Efficacy and Safety of Teriflunomide in Chinese Patients with Relapsing Forms of Multiple Sclerosis: A Subgroup Analysis of the Phase 3 TOWER Study / 中华医学杂志(英文版)

Background@#Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study.@*Methods@#TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54).@*Results@#Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning.@*Conclusions@#Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China.@*Trial Registration@#ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.

Neutralization of Interleukin-9 Decreasing Mast Cells Infiltration in Experimental Autoimmune Encephalomyelitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Th9 cells are a newly discovered CD4+ T helper cell subtype, characterized by high interleukin (IL)-9 secretion. Growing evidences suggest that Th9 cells are involved in the pathogenic mechanism of multiple sclerosis (MS). Mast cells are multifunctional innate immune cells, which are perhaps best known for their role as dominant effector cells in allergies and asthma. Several lines of evidence point to an important role for mast cells in MS and its animal models. Simultaneously, there is dynamic "cross-talk" between Th9 and mast cells. The aim of the present study was to examine the IL-9-mast cell axis in experimental autoimmune encephalomyelitis (EAE) and determine its interaction after neutralizing anti-IL-9 antibody treatment.</p><p><b>METHODS</b>Female C57BL/6 mice were randomly divided into three groups (n = 5 in each group): mice with myelin oligodendrocyte glycoprotein (MOG)-induced EAE (EAE group), EAE mice treated with anti-IL-9 antibody (anti-IL-9 Abs group), and EAE mice treated with IgG isotype control (IgG group). EAE clinical score was evaluated. Mast cells from central nervous system (CNS) were detected by flow cytometry. The production of chemokine recruiting mast cells in the CNS was explored by reverse transcription-polymerase chain reaction (RT-PCR). In mice with MOG-induced EAE, the expression of IL-9 receptor (IL-9R) complexes in CNS and spleen mast cells was also explored by RT-PCR, and then was repeating validated by immunocytochemistry. In vitro, spleen cells from EAE mice were cultured with anti-IL-9 antibody, and quantity of mast cells was counted by flow cytometry after co-culture.</p><p><b>RESULTS</b>Compared with IgG group, IL-9 blockade delayed clinical disease onset and ameliorated EAE severity (t = -2.217, P = 0.031), accompany with mast cells infiltration decreases (day 5: t = -8.005, P < 0.001; day 15: t = -11.857, P < 0.001; day 20: t = -5.243, P = 0.001) in anti-IL-9 Abs group. The messenger RNA expressions of C-C motif chemokine ligand 5 (t = -5.932, P = 0.003) and vascular cell adhesion molecule-1 (t = -4.029, P = 0.004) were significantly decreased after IL-9 neutralization in anti-IL-9 Abs group, compared with IgG group. In MOG-induced EAE, the IL-9R complexes were expressed in CNS and spleen mast cells. In vitro, splenocytes cultured with anti-IL-9 antibody showed significantly lower levels of mast cells in a dose-dependent manner, compared with splenocytes cultured with anti-mouse IgG (5 μg/ml: t = -0.894, P = 0.397; 10 μg/ml: t = -3.348, P = 0.019; 20 μg/ml: t = -7.639, P < 0.001).</p><p><b>CONCLUSIONS</b>This study revealed that IL-9 neutralization reduced mast cell infiltration in CNS and ameliorated EAE, which might be relate to the interaction between IL-9 and mast cells.</p>

