慢性下肢溃疡的中医诊治

提出"虚、瘀"为本,"虚、邪、瘀、腐、损"为特点的慢性下肢溃疡的病机学说,确立内治与外治相结合的分期辨证的序贯治疗方案。内治以扶正化瘀贯穿治疗始终,注重益气健脾、补肾益精、通络生新;外治动态应用祛腐祛瘀补虚活血生肌的外治疗法,注重祛瘀化腐、活血生肌、煨脓湿润、煨脓祛腐、煨脓长肉的应用。丰富了中医学的创面修复理论,具有重要理论意义和临床应用价值。     

“扶正治癌”理论的科学内涵

恶性肿瘤已经成为全球第二位致死原因，急需提高整体防治效果，中西医结合治疗具有一定的优势和疗效。国医大师刘嘉湘先生融汇中西医学治疗肿瘤的优势，于1972年首先系统提出“扶正法”治癌的观 点，经过长期系统研究，构建了“道、法、术、理”完备的“扶正治癌”学术体系，推动恶性肿瘤的治疗原则从以“消 瘤为主”向“以人为本，人瘤并重”转换，提高了晚期肺癌的疗效，5年生存率达到24.22%的国内领先水平。本文 分别从机体免疫调控及诱导肿瘤细胞凋亡和衰老的角度揭示“扶正治癌”的科学内涵，并引入抑制静止期癌细 胞等新的研究方法和思路，以期进一步突破制约癌症防治效果的瓶颈。     

3-Hydroxy-3-methylglutaryl flavonol glycosides from Oxytropis falcata

Five new 3-hydroxy-3-methylglutaryl (HMG) flavonol 3-O-glycosides, named oxytroflavosides A-E (1-5), and two new rhamnocitrin 3-O-glycosides, oxytroflavosides F and G (6 and 7) were isolated from the n-BuOH-soluble fraction of an EtOH extract of Oxytropis falcata together with seven known kaempferol glycosides (8-14), of which six were isolated from the genus Oxytropis for the first time. The structures of these compounds were elucidated by spectroscopic techniques and chemical methods. The absolute configuration of HMG in compounds 1-5 was determined to be S through spectroscopic analysis of the mevalonamide obtained by amidation and reduction of the HMG moiety. Compounds 1-10 were evaluated for anti-inflammatory activities using lipopolysaccharide-induced RAW 264.7 cells, but none of them showed inhibitory effects on NO production.     

Transient up-regulation of gamma-aminobutyric acid(A) receptor binding by lubeluzole after neocortical specify lesion in rats

The effect of the neuroprotective drug lubeluzole on cortical receptor binding was investigated in animals with photothrombotic ischemic lesions. Control animals were treated with the inactive stereoisomer of the drug. Lubeluzole was applied intravenously as a single bolus (0.31 mg/kg) followed by a 1-h infusion of 0.31 mg/kg. Lubeluzole selectively increased gamma-amino-butyric acid(A) (GABA(A)) receptor binding but had no significant and/or consistent effects on N-methyl-D-aspartate (NMDA), (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), and kainate receptors. Lubeluzole caused a significant up-regulation of GABA(A) receptor binding in the lesioned area as well as in unimpaired cortical areas of both hemispheres. This effect appeared in the hours following the lesion and peaked at 24 h. Our findings suggest that reduced cortical excitability brought about by increased binding capacities of GABA(A) receptors may contribute to the neuroprotective effect of lubeluzole.     

The use of urine proteomic and metabonomic patterns for the diagnosis of interstitial cystitis and bacterial cystitis

The advent of systems biology approaches that have stemmed from the sequencing of the human genome has led to the search for new methods to diagnose diseases. While much effort has been focused on the identification of disease-specific biomarkers, recent efforts are underway toward the use of proteomic and metabonomic patterns to indicate disease. We have developed and contrasted the use of both proteomic and metabonomic patterns in urine for the detection of interstitial cystitis (IC). The methodology relies on advanced bioinformatics to scrutinize information contained within mass spectrometry (MS) and high-resolution proton nuclear magnetic resonance (1H-NMR) spectral patterns to distinguish IC-affected from non-affected individuals as well as those suffering from bacterial cystitis (BC). We have applied a novel pattern recognition tool that employs an unsupervised system (self-organizing-type cluster mapping) as a fitness test for a supervised system (a genetic algorithm). With this approach, a training set comprised of mass spectra and 1H-NMR spectra from urine derived from either unaffected individuals or patients with IC is employed so that the most fit combination of relative, normalized intensity features defined at precise m/z or chemical shift values plotted in n-space can reliably distinguish the cohorts used in training. Using this bioinformatic approach, we were able to discriminate spectral patterns associated with IC-affected, BC-affected, and unaffected patients with a success rate of approximately 84%.     

<Emphasis Type="Italic">Staphylococcus aureus</Emphasis> carriage at admission predicts early-onset pneumonia after burn trauma

Early-onset pneumonia (EOP) is frequent after burn trauma, increasing morbidity in the critical resuscitation phase, which may preclude early aggressive management of burn wounds. Currently, however, preemptive treatment is not recommended. The aim of this study was to identify predictive factors for EOP that may justify early empirical antibiotic treatment. Data for all burn patients requiring ≥4 h mechanical ventilation (MV) who were admitted between January 2001 and October 2012 were extracted from the hospital’s computerized information system. We reviewed EOP episodes (≤7 days) among patients who underwent endotracheal aspiration (ETA) within 5 days after admission. Univariate and multivariate analyses were performed to identify independent factors associated with EOP. Logistic regression was used to identify factors predicting EOP development. During the study period, 396 burn patients were admitted. ETA was performed within 5 days in 204/290 patients receiving ≥4 h MV. One hundred and eight patients developed EOP; 47 cases were caused by Staphylococcus aureus, 37 by Haemophilus influenzae, and 23 by Streptococcus pneumoniae. Among the 33 patients showing S. aureus positivity on ETA samples, 16 (48.5 %) developed S. aureus EOP. Among the 156?S. aureus non-carriers, 16 (10.2 %) developed EOP. Staphylococcus aureus carriage independently predicted EOP (p?<?0.0001). We identified S. aureus carriage as an independent and strong predictor of EOP. As rapid point-of-care testing for S. aureus is readily available, we recommend testing of all patients at admission for burn trauma and the consideration of early preemptive treatment in all positive patients. Further studies are needed to evaluate this new strategy.     

