高海拔地区缺血性卒中患者单核 细胞/HDL-C比值与脑动脉粥样硬化性狭窄的相关性

目的 研究高海拔地区缺血性卒中患者单核细胞/HDL-C比值（monocyte/HDL-C ratio,MHR）与颅内动脉粥样硬化性狭窄（intracranial atherosclerotic stenosis,ICSA）程度的相关性。 方法 回顾性连续纳入2017年6月-2021年6月在青海省人民医院住院治疗的高海拔地区（海拔2260～4080?m）的急性缺血性卒中患者,依据DSA上脑血管狭窄程度（以狭窄最严重的动脉为准）分为无狭窄组、轻度狭窄（狭窄率≤50%）组、中度狭窄（狭窄率50%～70%）组、重度狭窄（狭窄率≥70%）组及闭塞（100%）组。比较5组患者的临床资料、实验室检查指标和MHR,并采用logistic回归模型计算不同程度血管狭窄的独立危险因素。 结果 共纳入349例患者,其中无狭窄组69例、轻度狭窄组78例、中度狭窄组41例、重度狭窄组84例、闭塞组77例。5组中年龄、性别分布、吸烟、饮酒、高血压、糖尿病比例方面差异均有统计学意义,实验室检查中白细胞、单核细胞、中性粒细胞、血小板计数以及血红蛋白、HDL-C水平和MHR差异也有统计学意义。多因素logistic回归分析显示,相对于无动脉狭窄,高龄为脑血管轻度狭窄（OR?1.061,95%CI?1.027～1.097,P＜0.001）,中度狭窄（OR?1.057,95%CI?1.017～1.099,P＝0.005）,重度狭窄（OR?1.096,95%CI?1.057～1.137,P＜0.001）,闭塞（OR?1.036,95%CI?1.001～1.072,P＝0.046）的独立危险因素;相对于无动脉狭窄,高MHR为轻度狭窄（OR?1.041,95%CI?1.009～1.074,P＝0.011）,中度狭窄（OR?1.082,95%CI?1.045～1.119,P＜0.001）,重度狭窄（OR?1.096,95%CI?1.062～1.131,P＜0.001）,闭塞（OR?1.101,95%CI?1.067～1.136,P＜0.001）的独立危险因素;相对于无动脉狭窄,单核细胞计数升高是中度狭窄（OR?1.684,95%CI?1.569～2.725,P=0.027）、重度狭窄（OR?3.529,95%CI?1.541～5.766,P=0.002 ）和闭塞（OR?5.446,95%CI?4.453～6.917,P=0.002）的独立危险因素。 结论 高龄、高MHR和单核细胞计数升高在高海拔地区对急性缺血性卒中患者的脑动脉粥样硬化性狭窄程度具有一定预测价值。     

残留白血病细胞抗药再生长的实验研究

目的：阐明残留白血病形成及抗药再生长的机制。方法：用可移植性白血病模型Ｌ６１５和Ｌ７８１１小鼠骨髓作长期培养，用柔红霉素模拟体内治疗。结果：发现少数粘附于基质滋养层的残留白血病细胞逃避了柔红霉素的杀伤作用，并在药物作用下再生长。粘附的白血病细胞群中含有许多分化程度较低的静止期细胞，表达ｂｃｌ－２基因，有一定抗药能力，是残留白血病细胞的来源。结论：骨髓基质细胞滋养层是残留白血病细胞生存和再生长的微环境，可能通过上调ｂｃｌ－２基因表达增强其抗药能力。     

Effectiveness of the endotracheal tube cuff on the trachea: physical and mechanical aspects

Introduction

The inflation pressure of the endotracheal tube cuff can cause ischemia of the tracheal mucosa at high pressures; thus, it can cause important tracheal morbidity and tracheal microaspiration of the oropharyngeal secretion, or it can even cause pneumonia associated with mechanical ventilation if the pressure of the cuff is insufficient.

Objective

In order to investigate the effectiveness of the RUSCH® 7.5 mm endotracheal tube cuff, this study was designed to investigate the physical and mechanical aspects of the cuff in contact with the trachea.

Methods

For this end, we developed an in vitro experimental model to assess the flow of dye (methylene blue) by the inflated cuff on the wall of the artificial material. We also designed an in vivo study with 12 Large White pigs under endotracheal intubation. We instilled the same dye in the oral cavity of the animals, and we analyzed the presence or not of leakage in the trachea after the region of the cuff after their deaths (animal sacrifice). All cuffs were inflated at the pressure of 30 cmH₂O.

Results

We observed the passage of fluids through the cuff in all in vitro and in vivo experimental models.

