超声心动图联合动态心电图检查对急性心肌梗死诊断和预后评估的价值

为探讨超声心动图联合动态心电图检查在急性心肌梗死(AMI)患者诊断和预后评估中的应用价值,本研究选取2016年6月~2018年6月我院收治并确诊的100例AMI患者作为观察组,另选取同期100例非冠心病患者作为对照组。以AMI患者心源性死亡为终点事件,将观察组分为死亡组(n=15)和存活组(n=85)。所有患者均采用飞利浦IU-Elite及EPIQ5彩色多普勒超声诊断仪进行超声心动图检查,采用DMS-3004A进行标准的12导联动态心电图检查。比较各组患者心率震荡指标[震荡起始(TO)、震荡斜率(TS)]、心率变异性指标[NN间期标准差(SDNN)、QT离散度(QTd)、经心率校正的QT离散度(QTcd)]及心功能指标[左心室舒张末期内径(LVEDD)、左心室射血分数(LVEF)]水平的变化。结果显示,观察组TO、QTd、QTcd、LVEDD均明显高于对照组,TS、SDNN、LVEF均明显低于对照组,差异有统计学意义(P<0.05)。死亡组TS、SDNN均明显低于存活组,差异有统计学意义(P<0.05);死亡组TO高于存活组,QTd、QTcd、LVEF、LVEDD均低于存活组,但差异无统计学意义(P>0.05)。本研究结果表明,AMI患者心率震荡(HRT)明显减弱甚至消失,HRV、LVEF明显降低,LVEDD、QTd明显增大,QT间期明显延长。超声心动图和动态心电图联合检查对AMI患者诊断及预后评估均有重要的临床应用价值。     

柔性PDA薄膜阵列用于双模光学检测VOC标志物气体

本研究以亲油性的双面胶作为基底,利用滴涂二乙炔单体结合紫外光聚合来制备均匀的聚二乙炔(PDA)薄膜,通过荧光和颜色两种信号变化模式(即"双模光学检测")研究了PDA薄膜对VOC气体的响应性,发现制备的PDA薄膜在2 min内就可以实现明显的荧光和颜色变化,有效解决了目前PDA薄膜在VOC气体检测方面存在响应速度慢、薄膜均一性差等问题.此外,为解决单一PDA薄膜的交叉响应性问题,本研究制备了四种不同的基于双面胶基底的PDA薄膜,并将制备的4种PDA薄膜集成到一片PDMS薄膜基底上来构建柔性的传感阵列,利用阵列的颜色变化结合模式识别技术,实现了对8种VOC气体的快速、灵敏区分.进一步将制备的PDA薄膜阵列用于健康人、模拟糖尿病及肾病患者呼出气体中VOC标志物的辨别和分析研究,发现可以将三类人的呼出气体清晰地区分,说明了该阵列在呼气疾病诊断中的应用前景.与目前报道的PDA薄膜阵列相比,本研究中基于双面胶基底的PDA薄膜阵列具有气体响应速度快、灵敏性高、柔韧性好、制备工艺简单、成本低、易于大规模制备等优点,有望用于实VOC气体检测研究中.     

Examination of Changes in 6-minute Walk Distance and Related Factors in Patients with Perioperative Peripheral Arterial Disease

Objective: This study aimed to clarify the effects of pre- and postoperative physical function on the 6-minute walking distance (6MWD) in patients with peripheral arterial disease (PAD). Method: Forty-two elderly patients with PAD who were hospitalized for revascularization and able to walk independently were included in the study. The 6MWD, ankle brachial index (ABI), weight-bearing index (WBI), gait, and intermittent claudication distance (ICD) were measured before and after the surgery, and skeletal muscle index was measured only before surgery. Analyses were performed by comparing the pre- and postoperative values of each factor using a paired t-test. In addition, multiple regression analysis was performed with 6MWD as the dependent variable before and after surgery. Results: Postoperatively, pain disappeared in 22 patients, and ABI, ICD, 6MWD, and stride length improved significantly. ICD and stride length were extracted as factors related to 6MWD before and after surgery, and ABI, WBI, and stride length were extracted as factors related to 6MWD after surgery. Conclusion: The improvement of intermittent claudication associated with revascularization suggests a stronger influence of functional aspects on postoperative 6MWD.     

