Myasthenia gravis (MG) is a CD4+ T cell-dependent autoimmune disease resulting from aberrant immune response mediated by circulating autoantibodies at the neuromuscular junction. Intravenous immunoglobulin (IVIg) is an expensive and commonly used immunotherapeutic approach to treat patients with MG. The mechanisms of actions involved in IVIg treatment, however, remain to be investigated. In an effort to examine the roles of various subsets of CD4+ T cells in the periphery blood of MG and uncover the mechanisms that contribute to the therapeutical effects of IVIg, we first demonstrated that a subset of CD4+ T cells, CTLA-4-expressing regulatory T (Treg) cells, were underrepresented and functionally defective in MG patients. The dynamic profiling during the IVIg therapy course further revealed an inverse relationship between the frequency of CTLA-4+ Treg and the quantitative MG (QMG) score that represents disease severity. Our mechanistic studies indicated that IVIg expands CTLA-4-Treg cells via modulating antigen-presenting dendritic cells (DCs). To determine the molecular defects of CTLA-4 in abnormities of Treg in MG patients, we demonstrated hypermethylation at -658 and -793 CpGs of CTLA-4 promoter in MG Tregs. Interestingly, IVIg therapy significantly reduced the methylation level at these two sites in MG patients. Overall, our study may suggest a role of CTLA-4 in functionally defected Treg cells in MG and its actions involved in IVIg therapy.

A high glucose state readily causes peripheral axon atrophy, demyelination, loss of nerve fiber function, and delayed regeneration. However, few studies have examined whether nitration is also critical for diabetic peripheral neuropathy. Therefore, this study investigated the effects of high glucose on proliferation, apoptosis, and 3-nitrotyrosine levels of Schwann cells treated with butylphthalide. In addition, we explored potential protective mechanisms of butylphthalide on peripheral nerves. Schwann cells were cultured in vitro with high glucose then stimulated with the peroxynitrite anion inhibitors uric acid and 3-n-butylphthalide for 48 hours. Cell Counting Kit-8 and flow cytometry were used to investigate the effects of uric acid and 3-n-butylphthalide on proliferation and apoptosis of Schwann cells exposed to a high glucose environment. Effects of uric acid and 3-n-butylphthalide on levels of 3-nitrotyrosine in Schwann cells were detected by enzyme-linked immunosorbent assay. The results indicated that Schwann cells cultured in high glucose showed decreased proliferation, but increased apoptosis and intracellular 3-nitrotyrosine levels. However, intervention with uric acid or 3-n-butylphthalide could increase proliferation of Schwann cells cultured in high glucose, and inhibited apoptosis and intracellular 3-nitrotyrosine levels. According to our data, 3-n-butylphthalide may inhibit cell nitrification and apoptosis, and promote cell proliferation, thereby reducing damage to Schwann cells caused by high glucose.

目的:观察多中心Wilson病(WD)患者在中西医结合长期驱铜治疗前后WD综合评定量表(Globle Asessment Scale,GAS)各项目评分的改变并评估其疗效,为建立疗效好、不良反应小的WD长期综合治疗方案提供循证医学依据.方法:参与研究的4个中心共纳入1001例WD确诊患者,随机分成青霉胺(PCA)组、二巯基丁二酸(DMSA)组、肝豆片组和中西医结合组(肝豆片+PCA/DMSA)4组(各组按1∶1∶1∶3平行设计,各组的条件除了治疗方案不同外,其他条件完全相同).在首次入院时、维持治疗1年时(第2次入院时)、维持治疗2年时(第3次入院时)进行GAS量表各项目(GAS-L、C、M、O项目及神经功能)评分,通过治疗前后自身比较及组间比较,评估各组患者的疗效.结果:各治疗组WD患者GAS各项目评分均较治疗前明显降低,在维持治疗2年时的疗效较维持治疗1年时更为明显,尤以中西医结合组评分改善最显著.结论:4种长期驱铜治疗方法均可改善WD患者的病情,中西医结合长期驱铜治疗的疗效更为显著,是目前WD患者长期治疗最有效的方案.

