幼兔重度肺冲击伤动物模型的建立

目的建立稳定的幼兔重度肺冲击伤实验动物模型,为未成熟肺冲击伤机制和肺损伤救治研究提供理想的动物模型。方法致伤驱动压初筛:选取4周龄新西兰白兔16只,随机分为驱动压4.0 MPa组和4.5 MPa组,采用BST-Ⅰ型生物激波管,以相应的驱动压力致伤,对比2组肺冲击伤伤情。肺冲击伤伤情特点观察:选取4周龄新西兰白兔48只,随机分为正常对照组(8只)和冲击伤组(40只),依前面研究结果,冲击伤组采用4.5 MPa驱动压进行致伤;分别于伤即刻(0 h)、2 h、4 h、6 h、12 h、24 h、48 h及72 h观测动物生命体征和生理指标、肺大体解剖和光镜病理、测定肺组织含水量等。结果致伤驱动压初筛:2组动物均存活,4.0 MPa组冲击波超压为(328.16±4.78)kP a,重度肺冲击伤率为12.5%,AIS评分(3.38±0.52)分;4.5 MPa组冲击波超压为(395.04±11.74)kP a,重度肺冲击伤率为87.5%,AIS评分(4.13±0.64)分。肺冲击伤伤情特点观察:致伤动物均存活,伤后即刻出现持续约0.5 h的精神萎靡等情况,随后动物呼吸和心率等加快,肺出现广泛片状出血和水肿,肺含水量显著增加,多为重度冲击伤,AIS评分(3.98±0.55)分,肺光镜病理以肺组织断裂、出血、水肿,伴炎细胞浸润为主。结论利用BST-Ⅰ型生物激波管,采用4.5 MPa驱动压可建立稳定的4周龄新西兰白兔重度冲击伤模型,此模型伤情稳定,可用于未成熟肺冲击伤机制和肺损伤救治的实验研究模型。     

兔胸腹部爆炸伤后的血液浓缩及其可能机制

目的 :探讨爆炸性冲击伤后血液浓缩的特点及其可能的机制。方法 :采用雷管所致兔爆炸性冲击损伤模型 ,以1 2 5I 白蛋白标记的方法 ,观察爆炸性冲击伤前后红细胞压积与血浆外渗情况。结果 :距爆源 2 0cm处的爆炸冲击波作用时 ,红细胞压积增加 14 .9% ,血浆丢失为对照的 5 .12倍 ,白蛋白漏出率为伤前的 1.3倍 ,左肺组织中残留放射性较对照组增加约 18% ,该点平均压力峰值为 174 .4kPa。结论 :爆炸冲击伤后的红细胞压积增加、血浆丢失是伤后微循环功能障碍的重要原因     

兔胸腹部爆炸伤后的血液浓缩与肺微血管通透性改变

目的：探讨爆炸冲击伤后血液浓缩的特点及微血管通透性的变化。方法：采用雷管对兔的爆炸性冲击损伤模型与[¹²⁵I]-白蛋白标记的方法，观察爆炸性冲击波对兔肺微血管通透性的影响。结果：距爆源20 cm处的爆炸冲击波压力平均峰值为174.4 kPa，红细胞压积的增加为14.9%，白蛋白漏出率为伤前的1.3倍，左肺组织中残留放射性较对照组增加约18%。结论：100 kPa以上的爆炸冲击波能引起红细胞压积与肺组织中的残留放射性的明显增加。     

兔胸腹部爆炸伤后不同器官微血管通透性的变化

目的探讨爆炸性冲击伤后不同组织器官微血管通透性变化的特点及其可能的机理。方法采用雷管对兔的爆炸性冲击损伤模型 ,以及 125I-白蛋白标记的方法 ,观察爆炸性冲击波对兔心、脑、肺、肾、肝组织中的微血管通透性的影响。结果距爆源20cm处的爆炸冲击波平均压力峰值为174 .4kPa,可引起红细胞压积增加为14.9 % (与对照组相比 ) ,血浆丢失为对照的5.12倍 ;距爆源10cm时 ,爆炸冲击波的压力峰值可陡增至1000kPa以上 ,所致白蛋白漏出率为伤前的1.5倍 ,心、脑、肺、肾组织中的残留放射性较对照组增加约1 .6～1.9倍。结论爆炸冲击波能引起红细胞压积明显增加 ,血浆丢失 ,以及心、脑、肺、肾组织中微血管通透性的增加。     