Effects of Naoxintong on atherosclerosis and inducible nitric oxide synthase expression in atherosclerotic rabbit / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>High levels of nitric oxide (NO) produced by inducible NO synthase (iNOS) have been associated with atherosclerosis processes. Naoxintong is a traditional Chinese medicine for treatment of cerebrovascular and cardiovascular disease. The aim of the present study was to detect and quantify changes of iNOS mRNA and NO levels in the vessel wall after the administration of Naoxintong in an atherosclerotic rabbit model.</p><p><b>METHODS</b>Forty New Zealand white rabbits were randomly divided into five groups (n = 8). Rabbits were fed a standard diet (group A), an atherogenic diet consisting of 79% standard feed + 1% cholesterol + 5% lard + 15% egg yolk powder (group B), an atherogenic diet with Naoxintong 0.25 mg×kg(-1)×d(-1) (group C), an atherogenic diet with Naoxintong 0.5 mg×kg(-1)×d(-1) (group D), or atherogenic diet with Naoxintong 1.0 mg×kg(-1)×d(-1) (group E) for 12 weeks.</p><p><b>RESULTS</b>Supplemented administration of Naoxintong led to a down-regulation of cholesterol (CHOL) (P < 0.001) and low-density lipoprotein (LDL) (P < 0.001). The trend became more notable as the dose of Naoxintong increased; group C vs. group B (CHOL, P = 0.568; LDL-cholesterol (LDL-C), P = 0.119), group D vs. group B (CHOL, P = 0.264; LDL-C, P = 0.027), group E vs. group B (CHOL, P = 0.028; LDL-C, P = 0.002). Atherosclerotic lesions in aorta were reduced in Naoxintong groups (groups C, D, E) compared to group B. Group B had higher iNOS mRNA (P = 0.001) and NO level (P < 0.001) than group A. Compared with the atherogenic diet fed-rabbits, Naoxintong supplements decreased the expression of iNOS mRNA (P < 0.001) and the NO level (P < 0.001) in the vessel wall. Groups given a higher Naoxintong dose exhibited greater benefits. iNOS mRNA and NO levels seemed to be reduced in group C, although the difference did not quite reach statistical significance (iNOS mRNA, P = 0.130; NO, P = 0.038). iNOS mRNA and NO levels significantly decreased in group D (iNOS mRNA, P = 0.019; NO, P = 0.018) and group E (iNOS mRNA, P = 0.004; NO, P < 0.001).</p><p><b>CONCLUSION</b>Naoxintong has beneficial effects on atherosclerosis treatment by reducing expression of iNOS mRNA and the NO level in the vessel wall.</p>

Combined therapy with methylprednisolone and ulinastatin in experimental autoimmune encephalomyelitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Our previous study had demonstrated that ulinastatin (UTI) had a neuroprotective effect in experimental autoimmune encephalomyelitis (EAE). Methylprednisolone has been recommended to be a standard drug in multiple sclerosis (MS) therapies. The present study was to investigate the protective effects of UTI combined methylprednisolone in EAE.</p><p><b>METHODS</b>Mice were divided into a UTI treatment group, a methylprednisolone treatment group, a combined treatment group with UTI and methylprednisolone, a normal saline treatment group, and a normal control group. EAE mice were induced in groups receiving different combined treatments, or respective monotherapies. Demyelination was evaluated by Solochrome cyanin staining. 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP)/ myelin basic protein (MBP)/ the precursor form of nerve growth factor (proNGF)/p75/ inducible nitric oxide synthase (iNOS) proteins in cerebral cortex of EAE were detected by Western blotting.</p><p><b>RESULTS</b>The combined treatment group had a lower clinical score (0.61 ± 0.06) and demyelinating score (1.33 ± 0.33) than the groups with normal saline (clinical score: 1.39 ± 0.08, P < 0.001; demyelinating score: 2.75 ± 0.49, P < 0.05) or monotheraphies. Compared with the saline treated EAE group, UTI combined methylprednisolone significantly increased expressions of CNP (1.14 ± 0.06 vs. 0.65 ± 0.04, P < 0.001), MBP (1.28 ± 0.14 vs. 0.44 ± 0.17, P < 0.001), and decreased expressions of proNGF (1.08 ± 0.10 vs. 2.32 ± 0.12, P < 0.001), p75 (1.13 ± 0.13 vs. 2.33 ± 0.17, P < 0.001), and iNOS (1.05 ± 0.31 vs. 2.17 ± 0.13, P < 0.001) proteins in EAE. Furthermore, UTI combined methylprednisolone could significantly upregulate MBP (1.28 ± 0.14 vs. 1.01 ± 0.15, P < 0.05) expression and downregulate iNOS (1.05 ± 0.31 vs. 1.35 ± 0.14, P < 0.05) expression compared to methylprednisolone treatment EAE group. And proNGF expression was significantly lower in combined treatment (1.08 ± 0.10) than that in UTI (1.51 ± 0.24, P < 0.05) or methylprednisolone (1.31 ± 0.04, P < 0.05) treatment group.</p><p><b>CONCLUSION</b>Combination treatment of UTI with methylprednisolone was shown to protect EAE, suggesting that combination therapy is a potential novel treatment in MS.</p>

