目的:通过核磁共振氢谱技术(1H-NMR)分析阿尔茨海默病(AD)患者的血清代谢物,以期寻找AD稳定、可靠的早期诊断标志物.方法:将2014年4月至2016年4月就诊于乌鲁木齐市第四人民医院的AD患者50例作为AD组,纳入同期健康体检者50例作为对照组.应用1H-NMR检测其血清代谢物,采用正交偏最小二乘判别分析法分析代谢物的分布特征,并在构建代谢模型后,对两组的血清差异代谢物进行代谢通路富集分析.结果:与健康体检者比较,AD患者血清中亮氨酸、瓜氨酸、脯氨酸、异亮氨酸、蛋氨酸、缬氨酸、丙氨酸、β-葡萄糖、乳酸及极低密度脂蛋白等代谢产物的水平差异有统计学意义(P＜0.05).结论:AD患者血清氨基酸、糖及脂类代谢紊乱,尤以必需氨基酸较为明显,提示AD的发生与能量代谢失衡相关.

Objective:To investigate the effects of prolonged exposure time on the behavior and hypothalamus-pituitary-thyriod(HPT) axis in post-traumatic stress rats.Methods:Fifty female rats and fifty male rats were respectively divided into 5 groups according to the random number table( n=10 in each group): blank group, D1F group(exposed in trauma environment for 2 min, sampled immediately after exposure), D1Y group(exposed in trauma environment for 90 min, sampled immediately after exposure), D4F group(exposed in trauma environment for 2 min, sampled after trauma environment fear memory test on the fourth day), D4Y group(exposed in trauma environment for 90 min, sampling after fear memory test of trauma environment on the fourth day). The anxiety and fear behaviors of rats were measured by capture rejection test, and the serum levels of thyrotropin-releasing hormone(TRH), thyrotropin(TSH), free triiodothyronine(FT 3), and free tetraiodothyronine(FT 4) were measured by enzyme-linked immunosorbent assay(Elisa). Results:(1)The rejection degree of male D4Y group and male D4F group were lower than that of blank group((1.70±1.77)points, (0.80±1.23)points, (3.60±1.43)points, P<0.05). There was no difference between female D4F group and blank group( P>0.05), and the rejection degree of female D4F group was lower than that of blank group((0.90±1.29)points, (3.30±1.57)points, P<0.05). (2)The levels of FT 3 and FT 4 in male D4F group were higher than those in blank group( P<0.05). Compared with male D4F group, the levels of FT 3 in male D1F group, D1Y group and D4F group were lower( P< 0.05). Compared with male D4F group, the levels of FT 4 in male D1F and D1Y group were lower((12.19±0.97)pmol/L, (11.19±0.21)pmol/L, (11.24±0.73)pmol/L, P<0.05). Compared with female blank group, female D1F group and female D4Y group, TRH level of female D1Y group decreased( P<0.05). Conclusion:Prolonging the exposure time in the trauma environment can reduce the stress activity of HPT axis in male rats, and the anxiety and fear behavior tend to be more obvious, while for female rats, although the anxiety and fear behavior tend to be normal, the HPT axis should not be activated after trauma.

本文采用血清拉曼光谱方法探究了创伤后应激障碍(PTSD)的发病率与创伤环境中暴露时间长短相关联的原因与机理分析.在本实验中以大鼠为研究对象,测试了28例延长创伤环境暴露时间和27例非延长创伤环境暴露时间的大鼠血清样品.在被测大鼠血清拉曼光谱中特征峰的暂定分配表明各组之间的特定生物分子具有一定的差异性.采用主成分分析提取特征,用以减少高维光谱的维数,来提高判别模型的速率,并对提取后的特征分别采用BPNN,ELM和SVM进行分类,其中SVM算法又分别用线性核函数、多项式核函数和RBF核函数(高斯核函数)三种不同的核函数来建立模式识别模型.PCA-RBF-SVM取得的结果最好,准确率为94.5％.研究结果表明,不同创伤环境暴露时长的血清拉曼光谱存在明显的差异性,暴露时长使其化学或分子物质发生了改变,继而可能导致创伤后应激障碍的发病率发生变化.

