Kellerin alleviates cognitive impairment in mice after ischemic stroke by multiple mechanisms

Ischemic stroke is a global disease with high disability and mortality rates. Cognitive impairment is one of the major clinical features of ischemic stroke, and microglia‐mediated inflammation has been shown to be an important contributor to the pathogenesis of ischemic stroke. Kellerin, extracted from Ferula sinkiangensis, was previously shown to inhibit microglial activation and exert a strong anti‐neuroinflammatory effect. However, there is no report of the potential therapeutic effect of kellerin on ischemic stroke by targeting microglial cells. In this study, we wanted to examine the effects of kellerin on ischemic stroke in the bilateral common carotid artery occlusion (BCCAO) model and the lipopolysaccharide (LPS)‐activated microglia model. We found that kellerin alleviated cognitive impairment, decreased neuronal loss, suppressed microglial activation, and transformed microglia from the pro‐inflammatory M1 phenotype to the anti‐inflammatory M2 phenotype in BCCAO mice. Moreover, in in vitro studies, we found that kellerin regulated microglial polarization and inhibited the NLRP3 and MAPK signaling pathways after LPS treatment. These findings provide a new understanding of the function of kellerin in ischemic stroke, and suggest that kellerin could be a potential therapeutic agent for the treatment of ischemic stroke.     

Dysregulation in nucleic acid‐sensing pathway genes is associated with cancer patients’ prognosis

The innate immune system, the first line of defense against pathogens, is activated by nucleic acids from microbial invaders that are recognized by nucleic acid‐sensing receptors. Recent evidence affirms the ability of these receptors to respond to nucleic acids released by damaged cancer cells. The innate immune system is also involved in cancer immunosurveillance, and could be modulated for devising effective antitumor therapies by targeting nucleic acid‐sensing pathways. A systematic, comprehensive analysis of dysregulation in nucleic acid‐sensing pathways in cancer is required to fully understand its role. Based on multidimensional data of The Cancer Genome Atlas pan‐cancer cohort, we revealed that upregulation of cytosolic DNA‐sensing genes like AIM2 and CGAS was common in tumor tissues. We used 15 genes in the nucleic acid‐sensing pathway to cluster all tumor patients into 2 subgroups and found that the subgroup with higher expression of nucleic acid‐sensing pathway genes was associated with poorer prognosis across cancer types. However, in homologous recombination deficient patients, the nucleic acid recognition activated subgroup was associated with better prognosis, which confirms the therapeutic effect of nucleic acid recognition. This study contributes to a better understanding of the functions and mechanisms of nucleic acid recognition in cancer, lays the foundation for new therapeutic strategies, and enlarges the scope of development of new drugs.     

婴幼儿多发性大动脉炎14例临床特点分析

目的通过分析总结14例婴幼儿多发性大动脉炎(TA)的临床特点,并结合文献复习总结,以提高对该病的认识及诊疗水平。方法回顾性分析2016年7月至2019年5月在首都儿科研究所附属儿童医院住院的TA婴幼儿的临床资料及随访情况,并结合文献,分析总结该病的临床特点。结果14例患儿年龄为1个月23 d^28个月,男6例,女8例。临床表现中最常见的是发热[10例(71.4%)],高血压9例(64.3%),脉弱或无脉5例(35.7%)。按照病变血管部位的临床分型,广泛型11例(78.5%),头臂动脉型3例(21.4%),本组患儿无胸腹主动脉及单纯肺动脉型。14例TA患儿中,12例有颈总动脉、颈动脉、锁骨下动脉及冠状动脉及其分支(前降支、回旋支)受累(85.7%);11例肾动脉受累(78.6%);9例腋动脉受累(64.2%);8例腹主动脉受累(57.1%);6例降主动脉受累(42.9%);6例胸主动脉受累(42.9%);6例肠系膜上动脉受累(42.9%);5例股动脉受累(35.7%);5例肺动脉受累(35.7%);4例肱动脉受累(28.6%)。14例患儿中,误诊11例,诊断不清3例,误诊时间为18 d^2个月。误诊病例中,8例误诊为不典型川崎病。14例患儿中,7例治疗后大部分病变血管范围逐渐减少,受累较轻血管甚至可以完全恢复正常血管状态。4例患儿血管影像学检查较前无明显加重或好转。9例出现高血压患儿应用降压药血压能控制在正常范围,但不能停用降压药。5例查体发现脉弱或无脉患儿均未改善。14例患儿中7例生长发育同正常同龄儿,7例落后于正常同龄儿身高体质量第25百分位。14例患儿随访2~22个月,均规律治疗,未出现复发。结论3岁以内TA累及血管较多,病情严重,误诊率高,经过治疗病情很快能够控制,但容易遗留血管病变,部分患儿预后不佳。     

Paired associated magnetic stimulation promotes neural repair in the rat middle cerebral artery occlusion model of stroke

