血管内皮生长因子结合可降解壳聚糖治疗大鼠心肌梗塞的研究

摘要:目的 研 究 血 管 内 皮 生 长 因 子 ( vascular endothelial growth factor, VEGF ) 结 合 可 降 解 壳 聚 糖 ( degradablechitosan,DC)对心肌梗塞大鼠的治疗作用。 方法 将 32 只 SD 大鼠随机分为假手术组、模型组、VEGF 组和 VEGF+ DC 组,每组 8 只。 4 组大鼠均采用结扎冠状动脉左前降支的方法进行造模,其中假手术组只穿线不结扎。 造模后, 向模型组大鼠心肌注射 100 μL 生理盐水,VEGF 组大鼠于同一位置注射同体积 VEGF 溶液,VEGF+DC 组大鼠注射 VEGF+DC 溶液。 造模 4 周 后,对 所 有 实 验 大 鼠 进 行 超 声 心 功 能 检 测,考 察 左 心 室 收 缩 期 及 舒 张 期 前 壁 厚 度( LVAW;s 和 LVAW;d) 、左心室收缩期及舒张期内径( LVID;s 和 LVID;d) 、左心室收缩期及舒张期容积( LV Vol;s 和 LV Vol;d) 、左室射血分数( EF% )及短轴缩短率( FS% ) ,血流动力学考察左室舒张末压( EDP ) 和等容收缩期及 舒张期左心室内压力上升最大速率( + dp / dt 和 - dp / dt) ,计算左心室指数( LVM / BW) 并对心肌进行苏木素-伊红 ( HE)染色观察各组实验大鼠心肌病理变化。 结果 VEGF 组和 VEGF+DC 组大鼠的心肌梗塞均得到有效改善,其 中 VEGF+DC 组的改善作用更加显著。 结论 VEGF 结合 DC 对心肌梗塞大鼠的心功能具有改善作用,具有一定的治疗作用。     

球形压头的滑动速度对材料微米划痕响应的影响

在恒定的法向载荷下,使用Rockwell C 120°金刚石压头对聚碳酸酯(PC)、熔融石英、紫铜和镁合金AZ31进行微米划痕测试,研究滑动速度对试样划痕响应的影响.压入深度小于压头的球锥转变深度,确保仅有压头顶端的圆球部分与试样接触.结果表明:随着滑动速度的增加,压入深度、残余深度和划痕沟槽的宽度均非线性减小,划痕硬度和弹性恢复率均非线性增大;PC和紫铜的划痕摩擦系数先增大后减小,PC的黏弹性行为对其摩擦响应有显著影响;熔融石英的划痕摩擦系数先增大后减小,最后趋于稳定;镁合金AZ31的划痕摩擦系数先减小后增大.熔融石英、紫铜和镁合金AZ31的划痕摩擦系数的变化趋势可通过几何接触模型进行解释.     

加速寿命数据的贝叶斯建模与分析

在加速寿命试验的可靠性设计中, 随机化设计的限制以及删失数据不可避免地导致低分位数估计出现较大的偏差。针对上述的问题, 结合贝叶斯抽样技术以及非线性混合模型(nonlinear mixed model, NLMM)提出了一种可靠性改进的分析方法。首先, 需要检验所收集的数据是否服从威布尔分布以及验证形状参数是否是恒定常数。其次, 考虑随机效应对尺度参数和形状参数的影响, 运用NLMM构建了尺度参数和形状参数与试验因子之间的函数关系。然后, 利用贝叶斯方法估计低分位数的可靠性寿命。最后, 实际案例研究表明, 在考虑删失问题和未完全随机设计的影响时, 所提方法能够获得更为稳健和可靠的估计结果。     

Blockage of the NLRP3 inflammasome by MCC950 improves anti-tumor immune responses in head and neck squamous cell carcinoma

The NLRP3 inflammasome is a critical innate immune pathway responsible for producing active interleukin (IL)-1β, which is associated with tumor development and immunity. However, the mechanisms regulating the inflammatory microenvironment, tumorigenesis and tumor immunity are unclear. Herein, we show that the NLRP3 inflammasome was over-expressed in human HNSCC tissues and that the IL-1β concentration was increased in the peripheral blood of HNSCC patients. Additionally, elevated NLRP3 inflammasome levels were detected in tumor tissues of Tgfbr1/Pten 2cKO HNSCC mice, and elevated IL-1β levels were detected in the peripheral blood serum, spleen, draining lymph nodes and tumor tissues. Blocking NLRP3 inflammasome activation using MCC950 remarkably reduced IL-1β production in an HNSCC mouse model and reduced the numbers of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and tumor-associated macrophages (TAMs). Moreover, inhibiting NLRP3 inflammasome activation increased the numbers of CD4⁺ and CD8⁺ T cells in HNSCC mice. Notably, the numbers of exhausted PD-1⁺ and Tim3⁺ T cells were significantly reduced. A human HNSCC tissue microarray showed that NLRP3 inflammasome expression was correlated with the expression of CD8 and CD4, the Treg marker Foxp3, the MDSC markers CD11b and CD33, and the TAM markers CD68 and CD163, PD-1 and Tim3. Overall, our results demonstrate that the NLRP3 inflammasome/IL-1β pathway promotes tumorigenesis in HNSCC and inactivation of this pathway delays tumor growth, accompanied by decreased immunosuppressive cell accumulation and an increased number of effector T cells. Thus, inhibition of the tumor microenvironment through the NLRP3 inflammasome/IL-1β pathway may provide a novel approach for HNSCC therapy.     

