HHT方法在脉搏波信号分析中的应用

目的采用HHT(Hibert-HuangTransformation)时间序列分析方法处理从人体采集到的脉搏波信号。方法通过经验模态分解(EMD)技术将一非线性、非稳态过程的原始离散数据序列分解为一组内在模态函数(IMFs),然后对每一个IMF进行HT变换,这样得到的信号幅度和瞬时频率都是时间的函数,即获得脉搏波信号幅度和频率的时间分布。再根据已获得的HH谱,进而得到边际谱。这是一种更具适应性的、新型的、基于模态分解的时间序列数据处理方法。结果首先对一系列由标准的周期函数构造而成的时间序列信号进行了EMD处理,验证HHT方法分解的可行性、有效性;然后分别对一例正常人脉搏波信号和一例典型的冠心病人脉搏波信号进行分解处理,对得到结果进行了比较。结论HHT方法在生物医学信号处理领域将会有广阔的应用前景。     

一种基于经验模态分解的时频分布及其在EEG分析中的应用

Hilbert-Huang变换是一种新的分析非线性非平稳信号的时频方法,这种方法的关键部分是经验模态分解(EMD)方法,任何复杂的信号都可以通过EM D分解为有限数目并且具有一定物理意义的固有模态函数。我们结合该方法给出一种抑制Wigner-Ville分布交叉项的新方法,并将其应用于癫痫脑电信号(EEG)中,且得到了比较好的结果。     

Efficiency of manual ventilation using the original EMO system

The efficiency of the Oxford Inflating Bellows for intermittent positive pressure ventilation using a partially closed Heidbrink expiratory valve has been assessed by measuring the arterial carbon dioxide tension (PaCO2) after various intervals of IPPV on eight patients. It was found that satisfactory alveolar ventilation was achieved if a degree of hyperventilation was employed.     

NHE-1-dependent intracellular sodium overload in hypertrophic hereditary cardiomyopathy: prevention by NHE-1 inhibitor

The purpose of this study was to verify whether myocardial intracellular Na(+) overload may take place in the hereditary cardiomyopathic hamster (CMH), as a result of an increased activity of the Na(+)-H(+) exchanger isoform-1 (NHE-1). Our results showed that simultaneous intracellular Na(+) and Ca(2+) overloads as well as an increase of NHE-1 protein level took place during the development of necrosis and hypertrophy in the CMH. Treatment of 30-day-old CMHs during the development of necrosis and in the absence of hypertrophy with the specific NHE-1 inhibitor EMD87580 (EMD) for 50 days significantly prevented the increase of NHE-1 protein level and intracellular Na(+) and Ca(2+) overloads as well as necrosis. Treatment of CMHs during the development of hypertrophy with EMD for 198 days prevented the development of both necrosis and hypertrophy. In conclusion, our results suggest that NHE-1 overexpression as well as Na(+) and Ca(2+) overloads do take place during the development of necrosis and hypertrophy in hereditary CMHs. Moreover, our results suggest that the blockade of NHE-1 by EMD87580 prevents these diseases by preventing the increase of Na(+) influx through the NHE-1.     

Phase I study of the humanised anti-EGFR monoclonal antibody matuzumab (EMD 72000) combined with gemcitabine in advanced pancreatic cancer

The humanised anti-epidermal growth factor receptor (EGFR) monoclonal antibody matuzumab (formerly EMD 72000) is active against pancreatic cancer in preclinical studies. This phase I study assessed the safety and potential benefit of combined treatment with matuzumab and standard-dose gemcitabine. Three groups of chemotherapy-naive advanced pancreatic adenocarcinoma patients (n=17) received escalating doses of matuzumab (400 mg weekly, 800 mg biweekly, or 800 mg weekly) and gemcitabine (1000 mg m-2 weekly in weeks 1-3 of each 4-week cycle). Toxicity, antitumour activity, pharmacokinetic (PK) parameters, and pharmacodynamic (PD) markers in skin biopsies were evaluated. Severe treatment-related toxicities were limited to grade 3 neutropenia (n=3), leucopenia (n=1), and decreased white blood cell count (n=1). Common study drug-related adverse events were skin toxicities (grade 2=6, grade 1=7) and fever (grade 1=4). Matuzumab inhibited phosphorylated EGFR and affected receptor-dependent signalling and transduction; effects were seen even in the lowest-dose group. Pharmacokinetic data were consistent with results of matuzumab monotherapy. Partial response (PR) or stable disease occurred in eight of 12 evaluated patients (66.7%), with three PRs among six evaluated patients in the group receiving 800 mg weekly. Matuzumab in biologically effective doses with standard gemcitabine therapy appears well tolerated. The combination is feasible and may have enhanced activity.     

