Involvement of ERK, p38 and NF-kappaB signal transduction in regulation of TLR2, TLR4 and TLR9 gene expression induced by lipopolysaccharide in mouse dendritic cells

Toll-like receptors (TLR) are sentinel receptors capable of recognizing pathogen-associated molecule patterns (PAMP) such as lipopolysaccharide (LPS) and CpG-containing oligonucleotides (CpG ODN). TLR2 and TLR4 are major receptors for Gram-positive and Gram-negative bacterial cell wall components, respectively. TLR9 is necessary for CpG signalling. LPS or CpG ODN can activate immature dendritic cells (DC) and induce DC maturation characterized by production of cytokines, up-regulation of co-stimulatory molecules, and increased ability to activate T cells. However, little is known regarding the regulation of TLR gene expression in mouse DC. In this study, we investigated the regulation of TLR2, TLR4 and TLR9 gene expression by LPS in murine immature DC. TLR2, TLR4 and TLR9 mRNA were up-regulated following LPS stimulation. The up-regulation of TLR9 expression coincided with significantly increased production of tumour necrosis factor-alpha induced by LPS plus CpG ODN. While inhibition of extracellular signal-related kinase and NF-kappaB activation suppressed the up-regulation of the expression of TLR2, TLR4 and TLR9 mRNA, inhibition of p38 kinase prevented the up-regulation of TLR2 and TLR4 mRNA expression but enhanced the up-regulation of TLR9 expression. These results demonstrated that TLR2, TLR4 and TLR9 gene expression was differently regulated by LPS in mouse immature DC. Up-regulation of TLR2, TLR4 and TLR9 expression by LPS might promote the overall responses of DC to bacteria and help to explain the synergy between LPS and other bacterial products in the induction of cytokine production.     

Light Emitting Diodes Irradiation Regulates miRNA-877-3p to Promote Cardiomyocyte Proliferation

Mammalian cardiomyocytes (CMs) maintain a low capacity for self-renewal in adulthood, therefore the induction of CMs cycle re-entry is an important approach to promote myocardial repair after injury. Recently, photobiomodulation (PBM) has been used to manipulate physiological activities of various tissues and organs by non-invasive means. Here, we demonstrate that conditioned PBM using light-emitting diodes with a wavelength of 630 nm (LED-Red) was capable of promoting the proliferation of neonatal CMs. Further studies showed that low-power LED-Red affected the expression of miR-877-3p and promoted the proliferation of CMs. In contrast, silencing of miR-877-3p partially abolished the pro-proliferative actions of LED-Red irradiation on CMs. Mechanistically, GADD45g was identified as a downstream target gene of miR-877-3p. Conditioned LED-Red irradiation also inhibited the expression of GADD45g in neonatal CMs. Moreover, GADD45g siRNA reversed the positive effect of LED-Red on the proliferation of neonatal CMs. Taken together, conditioned LED-Red irradiation increased miR-877-3p expression and promoted the proliferation of neonatal CMs by targeting GADD45g. This finding provides a new insight into the role of LED-Red irradiation in neonatal CMs biology and suggests its potential application in myocardial injury repair.     

A molecularly integrated grade for meningioma

BackgroundMeningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management.MethodsWe evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms.ResultsWe developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score.ConclusionWe propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.     

不同年龄儿童脊柱侧弯矫正术中局部脑氧饱和度的研究

目的 探讨不同年龄儿童脊柱侧弯矫正术中局部脑氧饱和度(regional cerebral oxygen saturation,rScO2)的变化,以提高麻醉和手术的安全性.方法 选取2018年3月至2019年9月首都医科大学附属北京儿童医院行脊柱侧弯矫正术的患儿60例,按年龄分为A组(≤6岁,20例)和B组(＞6岁,40例).分析两组麻醉诱导插管后(T1)、俯卧位后(T2)、切皮后(T3)、植入椎弓根螺钉(T4)、截骨(T5)、矫形(T6)和术毕(T7)7个时间点的双侧rScO2,并记录术中出血量、手术时间和麻醉时间.结果 A组术中出血量(260.0ml比680.0 ml)、晶体液使用量[(917.5±282.5)ml比(1671.3±478.0)ml]、手术时间(139.0 min比244.0 min)和麻醉时间(195.0 min比300.5 min)均低于B组,且A组术中自体血量低于B组(148.0 ml比340.0 ml),差异有统计学意义(P＜0.05).T5时A组LrScO2和RrScO2均低于B组,差异有统计学意义(P＜0.05);其余各时间点两组LrScO2和RrScO2比较,差异均无统计学意义(P＞0.05).结论 行脊柱侧弯后路矫形内固定术的低龄患儿较年长患儿截骨时rScO2下降明显,需加强术中脑保护,以保证手术安全,减少术后并发症.     