Paired associative stimulation has been used in stroke patients as an innovative recovery treatment. However, the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological function remain unclear. In this study, rats were randomly divided into middle cerebral occlusion model(MCAO) and paired associated magnetic stimulation(PAMS) groups. The MCAO rat model was produced by middle cerebral artery embolization. The PAMS group received PAMS on days 3 to 20 post MCAO. The MCAO group received sham stimulation, three times every week. Within 18 days after ischemia, rats were subjected to behavioral experiments—the foot-fault test, the balance beam walking test, and the ladder walking test. Balance ability was improved on days 15 and 17, and the footfault rate was less in their affected limb on day 15 in the PAMS group compared with the MCAO group. Western blot assay showed that the expression levels of brain derived neurotrophic factor, glutamate receptor 2/3, postsynaptic density protein 95 and synapsin-1 were significantly increased in the PAMS group compared with the MCAO group in the ipsilateral sensorimotor cortex on day 21. Resting-state functional magnetic resonance imaging revealed that regional brain activities in the sensorimotor cortex were increased in the ipsilateral hemisphere, but decreased in the contralateral hemisphere on day 20. By finite element simulation, the electric field distribution showed a higher intensity, of approximately 0.4 A/m~2, in the ischemic cortex compared with the contralateral cortex in the template. Together, our findings show that PAMS upregulates neuroplasticity-related proteins, increases regional brain activity, and promotes functional recovery in the affected sensorimotor cortex in the rat MCAO model. The experiments were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval No. 201802173 S) on March 3, 2018.     

电针干预佐剂性关节炎大鼠踝关节滑膜细胞凋亡的MMP-3、MMP-9分子调节机制

目的观察电针干预对佐剂性关节炎大鼠踝关节滑膜细胞凋亡和相关蛋白基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶-9(MMP-9)表达的影响。方法32只雄性SD大鼠被随机分为生理盐水组、模型组、电针干预组和假电针干预组,每组8只。生理盐水组大鼠在双侧足垫部注射模拟造模,其余大鼠用弗氏完全佐剂在双侧足垫部注射造模。电针干预组大鼠予以电针干预。假电针干预组予以假电针刺激处理。HE染色观察模型大鼠踝关节炎症进展情况,Tunnel法检测模型大鼠踝关节滑膜细胞凋亡情况,RT-PCR检测踝关节滑膜的MMP-3、MMP-9的mRNA表达,Western blot检测踝关节滑膜的MMP-3、MMP-9的蛋白表达。结果HE染色显示,电针干预组大鼠的关节炎症显著轻于模型组。Tunnel法检测,电针干预可以促进关节炎大鼠的滑膜细胞凋亡。RT-PCR和Western blot检测结果显示,电针干预可以显著降低关节炎大鼠踝关节滑膜组织中的MMP-3、MMP-9 mRNA和蛋白表达水平(P<0.05)。结论电针干预可以显著减轻佐剂性关节炎大鼠的关节炎症和增殖的滑膜细胞数量,其分子机制可能和电针降低局部的MMP-3、MMP-9蛋白的表达有关。     

Hisense计算机辅助系统辅助腹腔镜精准手术治疗儿童肾上腺区巨大肿瘤

目的探讨计算机辅助手术系统(computer-aided system,CAS)对于腹腔镜手术切除肾上腺巨大肿瘤(瘤体直径≥5 cm)的指导价值。方法回顾性分析青岛大学附属医院2015年9月至2018年6月收治的13例肾上腺区巨大肿瘤病例,13例术前均完善相关辅助检查并行Hisense CAS三维重建,依据三维重建结果指导完成腹腔镜手术。结果13例肾上腺区巨大肿瘤患儿术前和术中在Hisense CAS三维重建结果的指导下均顺利完成腹腔镜手术。术后病理检查:神经母细胞瘤7例,节细胞性神经母细胞瘤2例,节细胞神经瘤1例,嗜铬细胞瘤2例,肾上腺皮质癌1例。结论Hisense计算机辅助系统能够清晰显示肿瘤位置及其与周围重要脏器结构的毗邻关系,可用于指导手术治疗儿童肾上腺区巨大肿瘤。     

腹腔镜直肠癌前切除术肠系膜下动脉不同结扎平面对患者预后的影响

目的分析腹腔镜直肠癌前切除术中肠系膜下动脉不同结扎平面对患者预后的影响。 方法选取2007年6月至2014年6月间青岛市市立医院收治的行腹腔镜直肠癌前切除术136例患者为研究对象，根据肠系膜下动脉不同的结扎平面，分为保留左结肠动脉的低位结扎组（LL组）76例和不保留左结肠动脉的高位结扎组（HL组）60例。比较两组患者围手术期指标，随访并评价两组的预后。 结果两组手术时间、术中出血量、术后肛门排气时间、淋巴结清扫总数和第253组淋巴结清扫个数差异无统计学意义（t=6.109、4.339、8.386、0.233、0.198，P=0.318、0.416、0.512、0.821、0.669）；LL组术后吻合口瘘的发生率明显低于HL组（χ²=5.186，P=0.029）。HL组术后3、5年总体生存率分别为80.00%和73.33%，LL组分别为77.63%和72.37%，两组比较差异无统计学意义（χ²=1.536、2.156，P=0.863、0.698）。 结论腹腔镜直肠癌前切除术中肠系膜下动脉不同结扎平面可获得相近的淋巴结清扫效果，保留左结肠动脉的低位结扎平面术后吻合口瘘的发生率更低，其他围手术期指标没有差异，联合第三站中央淋巴结清扫值得应用推广。