目的 探讨晚发型阿尔兹海默病(LOAD)患者载脂蛋白E(apo E)基因多态性与血脂水平之间的关系.方法 采用基因芯片法检测150例LOAD患者(LOAD组)及150名体检健康者(正常对照组)apo E基因多态性,同时检测总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、小而密低密度脂蛋白胆固醇(sd-LDL-C)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白B(apo B)、脂蛋白(a)[Lp(a)]水平.采用多因素非条件Logistic回归分析筛选LOAD的相关危险因素.结果 LOAD组E2/3和E3/3基因型频率均低于正常对照组(P<0.05),E3/4和E2/4基因型频率均高于正常对照组(P<0.01).LOAD组ε3等位基因频率低于正常对照组(P<0.05),ε4等位基因频率高于正常对照组(P<0.01).与正常对照组比较,LOAD组TC、LDL-C和sd-LDL-C水平明显升高(P<0.01),HDL-C水平明显降低(P<0.01),其他血脂项目差异均无统计学意义(P>0.05).TC及LDL-C水平在LOAD组ε2、ε3和ε4表型患者中依次升高(P<0.05).正常对照组ε4表型LDL-C水平明显高于ε2表型(P<0.05).apo Eε4等位基因和LDL-C升高是LOAD发生的危险因素[比值比(OR)值分别为14.454、5.824,95％可信区间(CI)分别为5.793～16.368、2.582～7.973],HDL-C升高则是LOAD的保护因素(OR=0.020,95％CI为0.006～0.352).结论 apo E基因多态性与脂质代谢密切相关,ε4等位基因可能是LOAD发病的重要遗传因素之一.

目的 探讨从团队为基础(TBL)+从问题为中心(PBL)+以案例为基础(CBL)融合式教学法结合ISO15189相关要素在血栓与止血检验临床见习带教中的效果.方法 选择首都医科大学2014级临床医学专业五年制学生63例,七年制学生49例为研究对象,随机分为传统教学组和实验教学组.传统教学组采用讲授式教学模式(LBL),实验教学组采用TBL+ PBL+ CBL教学方法并结合ISO15189进行授课.观察教学效果及学生对教学方法的满意度.结果 实验组理论知识、操作技能和检验综合分析能力得分均高于传统组,差异有统计学意义(P＜0.05).实验组专业知识掌握程度、学习兴趣、团队协作、表达沟通能力、动手能力、ISO15189融入见习认可度等均高于传统组,差异有统计学意义(P＜0.05).结论 在血栓与止血检验见习带教中,融合式教学法结合ISO15189有利于提高教学效果,值得在实验诊断学的临床见习中推广.

目的 采用不同方法检测急性脑梗死患者血浆中蛋白C抗凝活性,并评价2种方法的相关性、一致性及临床可替代性.方法 收集294例临床血浆样本,用发色底物法和凝固法同时测定血浆中蛋白C抗凝活性,比较2组数据的相关性和一致性.结果 2种方法检测急性脑梗死患者蛋白C抗凝活性结果差异无统计学意义(P>0.05),具有良好的相关性,但二者一致性检验较差.结论 实验室在比较不同方法检测一致性时应采取多种方法从不同角度进行联合评价,以避免某一方法评价中局限性的影响,使评价结论更合理、客观.

目的 分析北京地区妇科门诊因生殖道感染就诊的患者沙眼衣原体(CT)和人类乳头瘤病毒(HPV)感染及HPV基因型的分布情况.方法 选取2016年12月至2017年12月于首都医科大学宣武医院妇科门诊患者的宫颈细胞标本1768例,分别采用实时荧光聚合酶链反应(PCR)法和PCR导流杂交法对CT、HPV病原体进行检测.结果 在1768例患者中,CT阳性率为11.1％(196/1768),HPV阳性率为29.6％(524/1768).HPV感染单一亚型者414例(79.0％),多重亚型者110例(21.0％).524例HPV阳性样本中,有122例C T检测阳性(23.3％),其中单一亚型者48例(39.3％),多重亚型者74例(60.7％),多重亚型患者阳性率明显高于单一HPV感染患者,差异有统计学意义(P<0.05).在HPV合并CT感染患者中,多重亚型感染最常见的HR-HPV 16型的阳性率为13.0％(35/270),其次为52型11.1％(30/270),58型35.1％(26/270),33型8.1％(22/270).HPV合并CT感染患者多重亚型的阳性率均高于单一HPV感染患者,差异有统计学意义(P<0.05).结论 对CT和HPV感染及HPV基因型的相关分析,进一步证明CT感染对于HPV的感染具有促进作用,预防和积极治疗C T感染对HPV感染的防治应具有积极意义,进而降低H PV感染诱发宫颈癌的可能性.

