Background and Objectives Existing evidence indicates anti-GABAB receptor encephalitis (GABA(B)R-E) seems to occur more commonly later in life, yet the age-associated differences in clinical features and outcomes are not well determined. This study aims to explore the demographic, clinical characteristics, and prognostic differences between late-onset and early-onset GABABR-E and identify predictors of favorable long-term outcomes. Methods This is an observational retrospective study conducted in 19 centers from China. Data from 62 patients with GABA(B)R-E were compared between late-onset (aged 50 years or older) and early-onset (younger than 50 years) groups and between groups with favorable outcomes (modified Rankin scale (mRS) <= 2) and poor outcomes (mRS >2). Logistic regression analyses were applied to identify factors affecting long-term outcomes. Results Forty-one (66.1%) patients experienced late-onset GABA(B)R-E. A greater proportion of males, a higher mRS score at onset, higher frequencies of ICU admission and tumors, and a higher risk of death were demonstrated in the late-onset group than in the early-onset group. Compared with poor outcomes, patients with favorable outcomes had a younger onset age, a lower mRS score at onset, lower frequencies of ICU admission and tumors, and a greater proportion with immunotherapy maintenance for at least 6 months. On multivariate regression analysis, age at onset (OR, 0.849, 95% CI 0.739-0.974, p = 0.020) and the presence of underlying tumors (OR, 0.095, 95% CI 0.015-0.613, p = 0.013) were associated with poorer long-term outcomes, whereas immunotherapy maintenance for at least 6 months was associated with favorable outcomes (OR, 10.958, 95% CI 1.469-81.742, p = 0.020). Discussion These results demonstrate the importance of risk stratification of GABA(B)R-E according to age at onset. More attention should be paid to older patients especially with underlying tumors, and immunotherapy maintenance for at least 6 months is recommended to achieve a favorable outcome.

目的:总结抗神经束蛋白186(NF186)抗体阳性周围神经病的临床特点.方法:收集兰州大学第二医院1例抗NF186抗体阳性周围神经病患者的临床资料,并结合文献进行复习.结果:患者呈亚急性起病,临床表现为四肢无力、疼痛、共济失调、震颤等,合并脓疱型银屑病.肌电图检查示多发感觉、运动神经损害;脑脊液及血清抗NF186抗体IgG阳性.激素联合免疫抑制剂治疗后患者恢复良好.结论:抗NF186抗体阳性周围神经病患者具有特异的临床表型,且常合并1种或以上的其他自身免疫性疾病,对激素治疗反应良好.

IntroductionSpinal cord infarction secondary to ankylosing spondylitis is a rare but severe disorder.Case presentationHere we present a case of acute spinal cord infarction in a 54 years-old man with a medical history of ankylosing spondylitis, scoliosis, and hypotension. The patient complained of a sudden onset of lower limb weakness. A physical examination showed that he suffered from a dissociative sensory disorder, paralysis, and concomitant sphincter disturbances. After undergoing a whole-spine MRI, he was diagnosed with an acute ischemic injury from T2 to T5. As he did not treat his ankylosing spondylitis, it later caused a spinal deformity, making the lumbar puncture technically challenging. However, using Taylor’s approach, a CSF sample was successfully obtained. A CSF biochemical test ruled out myelitis, NMOSD, and MS. After receiving treatment with low-molecular-weight heparin, atorvastatin calcium, and methylprednisolone, his sphincter function gradually recovered, but his strength was only partially restored.ConclusionAlthough this is a rare entity, it is necessary for physicians to consider it when evaluating patients with a sudden loss of sensation and strength in their lower limbs.