Objective To investigate the effects of dipeptidyl peptidase-Ⅳ (DPP-Ⅳ) inhibitor sitagliptin on the proliferation,apoptosis and content of 3-nitrotyrosine (3-NT) in rat Schwann cells(RSC96) in high glucose.Methods Schwann cell model was established by culturing RSC96 under high glucose(100 mmol/L D-glucose).The model were treated with peroxynitrite anion (ONOO-) inhibitor uric acid (UA) (1 μmol/L) and sitagliptin (1 μmol/L) for 48 hours,the effects of UA and sitagliptin on the proliferation and apoptosis of RSC96 under high glucose were observed by CCK-8 and flow cytometry.The effects of UA and sitagliptin on the expression of 3-NT protein in RSC96 were detected by ELISA.Results Compared with normal control group,the hyperglycemia group inhibited cell proliferation,promoted cell apoptosis and expression of intracellular 3-NT protein (P ＜ 0.05);UA and sitagliptin could promote the proliferation of RSC96 under high glucose,inhibited apoptosis and intracellular 3-NT protein expression (P ＜ 0.05).Conclusion Sitagliptin can increase the proliferation activity of RSC96 under high glucose,inhibit apoptosis and reduce the damage of RSC96 cells induced by high concentration of glucose by inhibiting the nitrosylation stress of cells.

Objective To explore the dynamic changes of inflammatory cytokines and C-reactive protein(CRP)in patients with acute cerebral hemorrhage and its prognostic value.Methods TNF-α, IL-1β, IL-6, IL-8 and CRP were measured in 120 healthy persons and 120 patients after the onset of acute cerebral hemorrhage at 24 h, 3, 7 and 14 d.Correlation analyzes were performed respectively between bleeding quantity or serious degree in patients with acute cerebral hemorrhage and the above indicators.Receiver operating characteristic curve was emploied to analysis its clinical prediction significance to the deterioration of acute cerebral hemorrhage.Results Different periods of serum TNF-α,IL-1β, IL-6, IL-8, and CRP in patients with acute cerebral hemorrhage were higher than those in healthy controls(P<0.05).There was a positive correlation between brain bleeding quantity or severity and the contents of TNF-α, IL-1β, IL-6, IL-8, and CRP in patients with acute cerebral hemorrhage(P<0.05).The inflammatory cytokines and CRP in the patients had its clinical prediction significance to the deterioration of acute cerebral hemorrhage.Conclusion The serum levels of inflammatory cytokines and CRP is involved in cerebral hemorrhage in the pathophysiological process,and these indicators have important predictive value for patients.

BACKGROUND Diabetic peripheral neuropathy (DPN) is a common complication of diabetes with a complex pathogenesis. Study has reported that oxidative stress and nitrative stress are all involved in the DPN. However, the mechanism between them is still unclear. In the present study, we investigated whether miR-106a regulated 12/15-Lipoxygenase (12/15-LOX) of oxidative/nitrative stress (OS/NS) in DPN. METHODS Dorsal root ganglion (DRG) was isolated from 10 healthy mice and 10 DPN mice. DPN mouse model was established by the injection of streptozotocin (STZ), and high glucose was used for inducing the in vitro model of DPN. RESULTS In DPN mice, the levels of fasting blood-glucose (FBG) level, Methane Dicarboxylic Aldehyde (MDA) and the Inducible Nitric Oxide Synthase (iNOS) were increased, while the levels of motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV) and superoxide dismutase (SOD) were decreased. MiR-106a level in DRG cells of DPN was decreased. The 12/15-LOX expression and cell apoptosis were increased. DRG cells subjected to high glucose resulted in the same effects as above. MiR-106a was observed to target 12/15-LOX and regulated its expression. MiR-106a overexpression reversed the effect that was induced by high glucose, however, overexpression of 12/15-LOX reversed the effect that was induced by miR-106a overexpression. CONCLUSION MiR-106 may be associated with 12/15-LOX mediated OS/NS in DPN and may be considered as a potential therapeutic target.

