目的:分析伴精神行为症状(BPSD)的高龄痴呆患者抗精神病药使用情况.方法:采用回顾性分析方法,根据是否应用抗精神病药治疗,将住院治疗的伴BPSD的80岁以上痴呆患者分为抗精神病药组(56例)和非抗精神病药组(34例),比较两组间安全性.结果:抗精神病药组中血管性痴呆患者的比例(32.1％)明显高于非抗精神病药组(8.8％)(χ2=6.43,P<0.05);不同痴呆类型的患者间奥氮平、喹硫平、利培酮、阿立哌唑、氟哌啶醇的药物剂量比较,差异无统计学意义(P均>0.05).不同痴呆类型间发生不良事件的比较,差异无统计学意义(P均>0.05).结论:应用小剂量抗精神病药治疗伴有BPSD的高龄痴呆患者未升高不良事件发生的风险.

Objective:To explore the correlation between the prevalence of Beijing genotype Mycobacterium tuberculosis ( M. tb) and the resistance of anti-tuberculosis drugs in the initial treatment and retreatment patients with tuberculosis in Beijing. Methods:A total of 1 140 cases of Mycobacterium tuberculosis clinical strains from various districts in Beijing were randomly collected.The drug susceptibility test was carried out by proportional method.The Beijing genotype and non-Beijing genotype Mycobacterium tuberculosis were identified by Spoligotyping method.Statistical methods were used to analyze the association between drug resistance and the prevalence of Beijing genotypes.Results:Among the tuberculosis patients with initial treatment, the percentages of strains resistant to isoniazide, amikacin, capreomycin, para-aminosalicylic among Beijing genotype family strains were significantly lower than those among non-Beijing genotype strains ( χ2=2.670, 15.282, 16.219, 22.676, all P<0.05). Among the retreatment tuberculosis cases, the percentages of strains resistant to amikacin and para-aminosalicylic among Beijing genotype family strains were significantly lower than those among non-Beijing genotype strains ( χ2=15.167, 4.574, all P<0.05), the percentage of multidrug-resistant tuberculosis among Beijing genotype family strains was significantly lower than that among non-Beijing genotype strains ( χ2=7.046, P<0.05). Conclusions:There are different associations between the prevalence of Beijing genotypic Mycobacterium tuberculosis and the occurrence of the resistance to anti-tuberculosis drugs in initial treatment and retreatment cases.There are associations with the occurrence of drug resistance to isoniazide, amikacin, capreomycin and para-aminosalicylic in initial treatment cases, while there are associations only with the occurrence of drug resistance to amikacin and para-aminosalicylic in retreatment cases.Meanwhile, the percentage of multidrug-resistant tuberculosis occurred from Beijing genotypic strains is lower in retreatment cases.

目的 分析北京血液中心血浆报废的原因,在此基础上探讨有效的预防办法.方法 通过回顾性研究,对2014-2018年北京市血液中心制备的血浆相关数据采取独立样本采用秩和检验进行分析.结果 2014-2018年北京市血液中心成分科共制备血浆总数为1248817袋,报废总数为39124袋,总报废率为3.13％.因检测因素报废的占68.78％(26910/39124),非检测因素报废的占31.22％(12214/39124),2014-2018年检测因素报废率和非检测因素报废率间的差异有统计学意义(P=0.009).因梅毒检测报废率为19.08％,是血浆报废的首要原因,其次是丙型肝炎抗体(HCV-Ab)有反应性或可疑,报废率为14.36％,再次为因谷丙转氨酶(ALT)检测不合格,占血浆报废总数的13.47％;在因非检测因素报废的血浆中,血浆报废的主要原因是破损(13.15％),其次是乳糜(12.72％),再次是溶血与质量抽检,分别占1.92％、1.21％.结论 基于血浆报废的常见原因,应采取相应措施从各个方面确保血浆的质量,降低血浆的报废率.

目的 评价抗抑郁药治疗精神分裂症抑郁疗效与安全性.方法 系统检索万方数据库、维普中文科技期刊数据库、中国生物医学文献数据库和中国学术期刊全文数据库,检索时间截至201 7年9月1 7日,检索关键词为"精神分裂症""抑郁""随机""对照".根据纳入标准及排除标准筛选文献,选取治疗前后汉密尔顿抑郁量表(HAMD)减分值为主要疗效指标,简明精神病性评定量表(BPRS)或阳性和阴性综合征量表(PANSS)减分值为次要疗效指标.结果 共纳入1 0项随机对照研究,844例患者.Meta分析结果显示:疗效方面,研究组治疗前后HAMD减分值高于对照组(P＜0.01 );不同抗抑郁药的研究组疗效均优于对照组(P＜0.01 ).研究组和对照组治疗前后PANSS、BPRS减分值比较差异无统计学意义(P＞0.05).安全性方面,研究组与对照组治疗后TESS分值比较差异无统计学意义(P＞0.05 ).结论 精神分裂症抑郁患者应用抗抑郁药可改善抑郁症状,无恶化精神病性症状的风险,且耐受性良好.鉴于纳入研究局限性,结论仍需谨慎看待.

