Amyotrophic lateral sclerosis is a rare but fatal neurodegenerative disorder.Riluzole remains the only available drug for slowing the progression of the disease.In the past few years,significant advances have been made in both our understanding of pathogenesis and the development of new therapeutic approaches.The authors review the current understanding of the pathogeneic mechanisms and drug therapy.The outcome of phase Ⅲ clinical trials will benefit the further investigation in ALS.

Objective To investigate the pathogenesis of cerebral infarction after non-cardiac surgeries according to imaging.Methods Retrospective analyses of clinical and imaging data of 17 patients with postoperative cerebral infarction(average 68 years old,total incidence 0.049％)from departments of orthopedics and general surgery were conducted during 52 months.Results Cerebral infarction occurred 39.1 hours after operation on average.Among the 17 patients,eight were detected with disturbance of consciousness,ten with hemiplegia,six with speech disorder and two with unilateral sensory disturbance.Six (35.3％)had blood lipids tests.Five(29.4％)had neck vascular ultrasound and one had intracranial magnetic resonance angiography(MRA).When discharged,one patient was declared death and ten had impaired neurological function in various degrees.Among six patients with previous stroke,one(16.7％)received neurological consultation before surgery.According to the image manifestation,ten cases were territory circulation infarcts,four centrum ovale infarcts and three watershed infarcts.Conclusions This study suggests that total incidence of cerebral infarction after non-cardiac surgeries is lower than previously reported and there is greater involvement of atherosclerosis.Patients' conditions should be closely observed within at least four days after surgeries.Preoperative assessment should be strengthened in order to avoid occurrence of postoperative cerebral infarction.

Objective To identify the DNA tag sequences with the purpose of rapid and specific characterization of Y. pestis. Methods DNA microarray hybridization combined with PCR was used to perform genomic comparison between strains of Y. pestis and Y. pseudotuberculosis in order to screen and identify Y. pestis-specific genes. Results Twenty eight signature genes of Y. pestis were discovered. Three pairs of Y. pestis-specific primers were designed according to tag genes and proved to amplify the specific sequences of the target bacterium, showing no cross-reaction with the closely related Y. pseudotuberculosis and a large collection of genomic DNAs from other organisms. Conclusion DNA tag sequence is an ideal target for the rapid detection and identification of Y. pestis by PCR method.

Objective To study genetic variations of pgm locus and its flanking regions in Yersinia pestis isolated from Chinese natural focus so as to understand differences in virulence between different strains and to improve the prevention of plague. Methods We analysed the sequence variations of pgm locus and its flanking regions by using PCR-sequencing and allele-specific PCR among 260 strains of Y. pestis isolated from different foci and 7 strains of Yersinia pseudotuberculosis. Results For YP1666, only the strains of Xilin Gol grassland type and Microtus fuscus type had intact transmembrane helix, and the T-deletion at base 1406 was unique in strains of Orientalis. Same as Y. pseudotuberculosis, there was no IS100-insertion at the 3′ end of pgm locus of strains from Eastern section of North Tianshan Mountain type, Western section of North Tianshan Mountain type A and B, Xilin Gol grassland type and M. fuscus type. Only the strains of Xilin Gol grassland type and M. fuscus type had IS285-insertion in pigmentation segment and IS100-insertion at its downstream flanking region. pgm locus was deleted entirely from 36 strains, most of which came from Ordos plateau type, Song-liao plain type B , Kunlun Mountain type A and B. Conclusion Strains of Eastern section of North Tianshan Mountain type, Western section of North Tianshan Mountain type A and B, Xilin Gol grassland type and M. fuscus type are the oldest lineage of Chinese isolates. The pgm locus of the strains of these three types is very stable because there is no IS100-insertion at its 3′ terminal. We suggest that the strains of Xilin Gol grassland type and M. fuscus type should be grouped into a fourth biovar: Microtus. pgm locus is highly conserved among strains of different ecotypes, and its variations are well correlated with biovar, focus and ecotype, which indicates that pgm locus has played a role in strains′ adaptation to their environment.