Objective Early neurological deterioration ( END) is one of the causes of the poor prognosis of ischemic stroke . This study was to investigate the correlation of cerebral atherosclerosis score ( CAS) with END in patients with minor ischemic stroke . Methods We included 265 cases of minor ischemic stroke ( NIHSS≤3) treated in Anhui Provincial Hospital between January 2013 and December 2015, 226 with and the other 39 without END , which was defined as an increase of NIHSS≥2 in the first 72 hours after admission.We performed MRI, MRA and CTA for all the patients within 24 hours after admission and obtained cerebral atherosclerosis scores (CAS) of the middle cerebral (M1, M2, M3), anterior cerebral (A1, A2), posterior cerebral (P1, P2), basilar, intracrani-al carotid, vertebral, common carotid, innominate and subclavian arteries ( before the beginning of the vertebral artery ) , 1 point for stenosis ≥50%and CAS for the total score .We analyzed the correla-tion of CAS with END in minor ischemic stroke , assessed the value of CAS in predicting END , and calculated its sensitivity and specificity using the ROC curve and the area under the ROC curve . Results Logistic regression analysis indicated that the baseline NIHSS ( OR=2.272, 95%CI:1.352-3.823, P=0.002) and CAS ( OR=1.535,95%CI:1.162-2.011, P=0.002) were independent risk factors of END .The best cutoff value of CAS in identifying END was 2, with a sensitivity of 641.%and a specificity of 68.1%. Conclusion CAS≥2 is an independent predictor of END in patients with minor ischemic stroke .

Objective To study the correlation of the level of high-sensitivity C-reactive protein (Hs-CRP) in the acute phase of ischemic stroke and progressive stroke. Methods 101 patients with acute ischemic stroke were collected. Serum Hs-CRP of all patients were measured at 24 hours after admission , the onset of 48 hours, the onset of 72 hours by latex enhanced immune turbidity method. According to their serum Hs-CRP lev-els, the patients were divided into the group of Hs-CRP sustained growth (n = 35) and the group of non Hs-CRP sustained growth (n = 66). The NIHSS scores were assessed on two groups of patients , Logistic regression analysis was made to screen the related factors of Hs-CRP increase and the possible risky factors for progressive ischemic stroke. Results There was a significant difference of serum Hs-CRP level between the two groups (P <0.001). The incidence of progressive stroke in the group of Hs-CRP sustained growth was significantly higher than that in the group of non Hs-CRP sustained growth (χ2 = 32.710, P < 0.001). Logistic regression analysis showed blood glucose , white blood cell count , triglyceride level and NIHSS scores at admission were associated with sustained growth of Hs-CRP and the factors that they included Hs-CRP sustained growth , admission NIHSS scores, diabetes mellitus and pulmonary infection were regarded as independent risk factors. Conclusion The sustained growth of Hs-CRP in the acute phase of ischemic stroke is an independent predictor of progressive stroke.

目的 颈动脉支架内急性血栓形成(acute carotid stent thrombosis,ACST)是支架成形术中/后非常罕见的并发症,能够导致严重的神经功能缺失,且没有统一的治疗方案,及时诊断和合适的治疗对患者的预后至关重要.文中旨在探讨颈动脉支架成形术中,ACST后立即采取球囊扩张术治疗的临床效果和近期随访结果. 方法 回顾性分析安徽医科大学附属省立医院神经内科2011年3月至2014年12月收治的5例ACST患者的临床资料,统计分析其临床表现、治疗方案及影像学检查结果,并进行90d门诊随访,分析预后结果. 结果 5例患者中1例表现为言语不清伴右侧肢体无力,CT血管造影(computed tomography angiogram,CTA)显示左侧颈内动脉狭窄约90％;2例表现为左侧肢体无力,CTA显示右侧颈内动脉狭窄约70％;2例表现为短暂性脑缺血发作,其中1例反复发作性右侧肢体无力伴麻木,CTA显示左侧颈内动脉狭窄约90％,另1例反复发作性左侧肢体无力,CTA显示右侧颈内动脉狭窄约70％.5例患者均在支架植入后数分钟内发生支架内血栓形成且未完全堵塞血流,所有患者尚未发生神经功能缺损症状.行支架内球囊扩张术后瞬间血栓消失,脑血流恢复,术后磁共振检查均未出现新发脑梗死病灶.随访发现所有患者颈动脉超声检查无支架内血栓形成,CT检查无新发脑梗死. 结论 在行颈动脉支架成形术过程中,若发生支架内急性血栓形成且尚未形成血凝块,球囊扩张术是有效的治疗方法.

