Structure-Based Design of GNE-495, a Potent and Selective MAP4K4 Inhibitor with Efficacy in Retinal Angiogenesis

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天然产物对毛发色素的调节作用研究进展

毛发的颜色不仅受年龄、环境因素的影响,还受到众多因子的调控,其中主要有阿黑皮素原(POMC)、黑色素细胞刺激素(α-MSH)、黑色素1受体(MCIR)、小眼畸形相关蛋白因子(MITF)、酪氨酸酶(TYR)、酪氨酸相关蛋白酶1(TRP-1)、酪氨酸相关蛋白酶2(TRP-2)、刺鼠信号蛋白(ASIP)等。毛发颜色的异常常被认为是衰老的特征,给患者带来巨大的心理压力,但相关的治疗药物目前尚属空白。总结了天然药物对毛发颜色的影响程度和作用方式,以期阐明天然药物在治疗须发早白方面可能的作用途径及靶点,为从天然产物中寻找发掘新的药物奠定基础。     

产褥期可能罹患的罕见疾病

探讨产褥期可能罹患的罕见疾病,产褥期是指从胎盘娩出至产妇全身各器官(除乳腺外)恢复至未孕状态所需要的时期,一般为42d。在产褥期内发生的常见疾病表现为阴道出血、子宫复旧欠佳、阴道炎、会阴切口愈合欠佳、骨质疏松、贫血等,虽然滋养细胞疾病、产后溶血性尿毒症综合征、栓塞等罕见病的发病率较低,但也要提高警惕,避免医疗差错的发生。当遇到疑难病例一定要联系患者实际进行分析,要把不同症状发病时间顺序搞清楚,综合分析病情变化。当某个诊断出现无法解释的情况时,要对诊断提出质疑,考虑罹患其他科室疾病和罕见疾病的可能。如果上述罕见疾病在产后未能得到及时诊治,将会导致相应并发症的发生危及患者生命,严重危害女性的身心健康。     

造影剂致PICC堵管的根原因分析

应用根原因分析法分析1例造影剂导致PICC导管堵管的原因。通过事件调查、直接原因分析,确认根原因是PICC维护宣教流程不合理、增强CT检查流程不合理、对医护人员缺乏导管维护知识的培训。针对原因制定并执行设计健康教育检核表、制定增强CT检查流程、对医护人员进行培训等改进措施以避免类似事件的发生,保证PICC的正确使用与维护。     

Ⅰb2期巨块型宫颈癌术前不同治疗方法的疗效观察

背景与目的:Ⅰb2期巨块型宫颈癌行手术治疗时,因肿瘤体积大,术前多采取多种辅助治疗措施缩小瘤体,哪种方案更为安全有效目前尚无统一意见。本研究比较术前新辅助化疗、新辅助放化疗及直接手术3种不同治疗方法的疗效,为Ⅰb2期巨块型宫颈癌术前辅助治疗方案选择提供依据。方法:回顾分析2006年4月—2010年10月新疆医科大学附属肿瘤医院收治的133例术前新辅助化疗(49例)、新辅助放化疗(40例)及直接手术(44例)的Ⅰb2期巨块型宫颈癌患者的临床资料。结果:新辅助化疗组、新辅助放化疗组近期有效率为91.8%、92.5%,差异无统计学意义(P>0.05)。2组治疗后肿瘤直径与治疗前比较,差异有统计学意义(P<0.05);手术标本病理有效率为95.56%、97.30%,差异无统计学意义(P>0.05);新辅助放化疗组出血量明显高于其它2组,差异有统计学意义(158.9±50.7 vs 116.8±45.5,123.1±30.2,P<0.05),直接手术组术后感染率明显高于其它2组,差异有统计学意义(P<0.05)。新辅助化疗组、新辅助放化疗组、直接手术组平均手术时间,两两比较,差异均无统计学意义(P>0.05),新辅助化疗组与直接手术组出血量比较、新辅助化疗组与新辅助放化疗组术后感染比较、3组术后临近脏器损伤及盆腔淋巴囊肿比较,差异均无统计学意义(P>0.05);术后病理组织学检查,直接手术组脉管受侵,与其它2组相比,差异有统计学意义(P<0.05)。比较3组阴道切缘、淋巴结转移情况、脉管受侵程度,差异均无统计学意义(P>0.05)。3组3年总生存率、无瘤生存率比较,差异也均无统计学意义(P>0.05)。结论:对Ⅰb2期宫颈癌患者术前行新辅助化疗能有效缩小肿块,在提高手术切除率、降低术后切缘阳性率及术后感染方面优于单一手术或术前放化疗。新辅助放化疗比单一术前新辅助化疗能提高病理完全缓解率,但不能降低复发率,因此,对于Ⅰb2期宫颈癌患者建议可在新辅助化疗后选择手术。放化疗联合与新辅助化疗对预后影响有待长期随访或进行大样本的随机对照试验后进行评价。     

