高血压患者心脏变时性功能不良及其意义

目的:探讨原发性高血压(EH)患者心脏变时性功能不良(CI)及其意义。方法:随机选择EH患者60例,行活动平板运动试验,记录心率、血压变化,运动时间(time)、代谢当量(METs);计算2级运动的心率变时性反应指数(CRI2)、最大心率收缩压二项乘积(RPP)和心肌耗氧量(MV.O2)并与正常对照组40例比较。结果:EH组峰值心率及心率上升幅度小于对照组(148.75±11.81):(154.27±12.05)次/min,(67.44±13.37):(74.12±14.43)次/min,P<0.05;CRI2低于对照组(0.94±0.22):(1.03±0.15),P<0.05;EH组CI的人数共29例(48.33%)明显多于对照组7例(17.5%),P<0.005,其中CRI2<0.8的人数20例(33.33%),CRI2>1.3的人数9例(15%),对照组为6例(15%)、1例(2.5%),两组间有显著性差异P<0.05;表明EH组存在CI;EH组运动时间(time)缩短(8.78±1.87):(9.77±1.88)min,P<0.05;运动贮量(METs)降低(9.21±1.39):(9.82±1.48),P<0.05;而RPP,MV.O2分别高于对照组[(26484.64±3573.49):(24118.39±3060.76),(30.78±5.0):(27.47±4.23)ml/kg.min,P<0.001]。结论:EH患者存在CI,提示有心脏自主神经损害,临床应引起重视。     

Foxp3+ regulatory T cells are activated in spite of B7‐CD28 and CD40‐CD40L blockade

Costimulatory signals are required for priming and activation of naive T cells, while it is less clear how they contribute to induction of regulatory T (Treg)‐cell activity. We previously reported that the blockade of the B7‐CD28 and CD40L‐CD40 interaction efficiently suppresses allogeneic T‐cell activation in vivo. This was characterized by an initial rise in Foxp3⁺ cells, followed by depletion of host‐reactive T cells. To further investigate effects of costimulatory blockade on Treg cells, we used an in vitro model of allogeneic CD4⁺ cell activation. When CTLA‐4Ig and anti‐CD40L mAb (MR1) were added to the cultures, T‐cell proliferation and IL‐2 production were strongly reduced. However, Foxp3⁺ cells proliferated and acquired suppressive activity. They suppressed activation of syngeneic CD4⁺ cells much more efficiently than did freshly isolated Treg cells. CD4⁺ cells activated by allogeneic cells in the presence of MR1 and CTLA‐4Ig were hyporesponsive on restimulation, but their response was restored to that of naive CD4⁺ cells when Foxp3⁺ Treg cells were removed. We conclude that natural Treg cells are less dependent on B7‐CD28 or CD40‐CD40L costimulation compared with Foxp3^? T cells. Reduced costimulation therefore alters the balance between Teff and Treg‐cell activation in favor of Treg‐cell activity.     

Exploring the utility of whole‐exome sequencing as a diagnostic tool in a child with atypical episodic muscle weakness

The advent of whole‐exome next‐generation sequencing (WES) has been pivotal for the molecular characterization of Mendelian disease; however, the clinical applicability of WES has remained relatively unexplored. We describe our exploration of WES as a diagnostic tool in a 3½‐year old female patient with a 2‐year history of episodic muscle weakness and paroxysmal dystonia who presented following a previous extensive but unrevealing diagnostic work‐up. WES was performed on the proband and her two parents. Parental exome data was used to filter potential de novo genomic events in the proband and suspected variants were confirmed using di‐deoxy sequencing. WES revealed a de novo non‐synonymous mutation in exon 21 of the calcium channel gene CACNA1S that has been previously reported in a single patient as a rare cause of atypical hypokalemic periodic paralysis. This was unexpected, as the proband's original differential diagnosis had included hypokalemic periodic paralysis, but clinical and laboratory features were equivocal, and standard clinical molecular testing for hypokalemic periodic paralysis and related disorders was negative. This report highlights the potential diagnostic utility of WES in clinical practice, with implications for the approach to similar diagnostic dilemmas in the future.     

