1.Effect of NR2B antagonist on behavior and related signal proteins in a rat model of levodopa-induced motor complications
Maowen BA ; Min KONG ; Xuwen SUN ; Xiaotong WANG
Chinese Journal of Behavioral Medicine and Brain Science 2011;20(11):967-969
ObjectiveTo investigate the role of N-methyl-D-aspartate receptor subunit 2B (NR2B) antagonist CP-101.606 in behaviour and expression of related signal proteins in a rat model of levodopa-induced motor complications.MethodsThe hemi-parkinsonian rat model was produced by injecting stereotaxically 6-OHDA to right medial forebrain bundle.Then,rats were intraperitoneally treated with levodopa (50 mg/kg with benserazide 12.5 mg/kg,twice daily) for 22 days.On 23th day,rats received CP-101.606 before levodopa administration.Rotational duration was estimated.After sacrificed,phosphorylated NR2B and Ca2+/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) and glutamate receptor 1 ( GluR1S831 ) were observed by western blot.ResultsThe results showed that NR2B antagonist CP-101.606 reversed the levodopa-induced shortened rotational duration.Chronic levodopa treatment increased abundance of the phosphorylated NR2B and downstream related signal proteins CaMKⅡ and GluR1S831 to (145.3±6.5)% and (132.5±5.7)% and (105.6±6.3)%,respectively.Moreover,CP-101.606 could reduce hyperphosphorylation of NR2B and CaMKⅡ and GluR1 S831 to (102 ± 4.9 )%,(98.4±3.9)% and (49.5 ± 4.2 )%,respectively.ConclusionsThese results indicate that the enhancement of N-methyl-D-aspartate (NMDA) receptor function mediated by NR2B phosphorylation contribute to development of motor complications,through a mechanism that involved the downstream signal mediators of NMDA receptor overactivation.Pharmaceuticals which act to inhibit NR2B may be useful in the treatment of the motor complications in parkinsonian patients.
2.Analysis on the clinical characteristics of the schizophrenia to make troubles and accidents likely
Dezhi ZENG ; Xuwen FAN ; Quanxin SUN ; Leigang WANG
Chongqing Medicine 2013;(34):4123-4125
Objective To explore the clinical characteristics of the patients with schizophrenia to make troubles and accidents likely ,to provide scientific evidence for preventing and controlling these patients to make troubles and accidents effectively .Methods 100 patients with schizophrenia to make troubles and accidents likely were randomly extracted and assigned to the study group from psychiatric department of this hospital .100 ordinary patients were divided into control group .Their data on illness were sur-veyed and analyzed retrospectively .The difference of the general condition and illness data along with mental symptoms between the both group were compared .Results The proportion of patients to be man peasant ,in rural area ,no a spouse and medical insurance , to have a lower degree of culture and to be 20 - 39 years old in the study group was significantly higher than those in the control group(P< 0 .05) .The social support and economic conditions of family in the study group were significantly poorer than those in the control group(P< 0 .05) .The proportion of patients to be paranoid schizophrenia ,to have a complications and the positive score of the positive and negative syndrome scale (PANSS) in the study group were significant higher than those in the control group but the negative score of PANSS and the course of disease were significantly lower (P< 0 .05) .The proportion of patients to have posi-tive symptoms such as illusion and delusion in the study group were significantly higher than that in the control group (P< 0 .05) . But the proportion of patients to have negative symptoms such as avoid social and emotional dull in the study group were signifi -cantly lower than that in the control group(P< 0 .05) .Conclusion The positive symptoms contribute to making troubles and acci-dents in SP patients .The patients to be paranoid schizophrenia ,a man and peasant ,in prime of life ,in rural area ,no a spouse and to have a lower degree of culture maybe make troubles and accidents more likely .Having a poor social support and economic conditions of family and no medical insurance cause the probability of their making troubles and accidents increase .
