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.

Insights into Initial Demyelinating Episodes of Central Nervous System during Puerperium / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Inflammatory demyelinating disease of central nervous system (CNS) is an inflammatory disease characterized by a high childbearing female predominance. Labor-related alterations for postpartum demyelinating attacks are not entirely clear. This study aimed to summarize clinical features of female patients of reproductive age with initial CNS inflammatory demyelinating attacks during puerperium.</p><p><b>METHODS</b>Fourteen female patients with initial demyelinating events during puerperium between January 2013 and December 2016 were retrospectively studied. Records of clinical features, neuroimaging, serum antibodies, cerebrospinal fluid (CSF) findings, annualized relapse rate (ARR), and treatment were analyzed.</p><p><b>RESULTS</b>Among 14 patients, 5 patients were diagnosed with multiple sclerosis (MS), four as neuromyelitis optica (NMO), two as longitudinal extensive transverse myelitis, two as clinical isolated syndrome (CIS), and one as acute brainstem syndrome. All the 14 puerperal female patients presented with more than one manifestation of hemiplegia, paraplegia, uroschesis, visual loss or dysarthria, and with mild to moderate abnormalities of CSF. Attacks occurred during the first trimester postpartum and cesarean section was the main delivery way (n = 10). Median Expanded Disability Status Scale (EDSS) scores were 5.0 (range: 2.0-9.0) at the onset and 2.5 (range: 0-7.0) at the end of follow-ups. Patients with MS and CIS had a significantly lower EDSS scores than patients with NMO spectrum disorders (P < 0.05). Median ARR was 0.46 (range: 0-1.16); all patients had a low ARR (0.49 ± 0.34, 95% confidence interval: 0.29-0.69) with standardized treatments.</p><p><b>CONCLUSION</b>Labor-related alterations in the mother's immune system might result in newly-onset demyelinating diseases of central nervous system.</p>

Effects of suppressed autophagy on mitochondrial dynamics and cell cycle of N2a cells / 华中科技大学学报（医学）（英德文版）

Autophagy dysregulation, mitochondrial dynamic abnormality and cell cycle re-entry are implicated in the vulnerable neurons of patients with Alzheimer's disease. This study was designed to testify the association among autophagy, mitochondrial dynamics and cell cycle in dividing neuroblastoma (N2a) cells. The N2a cells were cultured in vitro and treated with different concentrations of 3-methyladenine (3-MA). The cell viability was detected by methyl thiazolyl tetrazolium (MTT) assay. They were randomly divided into control group (cells cultured in normal culture medium) and 3-MA group (cells treated with 10 mmol/L 3-MA). The cell cycle was analyzed in the two groups 3, 6, 12, and 24 h after treatment by flow cytometry. Western blotting was used to evaluate the expression levels of mitofission 1 (Fis1), mitofusin 2 (Mfn2), microtubule-associated protein 1 light chain 3 (LC3), cell cycle-dependent kinase 4 (CDK4) and cdc2. The flow cytometry revealed that the proportion of cells in G(2)/M was significantly increased, and that in G0/G1 was significantly reduced in the 3-MA group as compared with the control group. Western blotting showed that the expression levels of Fis1, LC3, and CDK4 were significantly up-regulated in the 3-MA group at the four indicated time points as compared with the control group. Mfn2 was initially decreased in the 3-MA group, and then significantly increased at 6 h or 12 h. Cdc2 was significantly increased in the 3-MA group at 3 h and 6 h, and then dropped significantly at 12 h and 24 h. Our data indicated that 3-MA-induced suppressed autophagy may interfere with the cell cycle progression and mitochondrial dynamics, and cause cell death. There are interactions among cell cycle, mitochondrial dynamics and autophagy in neurons.

Effects of suppressed autophagy on mitochondrial dynamics and cell cycle of N2a cells / 华中科技大学学报（医学）（英德文版）