Objective:To study the situation of recurrent tuberculosis in Beijing, and clarify the percentage of relapse and reinfection among recurrent tuberculosis.Methods:A retrospective study was conducted, which included 4 694 tuberculosis cases collected randomly from each districts and countries in Beijing.The patients who had experienced two tuberculosis treatment episodes, interval for at least six months, with cure being the outcome of the first episode, were selected as recurrent cases.The data of recurrent tuberculosis cases were analyzed by statistical analysis, to seek the risk factors associated with recurrence.The type of recurrence tuberculosis clinical isolated strains was identified by variable number of tandem repeats.Results:Tuberculosis recurred in 265 of the 4 694 successfully treated tuberculosis patients, the recurrence rate was 6.7%.Those people in the 30-59-year old group compared with other age group ( OR=1.780, 95% CI: 1.406-2.255, P<0.05), and those retreated for pulmonary tuberculosis compared with primary treatment tuberculosis ( OR=1.032, 95% CI: 1.010-1.054, P<0.05) were more likely to have tuberculosis recurrence.Among paired recurrent cases, 64% (37/58) recurrent cases had identical genotypic patterns, indicating a relapse, 36% (21/58) had different genotypes, indicating reinfection by a new strain. Conclusions:In Beijing, those people who are 30-59-year old or retreated for pulmonary tuberculosis are more likely to have tuberculosis recurrence.It is indicated that relapse is more common than reinfection in recurrent tuberculosis cases in Beijing, but exogenous reinfection and recent transmission still happen.

目的 探讨维拉帕米联合氯沙坦钾治疗高血压的临床疗效.方法 选取2018年2月—2019年2月在首都医科大学附属北京天坛医院治疗的高血压患者96例,根据用药的差别分为对照组(48例)和治疗组(48例).对照组口服氯沙坦钾片,起始剂量50 mg/次,1次/d,必要时可增至100 mg/次,1次/d;治疗组在对照组的基础上口服盐酸维拉帕米片,起始剂量80 mg/次,3次/d,最大剂量360～480 mg/d,对于低剂量即有反应的老年人或体型瘦小者,起始40 mg/次,3次/d.两组患者治疗4周.观察两组患者临床疗效,同时比较治疗前后两组患者血压、C反应蛋白(CRP)、可溶性凝集素样氧化低密度脂蛋白受体1(sLOX-1)、可溶性细胞间粘附分子-1(sICAM-1)、基质金属蛋白酶-9(MMP-9)、转化生长因子 β1(TGF-β1)、单核细胞趋化蛋白1(MCP-1)和血管内皮功能.结果 治疗后,对照组临床有效率为81.25％,显著低于治疗组的97.92％,两组比较差异有统计学意义(P<0.05).治疗后,两组患者收缩压(SBP)、舒张压(DBP)均显著下降(P<0.05),且治疗组患者血压水平明显低于对照组(P<0.05).治疗后,两组患者血清CRP、sLOX-1、sICAM-1、MMP-9、TGF-β1、MCP-1水平均明显降低(P<0.05),且治疗组患者这些血清细胞因子水平明显低于对照组患者(P<0.05).治疗后,两组肱动脉内皮依赖性舒张功能(EDD)、肱动脉非内皮依赖的舒张功能(NMD)均明显升高(P<0.05),且治疗组患者血管内皮功能明显高于对照组(P<0.05).结论 维拉帕米联合氯沙坦钾治疗高血压可显著降低患者血压,改善患者临床症状和血管内皮功能.

