医院门诊候诊时间量化分析和研究

目的 通过对门诊患者候诊时间的量化统计和分析,发现影响候诊时间的关键因素以优化门诊就诊流程,缩短候诊时间.方法 通过信息系统,采集北京大学肿瘤医院2013年11月4-29日上午门诊就诊患者的候诊时间,按患者性别、年龄、医保类型和挂号号源类型进行统计分析.结果 门诊患者平均候诊时间为36.3（10.6,81.5） min,主任医师、副主任医师和主治医师号源的候诊时间分别为54.1（19.1,106.8）、34.0（10.3,74.7）、26.4（7.8,66.5） min,差异有统计学意义（P＜0.05）;34.7％ （3 984/11 471）的患者候诊时间超过60 min,外地医保就诊患者候诊时间[42.5（12.1,90.4） min]明显高于北京本地医保就诊患者[在职：33.8（9.8,77.3） min;离退：30.5（9.9,68.4） min].结论 候诊时间可作为门诊流程管理的监测指标,预约诊疗和流程优化有助于缩短候诊时间.     

p11 modulates L-DOPA therapeutic effects and dyskinesia via distinct cell types in experimental Parkinsonism

The reduced movement repertoire of Parkinson’s disease (PD) is mainly due to degeneration of nigrostriatal dopamine neurons. Restoration of dopamine transmission by levodopa (L-DOPA) relieves motor symptoms of PD but often causes disabling dyskinesias. Subchronic L-DOPA increases levels of adaptor protein p11 (S100A10) in dopaminoceptive neurons of the striatum. Using experimental mouse models of Parkinsonism, we report here that global p11 knockout (KO) mice develop fewer jaw tremors in response to tacrine. Following L-DOPA, global p11KO mice show reduced therapeutic responses on rotational motor sensitization, but also develop less dyskinetic side effects. Studies using conditional p11KO mice reveal that distinct cell populations mediate these therapeutic and side effects. Selective deletion of p11 in cholinergic acetyltransferase (ChAT) neurons reduces tacrine-induced tremor. Mice lacking p11 in dopamine D2R-containing neurons have a reduced response to L-DOPA on the therapeutic parameters, but develop dyskinetic side effects. In contrast, mice lacking p11 in dopamine D1R-containing neurons exhibit tremor and rotational responses toward L-DOPA, but develop less dyskinesia. Moreover, coadministration of rapamycin with L-DOPA counteracts L-DOPA–induced dyskinesias in wild-type mice, but not in mice lacking p11 in D1R-containing neurons. 6-OHDA lesioning causes an increase of evoked striatal glutamate release in wild type, but not in global p11KO mice, indicating that altered glutamate neurotransmission could contribute to the reduced L-DOPA responsivity. These data demonstrate that p11 located in ChAT or D2R-containing neurons is involved in regulating therapeutic actions in experimental PD, whereas p11 in D1R-containing neurons underlies the development of L-DOPA–induced dyskinesias.Parkinson’s disease (PD) is characterized by a progressive degeneration of dopaminergic neurons projecting from substantia nigra pars compacta (SNc) to striatum, eventually resulting in bradykinesia, rigidity, resting tremor, and postural imbalance (1). Dopamine replacement strategies are effective for many motor symptoms. At early stages, MAO-B inhibitors or dopamine D2 receptor agonists may provide sufficient symptomatic relief, but as the disease progresses essentially all patients will require treatment with levodopa (L-DOPA) (1). Following decarboxylation, L-DOPA is converted to dopamine acting on both dopamine D1 and D2 receptors. D1 and D2 receptors are segregated in striatonigral and striatopallidal pathway neurons, respectively (2). Activation of D1 and D2 receptors causes synergistic stimulation of locomotion, explaining the stronger anti-Parkinsonian action of L-DOPA compared with selective D2 receptor agonists (1, 2). Whereas dopaminergic agents often successfully treat bradykinesia and rigidity in PD, additional therapy with anticholinergic agents is sometimes required for optimal treatment of resting tremor (1). Moreover, the therapeutic effect of L-DOPA is gradually shortened as disabling dyskinetic side effects emerge (3). There is no licensed treatment against L-DOPA–induced dyskinesias (LIDs).Targeting the serotonergic, glutamatergic, and/or cholinergic systems have been reported to counteract LIDs (3). p11 (i.e., S100A10) is a member of the S100 EF-hand protein family, which increase the levels of distinct serotonin (5-HT_1BR and 5-HT₄R) and glutamate (mGluR5) receptors at the cell surface, resulting in enhanced effects on cell signaling via these receptors (4, 5). p11 is widely expressed in the brain with particularly high levels in cholinergic neurons (6–9). p11 is regulated by a variety of stimuli and therapies, most notably antidepressants (4). p11 is strongly up-regulated in the striatum following repeated treatment with L-DOPA in the 6-OHDA–lesioning model of experimental parkinsonism (10). p11 can therefore influence several pathways implicated in LIDs.In the present study, we examined global and cell-specific conditional p11 knockout (KO) mice in experimental Parkinsonism models to identify the brain circuitries that mediate p11-dependent therapeutic effects of L-DOPA as well as LIDs.     

