泻白散及其主药体外抗氧化活性研究

目的 建立泻白散和方中3味主药甘草、地骨皮、桑白皮的体外抗氧化活性测定方法,并对31批药材和10批泻白散煎液的抗氧化活性进行测定。方法 采用紫外可见分光光度法检测一定浓度的药材提取液引起DPPH溶液吸光度（A）值降低,考察波长为517 nm,分别探索3味药材抗氧化活性成分的提取条件;并进行不同溶剂的吸收考察、专属性考察、DPPH线性考察、药材提取液线性考察、精密度试验、重复性试验、耐用性考察等方法学验证;以清除DPPH自由基的半抑制浓度（IC₅₀）作为评价指标,对泻白散和方中3味药材的体外抗氧化活性进行考察。结果 地骨皮、甘草、桑白皮和泻白散提取液的IC₅₀均值为0.31、1.24、1.49和0.91 g/L,泻白散提取工艺对方中药物抗氧化活性的保留均值为56%。结论 建立的抗氧化活性测定方法可用于泻白散及方中主药的抗氧化活性测定,为多维度评价中药和中药材质量提供新思路。     

遗传性凝血因子Ⅴ缺乏症九例基因分析

目的分析9例遗传性凝血因子Ⅴ（FⅤ）缺乏症患者的临床表现及分子致病机制。方法对1999年4月至2019年9月就诊于中国医学科学院血液病医院的9例遗传性FⅤ缺乏症患者进行回顾性分析：应用活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）及FⅤ促凝活性（FⅤ∶C）测定进行表型诊断；使用高通量靶向测序筛查F5基因变异，Sanger测序验证并分析双亲携带情况；Swiss-model进行三维结构分析，ClustalX-2.1软件进行同源保守性分析。结果9例患者的FⅤ∶C为0.1～10.6 U/dl，其中8例患者有出血病史，以皮肤/黏膜出血最为多见（3例），其余1例未发生出血事件。所有患者中纯合子5例，复合杂合子4例，共检测到12个致病或疑似致病F5基因突变，其中c.6100C>A/p.Pro2034Thr、c.6575T>C/p.Phe2192Ser、c.1600_1601delinsTG/p.Gln534*、c.4713C>A/p.Tyr1571*和c.952+5G>C为首次报道。结论该研究新发现的基因突变丰富了与遗传性FⅤ缺乏症相关F5基因突变谱，高通量测序方法可以有效检测F5基因突变。     

Chronic effects of cannabis on sensory gating

Chronic cannabis use has been associated with neurocognitive deficits, alterations in brain structure and function, and with psychosis. This study investigated the effects of chronic cannabis use on P50 sensory-gating in regular users, and explored the association between sensory gating, cannabis use history and the development of psychotic-like symptoms. Twenty controls and 21 regular cannabis users completed a P50 paired-click (S1 and S2) paradigm with an inter-pair interval of 9 s. The groups were compared on P50 amplitude to S1 and S2, P50 ratio (S2/S1) and P50 difference score (S1–S2). While cannabis users overall did not differ from controls on P50 measures, prolonged duration of regular use was associated with greater impairment in sensory gating as indexed by both P50 ratio and difference scores (including after controlling for tobacco use). Long-term cannabis users were found to have worse sensory gating ratios and difference scores compared to short-term users and controls. P50 metrics did not correlate significantly with any measure of psychotic-like symptoms in cannabis users. These results suggest that prolonged exposure to cannabis results in impaired P50 sensory-gating in long-term cannabis users. While it is possible that these deficits may have pre-dated cannabis use and reflect a vulnerability to cannabis use, their association with increasing years of cannabis use suggests that this is not the case. Impaired P50 sensory-gating ratios have also been reported in patients with schizophrenia and may indicate a similar underlying pathology.     

Influence of MRE11, RAD50 and NIBRIN protein expression on survival in pancreatic carcinoma after curative resection

The MRE11/RAD50/NIBRIN complex, a protein complex that repairs DNA double-strand breaks, could serve as an early marker for new lesions in pancreatic cancer. We determined the expression of MRE11, RAD50 and NIBRIN, and their possible prognostic value regarding survival.     

Differences in airway cytokine profile in severe asthma compared to moderate asthma

BACKGROUND: Some studies of severe asthma suggest that persistence or alteration in the pattern of inflammation may be associated with the severity of the disease. Whether there are differences in the expression of the principal cytokines and chemokines relevant to eosinophilic and neutrophilic inflammation in the airway tissues of severe compared to moderate asthmatics has not been determined. The aim of this study was to compare the patterns of expression of representative T-helper (Th) type 1 (interferon [IFN]-gamma) and Th-2 cytokines (interleukin [IL]-4, IL-5) and the neutrophil- and eosinophil-associated chemokines (IL-8 and eotaxin) in the airway tissues of patients with severe and moderate asthma. METHODS: Subjects with severe asthma (n = 24) and a comparison moderate asthma group (n = 26) were assessed using spirometry, induced sputum, exhaled nitric oxide, and bronchial biopsy. The expression of proteins of interest in the epithelium and subepithelium of the airway wall was examined by immunocytochemistry. RESULTS: Subjects with severe asthma were more symptomatic, had a lower FEV(1), and had more sputum neutrophilia (p = 0.007) and eosinophilia (p = 0.001). Exhaled nitric oxide was similar between groups. IL-8 and IFN-gamma expression were increased and IL-4 expression was decreased in severe asthma compared to moderate disease (p < 0.001 for each comparison). Eotaxin and IL-5 expression did not differ between the groups. CONCLUSION: Patients with severe asthma have increases in neutrophils and eosinophils in the sputum, and differ in airway cytokine/chemokine expression from moderate asthmatics. Excess neutrophilia may be explained by increased expression of IL-8, but differences in eosinophilia do not appear to be associated with IL-5 and eotaxin expression.     