Objective? To understand the comorbid conditions of physical illness in hospitalized elderly patients over 80 years old with mental disorders. Methods? The study screened inpatients from Beijing Anding Hospital affiliated to Capital Medical University from January 1, 2010 to December 30, 2017. Patients with diagnosis based on ICD-10, age of＞ 80 years old, and complete clinical files were selected. The comorbid conditions of physical illness and other information in the selected patients were investigated. Results? Among the 187 patients, 183 patients had physical illness, with a comorbid rate of 97.9% and an average of 6.9 comorbidities. There was no significant difference in the number of comorbid physical diseases among patients with different mental disorders (P＞ 0.05). In terms of the average number of comorbidities, mental disorders and mood disorders caused by brain damage and dysfunction, and other physical diseases had significantly fewer comorbidities than other four types of mental disorders (P＜0.05). A total of 183 elderly psychiatric patients had a total of 1 297 cases of physical illness. There are 769 cases of diseases in the nervous system, circulatory system, endocrine system, respiratory system and digestive system, accounting for 59.29% of all cases of physical illness. The top five diseases were hypertension (115 cases, 62.8%), constipation (84 cases, 45.9%), cerebral infarction (71 cases, 38.8%), diabetes (54 cases, 29.5%), and coronary heart disease (48 cases, 26.2%). The number of comorbidities of physical illness in patients is related to age (P＜0.01). Conclusions? The physical comorbidity of elderly patients over 80 years old with mental disorders is very common. The number of comorbidities is large, with cardiovascular and metabolic diseases accounting for the majority.

目的 系统评价文拉法辛治疗老年抑郁症的疗效和安全性.方法 计算机检索中国生物医学文献数据库、万方数据库、中国学术期刊全文数据库和维普中文科技期刊数据库,全面检索文拉法辛治疗老年抑郁症相关文献,进行严格的质量评价后,使用Revman 5.3软件进行Meta分析.结果 共纳入17项随机对照研究,1053例患者.Meta分析结果显示,文拉法辛组治疗2周汉密尔顿抑郁量表(HAMD)减分值(SMD=0.15,95％CI:-0.12～0.42,P=0.29)、终点有效率(RR=0.98,95％CI:0.91～1.06,P=0.61)及终点痊愈率(RR=0.97,95％CI:0.84～1.13,P=0.71)与对照组药物相比均未见统计学意义;亚组分析结果表明,文拉法辛高低剂量组分别同对照组药物相比,在治疗2周HAMD减分值及治疗终点有效率、痊愈率的比较中亦未见统计学意义.与对照组药物相比,文拉法辛组体重增加及口干的发生率更低,但更容易导致血压升高及心悸.结论 文拉法辛能有效治疗老年抑郁症,但需留意其对血压的影响.

精神分裂症是精神科常见的慢性精神疾病,该疾病预后差、易复发,为家庭及社会带来沉重负担.精神分裂症的治疗措施多样,除药物治疗外,物理治疗中以无抽搐电休克治疗(modified electroconvulsive therapy,MECT)为主.尽管MECT在临床治疗中有着诸多优点,但MECT引起的认知不良反应一直是临床工作中的棘手问题.既往大多数研究认为MECT对精神分裂症患者的认知功能有损害作用.但是近年来这一传统观点正受到挑战,越来越多的研究表明,MECT在缓解症状的基础上,亦可能改善其认知功能.据此,本文总结了近年来国内外MECT对认知功能影响的研究,进而分析其对认知的影响及可能的机制.

目的 通过敲除环二鸟苷酸(c-di-GMP)合成酶基因Ra1362探讨该基因在结核分枝杆菌(MTB)H37Ra株生物膜发育和休眠中的作用.方法 以MTB H37Ra株为出发菌株,敲除合成酶基因Ra1362获得基因敲除株△Ra1362,通过体外实验比较细菌的生物膜形成变化;应用转录谱基因芯片和实时荧光定量PCR(RT-PCR)检测野生株和敲除株基因表达的情况变化;同时构建体外快速厌氧休眠模型比较细菌克隆形成、休眠相关基因的表达和活细胞染色情况.结果 △Ra1362株于痰液管中培养26 d时已形成较厚的皱褶生物膜,形成生物膜的速度明显快于野生株5d;转录谱基因芯片和定量RT-PCR结果也显示△Ra1362株中19个与休眠相关基因的表达水平下调并能通过基因回补和外源添加c-di-GMP所补偿;在快速厌氧模型中发现,迟缓期过后△Ra1362株对氧气的消耗比野生株组要快12h,且细菌处于不能恢复正常生长的休眠状态.结论 Ra1362基因通过控制c-dLGMP的合成调控MTB感应缺氧或者氧化还原压力,一方面调控生物膜的发育,另一方面在缺氧条件下通过调控DosR调节子基因的表达来调节细菌的休眠.