PTEN inhibits macrophage polarization from M1 to M2 through CCL2 and VEGF-A reduction and NHERF-1 synergism

PTEN has been studied in several tumor models as a tumor suppressor. In this study, we explored the role of PTEN in the inhibition state of polarized M2 subtype of macrophage in tumor microenvironment (TME) and the underlying mechanisms. To elucidate the potential effect in TME, RAW 264.7 macrophages and 4T1 mouse breast cancer cells were co-cultured to reconstruct tumor microenvironment. After PTEN was down-regulated with shRNA, the expression of CCL2 and VEGF-A, which are definited to promote the formation of M2 macrophages, have a dramatically increase on the level of both gene and protein in co-cultured RAW 264.7 macrophages. And at the same time, NHERF-1 (Na⁺/H⁺ exchanger regulating factor-1), another tumor suppressor has a similar tendency to PTEN. Q-PCR and WB results suggested that PTEN and NHERF-1 were consistent with one another no matter at mRNA or protein level when exposed to the same stimulus. Coimmunoprecipitation and immunofluorescence techniques confirmed that PTEN and NHERF-1 were coprecipitated, and NHERF-1 protein expression was properly reduced with rCCL2 effect. In addition, cell immunofluorescence images revealed a profound transferance, in co-cultured RAW 264.7 macrophages, an up-regulation of NHERF-1 could promote the PTEN marked expression on the cell membrane, and this form for the interaction was not negligible. These observations illustrate PTEN with a certain synergy of NHERF-1, as well as down-regulation of CCL2 suppressing M2 macrophage transformation pathway. The results suggest that the activation of PTEN and NHERF-1 may impede the evolution of macrophages beyond the M1 into M2 phenotype in tumor microenvironment.     

羊水过少胎儿的彩色多普勒超声特征

目的探讨羊水过少胎儿的心脑肾彩色多普勒超声特征并评价其临床价值。方法选取120例晚期妊娠胎儿,60例羊水过少者作为观察组,60例羊水量正常者作为对照组,根据二尖瓣及主动脉瓣血流频谱测算左室心肌做功指数(Tei指数),分析大脑中动脉及肾动脉的血流频谱并测算阻力指数(RI)。结果观察组中胎儿的Tei指数及肾动脉RI值高于对照组,大脑中动脉RI值低于对照组,且差异均有统计学意义(P<0.05);观察组内有窘迫者与对照组相比,上述差异更明显。结论彩色多普勒超声可显示羊水过少时胎儿心脑肾血流参数的变化,对指导临床干预、提高围产医学质量有重要意义。     

NOD2/CARD15基因突变与中国人克罗恩病相关性研究

背景 NOD21CARDl5 基因是人类克罗恩病(Crohn's disease,CD)第一个易感基因,既往研究发现P268S可能与中国人CD发病及临床特征相关.目的 本研究旨在证实P268S与中国人CD发病及其临床特征的相关性.方法 血样来自临床确诊的50例CD患者,60例溃疡性结肠炎(ulcerative colitis,uc) 患者及100 例健康体检者(healthy controls,HC).提取人血白细胞基因组DNA,PCR 扩增目的片段,PCR-RFLP发现突变位点,DNA 测序证实突变位点.结果 共有8例CD患者发现有P268S改变,而在UC患者和 HC 中分别发现2例和3例P268S改变,CD组明显高于UC和HC组(x2=10.829,P=0.004),而UC组和HC组无明显差异.8例有P268S改变的CD患者临床特征包括病变多位于回肠.发病年龄轻(6例<20岁),常并发肠腔狭窄而需手术治疗,中一重度患者比例高.结论 P268S可能是NOD21CARDl5 基因中与中国人CD相关的SNP.P268S与CD患者发病年龄、病变部位及并发症及病情严重程度可能相关.     

P-selectin-mediated platelet adhesion promotes tumor growth

Blood platelets foster carcinogenesis. We found that platelets are accumulated in human tumors. P-selectin deficiency and soluble P-selectin abolish platelet deposition within tumors, decreasing secretion of vascular endothelial growth factor and angiogenesis, thereby suppressing tumor growth. Binding of the P-selectin cytoplasmic tail to talin1 triggers the talin1 N-terminal head to interact with the β3 cytoplasmic tail. This activates αIIbβ3 and recruits platelets into tumors. Platelet infiltration into solid tumors occurs through a P-selectin-dependent mechanism.