The pathological process of Alzheimer disease (AD) is closely related to energy metabolism disorders. In the nervous system, monocarboxylate transporter 4 (MCT4) is expressed in the glial cell membrane and is responsible for transporting intracellular lactic acid. In this study, we found that MCT4 expression was elevated in the cerebrospinal fluid of patients with mild cognitive impairment. Two- and three-month-old APPswe/PS1dE9 (APP/PS1) mice and C57 mice were studied. The APP/PS1 mice began to show cognitive decline at 3 months of age and MCT4 in the hippocampus of 2- and 3-month old APP/PS1 mice was higher than that of C57 mice. This change is similar to that in people with mild cognitive impairment. Subsequently, MCT4 overexpression/siRNA lentiviral particles were used to establish stable primary astrocytes. Overexpression and knockdown of MCT4 had no significant effect on glial cell apoptosis. Transfected astrocytes were co-cultured with neurons. Overexpression of cytoplasmic MCT4 increased the expression of Aβ42, γ-secretase, and CD147 in the co-culture system; in addition, the growth ability of primary neurons decreased significantly, extracellular lactic acid increased, and neuronal apoptosis increased. In AD model mice, siMCT4 injection improved cognitive ability, reduced neuronal apoptosis, and reduced γ-secretase expression. Taken together, these results suggest that MCT4 is involved in energy metabolism during early pathological processes in AD, and suppression of MCT4 represents a new potential neuroprotective factor for AD.

目的 研究餐后不同时间抗凝血酶Ⅲ(ATⅢ)、蛋白C(PC)、蛋白S(PS)活性测定结果的差异.方法 选择30名健康志愿者,分别检测其空腹、餐后2h、餐后4hATⅢ、PC、PS水平,对测得的结果分别进行比较.结果 与空腹相比,餐后2h、餐后4h血浆ATⅢ、PC、PS水平均降低,差异有统计学意义(P＜0.05);而餐后4h三种抗凝蛋白的活性比餐后2h有所升高,但其差异不显著(P＞0.05).结论 进食是ATⅢ、PC、PS活性水平的重要影响因素,为保证检测结果的准确性,应严格要求空腹采集标本.

目的 探讨网织红细胞(RET)在判断检验性失血影响程度中的作用.方法 选取自2015年6月至2016年9月在首都医科大学宣武医院住院的105例患者为研究对象,通过实验室信息管理系统(LIS)记录患者的基本情况、日均采血量、血红蛋白(HGB)及RET等数据.采用多元线性回归分析不同因素对RET差的影响;采用线性相关分析不同因素与患者住院期间贫血及HGB差间的关系.结果 住院期间,患者的年龄、首次HGB值与HGB差具有相关性(P<0.05);首次RET百分率、日均采血量与RET差具有相关性(P<0.05).52例患者的HGB在住院期间呈现先降低后升高,其中,RET下降10例(19.2%),RET上升42例(80.8%);35例患者的 HGB 在住院期间下降,其中,RET 下降5例(14.3%),RET 升高30例(85.7%);18例患者住院期间HGB前后变化范围不大或者呈现上升趋势.结论 检验性失血导致患者的HGB明显下降,通过HGB与RET相关指标的联合运用,能更好地评价检验性失血对患者的影响,指导临床治疗.

OBJECTIVE:To investigate the effect of monocarboxylate transporter 4 (MCT4) on the apoptosis and glucose metabolism of prostate cancer cells.METHODS:We constructed an adenoviral vector containing shRNA-MCT4 and transfected it into the adenocarcinoma cell lines DU145 and PC-3, using the untransfected vector as the blank control and the negative vector as the negative control (shRNA-NC). We determined the MCT4 expression, lactic acid secretion, glucose consumption and apoptosis rate in different groups of cells.RESULTS:After transfection, the expression of MCT4 in the DU145 and PC-3 cells was significantly lower in the shRNA-MCT4 than in the blank control (P = 0.008 and 0.008) and shRNA-NC groups (P = 0.007 and 0.009), and so were the secretion of lactic acid (P = 0.009 and 0.009; P = 0.009 and 0.008) and single-cell glucose consumption (P = 0.007 and 0.007; P = 0.009 and 0.007). The apoptosis rate of the DU145 cells was remarkably higher in the shRNA-MCT4 than in the blank control and shRNA-NC groups (［22.11 ± 2.68］% vs ［9.81 ± 1.24］% and ［10.01 ± 1.46］%, P = 0.003 and 0.003), and so was that of the PC-3 cells (［23.38 ± 3.08］% vs ［10.21 ± 1.58］% and ［10.91 ± 1.63］%, P = 0.004 and 0.004).CONCLUSIONS:Inhibiting the expression of MCT4 can interfere with the glucose metabolism and promote the apoptosis of prostate cancer cells. The MCT4 gene is a potential therapeutic target for the treatment of prostate cancer.