Microsatellite instability in gastric cancer: molecular bases,clinical perspectives,and new treatment approaches

Gastric cancer is one of the most aggressive malignancies, with limited treatment options in both locally advanced and metastatic setting, resulting in poor prognosis. Based on genomic characterization, stomach tumour has recently been described as a heterogeneous disease composed by different subtypes, each of them with peculiar molecular aspects and specific clinical behaviour. With an incidence of 22% among all western gastric tumour cases, stomach cancer with microsatellite instability was identified as one of these subgroups. Retrospective studies and limited prospective trials reported differences between gastric cancers with microsatellite stability and those with instability, mainly concerning clinical and pathological features, but also in regard to immunological microenvironment, correlation with prognostic value, and responses to treatment. In particular, gastric cancer with microsatellite instability constitutes a small but relevant subgroup associated with older age, female sex, distal stomach location, and lower number of lymph-node metastases. Emerging data attribute to microsatellite instability status a favourable prognostic meaning, whereas the poor outcomes reported after perioperative chemotherapy administration suggest a detrimental role of cytotoxic drugs in this gastric cancer subgroup. The strong immunogenicity and the widespread expression of immune-checkpoint ligands make microsatellite instability subtype more vulnerable to immunotherapeutic approach, e.g., with anti-PD-L1 and anti-CTLA4 antibodies. Since gastric cancer with microsatellite instability shows specific features and clinical behaviour not overlapping with microsatellite stable disease, microsatellite instability test might be suitable for inclusion in a diagnostic setting for all tumour stages to guarantee the most targeted and effective treatment to every patient.     

不同基肥处理对赣南稀土尾矿种植皇竹草的农艺性状及产量的影响

试验研究在稀土尾矿上不施基肥(对照组),施用粪污处理后的牛场沼液(B)、发酵牛粪(C)、牛粪养殖的蚯蚓粪(E)、发酵牛粪+牛场沼液(C+B)、牛粪养殖的蚯蚓粪+牛场沼液(E+B)5种基肥处理后,对皇竹草农艺性状及产量的影响.结果表明:B处理未能提升皇竹草存活率、农艺性状和产量,显著低于其余4个处理组,C、E处理与C+B、E+B处理之间的存活率、农艺性状和产量差异不显著.C、E、C+B、E+B处理均能有效提升皇竹草的株高、分蘖数、茎粗、单株高重和产量,株高、单株重和产量上,以E和E+B处理效果最好,分蘖数、茎粗在4个处理组间差异不明显.综上所述,在赣南稀土尾矿上种植皇竹草,施用蚯蚓粪作为基肥对皇竹草农艺性状及产量的提升效果最好.     

超强筋小麦粉面包烘焙技术研究

为了烘焙出能充分表现超强筋小麦济麦229面粉品质特性的优良面包,设置了4种醒发时间处理、5种酵母和糖用量处理、4种配粉处理,对超强筋小麦面粉的面包品质进行了评价分析。结果表明,在4个醒发时间处理中,当面团醒发时间为30min和面包胚醒发时间为50min时,烘焙的面包品质最好。在5种酵母和糖用量的处理中,利用吐司面包程序时,干酵母和糖的用量分别为6g和24g时烘焙的面包品质最好；利用法式面包程序时,干酵母和糖的用量分别为3g和18g时烘焙的面包品质最好。在4个配粉处理中,200g超强筋小麦济麦229面粉中添加100g普通小麦济麦22面粉的混粉烘焙得到的面包品质最好。因此,适当调整超强筋小麦粉面包的面团、面包胚醒发时间及物料配比,可以烘焙出品质优良的面包。     

时标轴上二阶Dirichlet边值问题的弱解（英文）

采用变分方法和临界点理论研究一个时标轴上二阶Dirichlet边值问题弱解的存在性.     

腐蚀对风车联合作用下斜拉桥拉索 疲劳可靠性的影响分析

为探讨腐蚀对随机交通和风载联合作用下斜拉索疲劳可靠性的影响规律和机理,通过拉索高强钢丝的加速腐蚀和疲劳试验,提出了考虑腐蚀的斜拉索疲劳抗力模型;基于线性累积损伤准则,建立了考虑腐蚀影响的风车联合作用下拉索疲劳可靠性的分析方法和流程;依托工程实例,分析了腐蚀等级和时变腐蚀对拉索疲劳可靠性的影响.结果表明:随腐蚀加剧拉索动态疲劳可靠指标下降速率增大;等级达到Ⅲ级及以上的腐蚀对拉索疲劳可靠寿命影响显著,尤其对于靠近桥塔及辅助墩处拉索;Ⅳ级和Ⅴ级腐蚀时拉索疲劳寿命相对无腐蚀状况降幅最大分别达24%和44%;相对完好状况,时变腐蚀影响下拉索的动态疲劳可靠指标下降更为迅速,且降幅明显大于仅考虑腐蚀分级的状况.