目的 探讨精神分裂症与双相情感障碍患者的认知功能.方法 选择本院2015年4月-2016年6月收治的60例精神分裂症患者作为对照组,60例双相情感障碍患者作为研究组,通过对两组患者进行MATRICS共识认知成套测验(MCCB)进行认知功能检测,主要包括语言能力与操作能力的测试.结果 (1)两组患者的语言能力比较:通过比较后发现,研究患者中言语记忆、言语流畅、视觉记忆、情绪管理、迷宫等各项评分明显高于对照组,差异具有统计学意义(P<0.05);研究组患者语言能力总分明显高于对照组,差异具有统计学意义(P<0.05);(2)两组患者操作能力比较:通过比较后发现,研究患者中连线、空间广度、符号编码、持续操作、数字序列等各项评分明显高于对照组,差异具有统计学意义(P<0.05);研究组患者操作能力总分明显高于对照组,差异具有统计学意义(P<0.05).结论 精神分裂症与双相情感障碍的患者通过MCCB测试能有效的反映出认知功能的差异.

目的 探讨心境障碍患者自我病耻感程度,并对其相关因素进行总结分析.方法 收集乌鲁木齐市第四人民医院2015年1月-2016年1月间接收的患心境障碍的120例患者,通过精神疾病内在病耻感量表评估其自我病耻感情况,且分析不同特征患者的自我病耻感情况.结果 本组120例患者中,共有88例(73.33%)患者伴有病耻感,其中轻度59例,中度27例,重度2例.大专及大专以上文化者的ISMI总分较高中及高中以下文化者显著更低(t=2.4151,P=0.0173);处于发作期患者的ISMI总分较缓解期患者显著更高(t=2.0351,P=0.0441).年龄、HAMD评分和ISMI总分表现为正相关(P<0.05);受教育年龄和ISMI总分表现为负相关(P<0.05).结论 大多数心境障碍患者伴有自我病耻感,其相关因素包括男性、非在职、高龄、受教育程度较低及处于发作期等,临床需提高对以上患者病耻感的重视,多方面评估并及时进行干预.

目的 探讨氨磺必利与齐拉西酮治疗精神分裂症的临床疗效,及不良反应.方法 在本院于2015年2月-2016年3月所接收的患者中任选108例作为研究样本.齐拉西酮治疗的54例患者为对照组,氨磺必利治疗的54例患者为研究组,观察治疗状况,对比讨论,研究方式为前瞻性.结果 研究组治疗总疗效(90.74％)比对照组(77.78％)高,组间数据比较有统计学意义(P＜0.05).对比两组患者治疗前PANSS评分,包含精神病理、阴性症状、阳性症状、总分,组间数据无统计学意义(P＞0.05);各组间治疗后,PANSS评分对比,两组数据比较差异有统计学意义(p＜0.05).研究组不良反应总发生率7.41％比对照组20.37％低,组间数据有统计学意义(P＜0.05).结论 临床治疗精神分裂症疾病可考虑给予齐拉西酮或氨磺必利药物,此两种药物在精神分裂症疾病治疗上疗效相当,但氨磺必利药物的安全性相对来说稍微要高,发生不良反应的可能性小.

Objective To explore the relationship between cognitive impairment and carotid artery atherosclerosis in Uygur Alzhei-mer's disease(AD) patients.Methods Totally 180 AD patients were collected as AD group and 175 normal persons with similar age were ar-ranged as control group.The cognitive function was assessed by Mini-Mental State Examination(MMSE) and AD Assessment Scale-Cognitive portion(ADAS-Cog).The carotid artery atherosclerosis was measured by carotid artery ultrasound.Results Compared with those of control group,the scores of MMSE and ADAS-Cog,arteriosclerotic plaques,IMT in bilateral common carotid arteries(CCA) and right internal carotid artery(ICA)were significantly higher than those in AD group(P<0.05 or<0.01).Among all the related factors,IMT in bilateral CCA and right ICA were related to MMSE and ADAS-Cog remarkably(β=-0.871,0.642,0.572,-0.771,0.659,-0.512,P<0.05 or<0.01).Con-clusions Carotid artery atherosclerosis commonly occurs in Uygur AD patients,and meanwhile IMT in bilateral CCA and right ICA are close-ly associated with cognitive impairment.

