早期活动对脑梗死患者运动功能及日常活动能力的恢复作用

<正>脑梗死又称缺血性脑卒中,是由多种原因造成的局部脑组织区域血液供应障碍,导致患者的脑组织出现缺血缺氧性的坏死,最终可能会导致患者出现瘫痪、失语等后遗症状~([1-3])。多数研究~([4-5])表明,早期康复对脑梗死患者神经功能恢复具有积极的作用~([6])。本研究探讨早期活动对脑梗死患者运动功能及日常活动能力的恢复作用,现报告如下。     

脑源性神经营养因子Val66Met功能基因多态性与环境因素对抗抑郁剂临床疗效的影响

Objective To explore the effect of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism,environmental factor and their interactions on antidepressant treatment.Methods 340 patients of major depressive disorder (MDD) who met the diagnosis criteria of MDD ( DSM-Ⅳ Axis Ⅰ) were recruited.280 patients of them were finished 12 weeks antidepressant treatment.The severity of depression was measured with the Hamilton Depression Rating Scale (HDRS) before and after 12 weeks antidepressant treatment.Childhood Trauma Questionnaire,28-item Short Form (CTQ-SF) and Life Events Scale (LES) were used to evaluate childhood adverse and life stress before onset.Genotyping of BDNF Val66Met polymorphism was detected by Illumina GoldenGate assays.Results Male patients proportion were significantly higher in non-remitters than remitters (P =0.008 ).After adjusting by gender, the frequencies of genotype and allele for the BDNF Val66Met polymorphism were no significant difference between remitters (AA: AG: GG = 28: 79: 40, A:G = 135:159 ) and non-remitters (AA: AG: GG = 29:81:23 ,A: G = 139:127 ) (P ＞0.05 ).There was no significant difference of CTQ scores and LES scores between the two groups (P＞0.05 ).The regression analysis showed that social intercourse problem and age were the risk factor for the severity of depression.The gender, HDRS baseline scores and mental disorder family history were associated with the efficacy of 12 weeks antidepressant.However,there was no significantly relationship between the interaction of BDNF Val66Met polymorphism and environment with the antidepressant treatment.Conclusion The older men with the mental disorder family history, severe depression symptom would be less-response to antidepressant treatment.However, BDNF Val66Met polymorphism, childhood trauma, life events stress and the interaction of BDNF Val66Met polymorphism and environment have no significantly effect on the 12 weeks antidepressant treatment.     

脑源性神经营养因子Val66Met功能基因多态性与环境因素对抗抑郁剂临床疗效的影响

Objective To explore the effect of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism,environmental factor and their interactions on antidepressant treatment.Methods 340 patients of major depressive disorder (MDD) who met the diagnosis criteria of MDD ( DSM-Ⅳ Axis Ⅰ) were recruited.280 patients of them were finished 12 weeks antidepressant treatment.The severity of depression was measured with the Hamilton Depression Rating Scale (HDRS) before and after 12 weeks antidepressant treatment.Childhood Trauma Questionnaire,28-item Short Form (CTQ-SF) and Life Events Scale (LES) were used to evaluate childhood adverse and life stress before onset.Genotyping of BDNF Val66Met polymorphism was detected by Illumina GoldenGate assays.Results Male patients proportion were significantly higher in non-remitters than remitters (P =0.008 ).After adjusting by gender, the frequencies of genotype and allele for the BDNF Val66Met polymorphism were no significant difference between remitters (AA: AG: GG = 28: 79: 40, A:G = 135:159 ) and non-remitters (AA: AG: GG = 29:81:23 ,A: G = 139:127 ) (P ＞0.05 ).There was no significant difference of CTQ scores and LES scores between the two groups (P＞0.05 ).The regression analysis showed that social intercourse problem and age were the risk factor for the severity of depression.The gender, HDRS baseline scores and mental disorder family history were associated with the efficacy of 12 weeks antidepressant.However,there was no significantly relationship between the interaction of BDNF Val66Met polymorphism and environment with the antidepressant treatment.Conclusion The older men with the mental disorder family history, severe depression symptom would be less-response to antidepressant treatment.However, BDNF Val66Met polymorphism, childhood trauma, life events stress and the interaction of BDNF Val66Met polymorphism and environment have no significantly effect on the 12 weeks antidepressant treatment.     