Splenectomy protects experimental rats from cerebral damage after stroke due to anti-inflammatory effects / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A recent study demonstrated that the inflammatory response accompanying necrotic brain injury played an important role in stroke. Thus, inhibition of this response may help to stop the expansion of infarcts. It has been also shown that the spleen, a major peripheral immune organ, plays a role in stroke-induced immune responses. This study aimed to establish rat models of middle cerebral artery occlusion (MCAO) and to investigate the effect of splenectomy and possible mechanisms in that rat models.</p><p><b>METHODS</b>Infarct size in a stroke model was measured with the Nissl body staining method, numbers of inflammatory cells in ischemic regions were detected by immunofluorescence staining, and inflammatory factors were assayed by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (PCR) in brain homogenates and sera. The significance of differences was determined by one-way analysis of variance (ANOVA) followed by the least significant difference post hoc test.</p><p><b>RESULTS</b>Infarct size in the brain of rats that underwent splenectomies 2 weeks before permanent MCAO ((34.93 ± 3.23)%) was over 50% smaller than that of rats subjected to the stroke surgery alone ((74.33 ± 2.36)%, P < 0.001; (77.30 ± 2.62)%, P < 0.001). Lower numbers of T cells, neutrophils, and macrophages in brain tissue and lower levels of pro-inflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α, were observed in rats that underwent splenectomies, compared with the two other groups, but splenectomized rats showed higher levels of the anti-inflammatory factor IL-10 in the brain.</p><p><b>CONCLUSION</b>The mechanism(s) by which splenectomy protects brain from damage induced by stroke may correlate with the decreased numbers of inflammatory cells and changes in inflammatory cytokines.</p>

Correlation between severity of leukoaraiosis and plasma levels of homocysteine and fibrinogen in patients with Binswanger disease / 中华神经医学杂志

Objective To investigate the correlation between severity of leukoaraiosis (LA) and plasma levels of homocysteine and fibrinogen in patients with Binswanger disease (BD).Methods All patients with BD,admitted to our hospital from January 2005 to May 2011,were selected consistently with the diagnostic criteria of Bennett.The levels of plasma homocysteine (Hcy),fibrinogen (Hcy),low-density lipoprotein (LDL),apolipoprotein A (Apoa),apolipoprotein B (Apob),and high-density lipoprotein (HDL) were measured.According to the Kinkel's classification of BD,the severity of LA was graded as mild,moderate,or severe by its appearance under MRI.The relation between levels of plasma Hcy and Fib and severity of LA in BD patients were analyzed.Results Single factor analysis indicated that the dispositions of gender,age,hypertensive disease,stroke and hyperlipoidemia in BD patients with different severities of LA were significantly different (P＜0.05).The severity degree of LA was positively correlated with the levels of Hcy and Fib (P＜0.05).Ordered logistic regression analysis showed that female was severer than male in the severity of the LA in BD patients; age,stroke and level of plasma Fib were positively related to the severity of LA in BD patients (P＜0.05).Conclusion The high plasma level of Fib is an important factor for BD deterioration; reducing the level of plasma Fib may delay the aggravation of BD.

Relationship between neuromyelitis optica-IgG status and spinal cord magnetic resonance imaging in patients with neuromyelitis optica / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Despite the large scale technical innovations that have been made, a number of patients with neuromyelitis optica (NMO) are lacking NMO-IgG in both serum and cerebrospinal fluid. Longitudinally extensive spinal cord (LESC) lesions and linear lesions are associated with NMO. However, differences of spinal cord magnetic resonance imaging (MRI) features, including LESC lesions and linear lesions, between NMO-IgG positive and negative patients still remain unknown. The aim of the present study was to analyze the relationship between NMO-IgG status and spinal cord MRI features in NMO patients, particularly concerned about LESC lesions and linear lesions.</p><p><b>METHODS</b>Clinical data and spinal cord MRI of 52 NMO patients were retrospectively analyzed. Eight patients were NMO-IgG negative in both serum and cerebrospinal fluid, while 44 were NMO-IgG positive. Quantitative data between the two cohorts were compared by the Student's t test or Mann-Whitney U test, the chi-square test or Fisher's exact test was used to evaluate qualitative data.</p><p><b>RESULTS</b>NMO-IgG negative patients had a higher sex ratio (male/female) (P = 0.014). On axial MRI, lesions in the NMO-IgG negative group were mostly located in the peripheral cord (50%), and central lesions (55%) were more common in the NMO-IgG positive group (P = 0.051). LESC lesions were common in both cohorts. None of linear lesions was found in NMO-IgG negative patients, while the NMO-IgG positive cohort had significantly more linear lesions (48%) (P = 0.016).</p><p><b>CONCLUSIONS</b>Patients with NMO-IgG negativity may have different spinal cord lesion features compared to NMO-IgG positive patients. Diagnosis of NMO cannot be excluded even when NMO-IgG negativity and non-specific spinal lesions occur.</p>