Ras-related protein Rab-20 (Rab20) is induced in hypoxia and contributes to hypoxia-induced apoptosis. However, the role and mechanism of Rab20 in cerebral ischemia/reperfusion (I/R) injury need to be elucidated. We established a cerebral I/R injury model in the mice and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in HT22 cells to determine the effects of Rab20 in cerebral I/R injury. Rab20 expression was upregulated in mice after I/R and in HT22 cells after OGD/R. Upregulated Rab20 was mainly located in neurons. Rab20 inhibition significantly alleviated brain infarct volume, neurological deficits, and neuronal apoptosis in mice after I/R. Moreover, Rab20 knockdown significantly ameliorated the OGD/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Rab20 knockdown significantly alleviated OGD/R-induced mitochondrial fission by repressing mitochondrial dynamin-related protein 1 (Drp-1) recruitment and increasing Drp-1 (Ser637) phosphorylation and ameliorated mitochondrial dysfunction by reducing the mitochondrial reactive oxygen species (ROS) and cellular calcium accumulation and increasing the mitochondrial membrane potential. In addition, Rab20 knockdown significantly alleviated cytochrome c release from the mitochondria into the cytosol in HT22 cells after OGD/R. Rab20 contributes to cerebral I/R injury by regulating mitochondria-associated apoptosis pathways. Targeting Rab20 may be an attractive strategy for the treatment of cerebral I/R injury.

SERTA domain-containing protein 1 (Sertad1) is upregulated in the models of DNA damage and Alzheimer's disease, contributing to neuronal death. However, the role and mechanism of Sertad1 in ischemic/hypoxic neurological injury remain unclear. In the present study, our results showed that the expression of Sertad1 was upregulated in a mouse middle cerebral artery occlusion and reperfusion model and in HT22 cells after oxygen-glucose deprivation/reoxygenation (OGD/R). Sertad1 knockdown significantly ameliorated ischemia-induced brain infarct volume, neurological deficits and neuronal apoptosis. In addition, it significantly ameliorated the OGD/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Sertad1 knockdown significantly inhibited the ischemic/hypoxic-induced expression of p-Rb, B-Myb, and Bim in vivo and in vitro. However, Sertad1 overexpression significantly exacerbated the OGD/R-induced inhibition of cell viability and apoptotic cell death and p-Rb, B-Myb, and Bim expression in HT22 cells. In further studies, we demonstrated that Sertad1 directly binds to CDK4 and the CDK4 inhibitor ON123300 restores the effects of Sertad1 overexpression on OGD/R-induced apoptotic cell death and p-Rb, B-Myb, and Bim expression in HT22 cells. These results suggested that Sertad1 contributed to ischemic/hypoxic neurological injury by activating the CDK4/p-Rb pathway.

Calenduloside E (CE) isolated from Aralia elata (Miq.) Seem. is a natural triterpenoid saponin that can reportedly ameliorate myocardial ischemia/reperfusion injury. However, its potential roles and mechanism in cerebral ischemia/reperfusion injury are barely understood. In this study, we established an oxygen-glucose deprivation/reoxygenation (OGD/R) model in HT22 cells. We found that CE significantly attenuated the OGD/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Moreover, CE treatment significantly ameliorated OGD/R-induced mitochondrial fission by inhibiting mitochondrial dynamin-related protein 1 (Drp1) recruitment and increasing Drp1 phosphorylation at Ser637. CE treatment significantly ameliorated OGD/R-induced mitochondrial dysfunction by increasing the mitochondrial membrane potential and reducing the mitochondrial ROS and cellular calcium accumulation. Moreover, CE treatment significantly inhibited the OGD/R-induced release of mitochondrial Cytochrome C and increase in Bax, Cleaved-caspase3 and Cleaved-caspase9 protein levels, whereas CE treatment significantly reversed the OGD/R-induced decrease in Bcl-2 and full length of caspase3 and caspase9 protein levels. In vivo, we found that CE treatment significantly ameliorated ischemic/hypoxic-induced brain infarct volume, neurological deficits, and neuronal apoptosis in mice after middle cerebral artery occlusion and reperfusion. CE treatment also significantly ameliorated the mitochondrial transmembrane potential, decreased Cytochrome C release, and reversed the increase in Bax, Cleaved-caspase3 and Cleaved-caspase9 protein levels and the decrease in Bcl-2 and full length of caspase3 and caspase9 protein levels induced by cerebral ischemia/reperfusion (I/R). All these results indicated that CE treatment exerted a neuroprotective effect by ameliorating mitochondrial dysfunction during cerebral I/R injury.