Specific Recognition of β-Galactofuranose-Containing Glycans of Synthetic Neoglycoproteins by Sera of Chronic Chagas Disease Patients

Chagas disease (CD) can be accurately diagnosed by detecting Trypanosoma cruzi in patients’ blood using polymerase chain reaction (PCR). However, parasite-derived biomarkers are of great interest for the serological diagnosis and early evaluation of chemotherapeutic efficacy when PCR may fail, owing to a blood parasite load below the method’s limit of detection. Previously, we focused on the detection of specific anti-α-galactopyranosyl (α-Gal) antibodies in chronic CD (CCD) patients elicited by α-Gal glycotopes copiously expressed on insect-derived and mammal-dwelling infective parasite stages. Nevertheless, these stages also abundantly express cell surface glycosylphosphatidylinositol (GPI)-anchored glycoproteins and glycoinositolphospholipids (GIPLs) bearing nonreducing terminal β-galactofuranosyl (β-Galf) residues, which are equally foreign to humans and, therefore, highly immunogenic. Here we report that CCD patients’ sera react specifically with synthetic β-Galf-containing glycans. We took a reversed immunoglycomics approach that entailed: (a) Synthesis of T. cruzi GIPL-derived Galfβ1,3Manpα-(CH₂)₃SH (glycan G29_SH) and Galfβ1,3Manpα1,2-[Galfβ1,3]Manpα-(CH₂)₃SH (glycan G32_SH); and (b) preparation of neoglycoproteins NGP29b and NGP32b, and their evaluation in a chemiluminescent immunoassay. Receiver-operating characteristic analysis revealed that NGP32b can distinguish CCD sera from sera of healthy individuals with 85.3% sensitivity and 100% specificity. This suggests that Galfβ1,3Manpα1,2-[Galfβ1,3]Manpα is an immunodominant glycotope and that NGP32b could potentially be used as a novel CCD biomarker.     

Design,Synthesis, and Structure–Activity Relationship Study of Potent MAPK11 Inhibitors

Huntington’s disease (HD) is a rare single-gene neurodegenerative disease, which can only be treated symptomatically. Currently, there are no approved drugs for HD on the market. Studies have found that MAPK11 can serve as a potential therapeutic target for HD. Regrettably, no MAPK11 small molecule inhibitors have been approved at present. This paper presents three series of compounds that were designed and synthesized based on the structure of skepinone-L, a known MAPK14 inhibitor. Among the synthesized compounds, 13a and 13b, with IC₅₀ values of 6.40 nM and 4.20 nM, respectively, displayed the best inhibitory activities against MAPK11. Furthermore, the structure–activity relationship (SAR) is discussed in detail, which is constructive in optimizing the MAPK11 inhibitors for better activity and effect against HD.     

铁过量与人体健康

综述了机体铁储存过多与某些疾病之间的关系,包括:铁过量与肝脏疾病、心血管病、肿瘤、肾损伤、高血压等有关。铁过量主要是由于病理过程和通过各种途径进入人体的铁量增加。过量的铁在失控条件下,引起细胞成分的明显损伤,导致组织炎症和多器官的纤维化。因为铁是自由基反应的催化剂,可引起过氧化作用或细胞膜脂质和细胞内化合物的交联反应,致细胞老化或死亡。     

A New Series of Aryloxyacetic Acids Endowed with Multi-Target Activity towards Peroxisome Proliferator-Activated Receptors (PPARs), Fatty Acid Amide Hydrolase (FAAH), and Acetylcholinesterase (AChE)

A new series of aryloxyacetic acids was prepared and tested as peroxisome proliferator-activated receptors (PPARs) agonists and fatty acid amide hydrolase (FAAH) inhibitors. Some compounds exhibited an interesting dual activity that has been recently proposed as a new potential therapeutic strategy for the treatment of Alzheimer’s disease (AD). AD is a multifactorial pathology, hence multi-target agents are currently one of the main lines of research for the therapy and prevention of this disease. Given that cholinesterases represent one of the most common targets of recent research, we decided to also evaluate the effects of our compounds on the inhibition of these specific enzymes. Interestingly, two of these compounds, (S)-5 and 6, showed moderate activity against acetylcholinesterase (AChE) and even some activity, although at high concentration, against Aβ peptide aggregation, thus demonstrating, in agreement with the preliminary dockings carried out on the different targets, the feasibility of a simultaneous multi-target activity towards PPARs, FAAH, and AChE. As far as we know, these are the first examples of molecules endowed with this pharmacological profile that might represent a promising line of research for the identification of novel candidates for the treatment of AD.     

