神经生长因子治疗急性颅脑损伤的效果及对患者神经功能的影响

目的:研究神经生长因子在急性颅脑损伤中的治疗效果及对神经功能的影响。方法:选取2014年8月至2015年7月本院收治的82例急性颅脑损伤患者,随机分为观察组和对照组,每组41例。对照组采取常规对症治疗,观察组在对照组基础上采用神经生长因子治疗。观察并比较两组患者治疗前后血清S100β,白介素-6(IL-6),髓鞘碱性蛋白(MBP)及神经元特异性烯醇化酶(NSE)水平的变化情况以及临床疗效。结果:观察组总有效率高于对照组,差异具有统计学意义(P0.05)。与治疗前比较,两组患者治疗后血清S100β及IL-6水平均降低,差异具有统计学意义(P0.05);与对照组比较,观察组患者治疗后血清S100β及IL-6水平较低,差异具有统计学意义(P0.05);与治疗前比较,两组患者治疗后血清MBP及NSE水平均降低,差异具有统计学意义(P0.05);与对照组比较,观察组患者治疗后血清MBP及NSE水平较低,差异具有统计学意义(P0.05)。结论:神经生长因子治疗急性颅脑损伤的效果显著,能够改善患者免疫功能和神经功能,值得临床推广应用。     

优质护理模式对心肌梗死康复期患者心理障碍及不良情绪的影响研究

目的:研究优质护理模式对心肌梗死康复期患者心理障碍及不良情绪的影响程度,旨在为康复期患者护理方式的选取提供理论依据。方法:将本院2014年1月~2014年12月的70例心肌梗死康复期患者遵照随机数字表法分为对照组和观察组各35例,对照组采用常规的康复护理进行干预,观察组则以优质护理理念为指导进行护理干预,然后将两组护理前和护理后2周、4周及8周的心理障碍及不良情绪状态采用SECD6量表及HAD量表进行评估,并将评估结果进行比较。结果:观察组护理后2周、4周及8周的SECD6量表及HAD量表评估结果均明显优于对照组,P均0.05,均有显著性差异。结论:优质护理模式对心肌梗死康复期患者治疗信心及不良情绪的影响相对更为积极,为患者康复治疗的顺利进行奠定了基础。     

NEIL3-Dependent Regulation of Cardiac Fibroblast Proliferation Prevents Myocardial Rupture

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氨氮对中华小长臂虾的急性毒性及非特异性免疫指标的影响

采用生物毒性实验方法研究了氨氮对中华小长臂虾的急性毒性作用, 结果表明: 在温度为(18±1)℃, pH为7.3±0.1条件下, 氨氮对中华小长臂虾24h、48h、72h、96h 的半致死浓度(LC₅₀)分别为565.47、371.16、291.16和272.50 mg/L, 安全浓度为 27.25 mg/L。转化为非离子氨的LC₅₀分别为3.74、2.45、1.93 和1.80 mg/L, 安全浓度为0.18 mg/L。根据96h 的LC₅₀和安全浓度按照等差数列设置5个氨氮浓度梯度, 分别60、100、140、180和220 mg/L, 研究氨氮胁迫对中华小长臂虾非特异性免疫指标的影响。结果显示: 在24h时, 除了220 mg/L的肌肉组织, 中华小长臂虾肝胰腺和肌肉中的超氧化物歧化酶(SOD)活性显著性高于对照组, 并具有明显的剂量效应, 在48—96h均回落到正常水平; 在24h时, 中华小长臂虾氨氮处理组中肝胰腺的酸性磷酸酶(ACP)与对照组未发生显著变化, 而碱性磷酸酶(AKP)则显著高于对照组, 在48—96h两者的140、180和220 mg/L处理组均显著低于对照组; 除了140 mg/L 处理组的ACP活性外, 肌肉中的ACP和AKP活性从24h开始就出现了显著性下降, 始终低于对照组。研究获得了氨氮对中华小长臂虾的急性毒性结果和在高氨氮胁迫下非特异性免疫指标的变化规律, 发现中华小长臂虾对氨氮具有较强的耐受性, 但高浓度的氨氮会对中华小长臂虾的免疫酶活性产生抑制作用, 研究结果可为中华小长臂虾健康养殖发展提供科学依据。     

P2X7 receptor inhibition attenuated sympathetic nerve sprouting after myocardial infarction via the NLRP3/IL‐1β pathway