Herein, we reported a case of a young man diagnosed with MNOS (anti-myelin oligodendrocyte glycoprotein associated disease (MOGAD) and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis overlapping syndrome, i.e., MNOS), whose imaging findings in magnetic resonance imaging (MRI) mimicked chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). We reported a case of refractory anti-NMDAR encephalitis that recurred after standard first-line and second-line treatment. The patient presented with CLIPPERS on imaging at recent hospital admission, and his MOG antibodies were seropositive. After intravenous methylprednisolone (IVMP) treatment, the patient's symptoms were significantly alleviated. In this case, we demonstrated that MNOS could mimic the radiological characteristics of CLIPPERS. Future studies should focus on the diagnosis and treatment of antibody overlap syndrome.

This study was designed to investigate the clinical efficacy of benserazide AND levodopa tablets and DOPA hydrazine and levodopa controlled-release tablets in patients with Parkinson's disease while using commercial lead brands of both tablets. A total of 70 patients with Parkinson's disease were selected and randomly divided into control and study group. The control group was treated with doxazide (R) tablets while the study group was treated with Kazuo (R) double DOPA controlled release tablets. The clinical efficacy, adverse reactions, Webster score and MMSE score before and after treatment were observed and compared between. There was no significant difference (p > 0.05) in the incidence of adverse reactions between the study and control group while the efficacy of the study group was better than control group. In addition, the Webster score of the study group was significantly lower (p < 0.05), while the MMSE score was significantly higher than that of the control group. In clinical treatment of Parkinson's disease, the effect of DOPA hydrazine tablets combined with levodopa controlled-release tablets is more significant, which can significantly improve the movement disorder and non-movement disorder of Parkinson's disease, and will not increase the adverse reactions of patients. It has very high safety, and is worthy of application and promotion.

多巴反应性肌张力障碍(Dopa-responsive dystonia,DRD)[1]是1976年由Masaya Segawa首次报道,又称Segawa病,其临床特征包括肌张力障碍、步态障碍、僵硬、轻度帕金森病、日间波动和对左旋多巴的剧烈反应等.患者通常对左旋多巴反应良好,症状明显改善,甚至消失.多巴反应性肌张力障碍(DRD)是一种可治疗的遗传性疾病,因此识别它是非常重要的.本研究拟通过报道1例DRD GCH1基因新的移码突变,以提高临床对DRD诊断及预后的认识,以免误诊.

Background In this study, we report a case of a young female who was hospitalized for seizures and diagnosed with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Case presentation The main feature of this patient was bilateral temporal calcifications detected by routine head computed tomography (CT). The co-existence of anti-NMDAR encephalitis and cerebral calcifications has not been reported. We supposed that the patient had an incomplete form of celiac disease (CD), epilepsy and cerebral calcifications syndrome (CEC). The patient's symptoms were alleviated by a series of treatments, and she remained stable during the follow-ups. Conclusions Our findings confirm the rarity co-existing anti-NMDAR encephalitis and cerebral calcifications. In future clinical work, we need to elucidate the relationship between anti-NMDAR encephalitis and cerebral calcifications, and the association between anti-NMDAR encephalitis and other co-existing autoimmune disorders.

Repulsive guidance molecule a (RGMa) has now emerged as a molecule with pleiotropic roles, including repulsion, adhesion, migration and differentiation in the nervous system. In this study, adult male Sprague-Dawley (SD) rats received 90-min middle cerebral artery occlusion (MCAO) to observe RGMa/neogenin expression sites after ischemia/reperfusion injury and changes in angiogenesis after treatment with RNA interference using RGMa-specific recombinant adenovirus rAd5-shRNA-RGMa (rAd-shRGMa). To clarify how RGMa mediates angiogenesis, the RGMa function-blocking peptide six fibronectin type III (6FNIII) was also administered, and corresponding changes in vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang2), angiopoietin-1 (Ang1), and brain derived neurotrophic factor (BDNF) were determined by western blotting. Both RGMa and its receptor neogenin were expressed in neurons and vessel endothelial cells after ischemia/reperfusion injury, and angiogenesis, coupled with functional recovery, was enhanced after RNA interference against RGMa compared with the vehicle groups. VEGF, Ang2, Ang1 and BDNF expression levels were significantly increased after intervention with rAd-shRGMa or 6FNIII. Thus, RGMa might suppress angiogenesis via VEGF, Ang2, Ang1 and BDNF after cerebral ischemia/reperfusion injury, which has therapeutic potential by reducing these endogenous detrimental mechanisms.

