HMGB1 gene silencing inhibits neuroinflammation via down-regulation of NF-κB signaling in primary hippocampal neurons induced by Aβ25–35

High mobility group box 1 protein (HMGB1) is potentially triggered by Aβ oligomers and other sterile injuries, and is a non-histone DNA binding nuclear protein with roles in neural development and neurodegeneration, which contribute to memory impairment and chronic neuroinflammation in the brain. However, the exact molecular mechanisms of HMGB1 activation in Alzheimer's disease (AD) were previously unknown. The present study aimed to elucidate the effects of HMGB1 in Aβ_25–35-induced neuroinflammation in hippocampal neuron cultures. RNA interference (RNAi) HMGB1 treatment significantly reduced Aβ_25–35-induced HMGB1 expression by almost 70% in primary hippocampal neurons. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and enzyme-linked immunosorbent assay (ELISA) demonstrated that short hairpin RNA (shRNA) for HMGB1 ameliorated Aβ_25–35-treated neuroinflammation, including activation of advanced glycosylation end product-specific receptor (RAGE), toll-like receptor 4 (TLR4), and nuclear factor-kappa B (NF-κB)-p65, as well as induced the release of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), IL-6, and HMGB1 in primary hippocampal neurons and the culture supernatant. In addition, pretreatment with HMGB1-shRNA dramatically reduced both the degree of nuclear-cytoplasmic HMGB1 translocation of HMGB1 and NF-κB DNA binding. Together, the data indicate that HMGB1 mediates the pathogenesis of AD by activating RAGE/TLR4 signaling and that shRNA targeting HMGB1 may be a promising therapeutic strategy for treating AD.     

下肢血管微创介入在缺血型糖尿病足中的应用效果分析

【摘要】目的 探讨下肢血管微创介入在缺血型糖尿病足中的应用效果。方法 选取2013年8月至2018年6月牡丹江心血管病医院糖尿病分院内分泌科收治的116例糖尿病足患者作为研究对象,并按照不同干预方法将其分为观察组（60例,92处创面）与对照组（56例,70处创面）,观察组患者在常规综合治疗的基础上行下肢血管微创介入治疗,对照组患者在常规综合治疗的基础上行保守溶栓治疗,对比观察两组患者踝肱指数（ankle brachial index,ABI）、创面愈合率、临床疗效及截肢情况。结果 治疗第7、28天,观察组患者ABI均显著高于对照组（t=9.909、8.575,P均=0.000）;治疗第28天,观察组患者创面愈合率显著高于对照组（t=10.930,P=0.000）,临床疗效显著优于对照组（Z=-3.550,P=0.000）;治疗过程中,观察组患者截肢率明显低于对照组（χ2=10.881,P=0.004）。结论 下肢血管微创介入治疗能够有效改善糖尿病足患者下肢血液供应,降低截肢率或截肢平面,促进创面愈合,改善患者预后。     

Paracrine factors from mesenchymal stem cells: a proposed therapeutic tool for acute lung injury and acute respiratory distress syndrome

Despite extensive researches in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), current pharmacological therapies and respiratory support are still the main methods to treat patients with ALI and ARDS and the effects remain limited. Hence, innovative therapies are needed to decrease the morbidity and mortality. Because of the proven therapeutic effects in other fields, mesenchymal stem cells (MSCs) might be considered as a promising alternative to treat ALI and ARDS. Numerous documents demonstrate that MSCs can exert multiple functions, such as engraftment, differentiation and immunoregulation, but now the key researches are concentrated on paracrine factors secreted by MSCs that can mediate endothelial and epithelial permeability, increase alveolar fluid clearance and other potential mechanisms. This review aimed to review the current researches in terms of the effects of MSCs on ALI and ARDS and to analyse these paracrine factors, as well as to predict the potential directions and challenges of the application in this field.     

