Excitotoxicity refers to a process of neuronal death caused by excessive or prolonged activation of receptors for the excitatory amino acids, which is related to the overload of intracellular calcium ([Ca2+]i) and mitochondrial depolarization. The well accepted hypothesis that Ca2+ plays a central role in neurotoxicity, and it mediated excitotoxicity is deeply involved in both acute and chronic neurodegeneration suggests that inhibitors of Ca2+ transduction, such as NMDA antagonists, might block the pathological process at an early stage and provide more effective protections.

Objective To explore the oxidative stress pathogenesis of Parkinson's disease(PD) induced by paraquat in substantia nigra of mice. Methods The model of PD was established by oral administration of paraquat to mice.The spectrophotometry was used to determine the activities of superoxide dismutase(SOD) and glutathione peroxidase(GSH-PX) and the content of malondialdehyde(MDA) in substantia nigra.At the same time,number of tyrosine hydroxylase(TH) positive neurons in substantia nigra of mice was estimated by immunohistochemistry. Results The activities of SOD and GSH-PX were significantly decreased,and the content of MDA was increased in paraquat-treated mice compared to that of mice treated by saline taken orally(P

Objective To construct markless gene deletion mutant at the clpP loci on the chromosome of Streptococcus mutans(S.mutans).Methods ASp resistance gene was amplified by PCR,to construct the Sp resistance cassette where the Sp resistance gene was flanked with two loxP site.After the clpP gene was cloned into the pGEM-T-Easy TA cloning vector,it was digested and linked with the Sp resistance cassette,yielding homologous recombination vector pIB △ clpP-Sp.The vector was linearized and used for the transformation of S.mutans UA159,with transformants selected on TPY plates containing Sp.The selected strain was transformed with the thermosensitive plasmid pCrePA to excise the Sp resistance gene.The pCre-PA was then easily eliminated at nonpermissive temperature,resulting in a markless mutant strain carrying a deletion at the clpP loci,which was verified by PCR and DNA sequencing.Results The result of the PCR analysis and DNA sequencing indicated that a part of the clpP gene was deleted.There was a loxP at this loci without the Sp resistance gene.Conclusion The markless clpP-deletion mutant of S.mutans was constructed successfully,which laid a foundation for further study of its biological function and its influence on the cariogenicity of S.mutans.

Objective To investigate the changes of time-course of dopamine transporter (DAT) mRNA and vesicular monoamine transporter2 (VMAT2) mRNA in the substantia nigra of Parkinsonian mice induced by paraquat orally. Methods RT-PCR technique was used to detect the changes of expressions of DAT and VMAT2 mRNA in the substantia nigra of mice after paraquat taken orally for different days. Results The gene expressions of DAT and VMAT2 were decreased gradually two weeks after paraquat. Conclusion In the early stage of paraquat-induced parkinsonian mice, the expressions of DAT and VMAT2 mRNA were decreased, and the degree of reduced expression was more severe with the development of Parkinson disease. DAT and VMAT2 may be involved in the pathogenesis of Parkinson disease.

Objective:To explore the status of STAT3 phosphorylation in myeloid-derived suppressor cells (MDSCs) of breast cancer and its function in the immunosuppressive effect of MDSCs on proliferation and cytokine secretion of T cells. Methods:CCD33+cells were isolated from healthy umbilical cord, blood-derived, peripheral blood mononuclear cells and were co-cultured with breast cancer cell line MDA-MB-231 in vitro using Transwell plates to induce MDSCs. The untreated CD33+cells were used as con-trols. Idoxuridine (IDO) suppressor expression and STAT3 phosphorylation were examined using Western blot assay. The proliferation and cytokine secretion of T cells, which were co-cultured with MDSCs, were determined by methyl thiazol tetrazolium assay and en-zyme-linked immunosorbent assay. 1-MT and JSI-124 were used to investigate the function of IDO and pSTAT3 in MDSC-mediated T cell immunosuppression. Results:The protein levels of IDO and pSTAT3 in MDSCs were significantly upregulated. MDSCs obviously suppressed T-cell proliferation, which was reversed by 1-MT or JSI-124 (P<0.05). MDSCs could promote TGF-βand IL-10 secretions, but could also remarkably inhibit IFN-γsecretion (P<0.05). After incubation with 1-MT or JSI-124, the increase in TGF-βand IL-10, as well as the decrease in IFN-γ, was significantly reversed. Conclusion:The upregulated pSTAT3 induced the IDO increase in MDSCs. JSI-124 can block MDSC-mediated immunosuppressive effect on T cells in breast cancer.