A review of computational modeling and deep brain stimulation: applications to Parkinson's disease

Biophysical computational models are complementary to experiments and theories, providing powerful tools for the study of neurological diseases. The focus of this review is the dynamic modeling and control strategies of Parkinson's disease (PD). In previous studies, the development of parkinsonian network dynamics modeling has made great progress. Modeling mainly focuses on the cortex-thalamus-basal ganglia (CTBG) circuit and its sub-circuits, which helps to explore the dynamic behavior of the parkinsonian network, such as synchronization. Deep brain stimulation (DBS) is an effective strategy for the treatment of PD. At present, many studies are based on the side effects of the DBS. However, the translation from modeling results to clinical disease mitigation therapy still faces huge challenges. Here, we introduce the progress of DBS improvement. Its specific purpose is to develop novel DBS treatment methods, optimize the treatment effect of DBS for each patient, and focus on the study in closed-loop DBS. Our goal is to review the inspiration and insights gained by combining the system theory with these computational models to analyze neurodynamics and optimize DBS treatment.     

On the Variability of Heart Rate Variability—Evidence from Prospective Study of Healthy Young College Students

Heart rate variability (HRV) has been widely used as indices for autonomic regulation, including linear analyses, entropy and multi-scale entropy based nonlinear analyses, and however, it is strongly influenced by the conditions under which the signal is being recorded. To investigate the variability of healthy HRV under different settings, we recorded electrocardiograph (ECG) signals from 56 healthy young college students (20 h for each participant) at campus using wearable single-lead ECG device. Accurate R peak to R peak (RR) intervals were extracted by combing the advantages of five commonly used R-peak detection algorithms to eliminate data quality influence. Thorough and detailed linear and nonlinear HRV analyses were performed. Variability of HRV metrics were evaluated from five categories: (1) different states of daily activities; (2) different recording time period in the same day during free-running daily activities; (3) body postures of sitting and lying; (4) lying on the left, right and back; and (5) gender influence. For most of the analyzed HRV metrics, significant differences (p < 0.05) were found among different recording conditions within the five categories except lying on different positions. Results suggested that the standardization of ECG data collection and HRV analysis should be implemented in HRV related studies, especially for entropy and multi-scale entropy based analyses. Furthermore, this preliminary study provides reference values of HRV indices under various recording conditions of healthy young subjects that could be useful information for different applications (e.g., health monitoring and management).     

Ultrasonic stimulation of the brain to enhance the release of dopamine – A potential novel treatment for Parkinson’s disease

Parkinson’s disease (PD) is characterized by the decrease of dopamine (DA) production and release in the substantia nigra and striatum regions of the brain. Transcranial ultrasound has been exploited recently for neuromodulation of the brain in a number of fields. We have stimulated DA release in PC12 cells using low-intensity continuous ultrasound (0.1 W/cm² − 0.3 W/cm², 1 MHz), 12 h after exposure at 0.2 W/cm², 40 s, the amount of DA content eventually increased 78.5% (p = 0.004). After 10-day ultrasonic treatment (0.3 W/cm², 5 min/d), the DA content in the striatum of PD mice model restored to 81.07% of the control (vs 43.42% in the untreated PD mice model). In addition to this the locomotion activity was restored to the normal level after treatment. We suggest that the low intensity ultrasound-induced DA release can be attributed to a combination of neuron regeneration and improved membrane permeability produced by the mechanical force of ultrasound. Our study indicates that the application of transcranial ultrasound applied below FDA limits, could provide a candidate for relatively safe and noninvasive PD therapy through an amplification of DA levels and the stimulation of dopaminergic neuron regeneration without contrast agents.