Serum alkaline phosphatase and γ-glutamyl transpeptidase levels in patients with neuromyelitis optica and multiple sclerosis / 中华神经医学杂志

Objective To investigate the serum alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (GGT) levels in patients with neuromyelitis optica (NMO) and multiple sclerosis (MS).Methods Serum ALP and GGT levels in patients with NMO and MS from the database of demyelinating diseases in our hospital were analyzed.Eighty-five healthy controls were chosen.The differences of serum ALP and GGT levels in patient groups and controls were compared, and the correlations between clinical features (age of the subjects, course of disease, times of relapse and scores of EDSS) and both ALP and GGT levels were analyzed. Results The serum ALP and GGT levels in patients with NMO were significantly higher than those in patients with MS and the controls (P<0.05).Patients with NMO still had significantly higher serum ALP level in acute phase than patients with MS,and the serum ALP levels in male patients with NMO and the serum GGT levels in female patients with NMO were, respectively,statistically higher than that of male patients with MS and female patients with MS (P<0.05). In patients with NMO, significantly positive correlations between serum GGT level and both age and times of relapse were noted (P<0.05). Conclusion Serum ALP and GGT levels differ in patients with NMO and MS, indicating their differential diagnostic value in NMO and MS to certain extent.

Role of IL-17 in the pathogenesy and differential diagnosis of CNS infections YOU Wen-xia, / 中华神经医学杂志

Objective To study the role of IL-17 in the pathogenesy and differential diagnosis of the 3 types of CNS infections (tubercular meningitis [TBM], cryptococcal meningitis [CM], viral meningoencephalitis [VM]). Methods One hundred and twelve patients with CNS infections,admitted to out hospital from February 2008 to December 2009, were chosen and divided into TBM group, CM group and VM group;another 36 patients without CNS infections either autoimmune disease at the same period were chosen as control group. ELISA was employed to determine the levels of IL-17,IL-12, IFN-γ in the cerebrospinal fluid in these 4 groups. Results IL-17 level in the cerebrospinal fluid of the 3 groups with CNS infections were obviously different, but all of them were significantly higher than that in control group (P＜0.05), with CM group enjoying the highest level, following by TBM group,VM group and control group. The levels of IL-12 and IFN-γ in patients with TBM and CM were higher than those in patients with VM and controls. Through the correlation analysis of IL-17, IL-12 and IFN-γ in patients with TBM, we found that IL-17 level was negatively correlated with IL-12 level (r=-0.3 11,P=0.033);the levels of these 3 cytokines were positively correlated with the quantity of leucocytes (r=0.219, 0.434 and 0.341, P=0.031, 0.027 and 0.001). ROC curves were established for differential diagnosis among these 3 groups according to CSF IL-17 levels, and all of the areas under the curve were bigger than 0.7. Conclusion Thl7 pathway is widely involved in the immune responses of CNS infection, and interacts with Thl pathway. The different levels of IL-17 in the cerebrospinal fluids in patients with various CNS infections may contribute to differential diagnosis.