坐姿下不同组织压力性损伤生物力学研究

目的 探讨坐姿下臀部压力性损伤易发部位以及不同软组织的生物力学响应,为有效预防深层组织压力性损伤提供参考。 方法 基于臀部 CT 扫描数据,建立坐位臀部有限元模型,包括骨骼、肌肉、脂肪和皮肤组织及坐垫模型,利用生死单元模拟组织损伤。 对比实验坐垫界面压力测量数据与有限元模拟结果,验证模型有效性。 模拟坐位力学状态,研究软组织的应力、应变情况,分析不同软组织中的压应力及超出极限值后可能造成的损伤情况。结果 通过对比坐垫模型仿真结果与实验界面压力测量结果,证明模型有效。 坐位时坐骨结节下方软组织区域出现应力集中现象。 其中,臀大肌组织中的横向压应力峰值约为 38 kPa,剪切应力峰值约为 3. 4 MPa;而脂肪组织中的最大压应力与剪切应力峰值分别为 22 kPa 与 4. 5 MPa,均未出现在坐骨结节正下方。 结论 软组织受到一定时间和大小的压力载荷作用,可能出现深层组织损伤。 当保持坐姿一定时间后,应及时变换体位,以降低压力性损伤出现的概率。 研究结果为预防压力性损伤提供生物力学依据,具有重要的临床研究价值。     

癌基因诱导的细胞衰老

癌基因诱导的衰老（OIS）是指癌基因突变所产生的异常增殖信号,通过MAPK和PI3K信号通路,使细胞处于生长停滞的状态,抑制细胞增殖。它的发生机制与异染色质的形成以及DNA 损伤检测点反应的作用相关。衰老相关的β-半乳糖苷酶和异染色质灶是OIS的标记。随着人们对OIS的认识,新的肿瘤发生模式不断提出。对OIS机制的了解,有利于我们重新认识肿瘤的发生机制,为肿瘤治疗提供新的思路和方法。     

CT灌注成像在急性缺血性卒中患者诊断及预后评估中的应用

目的 探讨CT灌注成像在急性缺血性卒中（AIS）患者诊断及预后评估中的应用价值。方法 回顾性研究。纳入2020年2月—2021年7月河南省直第三人民医院收治的AIS患者104例,其中,男61例、女43例,年龄46~81（62.7±12.3）岁。患者均接受急诊脑CT灌注成像检查,获取核心梗死面积,以及脑血流量（CBF）、脑血容量（CBV）、对比剂平均通过时间（MTT）和峰值时间（TTP）等CT灌注成像血流动力学参数,对比分析患者脑梗死区和缺血半暗带脑组织间CBF、CBV、MTT、TTP值的差异。以《中国急性缺血性脑卒中诊疗指南2018》为金标准,分析CT灌注成像AIS患者的检出率。入院时进行美国国立卫生研究院卒中量表（NIHSS）评分评估患者神经功能状态。治疗后3个月采用改良Rankin量表（mRS）评分评估患者预后,并按照预后评估结果进行分组观察。采用logistic回归分析AIS预后的预测因素。结果 本组104例AIS患者中,经CT灌注成像检查显示梗死区及半暗带血流异常者共96例（检出率为92.31%）。CT灌注成像检出的96例中,mRS评分评估预后良好者69例、预后不良者27例。脑梗死区和缺血半暗带分别与健侧对应部位的正常脑组织相比,CBF、CBV值降低,MTT、TTP延长,差异均有统计学意义（P值均<0.05）。预后不良组核心梗死面积、发病至溶栓时间及高脂血症比例、NIHSS评分及缺血半暗带CT灌注参数MTT、TTP均高于预后良好组,CT灌注参数CBF、CBV均低于预后良好组,差异均有统计学意义（P值均<0.05）。logistic回归分析结果显示,核心梗死面积、发病至溶栓时间、高脂血症,NIHSS评分,以及缺血半暗带CT灌注成像血流动力学参数CBF、CBV、MTT、TTP等均是AIS患者预后的预测因素（P值均<0.05）。结论 CT灌注成像检查可快速反映脑部组织灌注损伤情况,对AIS患者的及时诊断具有重要意义;且CT灌注成像血流动力学参数可有效反映AIS患者溶栓治疗后受累血管再通情况,为其预后评估提供一定依据。     