ABCBl基因rsl045642位点多态性与文拉法辛疗效的关联研究

目的：探讨ABCB1基因rs1045642位点多态性对抗抑郁剂文拉法辛疗效的影响。方法：纳入统计的89例抑郁症患者服用抗抑郁剂文拉法辛75～150 mg并随访6周,其中88例随访8周。使用汉密尔顿抑郁17项量表（ HAMD-17）评定抑郁症状的严重程度和治疗效果。采用基因芯片检测ABCB1基因的单核苷酸多态性（ SNPs） rs1045642,并通过Unphased3.0.13软件分析rs1045642位点与文拉法辛疗效的关联性。结果：（1）6周有效组和无效组间在性别、年龄、教育程度、家族史、发病次数及HAMD-17项基线分数之间差异无统计学意义（均P＞0.05）。（2）8周痊愈组和未痊愈组间性别、年龄、教育程度、家族史、发病次数及HAMD-17项基线评分之间差异无统计学意义（均 P ＞0.05）。（3）单个位点的关联分析发现, ABCB1基因rs1045642位点的基因型和等位基因分布频率在有效组、无效组间和痊愈组、非痊愈组间差异无统计学意义（均P＞0.05）。结论：ABCB1基因rs1045642位点多态性与抗抑郁剂文拉法辛疗效无显著相关,尚需在更加同质、更大样本中进一步验证。     

抗抑郁剂治疗效应基因组学研究进展

抑郁症是以持续情绪低落、兴趣减退、精力缺乏等为核心症状,常伴有各种认知障碍、行为紊乱及躯体症状的心境障碍[1],其终生患病率10%～20%,自杀率高达10%～25%,给患者、家庭和社会带来精神和经济上的沉重负担,抗抑郁剂临床应用显著改善了抑郁症的病程与预后,但仍有约30%～50%的患者治疗无显效甚至无效.基因遗传差异是抗抑郁剂临床疗效存在个体差异的重要原因之一.本文综述抗抑郁剂治疗效应基因组学研究现状与进展.     

血清MBP、MMP-9水平与脑白质疏松症的相关性

目的 探讨血清髓鞘碱性蛋白(MBP)、基质金属蛋白酶-9 (MMP-9)水平与脑白质疏松症(LA)的相关性。方法 选取2018年1月至2020年12月南京医科大学附属无锡市人民医院神经内科门诊治疗的77例LA患者为LA组,同期40例体检健康者为对照组。对比两组血清MBP、MMP-9水平差异,分析两项指标与LA病变程度的相关性,评估MBP、MMP-9对LA的诊断价值。结果LA组患者血清MBP、MMP-9水平高于对照组(P<0.05),随着病变程度的加重,LA患者血清MBP、MMP-9水平呈明显升高趋势(P<0.05)。LA患者血清MBP、MMP-9水平与Fazekas评分呈正相关,且与MoCA评分呈负相关(^均P<0.05)。血清MBP、MMP-9对LA诊断的AUC为0.801、0.790。Logistic分析显示,血清MBP、MMP-9高表达是LA发生的独立危险因素(P<0.05)。结论 血清MBP、MMP-9水平与LA的发生及病变程度密切相关,两项指标可作为LA诊断的参考指标。     

MTHFR基因多态性对于抗抑郁剂疗效的影响

目的 探讨亚甲基四氢叶酸还原酶(methylenetet rahydro folate reductase,MTHFR)基因多态性对于抗抑郁剂疗效的影响.方法 纳入281例服用单一抗抑郁药物的患者并随访6周,其中275例随访8周.使用汉密尔顿抑郁17项量表(HAMD-17)评定抑郁症状的严重程度和治疗效果.采用基因芯片检测MTHFR基因的单核苷酸多态性,并用Unphased 3.0.13软件分析单个单核苷酸多态性位点及其单倍型与抗抑郁疗效的关联性.结果 6周有效组和无效组间性别、年龄、教育程度、家族史、发病次数及抗抑郁剂种类之间差异无统计学意义,但两组间HAMD-17项基线分数有显著统计学意义(t=2.891,P=0.004);8周痊愈组和未痊愈组间年龄、教育程度、家族史、HAMD-17项基线评分及抗抑郁剂种类之间差异无统计学意义,但未痊愈组中男性患者比例显著高于痊愈组(t=2.381,P=0.018),且发病次数更多(t=-1.983,P=0.049).通过单个位点的关联分析发现,MTHFR基因位点A1298C(rs1801131)和C677T(rs1801133)与抗抑郁疗效无显著关联(P＞0.05).单倍型关联分析发现,在总体组(x2=11.39,P=0.0007)、男性亚组(x2=8.767,P=0.003)和5-羟色胺-去甲肾上腺素再摄取抑制剂亚组(x2=10.51,P=0.001)中,MTHFR基因rs1801131和rs1801133构成的单倍型A-C型抗抑郁疗效更显著.结论 MTHFR基因多态性可能与抗抑郁药疗效相关,其中rs1801131和rs1801133构成的A-C单倍型携带者抗抑郁剂疗效更为显著,尤其是在男性和使用5-羟色胺-去甲肾上腺素再摄取抑制剂类药物的人群中.     