肝内胆管细胞癌的CT诊断

本文报告１５例经手术病理证实的肝内胆管细胞癌的ＣＴ表现。主要的ＣＴ表现形式有３种：Ａ。境界清楚的囊性肿块，内部有乳头状或息肉样软组织肿块；Ｂ。分叶状混合性低密底肿块，内部呈蜂窝状低密度区并可见到病灶内残留扩张的胆管；Ｃ。不规则低密度肿块，增强后不同程度的强化。以上各型肿块均伴有中／重度胆管扩张。作者认为ＣＴ在现为Ａ型者可确诊本病，表现为Ｂ型者亦较有特征，而表现为Ｃ型时应高度怀疑本病。本病应与肝包虫病、先天性胆总管囊肿、肝癌、肝泡状棘球蚴病及肝门部转移癌相鉴别。     

姜黄素通过NLRP3/Caspase-1/IL-1β轴对低氧性肺动脉高压的干预作用

目的：探讨姜黄素对低氧性肺动脉高压（HPH）的作用及其机制。方法：同时研究肺动脉平滑肌细胞（PASMCs）和SD大鼠肺组织,PASMCs和SD大鼠都设置为常氧组（N）、低氧组（H）、低氧+姜黄素组（HC）3组。CCK-8法测3组PASMCs细胞活力,Western blot法检测3组PASMCs和肺匀浆中NLRP3、Caspase-1及IL-1β蛋白表达差异。血流动力学检测3组大鼠的平均肺动脉压（mPAP）及右心肥大程度,HE染色观察3组大鼠肺血管重塑程度。结果：与N组比,H组PASMCs的数量有明显增加（P＜0.05）,H组PASMCs和肺匀浆中NLRP3、Caspase-1、IL-1β蛋白表达均上升（均P＜0.05）,H组大鼠的mPAP及右心肥大指数明显升高（均P＜0.05）,发生明显肺血管重塑;与H组比,HC组PASMCs的数量明显降低（P＜0.05）,PASMCs和肺匀浆中NLRP3、Cas-pase-1、IL-1β蛋白表达均下降（均P＜0.05）,HC组大鼠的mPAP及右心肥大指数明显降低（均P＜0.05）,肺血管重塑改善。结论：姜黄素可能通过抑制NLRP3/Caspase-1/IL-1β轴,改善低氧PASMCs异常增殖、HPH大鼠肺血管重塑和右心肥大,降低肺动脉压力。     

SB203580对小脑颗粒神经元的保护作用

目的 :研究特异性p3 8分裂原激活的蛋白激酶 (MAPK)抑制剂SB2 0 3 580对低钾诱导的小脑颗粒神经元凋亡的作用及机制。方法 :体外神经元培养、凝胶电泳和SAPK/JNK分析盒测定JNK(c Jun氨基末端激酶 )活性。结果 :低钾 (KCl 5mmol/L)培养基诱导小脑颗粒神经元的具有典型形态学和生化特征的凋亡。但是 ,特异性的p3 8MAPK抑制剂SB2 0 3 580通过抑制凋亡 ,而促进低钾环境中培养的小脑颗粒神经元的存活。此保护作用具有浓度依赖性。培养于低钾环境中的神经元 ,其c Jun的表达和磷酸化水平升高 ,且激活了JNK的活性。当小脑颗粒神经元生长在含SB2 0 3 580 2 5μmol/L的低钾培养基中 ,c Jun的表达、磷酸化水平和JNK的活性都明显的降低。结论 :SB2 0 3 580可能通过抑制JNK的活性 ,降低c Jun的磷酸化水平而对低钾培养的小脑颗粒神经元具有保护作用。     