Autophagy dysregulation, mitochondrial dynamic abnormality and cell cycle re-entry are implicated in the vulnerable neurons of patients with Alzheimer's disease. This study was designed to testify the association among autophagy, mitochondrial dynamics and cell cycle in dividing neuroblastoma (N2a) cells. The N2a cells were cultured in vitro and treated with different concentrations of 3-methyladenine (3-MA). The cell viability was detected by methyl thiazolyl tetrazolium (MTT) assay. They were randomly divided into control group (cells cultured in normal culture medium) and 3-MA group (cells treated with 10 mmol/L 3-MA). The cell cycle was analyzed in the two groups 3, 6, 12, and 24 h after treatment by flow cytometry. Western blotting was used to evaluate the expression levels of mitofission 1 (Fis1), mitofusin 2 (Mfn2), microtubule-associated protein 1 light chain 3 (LC3), cell cycle-dependent kinase 4 (CDK4) and cdc2. The flow cytometry revealed that the proportion of cells in G(2)/M was significantly increased, and that in G0/G1 was significantly reduced in the 3-MA group as compared with the control group. Western blotting showed that the expression levels of Fis1, LC3, and CDK4 were significantly up-regulated in the 3-MA group at the four indicated time points as compared with the control group. Mfn2 was initially decreased in the 3-MA group, and then significantly increased at 6 h or 12 h. Cdc2 was significantly increased in the 3-MA group at 3 h and 6 h, and then dropped significantly at 12 h and 24 h. Our data indicated that 3-MA-induced suppressed autophagy may interfere with the cell cycle progression and mitochondrial dynamics, and cause cell death. There are interactions among cell cycle, mitochondrial dynamics and autophagy in neurons.

Extracts from the roots of Incarvillea younghusbandii on antioxidant effects and life span prolonging in Drosophila melanogaster / 中国天然药物

AIM@#To investigate antioxidant activities and life span prolonging effects of the extracts from the roots of Incarvillea younghusbandii Sprague, and to study the correlations between these activities and the polar intensity of the extracts.@*METHOD@#Five extracts (IYS1, IYS2, IYS3, IYS4 and YS5) with different polar intensity were prepared. Antioxidant activities in vitro were determined by LPO inhibitory and free radicals scavenging experiments. Life span prolonging effects in vivo were evaluated by feeding Drosophila melanogaster.@*RESULT@#Total phenolic content in extracts were solvent-dependent and decreased in the order of IYS4 > IYS1 > IYS3 > IYS5 > IYS2. Organic extracts (IYS1 and IYS4) showed excellent LPO inhibitory activity, O(2)(· -) and ·OH scavenging activity compared to ascorbic acid (or benzoic acid, or BHT), while aqueous extracts (IYS2, IYS3 and IYS5) did not. The antioxidant activities (in vitro) were solvent dependent and decreased in the order of IYS4 > IYS1 > IYS3 > IYS5 ≥ IYS2. Drosophila melanogaster was fed with organic extracts (IYS1 or IYS4) at 5.0 mg mL(-1). The mean life span were increased by 24.4% (IYS1) or 23.0% (IYS4) in female and 15.3% (IYS1) or 16.9% (IYS4) in male; the maximum life span were increased by 8.4% (IYS1) or 11.2% (IYS4) in female and 9.7% (IYS1) or 15.8% (IYS4) in male, and the survival curves were significantly shifted to the right after fifteen days in both sexes survival period. Feeding aqueous extracts (IYS2, IYS3 or IYS5) at 5.0 mg·mL(-1), the significant life span prolonging effects were not achieved. The life span prolonging effects of the extracts were solvent-dependent and decreased in the order of IYS4 ≥ IYS1 > IYS3 > IYS2 > IYS5.@*CONCLUSION@#Extracts from the roots of Incarvillea younghusbandii Sprague showed excellent antioxidant activities and significant life span prolonging effects in Drosophila melanogaster. Positive correlations existed between the antioxidant activities and total phenolic content. Life span prolonging effect was positively correlated with the total phenolic content or antioxidant activities. The extracts possess better life span prolonging effect in females than in males.

Isolation, purification and structure identification of two phenolic glycosides from the roots of Incarvillea younghusbandii Sprague and their antioxidant activities / 药学学报

Using a bioassay-guided fractionation technique, two compounds were isolated from the roots of Incarvillea younghusbandii Sprague through silica gel, reverse-phase C18 column chromatography and reverse-phase HPLC. Their structures were identified as acteoside (1) and isoacteoside (2) by ESI-MS, GC-MS, 1D- and 2D-NMR. 1 and 2 showed *OH scavenging capacity similar with benzoic acid, higher O2*- (or *OH) scavenging capacity than ascorbic acid, far higher hepatic LPO inhibitory activities than 2, 6-di-tert-butyl-4-methylphenol (BHT) or ascorbic acid, and more powerful effect on protecting erythrocytes from oxidative damage than ascorbic acid. The *OH scavenging capacity was positively proportional to the concentrations of 1 and 2 ranging from 0.015 6 to 0.500 0 mg x mL(-1). The hepatic LPO inhibitory activities increased with the increasing concentrations of 1 and 2 from 0.001 9 to 0.250 0 mg x mL(-1), but decreased slightly with the increasing concentration from 0.250 0 to 1.0000 mg x L(-1).