3.The research on the property of GluR1 subunit in rat models of motor complication of Parkinson' s disease after CaMKⅡ inhibitor KN-93 treatment
Maowen BA ; Min KONG ; Guoping YU ; Xuwen SUN ; Zhuli LIU
Chinese Journal of Behavioral Medicine and Brain Science 2010;19(10):888-890
Objective To investigate the alteration of phosphorylated GluR1Ser831 and behavioural effects in a rat model of levodopa-induced motor complications after Ca2 +/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) inhibitor KN-93 treatment. Methods The hemi-parkinsonian rat model was produced by injecting stereotaxically 6-OHDA to right medial forebrain bundle. Then, rats were intraperitoneally treated with levodopa ( 50 mg/kg with benserazide 12.5 mg/kg,twice daily) for 22 days. On day 23 ,rats received KN-93 before levodopa administration. Rotational duration was estimated. After sacrificed, subcellualr distribution of GluR1 and phosphorylated GluR1Ser831 were observed by western blot. Results The study showed that CaMKⅡ inhibitor KN-93 prolonged rotational duration. Moreover, KN-93 could regulate subcellular distribution of GluR1 and reduce hyperphosphorylation of GluR1 Ser831, which was closely associated with levodopa-induced motor complications. The expression of membrane GluR1 and phosphorylated GluR1Ser831 was (83.4 ±4.2)% and (47.2 ±5.2)% ,respectively. Conclusions These results indicated that activation of CaMKⅡ contributed to development of motor complications, through a mechanism that involved an increase in phosphorylated GluR1 Ser831. Pharmaceuticals which act to inhibit CaMKⅡ may be useful in the treatment of the motor complications in parkinsonian patients.
4.Clinical characteristics of epidemic Japanese encephalitis in adults
Fuxia SONG ; Xuwen SUN ; Bing LI ; Chuanyu LIU
Chinese Journal of Neurology 2010;43(2):118-121
Objective To study the clinical characteristics of epidemic Japanese encephalitis in 4 adult patients and to improve the level of diagnosis.Methods The clinical characteristics, laboratory results and MRI features of 4 adult patients with epidemic Japanese encephalitis hospitalized in our hospital between 2007 and 2008 was retrospectively reviewed and analyzed.Results All patients were sporadic.Two were female and others were male with the age from 34 to 68 years old and onset in summer and autumn.One patient had diarrhea at onset while others had fever and headache at onset.All patients had high fever and psychiatric symptoms.Two patients had respiratory failure.Obvious elevation of white cells in cerebrospinal fluid was seen in all patients and Japanese viral antibody of IgM was all positive whereas the image of MRI was abnormal only in one patient.Two patients had neurological sequelae.Conclusions The clinical manifestations of epidemic Japanese encephalitis in adults are severe and untypical and the respiratory failure is likely to occur.
5.Effects of transcranial magnetic stimulation on the learning and memory abilities of those with cerebral infarction
Chuanyu LIU ; Surong ZHOU ; Xuwen SUN ; Zhuli LIU ; Hongliang WU ; Yuanwu MEI
Chinese Journal of Physical Medicine and Rehabilitation 2011;33(1):6-9
Objective To study the effects of transcranial magnetic stimulation (TMS) on learning and memory, and angiogenesis and the dendritic structure of hippocampal CA3 pyramidal neurons after cerebral infarction. Methods Forty-eight male Sprague-Dawley rats were divided into a sham operated group, a model group and a TMS group (n = 16). Rat models of focal cerebral infarction were established with unilateral middle cerebral artery (MCA) suture occlusion in the model and TMS groups. The rats of the TMS group were given 4 weeks of TMS treatment beginning 1 day after the infarction (2 times per day, 30 pulses per time). Their learning and memory abilities were tested with a Y-maze. Angiogenesis and the dendritic structure of their hippocampal CA3 pyramidal neurons were detected after 4 weeks. Results Compared with the model group, learning and memory improved significantly in the TMS group. The average microvessel density of the hippocampus in the TMS group was significantly more than in the model group. The total length of apical dendrites of hippocampal CA3 pyramidal neurons in TMS group was significantly longer than in the model group. Conclusions The improved learning and memory observed following TMS treatment are likely to be related to changes in angiogenesis, the dendritic.structure of the hippocampal CA3 pyramidal neurons, and enhanced synaptic plasticity.