缬沙坦对老年高血压患者P波离散度的影响及临床意义

目的比较缬沙坦和氨氯地平对老年高血压患者P波离散度的影响。方法将68例年龄60岁以上的老年原发性轻中度(1~2级)高血压患者,随机分为实验组(34例)和对照组(34例),分别接受16周的缬沙坦和氨氯地平治疗。治疗期间监测血压,分别于治疗前和治疗16周后检测心电图和超声心动图。结果两组患者在用药后,血压(P<0.001)和左心室重量指数(P<0.05)均明显下降,下降程度无显著性差异;治疗后,两组患者P波离散度和P波最大时限均显著降低,实验组比对照组降低明显。结论缬沙坦和氨氯地平均能有效降压、逆转左心室肥厚,降低P波离散度,在同等降压条件下,缬沙坦能进一步降低P波离散度和P波最大时限。     

直视下左心房后壁射频消融微创迷宫术治疗风湿性心脏病心房颤动的临床对照研究

目的 通过对照观察探讨心脏瓣膜置换手术(换瓣术)过程中直视下微创迷宫术法射频消融左心房后壁治疗风湿性心脏病(风心病)慢性心房颤动(房颤)的可行性及疗效.方法 128例行心脏瓣膜置换术的风心病伴慢性房颤患者中,76例在换瓣术中直视下以微创迷宫术法射频消融左心房后壁,设计两条迷宫线路:一条为围绕4个肺静脉口外侧的环形线,另一条为连接左下肺静脉口下缘与二尖瓣后叶根部的最短直线.术中分次节段性消融,输出功率30～40W,放电时间45～60 S;术前3 d静脉应用胺碘酮,术后口服3个月停药;随访24个月.其余52例拒绝行射频消融微创迷宫术的风心病患者设为对照组,其换瓣术、胺碘酮应用及术后随访同射频消融微创迷宫术组(消融组).结果 随访24个月,消融组成功率81.58%(62/76),对照组成功率44.23%(23/52),P＜0.001,差异有统计学意义.结论 换瓣术中采用直视下在左心房后壁行射频消融微创迷宫术法能显著提高术后维持窦性心律的成功率,比传统的药物治疗疗效好,且方法简单,并发症少.胺碘酮有助于逆转心房电重构,减少房颤复发.     

支气管哮喘患者痰嗜酸粒细胞相对计数与糖皮质激素治疗反应性的关系

目的观察支气管哮喘（简称哮喘）患者不同气道炎症类型（嗜酸粒细胞炎症与非嗜酸粒细胞炎症）对吸人糖皮质激素（简称激素）治疗的反应性。方法选择近3个月内未接受激素治疗的慢性持续性哮喘患者42例，根据诱导痰嗜酸粒细胞百分比将患者分为嗜酸粒细胞增高组（嗜酸粒细胞〉3％，23例）与非嗜酸粒细胞增高组（嗜酸粒细胞〈3％，19例），进行哮喘症状评分、肺功能检查、诱导痰细胞分类计数。采用酶联免疫荧光法测定痰液嗜酸粒细胞阳离子蛋白（ECP）的浓度。吸人激素治疗1、3个月时进行随访，重复上述哮喘疗效的评价指标。结果嗜酸粒细胞增高组痰嗜酸粒细胞比值、ECP水平基线值分别为0．080（0．063～0．178）、（324±149）μg／L，非嗜酸粒细胞增高组分别为0．017（0．006～0．021）、（152±68）μg／L，两组比较差异有统计学意义（t值分别为4．40、3．33，P均〈0、01）。嗜酸粒细胞增高组第一秒用力呼气容积（FEV1）、FEV1占预计值百分比（FEV1占预计值％）、症状评分的基线值分别为（1．98±0．67）L、（65±20）％、7．0（5．0～10．0）分，非嗜酸粒细胞增高组分别为（2．07±1．05）L、（66±27）％、5．0（2．0～9．0）分，两组比较差异无统计学意义（t值分别为-0．62、-0．09、1．32，P均〉0．05）。吸入激素治疗1、3个月后嗜酸粒细胞增高组的嗜酸粒细胞比值、ECP水平、症状评分、FEV1和FEV1占预计值％分别为[0．019（0．010～0．060）、[0．036（0．006～0．070）、（173±153）μg／L、（173±122）μg／L、3．0（1．0～6．0）分、3．0（1．0～5．0）分、（2．42±0．64）L、（2．43±0．76）L、（77±13）％、（77±18）％，与基线值比较差异有统计学意义（F值分别为6．73、6．71、5．93、7．38、5．78，P均〈0．05）。非嗜酸粒细胞增高组分别为0．013（0．000～0．025）、0．012（0．004～0．031）、（111±50）μg／L、（117±50）μg／L、3．0（0．0～6．0）分、3．0（1．0～7．3）分、（2．22±0．86）L、（2．21±0．24）L、（71±20）％、（65±21）％，与基线值比较，嗜酸粒细胞比值、FEV1和FEV1占预计值％均无统计学意义（F值分别为1．98、0．80、1．37，P均〉0．05），而ECP水平和症状评分比较差异有统计学意义（F值分别为3．78、3．59，P均〈0．05）。多元线性回归分析显示，病情严重度、基线FEV1和痰嗜酸粒细胞百分比与FEV1改善程度相关（r值分别为-0．27、-0．02、0．03，P均〈0．05）。痰嗜酸粒细胞比值的基线值对激素治疗反应的阴性预测值最高（89．5％）。结论对于痰嗜酸粒细胞增高的哮喘患者，吸人激素治疗能够抑制嗜酸粒细胞炎症，改善肺功能和症状评分。非嗜酸粒细胞增高哮喘患者对激素治疗反应性差，FEV1无改善。痰嗜酸粒细胞比值不高是激素治疗反应性差的最佳预测指标。     