耳后窄蒂皮下蒂皮瓣修复耳廓内软组织缺损

目的探讨应用耳后窄蒂皮下蒂皮瓣修复耳廓内软组织缺损的方法及疗效。方法 2008年6月-2011年7月,收治11例耳廓内肿物切除后软组织缺损患者。男7例,女4例;年龄26～75岁,平均50岁。其中色素痣5例,基底细胞癌2例,混合性血管瘤2例,皮肤乳头状瘤2例。病程3～50年,平均35年。彻底切除肿物后,软组织缺损范围为1.5 cm×1.0 cm～3.5 cm×3.0 cm。沿颞浅动脉及耳后动脉走向,设计耳后"乒乓球拍状"窄蒂皮下蒂皮瓣,通过隧道移位修复缺损,皮瓣切取范围1.8 cm×1.3 cm～3.8 cm×3.3 cm,蒂宽0.4～0.7 cm、长2～5 cm。供区直接拉拢缝合或局部皮瓣移位修复。结果术后供、受区皮瓣均顺利成活,切口均Ⅰ期愈合。术后8例获随访,随访时间6个月～1年。皮瓣质地、弹性、色泽良好,耳廓外形良好。肿瘤患者无复发。结论耳后窄蒂皮下蒂皮瓣蒂部窄长、旋转角度大、修复范围广、不含知名血管,手术操作简便,供区隐蔽,是修复耳廓内软组织缺损的理想方法之一。     

柔性减影CE-Boost技术对下肢动脉CT血管造影图像质量的影响

目的 观察柔性减影CE-Boost技术对下肢动脉CT血管造影(CTA)图像质量的影响。方法 对50例疑诊下肢动脉疾病患者采集双下肢动脉CTA,之后以常规混合迭代算法重建获得常规重建图像(A组),以柔性减影CE-Boost技术对其进行处理而获得CE-Boost图(B组)。对比2组图像质量主观评分,以及下肢动脉不同位置CT值、图像噪声、信噪比(SNR)及对比度噪声比(CNR)。结果 B组图像质量主观评分[4(3,4)]高于A组[3(2,3),Z=-4.880,P<0.001]。B组下肢动脉不同位置CT值、SNR及CNR均高于A组(P均<0.001),图像噪声均低于A组(P均<0.001)。结论 采用柔性减影CE-Boost技术可提高下肢动脉CTA图像质量。     

上海市社区医务人员循证慢性病防控证据获取能力自我认知实证研究

背景　目前慢性病防控形势依然严峻,提升社区医务人员慢性病防控能力迫在眉睫。循证慢性病防控作为一种提升医务人员慢性病防控能力的手段在西方国家已取得了一定成效,但在我国却鲜有研究。目的　探讨社区医务人员慢性病防控证据的获取途径、能力及影响因素,为提升社区医务人员循证慢性病防控能力提供理论依据。方法　于2019年4-7月,采用分层抽样的方法,以上海市75家社区卫生服务机构的975例医务人员为研究对象,对其进行问卷调查。问卷内容包括个人基本信息、循证基本认知情况、慢性病防控证据获取途径、慢性病防控证据获取能力。慢性病防控证据获取途径和慢性病防控证据获取能力由被调查者依据Likert 7级评分自评。采用多元线性逐步回归分析社区医务人员循证慢性病防控证据获取能力的影响因素。结果　892例（91.5%）社区医务人员的问卷被有效回收。临床指南为被调查医务人员获取慢性病防控证据的最常用途径,自评得分为（4.583±1.177）分。被调查对象自评获得的循证慢性病防控证据精准有效平均得分为（4.312±0.979）分,能获取针对慢性病危险因素的证据平均得分为（4.244±1.028）分,能应用针对慢性病危险因素的证据平均得分为（4.280±0.995）分。多元线性逐步回归分析结果显示,单位是否为大学附属是社区医务人员获得的循证慢性病防控证据精准有效、能获取针对慢性病危险因素的证据、能应用针对慢性病危险因素的证据的影响因素（P<0.05）。结论　所在社区卫生服务机构是否为大学附属是社区医务人员循证慢性病防控证据获取能力的主要影响因素,社区应重视慢性病防控证据获取途径的提供,并加强对医务人员慢性病防控证据获取及利用能力的培养。