学龄前儿童胸腔镜手术两种单肺通气方法的临床观察

目的比较单腔支气管插管和Univent导管用于学龄前儿童（3～6岁）择期胸腔镜手术中单肺通气的临床效果。结论选择学龄前儿童择期胸腔镜手术患者34例,术中均需行单肺通气,随机分为支气管插管组（B组）和Univent组（U组）。观察并记录盲插成功率、插管定位时间、肺塌陷质量、术中导管移位次数、单肺通气期间气道峰压增加率、气道损伤评分、术后咽痛和声嘶发生率、术后24h胸片对比术前肺炎情况。结果两组的盲插成功率、插管定位时间、气道损伤评分和术后咽痛声嘶发生率差异无统计学意义。肺塌陷质量B组明显低于U组（P〈0.05）;单肺通气期间的气道峰压增加率、导管移动次数和术后肺炎加重率B组明显高于U组（P〈0.05）。结论 Univent导管用于单肺通气与单腔支气管插管相比可明显改善肺塌陷质量,降低单肺通气期间的气道峰压值,改善术中导管移位,降低术后肺炎发生率,比单腔支气管插管具有明显优势。     

双相气道正压结合反比通气应用于麻醉患者临床观察

目的观察双相气道正压结合反比通气应用于麻醉患者时对术中患者各项呼吸参数及血流动力学的影响,以探讨对正常肺如何实施肺保护策略。方法随机选择腹部肿瘤手术患者26例,其中男性15例,女性11例;年龄45～60岁,平均年龄45岁。美国麻醉学会（ASA）Ⅱ～Ⅲ级,术前无重大心肺疾病。全身麻醉,先以容量控制方式通气,吸呼比：1：2,90min后转换到双相气道正压结合反比通气,吸呼比=2：1。呼气终末正压（PEEP）从0．392kPa（4cmH2O）开始,吸气压（Pin）从0．686kPa（7cmH2O）开始,根据潮气量和呼气末CO2分压调整△P,保持与容量控制通气相同的潮气量。记录气道峰值压（Pmax）、平均气道压（Pmean）、呼气末CO2分压,血压、心率、脉搏氧饱和度变化,计算肺顺应性并在每一种通气方式90min稳定后抽取桡动脉血测血气分析。结果双相气道正压结合反比通气时,Pmean明显升高,肺顺应性明显升高,与容量控制通气相比,差异有显著统计学意义（P〈0．001）。凡。及动脉血CO2分压、氧分压、血流动力学差异无统计学意义。结论双相气道正压结合反比例通气应用于全身麻醉患者,‰。显著升高,肺顺应性明显改善,对血流动力学无显著影响,可安全用于全身麻醉患者术中机械通气维持。     

红景天苷调节CLP诱导的脓毒症小鼠肺纤维化及JAK2/STAT3的活化

目的：探讨红景天苷对盲肠结扎穿孔（CLP）诱导的脓毒症急性肺损伤小鼠肺纤维化和炎症的影响,并初步探究其作用机制。方法：50只BALB/c小鼠分为健康对照组、模型组、模型+5 mg/kg红景天苷组、模型+10 mg/kg红景天苷组、模型+20 mg/kg红景天苷组,10只/组。分别检测肺组织湿干重比、肺损伤评分和肺静息通气量,HE染色观察肺组织病理损伤程度,Masson染色观察肺纤维化程度,Western blot检测肺组织α-平滑肌肌动蛋白（α-SMA）、纤维连接蛋白（FN）、波形蛋白（Vimentin）、Ⅰ型胶原蛋白（ColⅠ）、诱导型一氧化氮合酶（iNOS）、IL-10、p-JAK2/JAK2、p-STAT3/STAT3蛋白表达水平,ELISA检测外周血中iNOS、IL-6、IL-4、IL-10含量。结果：与健康对照组相比,模型组小鼠肺功能低下,肺组织损伤严重（P<0.05）。与模型组相比,10 mg/kg和20 mg/kg红景天苷组小鼠肺损伤评分、肺组织湿干重比显著降低,肺静息通气量显著升高（P<0.05）。肺组织病理损伤和纤维化程度明显改善,α-SMA、FN、Vim...     

Distribution of Blood–Brain Barrier Disruption in Primary Blast Injury

Traumatic brain injury (TBI) resulting from explosive-related blast overpressure is a topic at the forefront of neurotrauma research. Compromise of the blood–brain barrier (BBB) and other cerebral blood vessel dysfunction is commonly reported in both experimental and clinical studies on blast injury. This study used a rifle primer-driven shock tube to investigate cerebrovascular injury in rats exposed to low-impulse, pure primary blast at three levels of overpressure (145, 232, and 323 kPa) and with three survival times (acute, 24, and 48 h). BBB disruption was quantified immunohistochemically by measuring immunoglobulin G (IgG) extravasation with image analysis techniques. Pure primary blast generated small lesions scattered throughout the brain. The number and size of lesions increased with peak overpressure level, but no significant difference was seen between survival times. Despite laterally directed blast exposure, equal numbers of lesions were found in each hemisphere of the brain. These observations suggest that cerebrovascular injury due to primary blast is distinct from that associated with conventional TBI.     