Objective To evaluate the different expression of the serum proteome of patient with severe acute pancreatitis (SAP) before and after treatment,and search for the protein that can predict SAP improvement.Methods SELDI-TOF-MS was used to analyze the expression of serum protein spectrum of 20 SAP patients before treatment and 7 days after treatment,and make the APACHE Ⅱ score at the same time.Results The APACHE Ⅱ score was 10.70 ± 3.47 in patients with SAP 7 days after treatment,which were significantly lower than that before treatment ( 13.00 ± 2.21,P ＜0.05 ).One hundred thirty-two spectral peak clusters were detected before and after treatment,there were 27 proteins that had significantly different signal intensities had been detected from 2000 Da to 50000 Da (P ＜ 0.05 ).The peak cluster at 47 000 Dawas significantly down-regulated after SAP attenuation.While the peak clusters at 1l700 Da and 15900 Dawere significantly up-regulated after treatment.Conclusions Serum analysis with SELDI-TOF MS can detect the different expression of the SAP serum proteomics before and after treatment,the increased expression of the protein with molecular weight of 11500 Da and 15900 Da and the decreased expression of 4700 Da may be asignal of improvement of SAP.

BACKGROUND:Simple pedicle screw fixation for thoracolumbar fractures has better outcomes, but there are some deficiencies, such as poor applicability for severe compression or burst fractures, strong vertebral pain, easy to cause vertebral wound denervation and paraspinal muscle injury, and slow recovery. OBJECTIVE:To investigate the clinical effects of pedicle screw fixation combined with artificial bone graft for the treatment of thoracolumbar fractures. METHODS:A total of 126 patients with thoracolumbar vertebral compression fractures, who had undergone pedicle screw fixation without bone graft (control group,n=62) and with bone graft (test group,n=64) were enroled. The fracture healing, anterior vertebral height ratio, sagittal Cobb angle, and loss rate of vertebral height after 6 months were observed by X-ray in the two groups. RESULTS AND CONCLUSION:Al patients were folowed up, and had complete fracture healing after 12-16 months. The anterior vertebral height and Cobb angle were both improved in the two groups at 1 week after operation (P < 0.01), but there was no difference between the two groups (P > 0.05). New bone formation was observed in the test group at 6 months after operation, and patients were pain-free; but the speed of bone formation was slower in the control group, and patients stil suffered from painful thoracolumbar fractures. There was no difference in the loss of anterior vertebral height and Cobb angle between the two groups (P> 0.05). These findings indicate that pedicle screw fixation combined with artificial bone graft lead to a better recovery in thoracolumbar fractures.

Objective:To investigate the characteristics of event-related potentials(ERPs)P300 in the development of attention cognitive function of school-age children.Methods:A total of 180 school-age children were divided into 3 groups according to their ages (7-8 years old group with 48 cases, 9-10 years old group with 44 cases and 11-12 years old group with 48 cases). All of the participants completed an Oddball task, and their behavioral data, P3a and P3b components of ERPs were analyzed by SPSS 21.0.Results:(1)The differences of hit numbers(49(47.25, 50), 50(49, 50), 50(50, 50) ), correct reaction time((533.37±56.94) ms, (486.91±61.12) ms, (411.55±51.97) ms), and Omission errors (2(1, 4), 2(1, 3), 1(0, 2) ) among the three groups were statistically significant( F/χ 2=20.635, 54.477, 13.169, all P<0.01). (2)There was a main effect of age( F=3.884, P=0.023) and an interaction effect between age and condition( F=3.314, P=0.038) on the amplitude of P3a, while the main effect of condition was not significant( F=0.111, P=0.740). The amplitude of P3a component in 11-12 years old group ((11.02±6.00)μV) was significantly larger than that of 7-8 years old group ((7.36±4.48)μV) and 9-10 years old group ((7.76±5.17)μV, both P<0.05). However, there was no significant interaction effect between age and condition on P3a latency, P3b amplitude and latency ( P>0.05). Conclusion:P3a may be a sensitive indicator of cognitive function in school-age children, and the age of 11-12 years old is a sensitive period for the development of children's attention orientation and selection ability, which may be related to the development of brain network.

