetitive Nerve Stimulation Test Predicts Conversion of Ocular Myasthenia Gravis to Generalized Myasthenia Gravis

Background and PurposeA major concern with ocular myasthenia gravis (MG) is the potential conversion to generalized MG. This study was conducted to determine if the repetitive nerve stimulation (RNS) test could predict the conversion from ocular to generalized MG.MethodsThe RNS test was conducted in a consistent manner on five muscles in the face and limbs in every patient. Subjects were divided into those who remained as ocular MG (ROMG group) and those who experienced conversion to generalized MG during follow-up (GOMG group).ResultsConversion to generalized MG occurred in 24 (21.4%) of 112 MG patients with ocular onset. The proportion of patients displaying abnormal decreases in responses in the trapezius, abductor digiti minimi, or flexor carpi ulnaris muscles on the RNS test was higher in the GOMG group (p<0.001, p=0.002, and p<0.001, respectively). The Cox proportional-hazards model revealed that an abnormal result on the RNS test was significantly associated with conversion to generalized MG [hazard ratio (HR)=3.13, 95% confidence interval (CI)=1.18–8.32]. Notably, the HR was higher for abnormal results on the RNS test for the limb muscles, at 5.19 (95% CI=2.09–12.90).ConclusionsAn abnormal result on the RNS test, especially in the limb muscles, is an independent predictor of the conversion from ocular to generalized MG. Applying the RNS test to limb muscles could be useful for predicting the conversion to generalized MG in patients with ocular onset.