目的 研究神经电生理F波检测时A波出现在急性吉兰-巴雷综合征(GBS)病程不同阶段中的特点,探索其对于GBS的诊断价值.方法 回顾性分析62例GBS患者(GBS组)和26名健康对照者(对照组)的尺神经、正中神经、腓神经及胫神经在电生理F波检测时A波出现情况.对A波在GBS组与对照组上/下肢中的出现情况、以及不同病程的急性炎性脱髓鞘性多发神经根神经病(AIDP亚组)与轴索型GBS患者(轴索型亚组)的A波出现情况进行x2检验分析.结果 GBS组与对照组上肢A波出现情况的差异有统计学意义(P=0.002);GBS病程及AIDP亚组对上肢A波出现的影响无统计学意义(PGBS=0.781,P轴索型=0.389),而轴索型亚组病程对上肢A波出现的影响有统计学意义(P=0.028);病程2周内,GBS分型对上肢A波出现的影响差异无统计学意义(P=0.065),病程3～6周时,GBS分型对上肢A波出现的影响差异有统计学意义(P＜0.001).AIDP患者中A波出现率低于F波异常率,但高于运动神经传导速度、远端运动潜伏期和复合肌肉动作电位波幅的异常率,且均差异有统计学意义(P＜0.005);轴索型亚组患者中A波的出现率低于复合肌肉动作电位波幅和F波的异常率,高于运动神经传导速度和远端运动潜伏期的异常率,但仅复合肌肉动作电位波幅和A波间的出现率差异有统计学意义(P＜0.001).结论 上肢A波对于GBS早期诊断具有一定的参考价值,对AIDP和轴索型的诊断具有鉴别意义.

抗癫痫药物（antiepileptic drugs ，AEDs）的致畸作用是指母体妊娠期间应用抗癫痫药物对其胎儿产生的任何有害效应。AEDs可产生各种毒副作用和致畸作用，并会对胎儿以后的认知和情感发育造成一定影响，如何为癫痫孕妇合理选择A ED s治疗具有重要的临床意义。

目的 探讨2型糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)相关危险因素.方法 回顾性分析710例2型糖尿病住院患者的病史资料,采用震动感觉阈值(vibration perception threshold,VPT)评估DPN病情严重程度,根据VPT评分将DPN严重程度分为轻、中、重3组,分别与无DPN组比较临床特征、血生化及常规指标等的差异;采用Ordinal回归分析探讨DPN发生的危险因素.结果 本组资料DPN的总发生率为57.2％,其中轻、中、重度3组患者DPN的发生率分别为22.4％、21.0％、13.8％.病程、体重指数(BMI)、糖化血红蛋白(HbAlc)、血清丙氨酸氨基转移酶(ALT)、天氡氨酸氨基转移酶(AST)、红细胞体积分布宽度(RDW-CV)、平均红细胞血红蛋白浓度(MCHC)、糖尿病视网膜病变(DR)发生率、外周动脉疾病(PAD)发生率在轻、中、重度DPN组和无DPN组间比较差异有统计学意义(均P＜0.05).Ordinal回归分析显示病程、HbAlc、BMI、AST、RDW-CV、DR、PAD为DPN发生的影响因素(均P＜0.05).结论 病程、HbAlc、BMI、AST、RDW-CV、并发PAD及并发DR可能是DPN发生的危险因素.

目的 观察肝豆汤合驱铜疗法对Wilson病(Wilson's disease,WD)患者生活质量的影响.方法 共纳入135例WD患者,在二巯基丙磺酸钠强力驱铜治疗及青霉胺和二巯基丁二酸维持驱铜治疗的基础上,口服肝豆片.治疗前及治疗1年后分别采用WHO生活质量简表评价患者的生活质量,并观察总体疗效.结果 与治疗前比较,135例WD患者治疗后WHO生活质量简表的生理领域、心理领域、社会领域、环境领域得分均显著提高(P＜0.01).135例WD患者中,临床痊愈5例,显效33例,有效88例,无效7例,恶化2例,无死亡病例,总有效率达93.3％.结论 肝豆汤口服合驱铜治疗可以明显改善WD患者的生活质量.