Effect of Danhong injection on intimal hyperplasia and expressions of bFGF and TF in carotid artery of rabbits after PTA / 中华神经医学杂志

Objecfive To study the effect of Danhong injection(DI)on intimal hyperplasia and expressions of basic fibroblast growth factor(bFGF)and tissue factor(TF)in carotid arteries of rabbits after percutaneous transluminal angioplasty(PTA). Methods Fifty New Zealand White rabbits were randomly divided into 5 groups (n=10),namely sham-operated group,model group,and DI treatment groups(low-,medium-and high-dose DI treatment groups).The animals in the sham-operated group were only given external carotid artery ligation.The rabbit models of carotid stenosis in the later 4 groups were established by ballon-injury.Before the carotid balloon injury,the animals in the DI treatment groups were given DI at doses of 1 mL/kg·d-1,2mL/kg·d-1 and 4 mL/kg·d-1,respectively,for 7 or 14 d via intravenous injection;the animals in the sham-operated and model groups were given saline solution(2mL/kg·d-1)instead.The animals were sacrificed and their common carotid arteries were removed on the 7th and 28th d of surgery;morphology changes of the arterial wall with hematoxylin eosin staining were observed by optical microscope,and the expressions ofbFGF and TF of the vascular wall were detected through immunohistochemical techniques;with the help of an image analysis system,semiquantitative analysis was performed.Results On the 7th d of surgery,the intimal area and intima area/media area (I/M)ratio in the model group showed no significant differences as compared with those in the other 4groups(P>0.05).On the 28th d of surgery,the intimai area and I/M ratio in the model group were increased markedly as compared with those in the sham-operated group (P<0.05), and the intimal area and I/M ratio in the medium and high dose DI treatment groups were significantly reduced as compared with those in the in the model group (P<0.05). The expressions of TF and bFGF in the neointima of carotid arteries of rabbits treated with medium and high dose of DI were significantly weaker than those of the model group (P<0.05), and those of rabbits treated with low dose of DI had no obvious differences as compared with those of the model group (P>0.05). Conclusion Medium and high dose of DI can inhibit the intimal hyperplasia resulting from percutaneous transluminal angioplasty, might through the inhibition of expressions of bFGF and TF in the neointima of the arterial wall.

Level of β-amyloid peptide in cerebrospinal fluid of patients with multiple sclerosis and clinically isolated syndrome and its significance / 中华神经医学杂志

Objective To investigate the concentration of β-amyloid peptide 42 (Aβ42) in cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and its first clinical event-clinically isolated syndrome (CIS), and explore its associations with duration, disability severity and total T2-hyperintense lesion numbers in MRI. Methods Thirty-three patients with MS, 23 patients with CIS and 13 controls were investigated in this study. The disability severity of patients with MS and CIS in attack period was assessed by Expanded Disability Status Scale (EDSS). MRI scanning of brain, spinal cord or optic nerve was performed. And Aβ42 concentration in CSF was assessed by liquid chip assay. Results No significant differences of Aβ42 concentrations in CSF from patients with MS and CIS in attack period were noted as compared with those from controls ([104.78±13.73]pg/mL, [134.13±25.06] pg/mL vs. [137.02±23.35]pg/mL, P>0.05). ButAβ42 concentration in CSF from patients with secondary progressive MS (SPMS, [167.99±36.39]pg/mL) was significantly higher than that from patients with relapsing-remitting MS (RRMS, [92.74±13.64] pg/mL, P=0.042). No correlations of Aβ42 concentration in CSF with the duration of MS and CIS and scores of EDSS were noted in patients with MS and CIS (P> 0.05). The concentration of Aβ42 in CSF from patients with MS with a duration for more than one year lower than the ones with a duration for less than one year, but the difference was not significant (P>0.05). Total T2-hyperintense lesion numbers in MRI of patients with MS and CIS were positively correlated with Aβ42 concentration in CSF (MS patients: r=0.507, P=0.038; CIS patients:r=0.485,P=0.049). Aβ42 concentration in CSF from patients with MS with total T2-hyperintense lesions ≥4 (129.34±19.96) was significantly higher than that from the ones with total T2-hyperintense lesions <4 (73.51±12.60, P=0.049). Conclusion Axonal damage in patients with SPMS is more severe than that in patients with RRMS.Increased CSF Aβ42-level in patients with MS is a feature of disease progression. There is a possible relation between T2-hyperintense lesion load and axonal damage in patients with MS.

