利伐沙班在缺血性脑卒中合并小腿肌间静脉血栓形成患者中的疗效与安全性影响因素分析

目的：探讨利伐沙班在缺血性脑卒中（IS）合并小腿肌间静脉血栓（CMVT）患者中疗效与安全性的影响因素。方法：将134例IS合并CMVT患者根据利伐沙班剂量分为低剂量（10 mg·d^-1和15 mg·d^-1）组（n=80）和标准剂量（20 mg·d^-1）组（n=54）,收集并比较2组患者临床基线资料。随访记录治疗后的无效事件和出血事件,采用单因素和多因素Logistic回归分析危险因素,并建立风险预测模型。结果：低剂量组患者肌酐清除率（CrCl）<50 mL·min^-1、合用阿司匹林比例显著高于标准剂量组（P<0.05）,低密度脂蛋白胆固醇（LDL-C）>2.6 mmol·L^-1比例显著低于标准剂量组（P<0.05）。低剂量组患者治疗无效事件发生率明显高于标准剂量组、出血事件发生率明显低于标准剂量组（P<0.05）。多因素分析显示,标准剂量（20 mg·d^-1）是影响无效事件和出血事件的独立危险因素（P<0.05）,美国国立卫生研究院卒中量表（NIHSS）评分、合并冠心病是影响出血事件的独立危险因素（P<0.05）。出血事件联合预测因子Z=-3.642+1.341X_剂量+0.153X_NIHSS+1.334X_{合并冠心病},ROC曲线的AUC值为0.833,表明有良好的预测性能。结论：低剂量利伐沙班（10 mg·d^-1和15 mg·d^-1）可能更适合IS合并CMVT患者,临床应结合剂量、NIHSS评分、合并冠心病3种危险因素综合评估出血风险。     

Reversed anterolateral thigh adipofascial flap for knee and proximal calf defects

BACKGROUND: Reconstruction of defects involving the knee and proximal one third of the lower leg presents a challenging problem in plastic surgery. AIM: To evaluate the reversed anterolateral thigh adipofascial flap for covering such defects. METHODS: Between September 2006 and May 2007, one man and four women with defects around the knee and upper calf underwent reconstruction with reversed anterolateral thigh adipofascial flaps. The patients' average age was 45 years (25-72 years). The size of the transferred flap ranged from 6cmx8cm to 12cmx13cm. RESULTS: Four flaps with overlying skin grafts healed uneventfully; one skin graft showed minor necrosis due to haematoma, but the adipofascial flap survived well. Postoperatively the appearance of the reconstructive flap was acceptable. CONCLUSIONS: The reversed anterolateral thigh adipofascial flap is an effective option for covering defects of the knee and proximal calf.     

KIOM-79 inhibits high glucose or AGEs-induced VEGF expression in human retinal pigment epithelial cells

We evaluated whether KIOM-79, a mixture of extracts obtained from Puerariae lobata, Magnolia officinalis, Glycyrrhiza uralensis and Euphorbia pekinensis, could inhibit vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial (RPE) cells cultured under high glucose (HG, 25mM) or S100b (a specific ligand of the receptor for advance glycation end products (RAGE), 5microg/ml). In this study, the effect of KIOM-79 on HG or S100b-induced VEGF expression was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, RT-PCR, ELISA, and Western blot on human RPE cells. The MTT assay (p<0.01) revealed that KIOM-79 (up to 1mg/ml) had no effect on cell growth. HG or S100b induced an increase in expression of VEGF at both mRNA and protein levels (p<0.05; p<0.01 versus control). The increase in VEGF expression by HG or S100b was dose- and time-dependently prevented by KIOM-79 (p<0.05 versus 25mM glucose; p<0.01 versus S100b). Also, KIOM-79 inhibited protein kinase C (PKC)-alpha/beta(alpha) and p38 mitogen-activated protein kinase (MAPK) activation. Our results demonstrate that KIOM-79 can inhibit VEGF expression via inhibition of the MAPK and PKC pathway.     