Mounting evidence supports the hypothesis that inflammation modulates sympathetic sprouting after myocardial infarction (MI). The myeloid P2X₇ signal has been shown to activate the nucleotide‐binding and oligomerization domain‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome, a master regulator of inflammation. We investigated whether P2X₇ signal participated in the pathogenesis of sympathetic reinnervation after MI, and whether NLRP3/interleukin‐1β (IL‐1β) axis is involved in the process. We explored the relationship between P2X₇ receptor (P2X₇R) and IL‐1β in the heart tissue of lipopolysaccharide (LPS)‐primed naive rats. 3′‐O‐(4‐benzoyl) benzoyl adenosine 5′‐triphosphate (BzATP), a P2X₇R agonist, induced caspase‐1 activation and mature IL‐1β release, which was further neutralized by a NLRP3 inhibitor (16673‐34‐0). MI was induced by coronary artery ligation. Following infarction, a marked increase in P2X₇R was localized within infiltrated macrophages and observed in parallel with an up‐regulation of NLRP3 inflammasome levels and the release of IL‐1β in the left ventricle. The administration of A‐740003 (a P2X₇R antagonist) significantly prevented the NLRP3/IL‐1β increase. A‐740003 and/or Anakinra (an IL‐1 receptor antagonist) significantly reduced macrophage infiltration as well as macrophage‐based IL‐1β and NGF (nerve growth factor) production and eventually blunted sympathetic hyperinnervation, as assessed by the immunofluorescence of tyrosine hydroxylase (TH) and growth‐associated protein 43 (GAP 43). Moreover, the use of Anakinra partly attenuated sympathetic sprouting. This indicated that the effect of P2X₇ on neural remodelling was mediated at least partially by IL‐1β. The arrhythmia score of programmed electric stimulation was in accordance with the degree of sympathetic hyperinnervation. In vitro studies showed that BzATP up‐regulated secretion of nerve growth factor (NGF) in M1 macrophages via IL‐1β. Together, these data indicate that P2X₇R contributes to neural and cardiac remodelling, at least partly mediated by NLRP3/IL‐1β axis. Therapeutic interventions targeting P2X₇ signal may be a novel approach to ameliorate arrhythmia following MI.     

Synthesis of (1,3,4-thiadiazol-2-yl)-acrylamide derivatives as potential antitumor agents against acute leukemia cells

A lead compound with the (1,3,4-thiadiazol-2-yl)-acrylamide scaffold was discovered to have significant cytotoxicity on several tumor cell lines in an in-house cell-based screening. A total of 60 derivative compounds were then synthesized and tested in a CCK-8 cell viability assay. Some of them exhibited improved cytotoxic activities. The most potent compounds had IC₅₀ values of 1–5 μM on two acute leukemia tumor cell lines, i.e. RS4;11 and HL-60. Flow cytometry analysis of several active compounds and detection of caspase activation indicated that they induced caspase-dependent apoptosis. It was also encouraging to observe that these compounds did not have obvious cytotoxicity on normal cells, i.e. IC₅₀ > 50 μM on HEK-293T cells. Although the molecular targets of this class of compound are yet to be revealed, our current results suggest that this class of compound represents a new possibility for developing drug candidates against acute leukemia.     

急性早幼粒细胞白血病巩固治疗现状及进展

急性早幼粒细胞白血病(APL)曾被认为是最迅速的致命白血病,特点为临床表现凶险,早期死亡率高,治愈率低。药物全反式维甲酸及亚砷酸的应用,使APL的治疗取得了很大成功,其完全缓解率可达90%。然而APL的复发率仍然较高,约15%-30%。降低复发率和提高长期生存已成为研究重点,如何选择合理的缓解后治疗策略至关重要。缓解后治疗一般包括巩固治疗和维持治疗,而最佳治疗方案的确定仍然有待商榷。因此,本文就APL缓解后巩固治疗回顾相关文献进行整合分析,综述APL巩固治疗的研究进展。     

Rutin decreases lipopolysaccharide-induced acute lung injury via inhibition of oxidative stress and the MAPK–NF-κB pathway

Acute lung injury (ALI) is a serious disease with unacceptably high mortality and morbidity rates. Up to now, no effective therapeutic strategy for ALI has been established. Rutin, quercetin-3-rhamnosyl glucoside, expresses a wide range of biological activities and pharmacological effects, such as anti-inflammatory, antihypertensive, anticarcinogenic, vasoprotective, and cardioprotective activities. Pretreatment with rutin inhibited not only histopathological changes in lung tissues but also infiltration of polymorphonuclear granulocytes into bronchoalveolar lavage fluid in lipopolysaccharide (LPS)-induced ALI. In addition, LPS-induced inflammatory responses, including increased secretion of proinflammatory cytokines and lipid peroxidation, were inhibited by rutin in a concentration-dependent manner. Furthermore, rutin suppressed phosphorylation of NF-κB and MAPK and degradation of IκB, an NF-κB inhibitor. Decreased activities of antioxidative enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase-1 caused by LPS were reversed by rutin. At the same time, we found that ALI amelioration by chelation of extracellular metal ions with rutin is more efficacious than with deferoxamine. These results indicate that the protective mechanism of rutin is through inhibition of MAPK–NF-κB activation and upregulation of antioxidative enzymes.     

趋化因子及趋化因子受体在急性胰腺炎中的研究进展

普遍认为,急性胰腺炎起始于腺泡细胞内的胰蛋白酶原激活,随后引起的炎症反应加剧病情,也是多器官功能衰竭的主要原因。然而,最新的研究表明,急性胰腺炎引起的炎症反应是不依赖于胰蛋白酶原激活的独立病理过程。趋化因子作为能引起细胞趋化的细胞因子,通过与趋化因子受体作用,不但能调控淋巴细胞的生长、成熟和迁移,也参与多种炎症疾病与癌症的病理过程。近年来,多项研究已经阐述趋化因子及趋化因子受体在急性胰腺炎的发病发展过程中起到至关重要的作用。本文总结了CC,CXC和CX3C趋化因子家族成员在参与急性胰腺炎的炎症反应及对胰腺损伤的修复的研究进展,这将为AP临床治疗方案的设计提供新思路。