Conclusion

We conclude that, as well as several other cuff models in the literature, the RUSCH® 7.5 mm tube cuffs are also not able to completely seal the trachea and thus prevent aspiration of oropharyngeal secretions. Other prevention measures should be taken.     

Time course of systemic oxidative stress and inflammatory response induced by an acute exposure to Residual Oil Fly Ash

It is suggested that systemic oxidative stress and inflammation play a central role in the onset and progression of cardiovascular diseases associated with the exposure to particulate matter (PM). The aim of this work was to evaluate the time changes of systemic markers of oxidative stress and inflammation, after an acute exposure to Residual Oil Fly Ash (ROFA). Female Swiss mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight) or saline solution, and plasma levels of oxidative damage markers [thiobarbituric acid reactive substances (TBARSs) and protein carbonyls], antioxidant status [reduced (GSH) and oxidized (GSSG) glutathione, ascorbic acid levels, and superoxide dismutase (SOD) activity], cytokines levels, and intravascular leukocyte activation were evaluated after 1, 3 or 5 h of exposure. Oxidative damage to lipids and decreased GSH/GSSG ratio were observed in ROFA-exposed mice as early as 1 h. Afterwards, increased protein oxidation, decreased ascorbic acid content and SOD activity were found in this group at 3 h. The onset of an adaptive response was observed at 5 h after the ROFA exposure, as indicated by decreased TBARS plasma content and increased SOD activity. The observed increase in oxidative damage to plasma macromolecules, together with systemic antioxidants depletion, may be a consequence of a systemic inflammatory response triggered by the ROFA exposure, since increased TNF-α and IL-6 plasma levels and polymorphonuclear leukocytes activation was found at every evaluated time point. These findings contribute to the understanding of the increase in cardiovascular morbidity and mortality, in association with environmental PM inhalation.     

Optimization of secondary drying condition for desired residual water content in a lyophilized product using a novel simulation program for pharmaceutical lyophilization

The aim of this study was to optimize the shelf temperature and the drying time, mainly dependent on the residual water content of a lyophilized product using a novel simulation program for the secondary drying of lyophilization. The simulation program was developed based upon heat transfer formulas, two empirical formulas, and a modified Fick’s second law. When a preliminary lyophilization run of secondary drying was carried out, the equilibrium product temperature at the end of secondary drying under various shelf temperatures was accurately predicted by the heat transfer formulas. The apparent diffusion coefficient of water, D_eff, and the apparent equilibrium residual water content, W_e, under the predicted equilibrium product temperature were estimated by two empirical formulas. These estimated D_eff and W_e allow the modified Fick’s second law to predict the residual water content in the lyophilized product. Using the developed simulation program, it was verified that the secondary drying condition to achieve the desired residual water content in the lyophilized product was successfully predicted. Therefore, the simulation program can be used to effectively design the secondary drying condition of lyophilization cycles without a trial and error approach.     

椎动脉起始部重度狭窄患者支架置入与药物治疗的疗效比较

目的观察比较重度椎动脉起始部狭窄患者支架置人治疗的疗效是否优于单纯药物治疗。方法选择127例椎动脉起始部重度狭窄（≥70％）的患者,分为支架置入组52例和药物治疗组75例,比较两组患者再发后循环缺血事件的随访结果。两组患者平均随访（18．3±10．9）个月。结果支架置入组再次发生后循环缺血事件1例（1．9％）,药物治疗组再次发生后循环缺血事件14例（18．6％）。结论椎动脉起始部重度狭窄患者支架置入治疗疗效优于药物治疗。     

早期中药湿热敷治疗腰椎间盘突出症术后残余痛的效果分析

目的观察早期中药湿热敷对腰椎间盘突出症术后残余痛的临床疗效。方法选取2010年2月～2013年2月在本院行腰椎间盘突出症后路开窗髓核摘除的患者106例,将其随机分为治疗组和对照组各53例,对照组患者进行常规药物治疗和康复锻炼,治疗组在常规治疗的基础上行中药湿热敷进行早期干预,于1、6个月比较两组的临床疗效。结果两组患者均按时随访,术后1个月治疗组优良率为92．45％,对照组为73．58％,术后6个月治疗组优良率为92．45％,对照组为71．70％,治疗组术后1、6个月的优良率均高于对照组,差异有统计学意义（P〈0．01）。结论早期对腰椎间盘突出症经后路髓核摘除的患者进行中药湿热敷,可明显减少术后残余痛的发生,且操作简单,安全经济,无副作用,值得临床推广。     

Cytokines can reduce clonal, CD34-positive cells in acute myeloid leukemia in vitro