Objective To study the application of ABCD3 score in predicting depression risk 3months after transient cerebral ischemic attack.Methods One hundred and fifty-seven cerebral TIA patients were divided into low-risk group with 0-3 ABCD3 scores(n=51),moderate-risk group with 4-6ABCD3 scores(n=91),and high-risk group with 7-8ABCD3 scores(n=15).The patients were followed up for 90 days,during which the incidence of depression was recorded.Results The incidence of depression was significantly lower in low-risk group than in moderate-and high-risk groups(3.9%vs 33.0%vs 73.3%,P0.05).The area under the ROC curve for ABCD3 was 0.779(95%CI:0.735-0.877).Conclusion ABCD3 score can effectively predict the depression risk 3months after transient cerebral ischemic attack.

OBJECTIVE:To observe blood uric acid levels and Goldstein grading, as well as their correlation in Wilson's disease (WD) patients with different Chinese medical syndrome types.METHODS:Totally 906 WD patients in line with inclusive criteria were assigned to 6 groups, i.e., the heart spirit confused by phlegm group (HSCP, 26 cases), the phlegm-fire disturbing heart group (PFDH, 90 cases), the retention of damp-heat group (RDH, 113 cases), deficiency of qi and blood group (DQB, 168 cases), the deficiency of Gan-yin and Shen-yin group (DGYSY, 327 cases), the deficiency of Gan and Shen group (DGS, 182 cases) due to different Chinese medical syndrome types. Recruited were another 160 healthy subjects having similar ages and diet structures, who came for medical examinations, as the healthy control group. Venous blood was collected from the medial cubital vein of each-patient on an empty stomach in early mornings to detect blood uric acid levels. Results Blood uric acid levels were lower in each syndrome type group than in the healthy control group (146.08 +/- 67.24 micromol/L in the HSCP group; 157.08 +/- 69.77 micromol/L in the PFDH group; 162.58 +/- 97.72 micromol/L in the RDH group; 156.20 +/- 62.63 micromol/L in the DQB group; 161.83 +/- 111.23 micromol/L in the DGYSY group; 194.41 +/- 90.01 micromol/L in the DGS group; 242.39 +/- 87.55 micromol/L in the healthy control group, P < 0.01). Blood uric acid levels were higher in the DGYSY group than in the other 5 syndrome groups (P < 0.01). Correlation analyses between Goldstein grading and blood uric acid showed that, along with increased Goldstein grade (that was aggravating disease conditions), WD patients' blood uric acid levels decreased (P < 0.01).CONCLUSIONS:WD patient's blood uric acid levels decreased more. Blood uric acid levels and Goldstein grading were different in various Chinese medical syndrome types. Blood uric acid levels had certain value in assessing the severity of WD.

Objective To evaluate the association between serum 25-hydroxyvitamin D (25 [OH] D) levels and the clinical severity in cerebral infarction patients, and to explore the inlfuence in prognosis of those patients who received 25 (OH) D treatment. <br> Methods Serum concentrations of 25 (OH) D were measured among 217 patients who developed acute cerebral infarction and 163 health control subjects who were free of stroke. These patients were divided into different groups based on the serum 25 (OH) D concentrations for analyzing the proportion of each group in patients with cerebral infarction and compared with healthy control group. The difference about clinical data and their correlation were evaluated among the cerebral infarction patients with different 25 (OH) D levels. All of the patients with the serum 25 (OH) D<20 ng/ml were divided into two subgroups according to whether received vitamin D therapy and compared in 1 year follow-up for indicators such as serum 25 (OH) D levels, recurrence rates of the endpoint events and average modiifed Rankin Scale scores. <br> Results The serum 25 (OH) D concentrations were signiifcantly decreased in the cerebral infarction patients compared with the healthy control group, the mean value was (13.67±1.16) ng/ml and (20.11±2.05) ng/ml, respectively (P=0.001). In the cerebral infarction group, the prevalence of 25 (OH) D deficiency and sufficiency, showed obvious differences compared with the healthy control group. Compared to the serum 25 (OH) D≥20 ng/ml, the serum 25 (OH) D<20 ng/ml was more often in the cerebral infarction patients with hypertension, diabetes and coronary heart disease (P=0.010, P=0.011, P=0.037). There was a negative correlation between serum 25 (OH) D level and admission National Institutes of Health Stroke Scale (NIHSS) score in patients (r=-0.720, P=0.001). Among all of the cerebral infarction patients with serum 25 (OH) D levels<20 ng/ml, the subgroup which received vitamin D treatment had a recurrence rate of transient ischemic attack (TIA) or cerebral infarction and an average modiifed Rankin Scale score within one year, both were lower than that not received vitamin D treatment, but showing no statistically signiifcant differences (P=0.080, P=0.079). <br> Conclusion The lower serum 25 (OH) D levels in the patients with cerebral infarction were associated with the severity, but the evidence was still lacking that vitamin D treatment would reduce the occurrence of risk of ischemic stroke and improve patient prognosis.