OBJECTIVELiraglutide (LIRA) is a novel antidiabetic therapy that may have anti-inflammatory and bone protective effects. Thus, we studied the potential therapeutic effect of LIRA on periodontitis by assessing the effects of LIRA on the proliferation, migration, inflammation, and osteogenic differentiation of human periodontal ligament cells (hPDLCs) after LPS stimulation.MATERIAL AND METHODSThe expression of glucagon like-peptide 1 receptor (GLP-1R) was measured using qRT-PCR. HPDLCs proliferation after LIRA were analyzed using MTT assays. Cell migration was quantified using a wound-healing assay. The expression of inflammatory (IL-6 and TNF-α) was measured by qRT-PCR and ELISA in hPDLCs. The effect of LIRA on the mineralization potential of hPDLCs was assessed by alizarin red S staining. Furthermore, the expression of Runx2 and ALP was measured by qRT-PCR and Western blot in hPDLCs.RESULTSGLP-1R mRNA was present on hPDLCs, and LIRA increased the expression of GLP-1R mRNA. When cultured with 25, 50, 75, 100 and 125 nM LIRA for 24 h, hPDLCs proliferation was enhanced in a dose-dependent manner (P < 0.05), and 100 nM was optimal. LIRA promoted hPDLCs migration in a time-dependent manner. LPS significantly increased the expression of IL-6 and TNF-α (P < 0.01), decreased the formation of mineralization nodes (P < 0.01), and inhibited the expression of ALP and Runx2 (P < 0.05). LIRA treatment blocked the expression of IL-6 and TNF-α (P < 0.01), increased the formation of mineralization nodes (P < 0.01), and enhanced the expression of ALP and Runx2 (P < 0.05).CONCLUSIONLIRA can enhance the proliferation, migration, and osteogenic differentiation of hPDLCs and inhibit the inflammatory response. Thus, LIRA may have potential therapeutic use as an adjuvant treatment for human periodontitis, and this effect is independent of hypoglycemic activity.

Methylene Tetrahydrofolate Reductase (MTHFR) catalyzes the conversion of methylene tetrahydrofolate to methylte trahydrofolate. The 677th nucleotide of the MTHFR gene is often regarded as a risk factor of cardiovascular disease. Previous studies demonstrated an elevated risk of ischemic stroke with the MTHFR677TT genotype. In this study, we employed a plasma proteomics method to investigate the connection between the polymorphism of the target nucleotide and stroke. In total, 28 protein spots were differentially expressed between the two groups, and of which, 25 protein spots were up-regulated and 3 were down-regulated. Five randomly selected spots were successfully identified as Haptoglobin (HPT) and Transferrin (TRFE). A functional analysis indicated that most of the differential expressed proteins (DEPs) were related to the inflammatory immune response. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEPs were involved in the complement cascade reaction. Meanwhile, protein-protein interactions (PPIs) analysis highlighted the novel association between the C677T MTHFR genotype and Vitamin D binding protein (DBP), which was confirmed by a molecular genetic analysis. The results suggested that the phenotype of the MTHFR might be associated with multiple proteins that have a synergistic effect, which might be related to the mechanism of ischemic stroke.