Peripheral blood CD4+CD8+ lymphocytes in cynomolgus monkeys are of resting memory T lineage

In this study, we analyzed peripheral blood CD4+CD8+ double-positive (DP) lymphocytes in adult cynomolgus monkeys (Macaca fascicularis). Forty of 55 monkeys had > 5% of the peripheral blood DP subpopulation (9.3 +/- 5.9%; mean +/- SD) in peripheral blood lymphocytes (PBL) in contrast to a low percentage of peripheral blood DP cells in humans and mice. In a cross-sectional study, the peripheral blood DP cells were found to increase in proportion with age. To clarify whether peripheral blood DP lymphocytes were immature precursors released from thymus without prior differentiation, the expressions of CD8 chains and CD1b on peripheral blood DP lymphocytes were compared with those on thymocytes. The peripheral blood DP lymphocytes were CD8 alpha + beta- and CD1b-, while thymic DP lymphocytes were CD8 alpha + beta + and CD1b +, suggesting that the peripheral blood DP cells are extrathymic T lymphocytes. Furthermore, the peripheral blood DP lymphocytes exhibited a resting memory T cell phenotype with CD2hiCD3+CD28-CD29hiCD49dhiCD69- CD80lo. Taken together, adult cynomolgus monkeys possess a unique peripheral blood DP T cell subpopulation which expresses a resting memory T cell phenotype. In addition, similar phenotypic properties of DP lymphocytes were distributed in the spleen and lymph nodes, although the proportion was less in the spleen and much less in lymph nodes than in PBL.      

Multifunctional superparamagnetic nanocarriers with folate-mediated and pH-responsive targeting properties for anticancer drug delivery

Multifunctional nanocarriers with multilayer core-shell architecture were prepared by coating superparamagnetic Fe(3)O(4) nanoparticle cores with a mixture of the triblock copolymer methoxy poly(ethylene glycol)-b-poly(methacrylic acid-co-n-butyl methacrylate)-b-poly(glycerol monomethacrylate) and the folate-conjugated block copolymer folate-poly(ethylene glycol)-b-poly(glycerol monomethacrylate). The model anticancer agent adriamycin (ADR), containing an amine group and a hydrophobic moiety, was loaded into the nanocarrier at pH 7.4 by ionic bonding and hydrophobic interactions. The release rate of the loaded drug molecules was slow at pH 7.4 (i.e. mimicking the blood environment) but increased significantly at acidic pH (i.e. mimicking endosome/lysosome conditions). Acid-triggered drug release resulted from the polycarboxylate protonation of poly(methacrylic acid), which broke the ionic bond between the carrier and ADR. Cellular uptake by folate receptor-overexpressing HeLa cells of the folate-conjugated ADR-loaded nanoparticles was higher than that of non-folated-conjugated nanoparticles. Thus, folate conjugation significantly increased nanoparticle cytotoxicity. These findings show the potential viability of a folate-targeting, pH-responsive nanocarrier for amine-containing anticancer drugs.     

Use of a Human-Like Low-Grade Bacteremia Model of Experimental Endocarditis To Study the Role of Staphylococcus aureus Adhesins and Platelet Aggregation in Early Endocarditis

Animal models of infective endocarditis (IE) induced by high-grade bacteremia revealed the pathogenic roles of Staphylococcus aureus surface adhesins and platelet aggregation in the infection process. In humans, however, S. aureus IE possibly occurs through repeated bouts of low-grade bacteremia from a colonized site or intravenous device. Here we used a rat model of IE induced by continuous low-grade bacteremia to explore further the contributions of S. aureus virulence factors to the initiation of IE. Rats with aortic vegetations were inoculated by continuous intravenous infusion (0.0017 ml/min over 10 h) with 10⁶ CFU of Lactococcus lactis pIL253 or a recombinant L. lactis strain expressing an individual S. aureus surface protein (ClfA, FnbpA, BCD, or SdrE) conferring a particular adhesive or platelet aggregation property. Vegetation infection was assessed 24 h later. Plasma was collected at 0, 2, and 6 h postinoculation to quantify the expression of tumor necrosis factor (TNF), interleukin 1α (IL-1α), IL-1β, IL-6, and IL-10. The percentage of vegetation infection relative to that with strain pIL253 (11%) increased when binding to fibrinogen was conferred on L. lactis (ClfA strain) (52%; P = 0.007) and increased further with adhesion to fibronectin (FnbpA strain) (75%; P < 0.001). Expression of fibronectin binding alone was not sufficient to induce IE (BCD strain) (10% of infection). Platelet aggregation increased the risk of vegetation infection (SdrE strain) (30%). Conferring adhesion to fibrinogen and fibronectin favored IL-1β and IL-6 production. Our results, with a model of IE induced by low-grade bacteremia, resembling human disease, extend the essential role of fibrinogen binding in the initiation of S. aureus IE. Triggering of platelet aggregation or an inflammatory response may contribute to or promote the development of IE.