We studied the influence of cytokine mixes on the survival of acute myeloid leukemia (AML) bone-marrow (BM) cells in a 14-day culture assay in vitro. Southern-blot analysis using a panel of different probes in combination with densitometry and flow cytometry were used to detect and compare the amount of clonal or CD34-positive BM cells before and after the culturing procedure. A significant reduction of CD34-positive cells after incubation with a cytokine mix [interleukin (IL)-1β, IL-3, IL-6, stem cell factor (SCF), erythropoietin (EP) with granulocyte macrophage/colony-stimulating factor (GM-CSF, Cytok1] could be achieved in all 16 cases with a CD34-positive blast phenotype studied at diagnosis (P<0.001), in 3 of 10 cases at relapse, and in 8 of 18 cases in complete remission. In healthy donors, an increase of CD34-positive cells was demonstrated in 5 of 5 samples. A reduction of clonal DNA through incubation with Cytok1 was achieved in 5 of 5 (100 %) cases studied at diagnosis, in 1 of 4 (25%) cases at relapse, and in 7 of 9 cases (78%) in complete remission. Cytokine cocktails with GM-CSF (Cytok1) were more efficient in reducing (clonal) CD34-positive cells than cocktails without GM-CSF (Cytok2). AML patients at diagnosis and in complete remission had a better survival probability if their CD34-positive or clonal cells could be reduced in vitro by cytokine cultivation (P<0.05). Vitality of BM cells was not influenced by 14-day cytokine treatment; however, the total cell count could be increased by Cytok1 and Cytok2 by 55–174%, but not by the control medium. Our data show that: (1) clonal cell populations can be regularly detected at diagnosis, during complete remission, and at relapse; (2) CD34-positive cells in AML can be demonstrated to be clonal, gene-rearranged cells; (3) incubation of AML BM-cells with Cytok1 leads to a reduction of the CD34-positive, clonal cell load in all cases at diagnosis and in 78% of the cases in complete remission of AML, but in only 25% of the cases at relapse; (4) in all healthy BM samples, proportions of ‘healthy’ CD34-positive cells were increased. Moreover, absolute cell counts were increased by cytokine incubation of cells obtained at diagnosis, relapse, or complete remission of AML and from healthy donors indicating a selective stimulation of healthy, but not of leukemic CD34-positive cells; (5) cytokine cocktails containing GM-CSF are more efficient in reducing leukemic cells than cocktails without GM-CSF; and (6) in vitro reactivity of clonal or CD34-positive BM cells against Cytok1 has clinical relevance. We conclude, that Southern-blot analysis and flow cytometry are suitable methods to detect and quantify leukemic disease and to distinguish between clonal or non-clonal CD34-positive cells. The ex vivo or clinical application of specific combinations of cytokines might be a feasible and successful application of immunotherapy in AML that merits further investigations. Received: 19 April 1999 / Accepted: 13 January 2000     

Renin–angiotensin system inhibition is not associated with increased sudden cardiac death,cardiovascular mortality or all-cause mortality in patients with aortic stenosis

Background

Renin–angiotensin system inhibition (RASI) is frequently avoided in aortic stenosis (AS) patients because of fear of hypotension. We evaluated if RASI with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) increased mortality in patients with mild to moderate AS.

Methods

All patients (n = 1873) from the Simvastatin and Ezetimibe in Aortic Stenosis study: asymptomatic patients with AS and preserved left ventricular (LV) ejection fraction were included. Risks of sudden cardiac death (SCD), cardiovascular death and all-cause mortality according to RASI treatment were analyzed by multivariable time-varying Cox models and propensity score matched analyses.

Results

769 (41%) patients received RASI. During a median follow-up of 4.3 ± 0.9 years, 678 patients were categorized as having severe AS, 545 underwent aortic valve replacement, 40 SCDs, 103 cardiovascular and 205 all-cause deaths occurred. RASI was not associated with SCD (HR: 1.19 [95%CI: 0.50–2.83], p = 0.694), cardiovascular (HR: 1.05 [95%CI: 0.62–1.77], p = 0.854) or all-cause mortality (HR: 0.81 [95%CI: 0.55–1.20], p = 0.281). This was confirmed in propensity matched analysis (all p > 0.05). In separate analyses, RASI was associated with larger reduction in systolic blood pressure (p = 0.001) and less progression of LV mass (p = 0.040).

Conclusions

RASI was not associated with SCD, cardiovascular or all-cause mortality in asymptomatic AS patients. However, RASI was associated with a potentially beneficial decrease in blood pressure and reduced LV mass progression.