Ischemia/reperfusion (I/R) injury after middle cerebral artery occlusion (MCAO) induces detrimental processes such as oxidative stress, inflammation, and apoptosis. All parts of the neurovascular unit are involved in these pathological processes. Fibulin-5 is a 66-kD glycoprotein secreted by various vascular cells, including vascular smooth muscle cells (SMCs), fibroblasts, and endothelial cells. As an extracellular matrix protein involved in cell adhesion, fibulin-5 has been widely studied in tumor growth and invasion. However, the effects of fibulin-5 on brain injury following ischemia/reperfusion have not been reported. In this study, we examined the effect of overexpressed fibulin-5 on reactive oxygen species (ROS) production. Fibulin-5 overexpression attenuated ROS expression, which in turn decreased apoptosis and blood–brain barrier (BBB) permeability following MCAO and reperfusion. Fibulin-5 also improved neurological deficits but had no effect on infarction volume. T2-weighted MRI and electron microscopy further confirmed brain edema reduction and decreased BBB disruption in fibulin-5 overexpression recombinant adenovirus (Ad-FBLN) treated rats. In addition, tight junction protein occludin was significantly degraded and matrix metalloproteinase 9 (MMP-9) immunoreactivity was significantly increased. Fibulin-5-mediated ROS decrease was not due to increased total superoxide dismutase levels but was instead correlated with the activation of Rac-1 pathway. The findings highlight the importance of antioxidant mechanism underlying cerebral ischemia/reperfusion.

Up to date, series of studies on ischemic stroke had resulted in inconsistent conclusion. In this study, we aimed to evaluate which specific genes were associated with increased predisposition to stroke in a Chinese population. To identify the specific genes and polymorphisms associated with predisposition to ischemic stroke, we performed high throughput sequenom based next-generation sequencing from 743 patient with history of ischemic stroke. Variants SNPs in nNOS, renalase, MTHFR, CELSR1 and XYLB genes were found significantly associated with IS, thus suggesting involvement of these loci to IS in Chinese patients. Because of different locations on chromosomes, haplotype analyses were not feasible. Our results demonstrate the top level genes that are related to normal vascular physiology, viz. genes of nitric oxide synthesis, endothelial health and smooth muscle biology. Further validation studies are awaited.

Neuro-inflammation plays an important role in global cerebral ischemia (GCI). The 72-kDa heat shock protein (Hsp70) has been reported to be involved in the inflammatory response of many central nervous system diseases. Preclinical findings implicate that 17-allylamino-demethoxygeldanamycin (17-AAG), an anticancer drug in clinical, provide neuroprotection actions in a rat model of traumatic brain injury, and the beneficial effects of 17-AAG were specifically due to up-regulation of Hsp70. However, no experiments have tested whether 17-AAG has beneficial or harmful effects in the setting of GCI. The present study was designed to determine the hypothesis that administration of 17-AAG could attenuate cerebral infarction and improve neuronal survival, thereby ameliorating memory impairment in a rat model of GCI. Furthermore, to test whether any neuroprotective effect of 17-AAG was associated with inflammatory response and neuronal autophagy, we examined the expression of multiplex inflammatory cytokine levels as well as autophagy-associate protein in hippocampal CA1 of rat brain. Our results showed that post-GCI administration of 17-AAG significantly protected rats against GCI induced brain injury, and 17-AAG is also an effective antagonist of the inflammatory response and thereby ameliorates hippocampal CA1 neuronal autophagic death. We therefore believe that the present study provides novel clues in understanding the mechanisms by which 17-AAG exerts its neuroprotective activity in GCI. All data reveal that 17-AAG might be a potential neuroprotective agent for ischemic stroke.

Objective To observe the clinical efficacy of modifiedShengjiang Powderin the treatment of pulmonary infection combined with sepsis of toxin-heat excess. Methods Fifty subjects were randomized into two groups: control group in which 25 cases were treated with routine modality and treatment group in which25 cases were treated with routine modality and modifiedShengjiang Powder,with a course of 7 days. The symptom scores,APACHEⅡ score,CRP,TNF-αand IL-6 were evaluated before and after treatment. Results After treatment,the symptom scores were reduced in both groups( P 0. 05),with lower score in the treatment group than in the control group( P 0. 05); the APACHEⅡ scores and the levels of CRP,TNF-α and IL-6 were decreased in both groups( P 0. 05),with more significant decrease in the treatment group than in the control group( P 0. 05). Conclusion ModifiedShengjiang Powderis effective for pulmonary infection combined with sepsis of toxin-heat excess by reduce the levels of inflammatory cytokines to depress inflammation.