Objective:To observe and analyze the clinical characteristics and correlation between the eye and nervous system in children with infantile gangliosideosis.Methods:From November 2018 to January 2021, 3 children with infantile ganglion lipidosis diagnosed by genetic examination in the Department of Ophthalmology and Neurology, Beijing Children's Hospital of Capital Medical University, and through China National Knowledge Infrastructure and Wanfang database and The National Library of Medicine of the United States (PubMed) were searched, and 53 cases of Chinese infantile gangliosideosis diagnosed by gene, enzyme activity or pathological examination were selected and a total of 56 cases were included in the study. The searching time was from the establishment of the database to February 2021, and the search keywords are"gangliosideosis", "cherry-spot" macula and "Chinese". The demographic characteristics of 56 cases of children and other system manifestations were analyzed such as eyes, nervous system, skin, bones. According to the presence or absence of cherry-spot (CS) on the fundus examination, the children were divided into a fundus CS group (group A) and a fundus without CS group (group B), with 20 and 27 cases, respectively. The age of onset, gender, different types and neurological manifestations of the two groups of children were compared and analyzed. The non-parametric rank sum test was used for age comparison between groups; the χ2 test or Fisher's exact test were used for the comparison of gender, disease type and incidence between groups. Results:Among the 56 children, 27 were males and 29 were females; the median age of onset was 7.0 months. There were 33 and 23 cases of GM1 and GM2, respectively. Among 44 children with visual function examination records, 41 cases (93.2%, 41/44) were unable to follow the visual object. Of 47 children who underwent ocular fundus examination, 20 cases (42.6%, 20/47) had CS on the fundus. The main manifestations of the nervous system are neuromotor development regression or retardation (100%, 56/56), convulsions (58.1%, 25/43), and "startle" phenomena (89.7%, 26/29). Among 42 patients with brain magnetic resonance imaging examination records, 39 cases (92.9%) were abnormal. The incidence of "startle" and seizures in group A was higher than that in group B, and the difference was statistically significant ( χ2=5.815, 6.182, P=0.021, 0.013). Conclusios:Chinese infantile gangliosideosis is more common in GM1 type. Ocular visual impairment is the visual object as the main manifestation, the incidence of fundus CS is 42.6%, and the symptoms of neurological damage in children with CS are more severe.

Objective To investigate whether the vohage-gated chloride channel CLC-2 gene— CLCN2 is associated with idiopathic generalized tonie-clonic seizures(often called a grand mal seizure, GME)of Jinuo people and Han people from Yunnan province.Methods Three regions,including Intron 2, Exon 5 and Exon 19(Intron 18),of CLCN2 were selected to conduct sequence analysis.The case-control study design was used to detect association between gene polymorphism and idiopathic generalized tonic- clonic seizures of Jinuo people and Han people from Yunnan province.Results No previously reported susceptible mutations were found in Intron 2,Exon 5 and Exon 19 in Jinuo people and Han people from Yunnan province.However we found a single nucleotide polymorphism(SNP)at site 146 of Intron 18. Case-control study were carried out,using this SNP.Distribution of the 3 genotypes(TT,TC,CC)has a significant difference between the IGTCS patients of Han people and the normal controls of Han people(9, 3,29 cases and 22,9,26,respectively,x~2=16.079,P