6.Polymethylmethacrylate augmentation of bone cement injectable cannulated pedicle screws was used to treat degenerative lumbar scoliosis with osteoporosis
Haolin SUN ; Chunde LI ; Xuwen LI ; Xiaodong YI ; Hong LIU ; Hailin LU ; Hong LI ; Zhengrong YU ; Yu WANG
Journal of Peking University(Health Sciences) 2017;49(2):256-261
Objective:To describe the application of polymethylmethacrylate (PMMA) augmentation of cement-injectable cannulated pedicle screws for the treatment of degenerative lumbar scoliosis with osteoporosis.Methods: Retrospective cohort study was used to compare cement injectable cannulated pedicle screws (CICPs) group with PMMA augmentation and control group with traditional method in the correction surgery for Lenke-silva level Ⅲ and level Ⅳ degenerative scoliosis cases with osteoporosis.Both groups were followed up for 1 year.The clinical results were assessed by visual analog scale (VAS) of pain on lumbar and lower limbers,Oswestry disability index (ODI) score and EuroQol-5 dimensions (EQ-5D) score.The coronal major curve Cobb angel in coronal plane and thoracic kyphosis Cobb angle,lumbar lordosis Cobb angle and sagittal vertical axis (SVA) in sagittal plane were tested in whole long spine X ray.The fusion rates were evaluated by lumbar X ray and dynamic X ray.Results: In this study 34 cases were enrolled,15 cases in CICPs group and 19 cases in control group.The general characteristics including age,gender,weight,height,BMI and BMD were without statistical difference between the two groups.There were (5.7±2.2)PMMA augmentation screws in CICPs group.The operation time,blood loss and blood transfusion were higher in CICPs group than in control group,but without statistical difference.Lumbar VAS,lower limbers VAS,ODI score and EQ-5D were all better in 1 month post-operation,6 months postoperation and 1 year postoperation than in preoperation in both groups.lumbar VAS scores of CICPs group in 6 months postoperation(CICPs group 3.1±1.3 vs.control group 4.4±1.4,P<0.01) together with lumbar VAS scores (CICPs group 3.3±1.0 vs.control group 5.2±1.4,P<0.01),ODI scores (CICPs group 22.7±17.2 vs.control group 31.4±18.5,P<0.01) and EQ-5D in 1 year postoperation (CICPs group 2.9±2.0 vs.control group 3.5±2.5,P<0.01)were lower than those of control group.The coronal major curve Cobb angels were all lower in 1 month postoperation,6 months postoperation and 1 year postoperation than in preoperation in both groups;thoracic kyphosis Cobb angle and lumbar lordosis Cobb angle were all higher in 1 month postoperation,6 months postoperation and 1 year postoperation than in preoperation in both groups.The coronal major curve Cobb angel was lower in CICPs group than that in control group in 1 year postoperation (CICPs group 17.6°±6.9° vs.control group 21.2°±7.2°,P<0.01)and thoracic kyphosis Cobb angle was higher in CICPs group than that in control group in 6 months postoperation (CICPs group-33.5°±8.8 °vs.control group-28.9°±8.3°,P<0.01)and 1 year postoperation(CICPs group-33.0°±8.1° vs.control group-26.3°±7.4°,P<0.01) together with lumbar lordosis Cobb angle were higher in CICPs group than that in control group in 1 year postoperation(CICPs group 26.4°±8.1° vs.control group 22.1°±7.3°,P<0.01).Conclusion: Polymethylmethacrylate augmentation of bone cement-injectable cannulated pedicle screws for the treatment of degenerative lumbar scoliosis with osteoporosis was effective and safe,the short-term clinical result was good.
7.Studies on methyl xestopongoate analogues:design, synthesis and antitumor activities
Dongyu SUN ; Jingxu GONG ; Xuwen LI ; Guanying HAN ; Yuewei GUO
Journal of China Pharmaceutical University 2018;49(4):413-421
Fifty-two methyl xestospongoate analogues were designed, synthesized and evaluated for the antiproliferative activity. Starting from alkynyl methyl ester and diyne, methyl xestospongoate analogues 4(a-m)-7(a-m)were synthesized by Cadiot-Chodkiewitz coupling and Sonogashira coupling reactions. Their structures were identified by 1H NMR, 13C NMR and HREI-MS. The cytotoxic inhibiton activities in vitro of some compounds were evaluated against human cancer cells A549 and P-388 by a CCK-8 method. Among them, compound 6k exhibited potent cell growth inhibitory activity against A549 and P-388 cancer cells, with IC50 values of 9. 36 and 9. 62 μmol/L, respectively.