Value of clinical and laboratory features in diagnosis of adult tuberculous meningitis / 中华神经医学杂志

Objective To create a simple differential diagnostic rule for tuberculous meningitis and cryptococcal meningitis in adults on the basis of basic clinical and laboratory features. Methods We compared the clinical and laboratory features of 219 adults admitted to our hospital during the period of 2000-2008; these patients satisfied the diagnostic criteria for tuberculous meningitis (n=100) and cryptococcal meningitis (n=119). Multivariate logistic regression analysis was employed to find the risk factors those could independently predict the tuberculous meningitis,so that the diagnostic rule could be created. Results Six risk factors those could independently predict the tuberculous meningitis were found, including gender, mind disorder, vision and/or hearing damage, amount of cerebrospinal fluid protein, total cerebrospinal fluid white-cell count and combination with periphery tuberculosis. A diagnostic rule developed from these features enjoyed a 78.0% sensitivity, a 95.2% specificity, a 92.9% positive predictive value and a 84.4% negative predictive value. Conclusion Simple clinical and laboratory features can help in the differential diagnosis between adult tuberculous meningitis and cryptococcal meningitis, which can be applied in primary hospital with limited microbiological resources.

Comparative analysis of the clinical symptoms and magnetic resonance imaging findings of the spinal cord in patients with neuromyelitis optica and multiple sclerosis / 中华神经医学杂志

Objective To investigate the differences in the clinical symptoms and magnetic resonance imaging (MPd) findings of the spinal cord lesions between patients with neuromyelitis optica (NMO) and multiple sclerosis (MS) and explore the mechanisms that result in these differences. Methods The clinical symptoms and MRI findings of the spinal cord were retrospectively analyzed in 21 MS patients and 23 NMO patients admitted in the Third Affiliated Hospital of Sun Yat-Sen University from January, 2004 to January, 2007. Results Female patients were more frequently affected by NMO, and the NMO patients had a older mean age at onset with higher Expanded Disability Status Scale (EDSS) score than the MS patients. Chi-square test showed significant differences in the rotes of bilateral deep sensory dysfunction, zonesthesia, and sphincter disturbance between the NMO and MS patients (P<0.05). The majority of these clinical symptoms were found to result form corresponding spinal cord lesions defined by MRI. Conclusion NMO is a demyelinating disease that represents an independent clinical entity from MS, and has special mechanisms responsible for its characteristic clinical symptoms and MRI findings of the spinal cord.

Clinical characteristics and diagnosis of nenrosyphilis: analysis of 36 cases / 中华神经医学杂志

Objective To analyze the clinical characteristics and diagnosis of neurosyphilis. Methods A retrospective study was conducted among 36 patients with neurosyphilis treated in our hospital between February, 2002 and November, 2008. The clinical classification, clinical features, misdiagnosis, laboratory findings of the eerebrospinal fluid (CSF), and findings in magnetic resonance imaging (MRI) of the patients were analyzed. Results The patients aged between 30 and 78 years (mean 48.1 years), and male subjects were more frequently affected than female subjects. Meningovaseular syphilis was the most common type (50%) of the disease, followed by general paresis (27.8%) and asymptomatie neurosyphilis (11.1%). The most common symptoms ofneurosyphilis are mental disorders and dementia, followed by focal neurological dysfunction such as paralysis and dysarthria. Misdiagnoses of neurosyphilis, most frequently as viral encephalitis and cerebrovascular accidents, occurred in 55.6% of the patients. CSF examination revealed increased leukocyte count and protein levels. The positivity rate of Treponema pallidum particle agglutination assay of the CSF was91.7%, significantly higher than that of Venereal Disease Research Laboratory (VDRL) test (55.6%) and CSF-ELISA-TP-IgM test (38.9%) (P<0.05). The MRI findings were diverse in these patients. Conclusion No golden standard has been available for the diagnosis ofneurosyphilis, which has diverse clinical manifestations and nonspecifie MRI findings. The presence of Treponemal antibody in the CSF is highly supportive for the diagnosis, which can be established after a comprehensive analysis of the laboratory and clinical evidences.