DNA interactions of new cytotoxic tetrafunctional dinuclear platinum complex trans,trans-[{PtCl2(NH3)}2(piperazine)

A new tetrafunctional dinuclear platinum complex trans,trans-[{PtCl2(NH3)}2(piperazine)] with sterically rigid linking group was designed, synthesized and characterized. In this novel molecule, the DNA-binding features of two classes of the platinum compounds with proven antitumor activity are combined, namely trans oriented bifunctional mononuclear platinum complexes with a heterocyclic ligand and polynuclear platinum complexes. DNA-binding mode of this new complex was analyzed by various methods of molecular biology and biophysics. The complex coordinates DNA in a unique way and interstrand and intrastrand cross-links are the predominant lesions formed in DNA in cell-free media and in absence of proteins. An intriguing aspect of trans,trans-[{PtCl2(NH3)}2(piperazine)] is that, using a semi-rigid linker, interstrand cross-linking is diminished relative to other dinuclear platinum complexes with flexible linking groups and lesions that span several base pairs, such as tri- and tetrafunctional adducts, become unlikely. In addition, in contrast to the inability of trans,trans-[{PtCl2(NH3)}2(piperazine)] to cross-link two DNA duplexes, the results of the present work convincingly demonstrate that this dinuclear platinum complex forms specific DNA lesions which can efficiently cross-link proteins to DNA. The results substantiate the view that trans,trans-[{PtCl2(NH3)}2(piperazine)] or its analogues could be used as a tool for studies of DNA properties and their interactions or as a potential antitumor agent. The latter view is also corroborated by the observation that trans,trans-[{PtCl2(NH3)}2(piperazine)] is a more effective cytotoxic agent than cisplatin against human tumor ovarian cell lines.     

Two-pedal ergometer for in vivo MRS studies of human calf muscles.

This article describes an ergometer that enables human subjects to exercise one or both limbs while (31)P NMR spectra are obtained. Two independent pedals, equipped with position and force transducers, were mounted on the ergometer in order to calculate mechanical work performance. First, the effect of the magnetic field upon the signal coming from the transducers was investigated. Then the ergometer was tested by performing a series of steady-state exercises of increasing intensity. Experimental data showed that actual mechanical power ranged from 1.5 +/- 0.2 W to 11.0 +/- 1.6 W, while the corresponding oxygen consumption increased from 0.28 +/- 0.04 l/min at rest to 0.48 +/- 0.10 l/min at the highest load, and the PCr/(PCr+P(i)) ratio, as calculated from the (31)P spectra, decreased from 0.94 +/- 0.01 at rest to 0.73 +/- 0.04. These results are consistent with the values reported in the literature and show that this ergometer, which is easy to use, is suitable for in vivo spectroscopy research when metabolic steady-state conditions are required.     

Lipid signal extraction by SLIM: application to 1H MR spectroscopic imaging of human calf muscles.

The measurement of intramyocellular lipid (IMCL) using in vivo (1)H MRS is important for better understanding muscle physiology. However, the accurate measurement of IMCL in muscle adjacent to subcutaneous fat (SF) and bone marrow (BM) is often hampered by contaminations from the fat. In this article a new postacquisition processing method is proposed that selectively removes unwanted lipid signals based on the spectral localization by imaging (SLIM) technique, which can localize spectra from arbitrarily shaped regions. The effectiveness of this lipid extraction method is demonstrated by both computer simulation and in vivo experiments in the human calf. The advantage of this method is that unwanted lipid signal, such as SF signal, can be selectively and completely removed. After the contaminating fat signals are removed, the quality of muscle spectra adjacent to SF improves such that it becomes comparable to that in uncontaminated muscle regions in (1)H MRSI of the calf.     

Regulatory T cell abundance and activation status before and after priming with HIVIS-DNA and boosting with MVA-HIV/rgp140/GLA-AF may impact the magnitude of the vaccine-induced immune responses