淫羊藿总黄酮调控Wnt/β-catenin信号通路对去卵巢大鼠抗骨质疏松作用研究

目的 通过淫羊藿总黄酮(TFE)对去卵巢大鼠骨组织Wnt/β-catenin信号通路及腰椎骨和股骨生物力学性能影响研究,探讨TFE对去卵巢大鼠抗骨质疏松的可能机制.方法 选用40只90天龄的SPF级SD雌性大白鼠,随机分为4组:对照组、去卵巢组(OVX)组、去卵巢+己烯雌酚(DES)组、去卵巢+淫羊藿总黄酮(TFE)组.实验持续12周后处死全部大鼠,取腰椎骨、股骨分别测量生物力学参数及骨密度.免疫蛋白印迹法检测各组大鼠胫骨骨皮质区p-GSK3-β(thr9)、RANKL、OPG、β-catenin蛋白表达水平.结果 与对照组比较,OVX组大鼠股骨、腰椎骨的生物力学性能及骨密度下降(P＜0.05);DES组、TFE组股骨和腰椎骨的生物力学性能和骨密度较去卵巢OVX组明显改善(P＜0.05);两治疗组的组间差异无统计学意义(P＞0.05).免疫蛋白印迹法提示去卵巢大鼠分别加用TFE、DES治疗后,胫骨蛋白β-catenin、OPG表达上调,p-GSK3-β(thr9)、RANKL表达下调.结论 淫羊藿总黄酮能够改善去卵巢大鼠的骨生物力学性能,上调Wnt/β-catenin信号通路,从而改善骨质疏松.     

The role of cognitive biases and personality variables in subclinical delusional ideation

Introduction. A number of cognitive biases, most notably a data gathering bias characterised by “jumping to conclusions” (JTC), and the “bias against disconfirmatory evidence” (BADE), have been shown to be associated with delusions and subclinical delusional ideation. Certain personality variables, particularly “openness to experience”, are thought to be associated with schizotypy.

Methods. Using structural equation modelling, we examined the association between two higher order subfactors (“aspects”) of “openness to experience” (labelled “openness” and “intellect”), these cognitive biases, and their relationship to subclinical delusional ideation in 121 healthy, nonpsychiatric controls.

Results. Our results suggest that cognitive biases (specifically the data gathering bias and BADE) and the “openness” aspect are independently associated with subclinical delusional ideation, and the data gathering bias is weakly associated with “positive schizotypy”. “Intellect” is negatively associated with delusional ideation and might play a potential protective role.

Conclusions. Cognitive biases and personality are likely to be independent risk factors for the development of delusions.     

慢性移植肾失功后的移植肾切除手术分析

目的:分析总结因慢性移植肾失功而行移植肾切除手术患者的临床治疗经过,进一步探讨这类手术的安全性和适应证。方法:以慢性移植肾失功患者76例为研究对象,年龄23~72(36.6±13.5)岁,以上患者发生慢性移植肾失功的时间为术后11~91(35.8±24.6)个月,转入血液透析的时间为3~33(10.4±6.2)个月。76例患者均实施了移植肾切除手术,移植肾切除术后随访时间为6个月~5年。结果:平均手术时间50(35~180)min;术中平均出血量450(200~2 600)ml,平均输血量300(400~2 400)ml,其中67例进行了自体血液回收后输血。术后平均引流量250(20~1 100)ml,平均住院时间11(5~23)d。术后主要并发症:切口血肿8例,切口感染10例,消化道出血7例,心衰7例,肺部感染5例,肾上腺危象2例,下肢跛行2例。死亡4例。多数患者的体重指数、血红蛋白及血清白蛋白含量较术前有所提高。结论:慢性移植肾失功后的移植肾切除手术为高风险手术,应积极做好术前准备,同时加强围手术期护理,以降低手术并发症的发生率;积极适时地切除已经完全失功了的移植肾,有助于改善患者身体素质,避免免疫抑制的不良反应,同时有利于减轻患者本人及社会的经济负担。