附属医院的临床研究室既是科研基地，又是教育和培养学生的重要场所，是提高我国医学和科研整体水平的重要力量。在这些研究室中由于历史和体制以及社会环境的因素，面临很多的问题。文章对出现的问题和形成原因进行了分析，并对问题的解决提出了一些见解和建议。

目的 探讨水通道蛋白1,5及尿素转运蛋白B1在慢性肾衰竭小鼠脑组织中表达水平的变化及影响,进一步揭示血液透析脑型失衡综合征可能的分子基础. 方法 选用6～8周龄,雄性BALB/c小鼠,将小鼠分为正常组(N)、假手术组(S)和慢性肾衰竭模型组(CRF组).CRF模型小鼠通过对其右肾2/3肾皮质透热毁损,并在1周后将左肾完全切除的方法建立.假手术组小鼠只进行麻醉和手术切口,肾脏不做处理.正常组的小鼠不做任何处理.模型建立后10、40和70天3个时间点每组各处死5只小鼠,并留取小鼠的肾脏、血清和脑组织标本.检测三组小鼠肾组织病理、血清肌酐和尿素氮;用Western Blotting方法测定在造模后10天、40天和70天3组小鼠脑组织内水通道蛋白1,5(Aquaporin,AQP)及尿素转运蛋白B1(Urea Transportprotein,UT-B1)的表达.结果 CRF模型组在造模后10天肾组织病理结果显示部分肾小囊扩张,球囊粘连,肾小管上皮细胞颗粒样变性.造模后40天、70天表现为部分肾小球增生硬化,部分肾小管萎缩.造模10,40,70,天CRF模型组血清肌酐分别是(841.80±336.93)umol/L、(1885.17±689.49)umol/L、(1276.56±496.09)umol/L,与正常组和假手术组肌酐值相比均显著升高(10d:F=26.768,P=0.007;40d: F=34.928,P=0.004;70d.: F29.998,P=0.005),提示慢性肾衰竭模型成功.Western Blotting检测实验各组脑组织AQP1、AQP5及UT-B1的表达,结果显示:在造模10,40,70天,CRF模型组UT B1均未表达,正常组及假手术组表达差别无统计学意义.在造模后10天正常组AQP1表达量与假手术组及CRF组比较均有统计学差异(P＜0.05).CRF模型组较正常组AQP1表达量升高46.67％(t=0.122,P=0.001);AQP-5表达量较正常组升高41.09％(t=0.012,P=0.001).在造模后40天,假手术组与正常组AQP-1,5表达量无显著性差异;而CRF模型组AQP-1表达量较正常组升高28.98％(t=4.926,p=0.001),AQP-5表达量较正常组升高20.83％(t=0.857,P=0.003).在造模后70天,假手术组与正常组AQP-1,5表达量无显著性差异,而CRF模型组AQP-1表达量较正常组升高30.26％(t=8.471,P=0.001);AQP-5表达较正常组升高45.67％(t=3.352,P=0.001).结论 CRF模型小鼠脑组织AQP1,5的表达明显增加,同时伴有尿素转运蛋白B1的不表达或表达明显下降,这一结果为揭示脑型失衡综合症提供了线索.脑组织尿素转运蛋白的低表达导致快速血液透析脑中尿素清除延迟,进而形成脑血尿素浓度梯度,驱动水分通过过多表达的水道蛋白进入脑组织,导致脑水肿.

目的探讨水通道蛋白1,5及尿素转运蛋白B1在慢性肾衰竭小鼠脑组织中表达水平的变化及影响,进一步揭示血液透析脑型失衡综合征可能的分子基础。方法选用6~8周龄,雄性BALB/c小鼠,将小鼠分为正常组（N）、假手术组（S）和慢性肾衰竭模型组（CRF组）。CRF模型小鼠通过对其右肾2/3肾皮质透热毁损,并在1周后将左肾完全切除的方法建立。假手术组小鼠只进行麻醉和手术切口,肾脏不做处理。正常组的小鼠不做任何处理。模型建立后10、40和70天3个时间点每组各处死5只小鼠,并留取小鼠的肾脏、血清和脑组织标本。检测三组小鼠肾组织病理、血清肌酐和尿素氮;用Western Blotting方法测定在造模后10天、40天和70天3组小鼠脑组织内水通道蛋白1,5（Aquaporin,AQP）及尿素转运蛋白B1（Urea Transportprotein,UT-B1）的表达。结果 CRF模型组在造模后10天肾组织病理结果显示部分肾小囊扩张,球囊粘连,肾小管上皮细胞颗粒样变性。造模后40天、70天表现为部分肾小球增生硬化,部分肾小管萎缩。造模10,40,70,天CRF模型组血清肌酐分别是（841.80±336.93）umol/L、（1885.17±689.49）umol/L、（1276.56±496.09）umol/L,与正常组和假手术组肌酐值相比均显著升高（10d：F=26.768,P=0.007;40d：F=34.928,P=0.004;70d：F=29.998,P=0.005）,提示慢性肾衰竭模型成功。Western Blotting检测实验各组脑组织AQP1、AQP5及UT-B1的表达,结果显示：在造模10,40,70天,CRF模型组UT-B1均未表达,正常组及假手术组表达差别无统计学意义。在造模后10天正常组AQP1表达量与假手术组及CRF组比较均有统计学差异（P〈0.05）。CRF模型组较正常组AQP1表达量升高46.67%（t=0.122,P=0.001）;AQP-5表达量较正常组升高41.09%（t=0.012,P=0.001）。在造模后40天,假手术组与正常组AQP-1,5表达量无显著性差异;而CRF模型组AQP-1表达量较正常组升高28.98%（t=4.926,P=0.001）,AQP-5表达�

<正>缺血性脑损伤(卒中)的研究始于20世纪70年代,在早期,通过对卒中发病机制和调节介质的研究,提示神经保护药是潜在、有效的干预和治疗药物。此后,大量研究采用动物模型来探讨缺血后脑内生化和分子生物学的改变,证实部分药物确实具有一定神经保护作用,为神经保护药物在临床中的应用提供了依据。通过MEDLINE检索引擎(PubMed)以"neuropro-

重组尿激酶原(u-PA)是我国自主研发的第2代具有纤维蛋白特异性、出血不良反应少的新型溶栓药物.重组尿激酶原用于急性心肌梗死溶栓治疗的大型临床研究显示,其溶栓效果好,且较链激酶原(t-PA)对全身纤维溶解系统的影响小.

尿激酶型纤溶酶原激活剂对促进生理和病理状况下血栓溶解有重要作用.本文就其结构、功能、活性调节、信号通路和溶栓应用作一综述.

Objective Pro-urokinase,a new thrombolytic agent that is currently being evaluated for the treatment of myocardial infarction,stroke and pulmonary embolism.However little research has been done about the effects of recombinant pro-urokinase on endothelial cells.The purpose of this article is to study the effects of pro-urokinase on the expression and release of urokinase type plasminogen activator receptor(u-PAR) and plasminogen activator inhibitor1(PAI-1) and to study the effects of pro-urokinase on the mRNA expression of urokinase type plasminogen activator(u-PA) in human pulmonary arterial endothelial cells(HPAECs).Methods The HPAECs were cultured in M200 medium with low serum growth supplement until became confluent.Then the HPAECs were starvated for 12 h,and ready to be used in different experiments.(1) HPAECs were incubated with pro-urokinase(0 or 150 IU/mL) for 8 h,then the medium was centrifuged for 10 min at 1 000 r/min and expression of u-PAR or PAI-1 in the medium detected with ELISA kits.(2) HPAECs was incubated with pro-urokinase 150 IU/mL for 0,4,8,12 and 24 hours.In each group,the total RNA of HPAECs was extracted by Trizol reagent and the gene expression of u-PA mRNA detected with RT-PCR and compared with that of GAPDH mRNA.All cells in these experiments were of 3 to 6 passages.Results The cells were flat with round or oval nuclei containing several prominent nucleoli.Six to seven days after plating,the cultured HPAECs formed a monolayer.In the ELISA tests,the u-PAR content in pro-urokinase treated cell was statistically increased as compared with the control ones((0.51±0.04)μg/L vs(0.58±0.05)μg/L,P=0.005);the PAI-1 content in serum was statistically decreased in pro-urokinase treated cells as compared with control ones((66.75±7.92)μg/L vs(53.38±12.18)μg/L,P=0.009).In RT-PCR experiments,after incubation with pro-urokinase 150 IU/mL for increasing hours(0,4,8,12 and 24 hours),the u-PA bd/GAPDH band ratio was(0.34±0.11),(0.51±0.12),(0.58±0.12),(0.50±0.18) and(0.35±0.10) respectively.Pro-urokinase(150 IU/mL) incubation could up-regulate the expression of u-PA mRNA in HPAECs in a time-dependent manner and the highest expression was shown at 8 hours.Conclusion Under normal conditions,HPAECs cue could express or release u-PA,u-PAR,and PAI-1.Pro-urokinase could inhibit the release of PAI-1 and enhance the release of u-PAR from cell surface.Pro-urokinase could enhance the expression of u-PA mRNA in HPAECs in a time-dependent manner.Pro-urokinase has direct effects on the expression of u-PA system in HPAECs,which may thus enhance thrombolytic process.