目的 探讨丁苯酞治疗帕金森病(PD)的效果及对氧化应激指标、核磁共振波谱的影响.方法 选取初次来该院住院治疗的PD患者64例,对照组32例给予常规美多芭治疗,研究组32例在对照组的基础上给予丁苯酞治疗,对两组患者行统一PD评定量表(UPDRS)评测、磁共振波谱检查,检测患者血中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、过氧化氢酶(CAT)、丙二醛(MDA)水平.结果 两组治疗后UPDRS评分均降低,且研究组低于对照组(P<0.05);与对照组比较,研究组治疗后SOD、GSH-PX、CAT水平均升高,MDA水平降低,磁共振波谱N-乙酰天门冬氨酸(NAA)/肌酸(Cr)及胆碱复合物(Cho)/Cr升高(P<0.05).结论 在口服美多芭治疗基础上联合应用丁苯酞对PD的治疗有更好的效果,其效果可能与丁苯酞调控抗氧化酶能力有关.

Abnormalities of autophagy can result in neurodegenerative disorders such as Alzheimer's disease (AD). Nevertheless, the regulatory mechanisms of autophagy in AD are not well understood. Here, we describe our findings that microRNA (miR)-299-5p functions as an autophagy inhibitor by suppressing Atg5 and antagonizing caspase-dependent apoptosis. We observed decreased levels of miR-299-5p both in primary neurons under conditions of starvation and in hippocampi of APPswe/PS1dE9 mice. Additionally, low levels of miR-299-5p were observed in cerebrospinal fluid of AD patients. MiR-299-5p treatment resulted in attenuation of Atg5 and autophagy in primary neurons from APPswe/PS1dE9 mice, N2a cells and SH-SY5Y cells, whereas antagomiR-299-5p enhanced autophagy. Atg5 was verified as a direct target of miR-299-5p by dual luciferase reporter assays. Furthermore, transfection of miR-299-5p into primary hippocampal neurons caused the attenuation of caspase-mediated apoptosis, which was reversed upon starvation-induced autophagy. Inhibition of autophagy by shRNA knockdown of LC3β reduced apoptotic neuron death induced by antagomiR-299-5p. Injection of agomiR-299-5p into the cerebral ventricles of AD mice inhibited both autophagy and apoptosis and also improved the cognitive performance of mice. Overall, our results suggest that miR-299-5p modulates neuron survival programs by regulating autophagy. Thus, miR-299-5p serves as a potential neuroprotective factor in AD.

The autophagy process is the major cellular degradation pathway for long-lived proteins and organelles. Dysfunction of autophagy may lead to several neurodegenerative disorders. However, the regulation and function of autophagy in sporadic Alzheimer's disease (SAD) remain unclear. In this study, we established SAMP8 mouse as a suitable SAD model and performed microarray profiling to identify miR-214-3p as a SAD associated microRNA that was downregulated in hippocampal neurons of SAMP8 mice upon the induction of autophagy. Furthermore, decreased miR-214-3p level was detected in cerebrospinal fluid from SAD patients. Overexpression of miR-214-3p in primary neurons from SAMP8 mice inhibited autophagy, demonstrated by decreased levels of LC3 beta II and Beclin1, and reduced number of GFP-LC3-positive autophagosome vesicles, and led to increased viability and decreased caspase-mediated apoptosis. Conversely, antagomiR-214-3p promoted autophagy and apoptosis in neurons from SAMP8 mice. Mechanistically, miR-214-3p negatively regulated Atg12 expression by targeting the 3'-untranslated region of Atg12. Treatment of SAMP8 mice with miR-214-3p attenuated neuronal apoptosis and improved behavioral performance. Taken together, these results suggest that miR-214-3p suppresses autophagy and alleviates hippocampal neuron apoptosis, which indicates that miR-214-3p represents a new potential neuroprotective factor for SAD. (C) 2016 Elsevier B.V. All rights reserved.