Phenotype classification using the combination of lung sound analysis and fractional exhaled nitric oxide for evaluating asthma treatment

Background

We report the utility of combining lung sound analysis and fractional exhaled nitric oxide (FeNO) for phenotype classification of airway inflammation in patients with bronchial asthma.We investigated the usefulness of the combination of the expiration-to-inspiration sound power ratio in the mid-frequency range (E/I MF) of 200–400 Hz and FeNO for comprehensively classifying disease type and evaluating asthma treatment.

Left ventricular function at high altitude examined by systolic time intervals and M-mode echocardiography

To better understand the effects of high-altitude hypoxia on cardiac performance, healthy lowlandresiding volunteers were studied in 2 groups: 10 subjects after acute ascent to 12,500 ft (3,810 m) (acute group) and 9 subjects after chronic exposure for 6 weeks to 17,600 ft (5,365 m) and 11,000 ft (3,353 m) (chronic group). Systolic time intervals and M-mode echocardiograms were recorded at low and high altitudes. Heart rate was 21% greater at high altitude for all subjects. Preejection period/left ventricular ejection time (PEP/LVET) increased by 16% in the acute group and by 22% in the chronic group. Heart size was smaller at high altitude in both groups, with left atrial and left ventricular (LV) diameters decreasing by 10 to 12%. These changes were statistically significant (p ≤ 0.01). Despite the increase in PEP/LVET, echocardiographic measurements of LV function (percent fractional shortening and mean normalized velocity of circumferential fiber shortening) remained normal. LV isovolumic contraction time was shorter at high altitude, suggesting heightened, rather than depressed, contractility. LV function does not appear to deteriorate at high altitude. Alterations in systolic time intervals probably result from decreased preload, as reflected by smaller heart size, rather than from heart failure or depressed LV contractility.     

Blunted muscle responsiveness to insulin in the neonatal rat

Peripheral muscle responsiveness to insulin was studied in neonatal rats in vivo by measuring net incorporation of radiolabeled glucose to glycogen in diaphragm. D(U-¹⁴C) glucose, 0.03 μCi/g rat pup weight, was injected i.p. with or without (control) insulin 5000 μU/g rat pup weight into pups from 86 litters of Sprague-Dawley rats as well as into 16 adult rats by the technique of Rafaelson. Diaphragms were excised after a 30-min in vivo exposure at birth, 24, 48, 72, or 168 hr of age and in the adult rats. Insulin increased net incorporation of radiolabeled glucose into diaphragm glycogen in comparison to age-matched controls (p < 0.025). The percent stimulation by insulin of labeled glucose into diaphragm glycogen was low at birth (250%) and at 24 hr (200%), but increased with advancing age and approached adult levels by 168 hr (1270%). At birth and at 24 hr, a 5-log insulin dose-response curve showed significant net incorporation only at 5000 μU insulin/g rat pup weight; by 72 hr a significant increase was noted at 50 μU insulin/g rat pup weight. Muscle glycogen concentration was high at birth ($\text{1.22 mg}\text{100 mg tissue}$), fell to 50% of the birth value from 24 through 168 hr, and could not account for the decreased insulin response noted. Decreased uptake of deoxyglucose into diaphragm in vivo paralleled the reduced net incorporation of radiolabeled glucose into diaphragm glycogen during the time period studied. The data are interpreted to indicate a blunted responsiveness of skeletal muscle to insulin during the first 48 hr in rats, which is related to decreased sensitivity of hexose transport to insulin.     

吸氧对听感觉门控P50的影响

目的研究呼吸纯氧对健康人听感觉门控P50的影响。方法右利手、健康男性大学生志愿者28名,根据随机数字表分为对照组(n=12)和实验组(n=16)。佩戴面罩,对照组呼吸空气,实验组呼吸医用纯氧60 min。应用条件-测试刺激,记录吸氧前(pre0)、吸氧20 min(Oxy20)、吸氧50 min(Oxy50)、吸氧后30 min(post30)的脑电图,计算听觉P50潜伏期和P50感觉门控电位(S1与S2振幅之差)。结果 S1刺激在4个时间点各组P50潜伏期相对稳定(P0.7);吸氧50 min时,实验组比对照组P50潜伏期缩短(P0.05)。S2刺激在4个时间点各组P50潜伏期相对稳定(P0.30),两组间比较无显著性差异(P0.05)。对照组P50门控电位比较稳定(P=0.70),而实验组随吸氧时间逐渐延长,电位越来越高,停止吸氧后,电位迅速回落,Oxy20和post30(P=0.04)、Oxy50和post30(P=0.02)相比均有显著性差异。组间比较,4个时间点均无显著性差异(P0.05)。结论健康人吸60 min纯氧,可能缩短对刺激的反应时间,有增强听觉门控电位的趋势。