Ultrasmall bimodal nanomolecules enhanced tumor angiogenesis contrast with endothelial cell targeting and molecular pharmacokinetics

Nonintrusive and precise imaging for tumor angiogenesis is critical in accurate assessment of cancer diagnosis and prognosis. However, reticulo-endothelial system (RES) capture and inadequate accumulation remain major bottlenecks for current nanoparticle to retain at tumor angiogenesis site. Herein, we report the ultrasmall contrast agent (cNGR-Au:Gd@GSH NMs) could accumulate at tumor vasculature site and enhance the tumor angiogenesis-contrast. It is demonstrated that by loading Au and Gd atom into the naturally-occurring glutathione (GSH) shell with cNGR peptide modification, cNGR-Au:Gd@GSH NMs exhibit the high X-ray photon absorption, longer rotational correlation time and efficient tumor vascular endothelia cell targeting. In vivo studies further indicate the cNGR-Au:Gd@GSH NMs prominently enhance tumor angiogenesis-contrast both on the computed tomography (CT) and magnetic resonance imaging (MRI) modalities by escaping the RES capture and target delivering. Our data imply that the cNGR-Au:Gd@GSH NMs may serve as the high-efficiency contrast agent to assess tumor angiogenesis in a nonintrusive technique.     

积极心理学视角下维持性血液透析患者生活质量现状及影响因素分析

目的 探讨维持性血液透析患者的生活质量现状及影响因素。方法 采用便利抽样方法抽取258例维持性血液透析患者,运用中文版慢性病自我效能量表、中文版简易心理弹性量表和中文版生活质量量表对其进行测量,采用多元线性回归分析生活质量影响因素。结果 维持性血液透析患者生活质量的8个维度得分均低于国内常模;多元线性回归分析结果显示,年龄、心理弹性和自我效能的症状管理维度可预测维持性血液透析患者的生理健康总评（调整R2=0.253,P<0.001）;每日尿量、医疗费用支付方式、心理弹性和自我效能的症状管理维度可预测维持性血液透析患者的心理健康总评（调整R2=0.375,P<0.001）。结论维持性血液透析患者的生活质量水平较低,且除一般资料中的年龄、每日尿量和医疗费用支付方式外,自我效能和心理弹性是其生活质量的重要预测因子。提示医护人员在临床工作中可提高对患者积极心理因素的关注,针对性采取措施改善其生活质量。     

The distribution and density of monocarboxylate transporter 2 in cerebral cortex,hippocampus and cerebellum of wild-type mice

Monocarboxylates cannot cross the blood-brain barrier freely to participate in brain energy metabolism. Specific monocarboxylate transporters (MCTs) are needed to cross cellular membranes. Monocarboxylate transporter 2 (MCT2) is a major monocarboxylate transporter encoded by the SLC16A7 gene. Recent studies reported that neurodegenerative diseases of the CNS, such as Alzheimer's disease (AD) and Parkinson's disease (PD), were related to energy metabolic impairment. MCT2 also plays an important role in energy metabolism in the CNS. To provide experimental evidence for future research on the role of MCT2 in the pathological process of CNS degenerative diseases, the distribution and density of MCT2 in different subregions of wild-type mouse brain was examined using immunohistochemistry, western blot and immunogold post-embedding electron microscopic techniques. The amount of MCT2 was higher in cerebellum than in cortex and hippocampus on western blots, and there was no statistical difference between cortex and hippocampus. Immunohistochemistry assay revealed the highest density of MCT2 in the CA3 of the hippocampus. The granular cell layer of the cerebellum contained more MCT2 than the molecular layer. The MCT2 density on the end feet of astrocytes of molecular layer was lower than in hippocampus, but the postsynaptic densities (PSDs) of asymmetric synapses in the molecular layer exhibited a high density using immunogold post-embedding electron microscopic techniques.