阿尔茨海默病(Alzheimer's disease,AD)是一种与年龄相关的进行性神经系统变性疾病,致残率高,且起病隐蔽、病程呈不可逆发展.因此,筛选并发现AD新的敏感和特异的生物标志物,尤其AD早期标志物,对提高AD患者生存率和生存质量意义重大,已成为AD早期诊断与治疗的关键.本文仅对AD蛋白生物标志物的研究现状综述如下.

OBJECTIVE:To investigate the prevalence and subtype distribution of human papillomavirus (HPV) infection and its correlation with age among women in Beijing urban area, and provide some epidemiological evidence for the clinical application of HPV vaccines. METHODS:We collected cervical specimens from 1999 women in the Outpatient Department of our hospital, performed genetyping of HPV-DNA, and analyzed the incidence of HPV infection in different age groups. RESULTS:HPV infection was detected in 502 (25.2%) of the 1999 women patients, with 391 (19.6%) cases of high-risk HPV, which included 326 (83.4%, 326/391) cases of single infection. HPV-16 was the most common type (21.2%, 69/326), followed by HPV-52 (19.3%, 63/326) and HPV-58 (16.0%, 52/326). The prevalence of HPV infection was the highest among the women aged 41 -50 years and the lowest among those over 60 years. CONCLUSION:The subtype- and age-specific distribution of HPV infection among women in Beijing urban area shows an obvious heterogeneity, which deserves due consideration in the clinical application of HPV vaccines.

<正>抗中性粒细胞胞浆抗体(anti-neutrophil cytoplastic antibody,ANCA)是针对存在于中性粒细胞和单核细胞胞质颗粒中的抗原的一组抗体,通常被认为是与中性粒细胞胞浆中的嗜苯胺蓝颗粒和特异性颗粒反应的自身抗体[1]。自1982年Da-vis首次报道以来,ANCA已逐渐成为系统性血管炎(systemic vasculitides,SV)诊疗的重要血清学标志物,在韦格纳氏肉芽

目的调查北京地区妊娠期女性人乳头瘤病毒(HPV)感染及基因型分布情况和特点。方法采用基因扩增合并导流杂交技术对北京地区296例妊娠期女性及167例非妊娠期健康女性进行21种HPV亚型分析。结果北京地区妊娠期女性HPV感染率为29.39%,其中高危型HPV-16、HPV-52、HPV-58、HPV-53感染率最高,占21种HPV亚型检出型别的百分率依次为29.17%、20.83%、12.50%、8.33%。3个年龄组感染率分别为40.00%、22.94%、36.36%。结论北京地区妊娠期女性HPV感染较为普遍,且以高危型为主,HPV亚型分布具有明显的地域特征。低龄段妊娠期女性感染率最高,应加强产后随访。

Objective: To determine the carbonic anhydrase IV auto-antibody,the level of cytokines and antioxidants in the patients with chronic heart failure(CHF).Methods: To determine the anhydrase IV auto-antibody,the level of 5 kinds of cytokines(IL-2,etc),6 kinds of antioxidants(SOD,etc) and erythrocyte sedimentation rate.Results: The level of anhydrase IV auto-antibody in CHF patients was significantly higher than those in the control group(P<0.05).The levels of SOD,GPx,CAT and TAC in CHF patients were significantly lower(P<0.05) while MDA level was significantly higher(P<0.05) than those in the control group.There was no significant difference of the levels of IL-3,IL-17,IFN-α and IFN-γ between CHF patients and the control group(P>0.05) while IL-2 level was significantly higher(P<0.05) than those in the control group.Conclusion: The change of the levels of cytokines may take part in the generation of carbonic anhydrase IV auto-antibody in CHF patients.

Objective: The exosomes of PC-12 cell mediums and blood samples from patients with mild cognitive impairment(MCI) and dementia of Alzheimer type(DAT) were extracted,and level of microRNA-135a(miRNA-135a) in the exosomes were determined.Methods: Extract the exosome of PC-12 cell mediums and blood samples from 7 MCI patients and 18 DAT patients and health control using ultracentrifugation method and then determine the level of miRNA-135a using real-time PCR.Results: MiRNA-135a were detected in PC-12 medium,serum and plasma.The levels of miRNA-135a in exosome from the serum and plasma of MCI and DAT patients were significantly lower than that of control group(P0.05),while the level of miRNA-135a in exosome from the serum and plasma of MCI patients were similar with the DAT group(P0.05).No correlation was observed between the levels of miRNA-135a in exosome of the serum and plasma from MCI and DAT patients(P0.05).Conclusion: The miRNA-135a exists in the exosome from blood and CSF.It is suggested that the miRNA detection of exosome may have potential value in the diagnosis of Alzheimer's disease.