The human immunodeficiency virus (HIV) causes acquired immumodeficiency syndrome (AIDS), one of the worst global pandemic. The virus infects human CD4 T cells and macrophages, and causes CD4 depletion. HIV enters target cells through the binding of the viral envelope glycoprotein to CD4 and the chemokine coreceptor, CXCR4 or CCR5. In particular, the CCR5-utilizing viruses predominate in the blood during the disease course. CCR5 is expressed on the surface of various immune cells including macrophages, monocytes, microglia, dendric cells, and active memory CD4 T cells. In the human population, the CCR5 genomic mutation, CCR5Δ32, is associated with relative resistance to HIV. These findings paved the way for the discovery and development of CCR5 inhibitors to block HIV transmission and replication. Maraviroc, discovered as a CCR5 antagonist, is the only CCR5 inhibitor that has been approved by both US FDA and the European Medicines Agency (EMA) for treating HIV/AIDS patients. In this review, we summarize the medicinal chemistry and clinical studies of Maraviroc.

目的 探讨过表达Fibulin-5对大鼠脑缺血再灌注损伤后血脑屏障的保护作用及其可能的机制.方法 将112只成年雄性SD大鼠分成4组:假手术组(S)、脑缺血组(I/R)、脑缺血加过表达Fibulin-5腺病毒载体干预组(I/R+ AdFBLN)以及脑缺血加空腺病毒载体干预组(I/R+ Ad-HK).大鼠在大脑中动脉阻塞前7d接受腺病毒注射,再灌注后24 h,采用Western blot、RT-PCR和免疫荧光检测各组大鼠脑组织Fibulin-5和紧密连接蛋白occludin的表达;伊文思蓝漏出评估血脑屏障的通透性;TTC染色检测脑梗死体积并进行神经功能缺损评分.结果 脑缺血再灌注24h,与S组比较,I/R组大鼠伊文思蓝明显漏出(P＜0.01),伴有紧密连接蛋白occludin表达降低(P＜0.01).I/R+ Ad-FBLN组Fibulin-5的mRNA水平和蛋白水平明显高于其他3组(P＜0.01),伊文思蓝漏出明显减少(P＜0.01),occludin的表达明显增高(P＜0.01),TTC梗死灶明显缩小(P＜0.01),神经功能缺损明显减轻(P＜0.01).而I/R+Ad-HK组与I/R组之间差异均无统计学意义(P＞0.05).结论 过表达Fibulin-5减轻大鼠脑缺血再灌注损伤后血脑屏障的损害,Fibulin-5促进紧密连接蛋白occludin的表达可能是其保护作用的机制之一.

Objective To evaluate the effectiveness of retention enema with combination of smectite mixed liquid and reduced glutathione in treating radiation proctitis(RP).Methods A total of 45 RP patients were randomly divided into intervention group(n=23)and control group(n=22).All patients were provided with liquid nourishment support during the preparation period.Then the control group were treated by retention enema with smectite mixed liquid(after defecation or before sleep;once daily,every two weeks),whereas the intervention group was further treated by reduced glutathione(1.2 g) in addition to the treatment in the control group.The effectiveness and adverse reactions were evaluated after two weeks.Results In the control group,3 patients were cured,7 improved,and 13 failed after the 2-week treatment;In the intervention group,on the contrary,6 cured,12 improved,and 4 failed(u=150.00,P0.05).Two patients in the control group and one in the intervention group experienced paroxysmal cramps at the lower abdomen and nausea during the treatment.Concluions Retention enema with combination of smectite mixed liquid and reduced glutathione is safe and effective for treating RP patients.