“They are interrelated,one feeds off the other”: A taxonomy of perceived disease interactions derived from patients with multiple chronic conditions

ObjectiveTo understand patients’ experiences with condition interactions and develop a taxonomy to inform care for patients with multiple chronic conditions.MethodsWe conducted qualitative and quantitative analysis of free-text data from patient surveys in which respondents were asked to indicate their most bothersome chronic condition and describe how their other conditions affect their self-care for that condition. Using standard content analysis, we developed a taxonomy comprising how patients perceive interactions among their conditions, and examined cross-cutting themes that reflect qualities of these interactions.ResultsAmong 383 eligible survey respondents, the mean (SD) number of chronic conditions was 4 (2); common conditions included hypertension (60%), chronic pain (49%), arthritis (41%), depression (32%), diabetes (29%), and post-traumatic stress disorder (26%). Patients’ perceived condition interactions took four broad forms: 1) unidirectional interactions among conditions and/or treatments, 2) cyclical or multidimensional interactions, 3) uncertain or indistinct interactions, and 4) no perceived interaction. Cross-cutting themes included beliefs about causal relationships between conditions, identification of interactions as negative vs. positive, and interactions between physical and mental health.ConclusionThis study presents a novel taxonomy of condition interactions from the patient perspective.Practice ImplicationsUnderstanding perceived condition interactions may support patient self-management and shared decision-making efforts.     

抗生素骨水泥链置入在慢性骨髓炎行病灶清除后的感染控制

目的探讨慢性骨髓炎在采用抗生素骨水泥链进行治疗后的感染控制。方法将我院收治的50例慢性骨髓炎患者随机分为研究组和对照组,病灶清除后,分别给予患者抗生素骨水泥链置入处理和闭合灌洗引流术,观察患者的平均住院时间、平均手术次数以及治愈率。结果研究组21例患者平均住院时间为(65±4.2)d;平均手术次数为(2.3±1.2)次;患者的治愈率为85.7%。对照组29例患者平均住院时间为(103±2.5)d;平均手术次数为(2.8±1.4)次;患者治愈率为55.2%。2组比较差异具有统计学意义(P0.05)。结论抗生素骨水泥链治疗慢性骨髓炎具有良好效果,减少患者的住院时间和手术次数,提高治愈率,病灶清除后的感染控制效果好。     

恶性肿瘤患者血栓分子标志物的临床评价

目的探讨血栓分子标志物在恶性肿瘤患者血栓形成的早期诊断价值,并对恶性肿瘤患者形成血栓危险因素进行评价。方法诊断性研究。选取2017年9月至2019年2月牡丹江医学院附属红旗医院及牡丹江市肿瘤医院的恶性肿瘤患者,共1366例[包括肺癌、乳腺癌及结直肠癌,男562例,女804例,年龄(59.45±15.10)岁],对照组为70名健康体检人群[男35名,女35名,年龄(50.41±18.90)岁],其中形成静脉血栓69例,男32例,女37例,平均年龄(61.20±15.71)岁。采用化学发光免疫分析法检测其静脉血浆中的血栓调节蛋白(TM)、凝血酶-抗凝血酶复合物(TAT)、组织型纤溶酶原激活物/抑制剂-1复合物(t-PAIC)、纤溶酶-抗纤溶酶复合物(PIC)。根据各项标志物的敏感度及特异度,采用受试者工作特征曲线评价各项标志物的诊断性能,采用Cox回归分析进行单因素及多因素风险分析。结果不同类型的恶性肿瘤患者静脉血栓栓塞(VTE)发生率具有统计学差异,肺癌最高,其次为结直肠癌及乳腺癌(P<0.05);肺癌、乳腺癌及结直肠癌血栓组的TM、TAT、t-PAIC及PIC水平高于对照组,非血栓组的TAT、t-PAIC及PIC水平均高于对照组,差异均具有统计学意义(均P<0.05)。TM的最佳截断水平为10.57 IU/ml(敏感度为50.30%,特异度75.50%,AUC=0.671),TAT的最佳截断水平为4.16 ng/ml(敏感度为80.30%,特异度为62.80%,AUC=0.757),t-PAIC的最佳截断水平为11.44 ng/ml(敏感度为52.50%,特异度为84.00%,AUC=0.682),PIC的最佳截断水平为1.18μg/ml(敏感度为67.20%,特异度为79.50%,AUC=0.790),四项分子标志物联合检测敏感度最佳,诊断性能最好(86.90%,AUC=0.807)。年龄、分期、转移、手术、肿瘤直径及PIC水平是影响恶性肿瘤VTE发生的独立影响因素(均P<0.05)。结论不同类型的恶性肿瘤血栓发生率不同,TM、TAT、t-PAIC及PIC联合检测诊断性能最好,可作为恶性肿瘤发生VTE的新型筛查方法。年龄、分期、转移、手术及肿瘤直径是恶性肿瘤发生VTE的高危因素,PIC水平可作为恶性肿瘤患者6个月内并发VTE风险的可靠标志物。     