Aim To compare the clinical outcome of the post-thymectomy between generalized myasthenia gravis (gMG) with acetylcholine receptor antibody (AChR-Ab) positive and AChR-Ab negative. Methods124 cases of gMG who were retrospectively reviewed had received video-assisted thoracoscopic thymectomy in the thoracic surgery. According to the type of the serum antibodies, the patients were divided in to AChR-Ab-positive group and AChR-Ab-negative group. The primary endpoint was to assess differences in the rate of complete stable remission (CSR) in patients in the two groups.ResultsThere were 81 patients in the AChR-Ab positive group, and 43 patients in AChR-Ab-negative group, there was no signiifcant difference among the three groups regarding sex, age at onset and disease duration, and thymus&nbsp;pathology. One case in AChR-Ab-positive group was lost, two cases in AChR-Ab-negative group were lost. Until the deadline of follow-up time of Sep. 2014, a total of 121 patients were followed, including 80 cases in AChR-Ab-positive group, 41 cases in AChR-Ab-negative group. Follow-up time was 15 to 84 months, mean (44.9±19.9) months in AchR-Ab positive group, mean (48.2±20.3) months in AChR-Ab-negative group. The complete stable remission rate (CSR) in AChR-Ab-positive group was 48.8%, in the AChR-Ab-negative group theP vaule was 26.8%. The CSR in the AChR-Ab-positive group was higer than that in the AChR-Ab-negative group [(χ2=5.372,P=0.020)]. The overall remission rate in the AChR-Ab-positive group was 85.1%, and 73.2% in the AChR-Ab-negative. There was no signiifcant difference in the overall remission rate between the two group. By Kaplan–Meier analysis, there was signiifcant difference in CSR rates between AChR-Ab-positive group and AChR-Ab-negative group (P=0.03).Conclusion Long-term post-thymectomy clinical outcome was better in AChR-Ab-positive group than in AChR-Ab-negative group, but our results showed no differences in the overall remission rate.

Objective To study the expression alteration of Foxp3 and intracellular CTLA-4 of CD4 +CD25 +regula-tory T cells in peripheral blood of myasthenia gravis patients under glucocorticoids treatment. Methods 34 patients with myasthenia gravis were selected, and subgrouped with no treatment group(8 cases) or glucocorticoids treat-ment group(26 cases) . Another 20 healthy subjects were set as the control group. 6-color flow cytometry was used to analyze the expression of Foxp3 and intracellular CTLA-4 of CD4 +CD25 + regulatory T cells in their peripheral blood of participants. Results ①Compared with the control group, the level of Foxp3 and intracellular CTLA-4 of CD4 +CD25 +regulatory T cells in peripheral blood of in no treatment group were significantly decreased ( P <0. 05 ) . ② the level of Foxp3 and intracellular CTLA-4 of CD4 +CD25 +regulatory T cells in peripheral blood of pa-tients with glucocorticoids treatment group were significantly higher than that of no treatment group(P<0. 05), but were still lower than that of the control group(P<0. 05). ③Foxp3 expression was positively correlated with intra-cellular CTLA-4 expression in CD4 +CD25 +regulatory T cells of patients with myasthenia gravis ( r=0. 870 , P<0. 001 ) . Conclusion Low expression of Foxp3 and intracellular CTLA-4 of CD4 +CD25 + regulatory T cells in pe-ripheral blood is present in patients with myasthenia gravis, glucocorticoids could significantly increase the expres-sion of Foxp3 and intracellular CTLA-4, however, which still do not reach the immune state of healthy subjects.