EMMPRIN、VEGF-C及淋巴管密度与乳腺癌浸润和转移的关系

目的探讨细胞外基质金属蛋白酶诱导因子(extracellular matrix metalloproteinase inducer,EMMPRIN)和血管内皮生成因子-C(vascular endothelial growth factor-C,VEGF-C)蛋白表达及D2-40标记的淋巴管密度(lymphatic vessel density,LVD)与乳腺癌其浸润和转移的关系。方法免疫组化法检测乳腺增生组21例、导管内癌组10例、浸润性导管癌68例病灶内EMMPRIN、VEGF-C和LVD情况。计数资料比较采用χ2检验进行分析,相关性分析采用Spearman等级相关分析,计量资料三组间比较采用方差分析,两两比较采用LSD法,P0.05为差异有统计学意义。结果三组EMMPRIN、VEGF-C的阳性率比较,差异均有统计学意义(均P0.05);与乳腺增生组比较,导管内癌、浸润性导管癌组EMMPRIN、VEGF-C的阳性率显著升高,差异均有统计学意义(均P0.05);乳腺增生组的LVD为(8.38±3.18),导管内癌、浸润性导管癌组分别为(9.80±2.78)、(10.82±5.51),三组LVD比较,差异有统计学意义(P0.05)。EMMPRIN和VEGF-C的阳性表达与有无淋巴结转移和淋巴结转移个数有关,差异均有统计学意义(均P0.05)。不同组织学分级EMMPRIN和VEGF-C的阳性率比较,差异均有统计学意义(均P0.05)。乳腺癌组织中EMMPRIN与VEGF-C的表达呈正相关(rs=0.390,P0.05)。结论 VEGF-C在乳腺癌淋巴管生成长过程中起着重要的作用,EMMPRIN和VEGF-C在乳腺癌的浸润和转移过程中起着协同作用。     

痛风的遗传基础

痛风是一种常见的由尿酸盐沉积引起的慢性炎症性关节炎。该文总结了最新的痛风遗传学基础,发现痛风的高风险基因多数与肾脏和肠道尿酸盐转运系统相关。糖酵解基因是一种异于肾和肠道尿酸排泄的血清尿酸调控路径,也为痛风和其他相关的代谢性疾病提供了新的病因学线索。基因之间的相互作用、基因与环境危险因素之间的相互作用均与痛风的发病风险相关。     

Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury

Human umbilical cord mesenchymal stem cells(hUC-MSCs)are a promising candidate for spinal cord injury(SCI)repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources.However,modest clinical efficacy hampered the progression of these cells to clinical translation.This discrepancy may be due to many variables,such as cell source,timing of implantation,route of administration,and relevant efficacious cell dose,which are critical factors that affect the efficacy of treatment of patients with SCI.Previously,we have evaluated the safety and efficacy of 4×10⁶ hUC-MSCs/kg in the treatment of subacute SCI by intrathecal implantation in rat models.To search for a more accurate dose range for clinical translation,we compared the effects of three different doses of hUC-MSCs-low(0.25×10⁶ cells/kg),medium(1×10⁶ cells/kg)and high(4×10⁶ cells/kg)-on subacute SCI repair through an elaborate combination of behavioral analyses,anatomical analyses,magnetic resonance imaging-diffusion tensor imaging(MRI-DTI),biotinylated dextran amine(BDA)tracing,electrophysiology,and quantification of mRNA levels of ion channels and neurotransmitter receptors.Our study demonstrated that the medium dose,but not the low dose,is as efficient as the high dose in producing the desired therapeutic outcomes.Furthermore,partial restoration of theγ-aminobutyric acid type A(GABAA)receptor expression by the effective doses indicates that GABAA receptors are possible candidates for therapeutic targeting of dormant relay pathways in injured spinal cord.Overall,this study revealed that intrathecal implantation of 1×10⁶ hUC-MSCs/kg is an alternative approach for treating subacute SCI.     

长期负性情绪应激对D-gal大鼠认知功能及海马NR2B基因甲基化表达的影响

目的探讨长期负性情绪应激对大鼠脑老化进程的影响机制。方法将雌雄各半的70只Wistar大鼠分别采用随机方法,分为空白对照组、D-gal脑老化模型组、应激脑老化组,每组14只且雌雄各半,其余大鼠做为攻击鼠参与负性情绪应激的诱导;采用颈后部皮下多点注射D-gal 0.1g/(kg·d)制备脑老化大鼠模型;采用不可预知性刺激,诱导应激脑老化组大鼠长期负性情绪应激;采用Morri′s水迷宫实验记录大鼠水下寻台时间(SPL),评价大鼠学习记忆功能;采用ELISA测定大鼠血浆促肾上腺皮质激素(ACTH)和皮质酮(CORT)含量;采集大鼠海马样本制备匀浆,采用甲基化特异性PCR法(MSP)检测海马N-甲基-D-天门冬氨酸受体-2B亚型(NR2B)基因调控区胞嘧啶-磷酸-鸟嘌呤位点(CpG)甲基化程度,采用ELISA法测定甲基化转移酶1(DNMT1)活性。结果与D-gal脑老化模型组比较,应激脑老化组大鼠的SPL明显延长,NR2B基因启动子区CpG甲基化程度及DNA DNMT1活性显著增高(P0.05),血浆CORT、ACTH水平显著升高(P0.05)。结论长期情绪调节不良能够加速机体大脑老化进程,其机制可能与慢性情绪应激引发机体特定基因甲基化程度增高有关。     

Lycium barbarum extract promotes M2 polarization and reduces oligomeric amyloid-β-induced inflammatory reactions in microglial cells

Lycium barbarum(LB)is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions,such as antioxidation,neuroprotection,and immune modulation.One of the main mechanisms of Alzheimer’s disease is that microglia activated by amyloid beta(Aβ)transform from the resting state to an M1 state and release pro-inflammatory cytokines to the surrounding environment.In the present study,immortalized microglial cells were pretreated with L.barbarum extract for 1 hour and then treated with oligomeric Aβfor 23 hours.The results showed that LB extract significantly increased the survival of oligomeric Aβ-induced microglial cells,downregulated the expression of M1 pro-inflammatory markers(inducible nitric oxide synthase,tumor necrosis factorα,interleukin-6,and interleukin-1β),and upregulated the expression of M2 anti-inflammatory markers(arginase-1,chitinase-like protein 3,and interleukin-4).LB extract also inhibited the oligomeric Aβ-induced secretion of tumor necrosis factorα,interleukin-6,and interleukin-1βin microglial cells.The results of in vitro cytological experiments suggest that,in microglial cells,LB extract can inhibit oligomeric Aβ-induced M1 polarization and concomitant inflammatory reactions,and promote M2 polarization.     

PFNA治疗股骨粗隆间骨折46例临床观察

目的:探讨PFNA治疗股骨粗隆间骨折的临床疗效。方法:46例患者采用PFNA治疗股骨粗隆间骨折,术后预防感染,使用抗凝药物预防血栓,抬高患肢以促进消肿。术后第2天可行髋关节屈伸锻炼,患肢8周内不负重,术后8周复查,依据骨折愈合情况逐步负重。结果:36例评为优,7例评为良,3例评为可,优良率为93.5%。结论:PFNA内固定治疗股骨粗隆间骨折在临床上取得了相对满意的效果,具有损伤小、操作简单、术后可及早下床活动、有利于术后康复、降低术后不良事件发生率等多重优点。