CT灌注参数在胃腺癌不同组织学类型上的临床应用价值

目的:探讨胃腺癌病理类型与胃CT灌注成像参数值间的相关性。方法:选取2015年1月到2019年7月期间在我院接受治疗的胃腺癌患者93例。经CT灌注成像,所得数据使用专用软件,进行分析,得血流量(blood flow,BF)、血容量(blood volume,BV)、平均通过时间(mean transit time,MTT)和表面通透性(the permeabil ity surface,PS)数据值。根据胃镜病理分三组:低分化组、中分化组及高分化组,并分析各组间的相互联系。结果:高分化胃腺癌患者21例、中分化腺癌患者27例、低分化胃腺癌患者45例,比较3组,高分化组与中分化组、高分化组与低分化组B F、B V和P S的差异均有统计学意义(P<0.05)。而3组M T T值无统计学差异(P>0.05)。B F、B V、MTT、PS与不同T分期差异有统计学意义。结论:胃CT灌注成像可前瞻性评估胃腺癌的病理类型。     

椎基底动脉迂曲扩张症的计算流体力学分析

目的 基于磁共振血管造影(MRA)的椎基底动脉迂曲扩张症(VBD)计算机流体力学分析。方法 选取2018年1月至2022年1月牡丹江医学院附属红旗医院诊断为VBD的40例患者,经MRI检查正常的40例患者图像。以椎基底动脉MRA图像构建椎基底动脉三维几何模型,分为VBD组与对照组,分析血流速度(V)、壁面剪切应力(WSS)及震荡剪切系数(OSI)。结果 VBD组V、WSS及OSI均高于对照组,差异有统计学意义(P <0.05)。在血流速度方面,高速血流集中于基底动脉及右侧大脑后动脉处。在WSS方面,VBD组高WSS位于右侧椎动脉、基底动脉、双侧大脑后动脉等大部分血管区域,以血管分叉处显著。在OSI方面,VBD组高OSI值以基底动脉末端至双侧大脑后动脉发出处明显,其余血管区域为波动性高OSI分布。结论 基于真实磁共振患者图像可建立三维个体化血管模型及进行血流动力学分析,获取VBD血流速度图、血管剪切应力云图及震荡剪切系数云图。建立VBD组及对照组模型,分析血流动力学发现,VBD组的基底动脉段具有高速血流、高WSS及高OSI,以末端显著,临床上应着重关注此区域。     

沙参麦冬汤对甲状腺癌术后免疫功能的影响:随机对照研究

目的观察沙参麦冬汤对甲状腺癌患者术后免疫功能的影响。方法选择甲状腺癌术后患者77例,采用随机数字表法分为观察组(41例)和对照组(36例)。对照组采用左甲状腺素钠片+安慰剂治疗;观察组采用左甲状腺素钠片+沙参麦冬汤治疗。疗程为6周。评价两组临床疗效改善率;采用癌症患者生活质量指数(QLI,包括:活动能力、日常生活、健康感受、外界支持和人生观)评估量表评价生活质量;比较两组自然杀伤细胞(NK)活性、T淋巴细胞亚群及免疫球蛋白A(IgA)、免疫球蛋白M(IgM)、免疫球蛋白G(IgG)水平。结果观察组总改善率[77.78%(28/36)]显著高于对照组[53.13%(17/32),P<0.05]。与治疗前比较,观察组和对照组治疗后活动能力、日常生活、健康感受、人生观评分和总分,NK细胞百分比,CD3^+、CD4^+T百分比和CD4^+/CD8^+比值,IgM、IgG水平升高(P<0.05,P<0.01),CD8^+T百分比降低(P<0.05,P<0.01)。与对照组比较,观察组治疗后活动能力、日常生活、健康感受、人生观评分和总分,NK细胞百分比,CD3^+、CD4^+T百分比和CD4^+/CD8^+比值,IgM、IgG水平升高(P<0.05,P<0.01),CD8^+T百分比降低(P<0.01)。结论沙参麦冬汤可提高甲状腺癌术后临床疗效,改善患者生活质量,增强患者免疫功能。     

高效液相色谱法测定咽炎片中芍药苷的含量

目的:建立高效液相色谱法测定咽炎片中芍药苷的含量。方法:以十八烷基硅烷键合硅胶为填充剂,乙腈-水(12:88)为流动相,检测波长230nm。结果:平均加样加收率为99．24％,(RSD=0．844％)。结论:方法简便、准确,适合于该产品质量检验分析。