激波载荷下绵羊胸部动力学响应的数学模型

本文利用单自由度非线性单腔模型描述激波作用下机体胸部动力学响应,并建立其数学模型,通过测定激波作用下的绵羊胸壁内向运动的位移、速度和加速度,检验这一模型的预测效果。实验结果表明,该模型基本上反映了激波作用下绵羊胸壁运动过程,但有待于发展和完善。     

A simple conceptual model of primary pulmonary blast injury

Primary pulmonary blast injury arises from direct exposure to blast overpressure, and may lead to severe lung injury and systemic air embolism. The phenomena of spallation and implosion can be explained by a simple conceptual model without invoking complex physical principles.     

Development of a Finite Element Model for Blast Brain Injury and the Effects of CSF Cavitation

Blast-related traumatic brain injury is the most prevalent injury for combat personnel seen in the current conflicts in Iraq and Afghanistan, yet as a research community,we still do not fully understand the detailed etiology and pathology of this injury. Finite element (FE) modeling is well suited for studying the mechanical response of the head and brain to blast loading. This paper details the development of a FE head and brain model for blast simulation by examining both the dilatational and deviatoric response of the brain as potential injury mechanisms. The levels of blast exposure simulated ranged from 50 to 1000 kPa peak incident overpressure and 1–8 ms in positive-phase duration, and were comparable to real-world blast events. The frontal portion of the brain had the highest pressures corresponding to the location of initial impact, and peak pressure attenuated by 40–60% as the wave propagated from the frontal to the occipital lobe. Predicted brain pressures were primarily dependent on the peak overpressure of the impinging blast wave, and the highest predicted brain pressures were 30%less than the reflected pressure at the surface of blast impact. Predicted shear strain was highest at the interface between the brain and the CSF. Strain magnitude was largely dependent on the impulse of the blast, and primarily caused by the radial coupling between the brain and deforming skull.The largest predicted strains were generally less than 10%,and occurred after the shock wave passed through the head.For blasts with high impulses, CSF cavitation had a large role in increasing strain levels in the cerebral cortex and periventricular tissues by decoupling the brain from the skull. Relating the results of this study with recent experimental blast testing suggest that a rate-dependent strain-based tissue injury mechanism is the source primary blast TBI.     

Altered gene expression in cultured microglia in response to simulated blast overpressure: Possible role of pulse duration

Blast overpressure has long been known to cause barotrauma to air-filled organs such as lung and middle ear. However, experience in Iraq and Afghanistan is revealing that individuals exposed to explosive munitions can also suffer traumatic brain injury (TBI) even in the absence of obvious external injury. The interaction of a blast shock wave with the brain in the intact cranial vault is extremely complex making it difficult to conclude that a blast wave interacts in a direct manner with the brain to cause injury. In an attempt to “isolate” the shock wave and test its primary effects on cells, we exposed cultured microglia to simulated blast overpressure in a barochamber. Overpressures ranging from 15 to 45 psi did not change microglial Cox-2 levels or TNF-α secretion nor did they cause cell damage. Microarray analysis revealed increases in expression of a number of microglial genes relating to immune function and inflammatory responses to include Saa3, Irg1, Fas and CxCl10. All changes in gene expression were dependent on pulse duration and were independent of pressure. These results indicate that microglia are mildly activated by blast overpressure and uncover a heretofore undocumented role for pulse duration in this process.     

Dynamic Properties of Human Tympanic Membrane After Exposure to Blast Waves

Blast overpressure causes dynamic damage to middle ear components, and tympanic membrane (TM) rupture is the most frequent middle ear injury. However, it is unclear how the blast waves change mechanical properties of the TM and affect sound transmission through the ear. This paper reports the current study on dynamic properties of the TM after exposure to blast waves by using acoustic loading and laser Doppler vibrometry (LDV). The TM specimens were prepared from human temporal bones following exposures to blast overpressure. Vibration of the TM specimen induced by acoustic loading was measured by LDV over a frequency range of 200–8000 Hz. An inverse-problem solving method with finite element modeling was used to determine the complex modulus of the TM specimen. The post-blast storage modulus ranged from 23.1 to 26.9 MPa, and loss modulus ranged from 0.09 to 3.78 MPa as frequency increased from 200 to 8000 Hz. Compared to the complex modulus of normal TM reported in the literature, the post-blast storage and loss modulus decreased significantly across the frequency range. The scanning electron microscopy (SEM) images of the post-blast TM samples showed microstructural changes of the tissue, which explained the alteration of mechanical properties of the TM samples.     