脑源性神经营养因子Val66Met功能基因多态性与环境因素对抗抑郁剂临床疗效的影响

目的 探讨脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)Val66Met功能基因多态性和环境因素及其相互作用对抗抑郁剂治疗抑郁症临床疗效的影响.方法 按照美国诊断和统计手册第4版(DSM-Ⅳ)入组340例抑郁症患者,其中280例完成12周抗抑郁剂治疗.治疗前后采用汉密尔顿抑郁量表(HDRS)评定抑郁严重程度和治疗疗效,采用儿童期创伤问卷(CTQ-SF)及生活事件量表(LES)分别评定早期负性生活事件及发病前应激事件刺激量,采用Illumina GoldenGate定制芯片分析患者BDNFVal66Met基因多态性并进行基因分型.结果 抑郁症未痊愈组患者中男性比例显著高于痊愈组(P=0.008).痊愈组BDNF Val66Met基因型分布(AA:AG:GG=28:79:40),等位基因分布(A:G=135:159)与未痊愈组中基因型分布(AA:AG:GG=29:81:23)和等位基因分布(A:G=139:127),经性别校正后差异无统计学意义(P＞0.05).将患者分为首发患者和复发患者,均未发现BDNF Val66Met基因型和等位基因分布频率在2组间差异有显著性(均P＞0.05).儿童期创伤问卷及生活事件量表分值2组间差异无统计学意义(P＞0.05);多元回归分析显示患者年龄和LES社交问题分值进入回归方程,是影响抑郁严重程度的主要因素,而Logistic回归分析显示患者性别、HDRS基线分值及精神疾病家族史进入回归方程,是抗抑郁剂近期疗效的影响因素(均P＜0.05).多因素Logistic回归模型分析显示BDNF Val66Met基因型及各量表赋值交互作用对抗抑郁剂疗效影响并无统计学意义(均P＞0.05).结论 伴有精神疾病家族史、抑郁症状严重、年龄较大的男性抑郁症患者近期疗效差,但BDNF Val66Met功能基因多态性、早期负性生活事件及其相互作用不是抗抑郁剂疗效的主要影响因素.     

脑源性神经营养因子Val66Met功能基因多态性与抗抑郁剂疗效

目的：探讨脑源性神经营养因子（BDNF）Val66Met功能基因多态性与抗抑郁剂临床疗效的相关性。方法：302例抑郁症患者给予抗抑郁剂治疗8周。于治疗前和治疗2、4、6、8周后采用汉密尔顿抑郁量表（HAMD）评定抑郁严重程度和疗效。以治疗后HAMD总分≤7分为临床痊愈,将302例患者分为痊愈组160例和未痊愈组142例,抽取患者静脉血,采用Illumina GoldenGate定制芯片分析BDNFVal66Met基因多态性并进行基因分型。结果：痊愈组基因型分布A/A31例（19.4%）、A/G92例（57.5%）和G/G37例（23.1%）,未痊愈组分别为28例（19.7%）、78例（54.9%）和36例（25.4%）（χ2=0.054,P=0.817）;痊愈组等位基因频率分布A154例（48.1%）和G166例（51.9%）,未痊愈组分别为134例（47.2%）和150例（52.8%）（χ2=0.247,P=0.884）。3种BDNFVal66Met基因型患者间在性别、年龄、受教育年限、病程、发病次数、有无精神疾病家族史、HAMD基线及减分率上差异均无统计学意义（P均〉0.05）。结论：BDNFVal66Met基因多态性不是影响抗抑郁剂治疗近期疗效的主要因素。     

帕金森病患者脑白质病变程度与血浆神经轴突导向因子1的相关性

目的 探讨帕金森病（PD）患者脑蛋白质病变程度与血浆神经轴突导向因子1（Netrin-1）的相关性。方法 选取2018年1月—2021年12月在南京医科大学附属无锡人民医院治疗的PD患者100例（PD组）。另取同期该院健康体检者100例作为对照组。比较两组血浆Netrin-1水平，分析不同脑白质病变程度PD患者血浆Netrin-1、H-Y分级、UPDRS-Ⅲ评分和MMSE评分。结果 PD组血浆Netrin-1低于对照组（P <0.05）。PD组H-Y分级、UPDRS-Ⅲ评分和MMSE评分中重度患者高于正常或轻度患者（P <0.05）。中重度PD患者H-Y分级、UPDRS-Ⅲ评分高于正常或轻度患者（P <0.05），血浆Netrin-1、MMSE评分低于正常或轻度患者（P <0.05）。血浆Netrin-1水平与脑白质病变程度（r_s =-0.574、P =0.003）、UPDRS-Ⅲ评分（r =-0.379，P =0.012）呈负相关，与MMSE评分呈正相关（r =0.377，P =0.010），与H-Y分级无相关性（r =0.110，P =0.223）。血浆Netrin-1水平诊断中重度脑白质病变的截断值为123.67 ng/L，ROC曲线下面积为0.856（95% CI：0.785，0.928），敏感性和特异性分别为81.60%（95% CI：0.725，0.892）和78.40%（95% CI：0.703，0.885）。结论 PD患者血浆Netrin-1水平明显降低，与患者脑白质病变程度呈负相关，在诊断脑白质病变程度方面有一定应用价值。