Objective To observe the adipose-derived cytokine changes and aggravate cognitive impairment in olanzapine-induced obese rats caused by glucose metabolic disorder.Methods 20 rats fed with ordinary fodder were used as normal control group,olanzapine group of 20 rats fed with olanzapine(1.2 mg · kg-1) and ordinary fodder for 4 weeks.Successfully established experimental model rats induced by olanzapine after 4 weeks.Serum tumor necrosis factor α(TNF-α),interleukins 6 (IL-6) and C-reactive protein (CRP) contents were measured by Elisa.Serum glucose contents were determined by biochemical colorimetric method and blood lipid contents determined with automatic biochemical analyzer.Learning,memory capacity and escape latency were detected with Maze test.Results After administration 4 weeks,the levels of body weight,blood glucose and blood lipid in olanzapine group were higher than those in control group.The serum TNF-α((1.57±0.04) ng/ml),IL-6((127.47±11.38) pg/ml) and CRP ((2.68±0.06) mg/ml) in olanzapine group rised,compared with control group ((0.59±0.03) ng/ml,(96.58± 8.77) pg/ml and (1.86±0.04) mg/ml respectively),the differences were statistically significant(P＜0.05).Electric shocks and escape latency in olanzapine group were higher than those in control group (P＜0.05).The FBS had positive correlation with hs-CRP,IL-6 and TNF-α respectively (r=0.385,0.260,1.280; all P＜0.05).Conclusion Olanzapine can induce metabolic disturbance of blood glucose,blood hpid,and the increase of serum TNF-α,IL-6 and CRP levels in rats.Positive correlation is showed between TNF-of and FBS.Hyperglycemia can promote cell toxicity and leads to cognitive dysfunction in rats.

OBJECTIVE:To conduct meta-analyses of all published association studies on the HTR2C -759C/T (rs3813829) polymorphism and olanzapine-induced weight gain in schizophrenia patients and on the HTR2C -759C/T, -697G/C (rs518147) and rs1414334:C> G polymorphisms and olanzapine/clozapine/risperidone-induced metabolic syndrome in schizophrenia patients.METHODS:Eligible studies were identified by searching PubMed and Web of Science databases. Meta-analyses were performed using Cochrane Review Manager (RevMan, version 5.2) to calculate the pooled odds ratio (OR) and its corresponding 95% confidence interval (CI).RESULTS:Our meta-analyses revealed both a significant positive association between the rs1414334 C allele and olanzapine/clozapine/risperidone-induced metabolic syndrome and a marginally significant positive association between the -697C allele and the induced metabolic syndrome in schizophrenia patients, but no significant association between the -759C/T polymorphism and the induced metabolic syndrome in schizophrenia patients. Our analysis further revealed a pronounced trend toward a significant negative association between the -759T allele and high olanzapine-induced weight gain and a trend toward a significant positive association between the -759C allele and high olanzapine-induced weight gain in Caucasian schizophrenia patients.CONCLUSIONS:Our results support that HTR2C polymorphisms play a role in antipsychotic-induced metabolic disturbance. More association studies are needed to further elucidate association of different HTR2C polymorphisms and antipsychotic-induced metabolic disturbance.