Background

Little is known about regulatory CD4 T cells (Tregs) in the context of HIV vaccines. Tregs can be differentiated into resting (FoxP3⁺CD45RA⁺ – rTregs), activated (FoxP3^HighCD45RA^? – aTregs) and memory (FoxP3^LowCD45RA^? – mTregs). Tregs, as CD4 T cells, are also frequent targets for HIV infection. We studied how the abundance and phenotypes of Tregs in terms of activation status and expression of HIV-1 binding molecules would have changed during vaccination in healthy volunteers participating in a phase IIa HIV vaccine clinical trial. Subjects were primed three times with HIVIS-DNA and boosted twice with MVA-CMDR-HIV alone (n?=?12) or MVA-CMDR combined with protein CN54rgp140 (n?=?13). The proportions of β7 integrin in all CD4 T cells and in the Tregs subset decreased moderately after the final vaccination (p?=?0.001 and p?=?0.033, respectively) and the rTregs proportion within the total Tregs were also decreased after the final vaccination (p?=?0.038). All these proportions returned to normal values within the three months after the final vaccination. The magnitude of HIV-Envelope-specific IFNγ?+?T cells after vaccination (r?=?0.66; p?=?0.021) correlated directly with the proportion of Tregs, and correlated inversely correlated with ratios of Th17/Tregs (r?=??0.75; p?=?0.0057) and Th17/mTregs (r?=??0.78; p?=?0.0065). Higher titers of IgG gp140 antibodies were observed in subjects with higher mTregs proportions (r?=?0.52; p?=?0.022). Interestingly, pre-vaccination levels of mTregs correlated with vaccine-induced Env-binding antibodies (r?=?0.57; p?=?0.01) and presence of neutralizing antibodies (r?=?0.61; p?=?0.01), while the pre-vaccination Th17/mTregs ratio correlated inversely with the magnitude of cellular IFN-γ ELISpot responses (r?=??0.9; p?=?0.002). Taken together, these results suggest that pre- and post-vaccination Tregs, their activation status, the Th17/Tregs ratio and other host factors affecting Treg abundance, have an impact on the magnitude of HIV vaccine-induced immune responses. Moreover, the DNA-HIVIS/MVA-HIV regimen, alone or in combination with CN54rgp140 induced moderate and temporary alterations of the Tregs activation status. We also show a decrease in expression of the HIV-1 ligand β7 integrin on Tregs and all CD4 T cells.     

New immunomodulatory role of neuropeptide Y (NPY) in Salmo salar leucocytes

Neuropeptide Y (NPY) plays different roles in mammals such as: regulate food intake, memory retention, cardiovascular functions, and anxiety. It has also been shown in the modulation of chemotaxis, T lymphocyte differentiation, and leukocyte migration. In fish, NPY expression and functions have been studied but its immunomodulatory role remains undescribed. This study confirmed the expression and synthesis of NPY in S. salar under inflammation, and validated a commercial antibody for NPY detection in teleost. Additionally, immunomodulatory effects of NPY were assayed in vitro and in vivo. Phagocytosis and superoxide anion production in leukocytes and SHK cells were induced under stimulation with a synthetic peptide. IL-8 mRNA was selectively and strongly induced in the spleen, head kidney, and isolated cells, after in vivo challenge with NPY. All together suggest that NPY is expressed in immune tissues and modulates the immune response in teleost fish.     

阿魏酸钠、小牛血清去蛋白联合高压氧治疗急性一氧化碳中毒的临床研究

目的 探讨阿魏酸钠(川芎素)、小牛血清去蛋白对急性一氧化碳中毒的治疗作用.方法 将有昏迷史的75例急性一氧化碳中毒患者按随机数字表法分为治疗组(37例)和对照组(38例),两组均应用高压氧、高流量吸氧及对症支持治疗,治疗组加用川芎素、小牛血清去蛋白;对照组加用胞磷胆碱等药物.结果 治疗组心肌损伤发生率和严重程度评分均低于对照组(P＜0.05),昏迷时间和住院时间均短于对照组(P＜0.05).治疗组迟发性脑病发生率为2.7％(1/37),对照组为23.7％ (9/38),两组比较差异有统计学意义(P＜0.05);治疗组病死率为2.7％(1/37),对照组为5.3％(2/38),两组比较差异无统计学意义(P＞0.05).结论 川芎素、小牛血清去蛋白对急性一氧化碳中毒有较好的治疗作用.     

小牛血去蛋白提取物在青光眼术后结膜漏水中的应用

目的：探讨小牛血去蛋白提取物眼用凝胶对术中用丝裂霉素C的青光眼术后结膜漏水的修复能力。 方法：采取回顾性研究方法,将2007-01/2010-12我院青光眼小梁切除术后结膜漏水的患者分成不用小牛血去蛋白提取物眼用凝胶的对照组(A组)和用20%小牛血去蛋白提取物眼用凝胶的治疗组（B组）,记录结膜在术后3,7,14d愈合的情况,评价其有效性。 结果：小牛血去蛋白提取物眼用凝胶治疗组能缩短结膜愈合时间,与不用小牛血去蛋白提取物眼用凝胶的对照组比较,差异有统计学意义（P<0.05）。 结论：小牛血去蛋白提取物眼用凝胶能有效促进结膜修复,减少丝裂霉素C使用后的并发症。