体外循环肺损伤与水通道蛋白1基因表达相关性的实验研究

目的观察羊体外循环模型中肺损伤的存在,探讨体外循环下肺损伤与水通道蛋白1(AQP-1)基因表达之间的关系。方法健康成年羊16只,雌雄不拘,体质量15～30 kg,羊龄8个月。分为脂多糖组和对照组,每组8只。通过建立浅低温体外循环模型,停跳90 min,复跳6 h,分别比较其血流动力学的指标变化及普通病理组织和超微病理组织的各自特点,测定AQP-1 mRNA表达。结果利用体外循环前指标作为自身对照,进行单因素方差分析和Q检验。体外循环缺血再灌注之后,血流动力学较平稳[中心静脉压在体外循环前、心脏复跳前、再灌注至平稳时分别为(5.86±1.12)kPa、(6.52±1.33)kPa、(6.36±1.04)kPa],肺干质量/肺湿质量比值(体外循环前、心脏复跳前、复跳后1 h、复跳后3 h、复跳后6 h分别为0.232±0.025、0.224±0.021、0.187±0.022、0.153±0.018、0.134±0.023)与体外循环时间呈反相关(P<0.001),血浆总渗透压与体外循环时间呈正相关(P<0.01)。病理组织证实,复跳之后3～6 h可以见到明显的肺间质水肿及血管内皮细胞损伤。肺内AQP-1 mRNA表达与体外循环时间呈反相关(体外循环前、心脏复跳前、复跳后1 h、复跳后3 h、复跳后6 h分别为100.0、98.1±24.4、80.2±20.3、78.1±17.7、55.3±16.4),在复跳后3 h与6 h分别降至术前水平的77.8%和54.6%(P<0.01)。结论体外循环造成的肺损伤在心脏复跳后3～6 h内表现严重,同时AQP-1的表达下降,存在肺血管内皮损伤。     

Brain Injuries from Blast

Traumatic brain injury (TBI) from blast produces a number of conundrums. This review focuses on five fundamental questions including: (1) What are the physical correlates for blast TBI in humans? (2) Why is there limited evidence of traditional pulmonary injury from blast in current military field epidemiology? (3) What are the primary blast brain injury mechanisms in humans? (4) If TBI can present with clinical symptoms similar to those of Post-Traumatic Stress Disorder (PTSD), how do we clinically differentiate blast TBI from PTSD and other psychiatric conditions? (5) How do we scale experimental animal models to human response? The preponderance of the evidence from a combination of clinical practice and experimental models suggests that blast TBI from direct blast exposure occurs on the modern battlefield. Progress has been made in establishing injury risk functions in terms of blast overpressure time histories, and there is strong experimental evidence in animal models that mild brain injuries occur at blast intensities that are similar to the pulmonary injury threshold. Enhanced thoracic protection from ballistic protective body armor likely plays a role in the occurrence of blast TBI by preventing lung injuries at blast intensities that could cause TBI. Principal areas of uncertainty include the need for a more comprehensive injury assessment for mild blast injuries in humans, an improved understanding of blast TBI pathophysiology of blast TBI in animal models and humans, the relationship between clinical manifestations of PTSD and mild TBI from blunt or blast trauma including possible synergistic effects, and scaling between animals models and human exposure to blasts in wartime and terrorist attacks. Experimental methodologies, including location of the animal model relative to the shock or blast source, should be carefully designed to provide a realistic blast experiment with conditions comparable to blasts on humans. If traditional blast scaling is appropriate between species, many reported rodent blast TBI experiments using air shock tubes have blast overpressure conditions that are similar to human long-duration nuclear blasts, not high explosive blasts.     

狗冲击伤的荷载机制及效应研究

本文通过对暴露于空中爆炸波(激波)中的动物所承受不同的激波压力模态进行分析,表明处于规则反射区(NRA)与马赫反射区(MRA)中的动物的荷载机制是明显不同的。有关动物的实验结果是采用BST—Ⅰ型生物激波管致伤。其一选用44只雄性杂种狗是有端板(即NRA或MRA有反射壁)状态,另外选用8只雄性杂种狗是开口(即MRA自由场)状态。两组实验表明其创伤严重特点和创伤的分布规律都存在显著的差异。所观察到的各个器官的病理形态学和超微结构改变的动物实验结果,能够为冲击伤防护和诊治的进一步研究提供理论和临床上的依据。