Objective To study regulatory role of metformin hydrochloride combined with simvastatin in glycometaboism and,metabolism disorder of blood lipid and tumor necrosis factor-α(TNF-α)level in olanzapine-induced obese rats. Methods Sixty SD rats were randomly divided into three groups:model group,observation group(metformin hydrochloride combined with simvastatin)and control group,with 20rats in each group.Control group was fed with normal diet.In addition to the normal diet,model group received gavage with olanzapine(1.2mg/kg),and observation group received gavage with olanzapine(1.2mg/kg),metformin hydrochloride(0.75g/d)combined with simvastatin(10 mg/d).The rat models were established after 4weeks.The levels of fasting plasma glucose,blood lipid and TNF-αwere detected.Results The levels of fasting plasma glucose,total cholesterol,triacylglyserol,low density lipoproteincholesterol and TNF-αwere significantly higher in model group than those in control group and observation group(P 0.01),and high density lipoprotein-cholesterol was lower(P0.01).The levels of fasting plasma glucose,total cholesterol,triacylglyserol and low density lipoprotein-cholesterol were lower in observation group than those in control group(P0.01),and TNF-αshowed no significant difference between two groups(P0.05).Conclusions The combination of metformin hydrochloride and simvastatin can reduce the levels of plasma glucose and TNF-α,as well as regulate the blood lipid levels in the olanzapine-induced obese rats.

目的 观察奥氮平诱导性肥胖大鼠糖脂代谢紊乱和脂肪源性细胞因子之间的相互调控.方法 20只普通饲料喂养大鼠为对照组,20只奥氮平诱导(普通饲料喂养合并奥氮平1.2 mg/kg灌胃4周)肥胖大鼠为研究组.采用酶联免疫测定法测定两组大鼠血清中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)和C-反应蛋白(CRP)的含量,生化比色法测定血清葡萄糖(FBS)含量.结果 研究组大鼠的体质量超过对照组平均体质量20％ (P ＜0.05).研究组大鼠血糖及血清甘油三酯(TG)、总胆固醇(TC)和低密度脂蛋白(LDL-C)水平显著高于对照组(P＜0.05);高密度脂蛋白(HDL-C)水平低于对照组(P＜0.05).研究组大鼠血清TNF-α、IL-6和CRP水平在灌胃4周后升高,较对照组明显增加(P＜0.05).研究组大鼠TNF-α、IL-6水平与CRP水平呈正相关(r1=0.672,P1=0.025;r2=0.824,P2=0.036).结论 奥氮平可以导致大鼠体质量增加,糖脂代谢紊乱,血清TNF-α,IL-6和CRP分泌增加,TNF-α和IL-6浓度变化与CRP水平呈正相关.

目的 观察奥氮平诱导性肥胖大鼠血清和大脑纹状体肿瘤坏死因子-α (TNF-α)含量的影响.方法 40只SD雄性大鼠随机分为对照组和奥氮平组,各20只,前者采用普通饲料喂养,后者在普通饲粮喂养基础上灌胃奥氮平(1.2mg· kg1)4周建立奥氮平诱导肥胖大鼠.采用酶联免疫测定法测定血清中TNF-α的含量,生化比色法测定血清葡萄糖(FBS)含量,对脑组织采用HE染色观察形态学变化,采用免疫组织化学方法观察两组大鼠脑组织中TNF-α的表达.结果 与对照组比较,奥氮平组大鼠的体重、血糖、血脂和血清TNF-α水平和纹状体TNF-α蛋白表达均有不同程度的升高,差异有统计学意义(P＜0.01).结论 奥氮平可以导致大鼠体重增加,糖脂代谢紊乱,血清及纹状体TNF-α升高,通过调节TNF-α异常变化可能改善奥氮平诱导肥胖大鼠中枢摄食活动.

目的:观察多奈哌齐联合尼莫地平治疗阿尔茨海默病的临床疗效。方法:将60例阿尔茨海默病患者随机分为治疗组和对照组,对照组,多奈哌齐每晚5mg临睡前口服,4周后将剂量调整为每晚10mg临睡前口服;治疗组,多奈哌齐用法同对照组,同时联用尼莫地平30mg,每日早晚各1次口服。疗程为8周。治疗4周后评价简易精神状态检查表(MMSE)、日常生活活动量表(ADL)、不良反应及副反应量表(TESS)量表,将结果进行统计学处理。结果:两组MMSE及ADL量治疗后与治疗前相比均有所改善,治疗组与对照组比较,在MMSE评分上治疗组的疗效更显著,差异有统计学意义(P<0.05)。两组不良反应的发生率差异无统计学意义。结论:多奈哌齐联合尼莫地平用于治疗阿尔茨海默病疗效优于单独使用多奈哌齐。