Objective To identify the gene mutation of Chinese Charcot-Marie-Tooth (CMT) pedigrees and investigate the association of gene mutation to the clinical manifestations and electrophysiology,and the underlying mechanisms.Methods A total of 105 pedigrees with CMT in our hospital were enrolled from January,2007 to December 2013.The clinical features,CMT neuropathy score (CMTNS) and electrophysiological data were collected.Gene mutations were analyzed using multiplex ligation-dependent probe amplification (MLPA) and Sanger gene sequencing.Results We found 31 (29.5％) PMP22 duplication pedigrees,8 (7.6％) GJB1 mutation pedigrees,4 (3.8％) MFN2 mutation pedigrees,4 (3.8％) HSPB1 mutation pedigrees,3 (2.9％) MPZ mutation pedigrees and 1 (1.0％) PMP22 mutation pedigree.In Chinese Han population,the proportion of PMP22 duplication was relatively lower than that in western countries and manifested with classical clinical characteristics of CMT.Subjects with axonal CMT often presented with isolated lower extremity injury and with central nervous system involvement.Hereditary motor neuropathy might be underestimated in clinical setting and should be differentiated from motor neuron disease.Conclusions The gene frequency distribution in patients with CMT in Chinese Han population is different from that in patients from western countries.We should establish our own epidemiological data of CMT in Chinese Han population.

Objective To study the genetic basis for biovar conversion of Y. pestis. Methods In silico comparative genomic analysis was conducted and some critical genetic variations of Yersinia pestis were comparatively analyzed by means of PCR and DNA sequencing. Results A 93bp in-frame deletion in glpD gene results in the glycerol negative characteristic of Orientalis strains. A point mutation in the napA gene may cause the negative characteristic of nitrate reduction in Mediaevalis and Microus strains. A 122-bp frameshift deletion in the araC gene may lead to the arabinose negative phenotype of Microus strains. Conclusion In this study, Microtus strains with their unique pathogenic, biochemical and molecular features, were proposed as a novel biovar Microtus. In the light of its differential ability to ferment glycerol and arabinose and to reduce nitrate, Y. pestis can be classified into four biovars-Antiqua(glycerol positive, arabinose positive and nitrate positive), Mediaevalis(glycerol positive, arabinose positive and nitrate negative), Orientalis(glycerol negative, arabinose positive and nitrate positive), and Microtus(glycerol positive, arabinose negative and nitrate negative).

Objective To study the genome dynamics of Y. pestis and look for the relationship between its genome microevolution and niche adaption.Methods The DNA microarray combined with PCR was used to perform comparative genomic analysis of natural populations of Y.pestis.Results It was revealed that considerable genome dynamics of Y. pestis were the result of gene acquisition and loss in genome. We established a genomotyping system to group homologous isolates of Y. pestis, drew an outline of parallel microevolution of the Y. pestis genome, and established the link between the bacterial niche adaptation and genome microevolution.Conclusion The transmission, colonization and expansion of Y. pestis in natural foci are the results of its parallel, directional and gradual adaptation to the complex interactions among the environment, the hosts, and the pathogen itself.

Objective To observe the effect of systemic chemotherapy on conditions of tumor infiltrating,metastasis and disease-specific survival (DSS) for advanced retinoblastoma (RB).Methods Forty-one patients with advanced RB who received enucleation were enrolled in this study.There were 26 males and 15 females,age at diagnosis was ranged from 2 to 72 months,with a mean of 23.08 months.There were 16 bilateral patients and 25 unilateral patients;13 group D eyes and 28 group E eyes.16 patients received enucleation as the primary treatment (operation group),25 eyes received chemotherapy before enucleation (chemotherapy group).There was no significant statistical difference between two groups for the gender,unilateral and bilateral,international staging or diagnostic age (P＞0.05).The histopathology report was performed to assess the risk of postoperative tumor-node-metastasis staging (pTNM) in each patient,and the extent of tumor invasion in the optic nerve,choroid and anterior chamber was divided into 3 levels of low risk,medium risk and high risk.Five deaths were all in the group E with chemotherapy before enucleation.Using R software survival analysis software package survfit function,the application of Kaplan-Meier estimation method,DSS of RB children was calculated from the time of diagnosis,up to the date of the death of patient.DSS differences between chemotherapy,operation group and eye removal time (more than 3 months,less than 3 months) in group E RB children were analyzed.Results The proportion of high risk pTNM stage in chemotherapy group was significantly lower than the operation group.But there was no significant difference between the two groups in the overall risk classification (x2 =3.130,P=0.077).For group D eyes,the overall risk classification in chemotherapy group was significantly lower than the operation group (x2 =5.870,P=0.015).There was no significant difference between the two groups in the overall risk of group E eyes (x2 =0.020,P=0.889).The DSS in chemotherapy group and operation group were 0.71 and 1.00,respectively;the difference was significant (x2 =3.700,P=0.05).The DSS in children whose enucleation delayed for more than 3 months and children whose enucleation performed within 3 months were 0.64 and 1.00,respectively;the difference was significant (x2 =4.800,P=0.028).Conclusion Systemic chemotherapy did not reduce the risk of tumor invasion and metastasis in patients with advanced RB.Instead,it will reduce the DSS in group E eyes of RB.