Bone marrow stromal cells transfected with ciliary neurotrophic factor gene ameliorates the symptoms and inflammation in C57BL/6 mice with experimental allergic encephalomyelitis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the anti-inflammatory effect of bone marrow stromal cells (MSCs) transfected with recombinant adenovirus-mediated ciliary neurotrophic factor (CNTF) gene in C57BL/6 mice with experimental allergic encephalomyelitis (EAE).</p><p><b>METHODS</b>An adenovirus vector containing CNTF gene Ad-CNTF-IRES-GFP was constructed and transfected in the MSCs (MSC-CNTF). After examination of CNTF expression, the transfected cells were transplanted in C57BL/6 mice with MOG 35-55-induced EAE, which were monitored for the changes in the symptoms scores. The levels of tumor necrosis factor-alpha (TNF-alpha), inteferon-gamma (IFN-gamma), interleukin-12P35 (IL-12P35), and IL-10 in the peripheral blood of the mice were detected, and the number of MSC-CNTF cells in the spleen and spinal cord was counted. CD3+ T cell infiltration and TNF-alpha and IFN-gamma expressions in the lesions were also observed after the cell transplantation.</p><p><b>RESULTS</b>CNTF gene transfection resulted in significantly increased CNTF expression in the MSCs. The mice receiving MSC-CNTF transplantation exhibited significantly improved symptoms with shortened disease course and lessened disease severity. The cell transplantation also resulted in significantly decreased peripheral blood TNF-alpha levels, ameliorated CD3+T cell infiltrations and lowered TNF-alpha expression in the lesions, while the levels of IFN-gamma underwent no significant changes.</p><p><b>CONCLUSION</b>Transplantation of CNTF gene-transfected MSCs results in decreased peripheral blood TNF-alpha and IFN-gamma levels and reduced inflammatory cells, CD3-positive cells and TNF-alpha expression in the lesion of EAE, therefore providing better effect than MSCs in relieving the symptoms of EAE in mice.</p>

Construction of ciliary neurotrophic factor and green fluorescence protein-transduced recombinant adenovirus / 中华神经医学杂志

Objective To construct an adenoviral vector carrying the gene encoding ciliary neurotrophic factor (CNTF). Methods The gene fragment encoding CNTF was amplified from pMEG-CNTF plasmid by PCR and the Psp-CNTF-IRES-GFP and PDC316-CNTF-IRES-GFP plasmids were constructed. Using PDC316-CNTF-IRES-GFP and PBHG plasmids, the Ad-CNTF-IRES-GFP vector was constructed, and the constructed vector was amplified, purified and identified in 293-LP cells. Ectopic overexpression of CNTF was induced using the constructed vector in human bone marrow-derived mesenchymal stem cells (MSCs) to investigate the role of CNTF in promoting remyelination. Results The Ad-CNTF-IRES-GFP vector was successfully constructed with a pfu of 2.3x1011. CNTF concentration in the MSCs transfeeted with Ad-CNTF-IRES-GFP vector was 20-fold higher than that in either non-transfected or Ad-EGFP-transfected MSCs. Conclusion The constructed Ad-CNTF-IRES-GFP vector allows CNTF overexpression in human MSCs by 20 folds, which provides a strategy for gene therapy targeting CNTF.

Clinical analysis of leptomeningeal carcinomatosis in 4 cases / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the characteristics of leptomeningeal carcinomatosis.</p><p><b>METHODS</b>We summarized the clinical presentation, magnetic resonance imaging (MRI) findings and cerebrospinal fluid (CSF) cytological findings in 4 cases of leptomeningeal carcinomatosis.</p><p><b>RESULTS</b>All the patients presented with signs of elevated intracranial pressure such as headache. Enlarged cerebral ventricles and dural enhancement were found by MRI, with also the presence of malignant cells in cytological slides.</p><p><b>CONCLUSION</b>CSF cytological examination is important for diagnosis of leptomeningeal carcinomatosis.</p>

Experimental study on effect of Buchang Naoxintong containing serum for antagonizing hypoxia-induced apoptosis of cortical neurons / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of Buchang Naoxintong containing serum (BNCS) for antagonizing hypoxia-induced apoptosis of primary cultured cortical neurons with the sero-pharmacological method.</p><p><b>METHODS</b>Primary cortical neurons from neonate rats (within 24 h) were cultured and induced into hypoxia model on the 7th day, which were then treated with different concentrations of BNCS. Cell apoptosis was detected qualitatively and quantitatively; and further verified by agarose gel electrophoresis through analyzing in-ternucleosomal DNA fragmentation of the neurons. Besides, neuron viability was tested by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and change of nuclear morphology was observed by Hoechst 33258 staining.</p><p><b>RESULTS</b>After treatment with BNCS, the viability of the hypoxia neurons improved with significantly reduced neuron apoptosis.</p><p><b>CONCLUSION</b>Buchang Naoxintong can protect cortical neurons from hypoxia-induced apoptosis.</p>