EMD56431与粉防已碱对犬血管平滑肌作用的比较性研究

目的：研究EMD56431（EMD）和粉防己碱（Tet)对犬血管平滑肌的松弛作用。方法：用20和60mmol/L KCl激动犬冠状动脉环，观察两药的松弛效应及对不同血管平滑肌的半数抑制浓度（IC50）。结果：犬冠脉环无论有无内皮存在，0．7μmol/L EMD和30μmol/L Tet可松弛50％，而．7μmol/L EMD是无松弛反应。给格列本脲（GLB）后，Tet对KCl致冠脉收缩反应无明显影响，而EMD的松弛反应则取消。EMD和Tet均可使KCl(5-30mmol/L)量效曲线非平行右移，但EMD对高钾（≥40mmol/L)则无拮抗作用（最大反应Emax不降低），Tet则仍具有松弛效应，pD'2为4．4．EMD和Tet使苯福林和KCl致标本的收缩产生浓度依赖性的松弛，对肠系膜动脉和冠脉的IC50分别为6．2（EMD）、4．1（Tet）和6．44（EMD），4．1（Tet)。结论：EMD和Tet为非内皮依赖性血管松弛剂。     

X连锁遗传的Emery-Dreifuss肌营养不良一家系的临床、病理及基因突变特点

目的报道1例X连锁遗传的Emery-Dreifuss肌营养不良(X-EDMD)患者家系的临床、病理及基因突变特点。方法总结作者单位收治的1例X-EDMD患者的临床及骨骼肌病理特点,并进行EMD及LMNA基因突变检测,同时对患者家系谱进行分析。结果该家系中有4例患者,主要表现为缓慢型心律失常,2例已猝死,先证者同时有轻度肘关节挛缩及肌萎缩。先证者心电图检查示房性心动过速合并Ⅲ度房室阻滞,交界区逸搏心律;超声心动图检查示全心扩大,二尖瓣及三尖瓣A峰消失,射血分数60%。肌电图检查示右肱二头肌、左第一骨间肌、左腓肠肌、左股四头肌运动单位电压均增高,神经传导未见异常。左肱二头肌活检示肌营养不良样改变,免疫组化染色显示肌核无伊默菌素蛋白表达。基因分析显示先证者存在EMD基因插入突变c.650_654dupTGGGC,为已报道的致病性突变,LMNA基因均未发现致病性突变。结论 EMD基因c.650_654dup TGGGC插入突变导致的X-EDMD患者心脏损害突出,以心房的电活动-机械活动及结构的严重受累为特征,而肌萎缩及关节挛缩症状相对轻微。     

5-HT(6) receptor agonists and antagonists enhance learning and memory in a conditioned emotion response paradigm by modulation of cholinergic and glutamatergic mechanisms

BACKGROUND AND PURPOSE

5-HT₆ receptors are abundant in the hippocampus, nucleus accumbens and striatum, supporting their role in learning and memory. Selective 5-HT₆ receptor antagonists produce pro-cognitive effects in several learning and memory paradigms while 5-HT₆ receptor agonists have been found to enhance and impair memory.

EXPERIMENTAL APPROACH

The conditioned emotion response (CER) paradigm was validated in rats. Then we examined the effect of the 5-HT₆ receptor antagonist, EMD 386088 (10 mg·kg⁻¹, i.p.), and agonists, E-6801 (2.5 mg·kg⁻¹, i.p.) and EMD 386088 (5 mg·kg⁻¹, i.p.) on CER-induced behaviour either alone or after induction of memory impairment by the muscarinic receptor antagonist, scopolamine (0.3 mg·kg⁻¹, i.p) or the NMDA receptor antagonist, MK-801 (0.1 mg·kg⁻¹, i.p).

KEY RESULTS

Pairing unavoidable foot shocks with a light and tone cue during CER training induced a robust freezing response, providing a quantitative index of contextual memory when the rat was returned to the shock chamber 24 h later. Pretreatment (−20 min pre-training) with scopolamine or MK-801 reduced contextual freezing 24 h after CER training, showing production of memory impairment. Immediate post-training administration of 5-HT₆ receptor antagonist, SB-270146, and agonists, EMD 386088 and E-6801, had little effect on CER freezing when given alone, but all significantly reversed scopolamine- and MK-801-induced reduction in freezing.

CONCLUSION AND IMPLICATIONS

Both the 5-HT₆ receptor agonists and antagonist reversed cholinergic- and glutamatergic-induced deficits in associative learning. These findings support the therapeutic potential of 5-HT₆ receptor compounds in the treatment of cognitive dysfunction, such as seen in Alzheimer''s disease and schizophrenia.