Objective To observe the characteristics of midbrain hyperechogenicity of amyotrophic lateral sclerosis (ALS) patients by transcranial sonography (TCS).Methods A total of 107 ALS patients,enrolled from January to July 2015 in Beijing University Third Hospital,with the diagnosis of possible or definite ALS according to revised E1 Escorial criteria were examined by transcrinal B-mode sonography.The area of midbrain and substantia nigra and the area ratio of hyper-substantia nigra/midbrain (S/M) were measured and compared between ALS and 40 age-and gender-matched controls.Results There were 29.0％ (31/107) of ALS patients and 7.5％ (3/40) of controls who displayed abnormal midbrain hyperechogenic areas for groups comparison (x2 =22.708,P ＜ 0.01).The hyperechogenic substantia nigra area and S/M were (0.40 ± 0.14) cm2 and 9.5％ (6.0％,13.0％) in ALS group,whereas (0.20 ± 0.06) cm2 and 5.0％ (2％,6.0％) in control group respectively,the difference between the two groups being statistically significant (t =12.727,Z =16.545,both P ＜0.01).No correlations of hyperechogenic area sizes in ALS patients were found in regard to age,gender,ALS duration or ALS Functional Rating Scale score (r=0.043,-0.088,0.018,0.202;P=0.251,0.512,0.894,0.190).However,there was significant correlation between TCS severity and ALS subtype (bulbar vs spinal form,r =0.386,P ＜ 0.01).Conclusion Hyperechogenicity of the substantia nigra was found in patients with sporadic ALS with a frequency higher than in controls.

Objective To study the relation between mitochondria damage and glutamate excitotoxicity in motor neuron disease.Methods Organotypic cerebral cultures were prepared from prefrontal brain of neonatal SD rats. Mitochondria was damaged by malonate sodium, and a NMDA receptor antagonist, MK-801 of 0.025,0.050,0.075,0.100 mmol/L, was respectively added into the cerebral cultures simultaneously in the protective experiment. The morphology of motor neurons was shown by Nissl and anti-high molecular weight filament (anti-NFH) immunohistochemical staining, and number of motor neurons was counted. The concentration of MDA in culture medium was measured by MDA assay. Results After exposed to malonate sodium (0, 1, 3, 5 and 7 mmol/L) for 1 week, the number of motor neurons in cerebral slices showed a dose-dependent decrease (49.78?4.30, 47.89?6.81, 25.67?6.18, 4.44?3.40, 1.22?1.99). The group treated with 3 mmol/L malonate sodium was selected as damage group. In protective experiment, the number of motor neurons in 0.050, 0.075 and 0.100 mmol/L MK-801-treated groups was significantly increased as compared with damage group, still less than that of controls. However, there was no difference of number of motor neurons among these three groups. The concentration of MDA in culture medium in normal control and 3, 5 mmol/L malonate sodium was (13.47?0.49), (15.87?0.74), (20.52?0.74) mmol/L. When treating cerebral cultures with 0.050 mmol/L MK-801 and 5 mmol/L malonate sodium simultaneously, the MDA was decreased to 14.45?0.78, close to normal level. Conclusion Glutamate excitotoxicity plays a role in motor neuron diseases caused by mitochondria damage, there exists a close relationship between glutamate exicitotoxicity and mitochondria damage.