Effects of tumor necrosis factor-alpha on the growth of rat osteoblasts / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of tumor necrosis factor alpha (TNF-alpha) on the growth of rat osteoblasts. To find out the mechanisms that TNF-alpha regulates the growth of osteoblasts.</p><p><b>METHODS</b>To assay osteoblasts proliferation by MTT. To assay alkaline phosphatase (ALP) activity of osteoblasts by PP-nitrophenyl phosphate (PNPP).</p><p><b>RESULTS</b>The osteblasts proliferation and the ALP activity decreased in treatment groups, and the significantly lower levels were observed in above 50 ng/mL groups (P<0.05).</p><p><b>CONCLUSION</b>TNF-alpha restrained osteoblasts proliferation and differentiation, and the effects were more significant in above 50 ng/mL groups.</p>

On Training Postgraduate of Oral and Maxillofacial Surgery / 中华医学教育探索杂志

Oral and maxillofacial surgery is one kind of special subjects involving multiple clinical disciplines.The postgraduate training is different from other professional postgraduate training model,which emphasizes the cultivation of students,should be first medical students,then dentist.In new situation,we advance the experiences in exploring how to cultivate high quality postgraduate of oral and maxillofacial surgery.

The expression and significance of EGF,TGF-? and EGFR in the natural concrescence course of rats gastric ulcer / 中国药理学通报

AIM To study the epidermal growth factor (EGF) and transforming growth factor ? (TGF ?)and the epidermal growth factor receptor(EGFR)during the course of rats gastric ulcer natural cure expressing and its possible biology meaning. METHODS We injected acetic acid to make the ulcer animal model, location expression characteristic of EGF and TGF ? and EGFR were studied by immunohistochemistry. RESULTS The normal rats stomach mucosa EGF,TGF ? and EGFR all expressed weakly at masculine. EGF and TGF ? was located at cytoplasm,and EGFR expressesed at cytoplasm and cell membrane and the expression position of the three ovrlopped with each other. EGF concentrated mainly on the cervical part of gastric gland, and TGF ? and EGFR, on the cervical and base parts of the gastric gland. Positive 9 expression cells were primarily parietal[FQ(11?46,X-WZ] and neck cells of the stamook muc. For materials taken during the course of ulcer natural recovery, regular ohanges were observed in TGF, TGF ? and EGFR expression. Higher expression was found in ulcer tissunes than in normal tissues, while the expression was not detectable in necrotic tissues and rarely detectable in granlation and scar tissnes. The expression became apparant only during healing and scar stages of ulcer but not in early stage. CONCLUSION ①TGF ?/EGFR autocrine system probably plays a leading role in maintaining rats mucosa completeness under the normal circumstances; ②EGF/EGFR and TGF ?/EGFR autocrine system may have important effect on the differentiation, hyperplasia, moving of cell and restraining the gastric acidity.

Bulbar myasthenia gravis:a clinical analysis of 166 patients / 中华神经科杂志

Objective To study the clinical characteristics of bulbar myasthenia gravis (MG). Methods Retrospective review was performed on 166 patients with bulbar type of myasthenia gravis, diagnosed at Tongji Hospital in the period of May 1983 through October 2005.Results Bulbar MG was a relatively rare type of MG,accounting for 5.7% (166/2888) of MG classifications.Females were more often affected than males (the ratio of male:female was 1:1.35).The peak of onset age was at 20—40 years.The incidence of myasthenia crisis in the group was 26.5% (44/166).Myasthenic crisis occurred in 10.8% (18/166) of the bulbar MG patients within 6 months after onset,resulting in a mortality rate of 6.0% (10/166) in the group.Out of the group,30 cases experienced puhnonary infections (18.1%). Thirty cases were initially misdiagnosed as other diseases such as nasopharyngeal disorders (33/166, 19.9%).The routine therapy was not very satisfactory.Median dose cyclophosphamide therapy appeared to be effective for ameliorating refractory MG.Thymectomy was performed in 25 patients,with optimistic efficacy rate up to 80.0% (20/25) in a 3-year follow-up.Conclusions The clinical analysis in the current study suggested that the bulbar MG had its own characteristics in such aspects as progression of the disease, complications,treatment and prognosis.The information of the clinical manifestations presented in this study may be useful in diagnosing and treating bulbar MG.