自体外周血单核细胞移植联合多孔髓芯减压修复股骨头坏死:11个月随访评价

背景：大量临床试验研究发现,股骨头坏死患者的股骨头颈及股骨近端骨髓干细胞的数量明显减少,同时伴随着活性减弱,这就使得此处成骨能力明显下降,即坏死骨在得到吸收后仍不能有效修复,从而导致股骨头的塌陷。目的：分析自体外周血单核细胞移植联合多孔髓芯减压治疗股骨头坏死的早期临床疗效。方法：选取45例(49髋)股骨头坏死患者作为研究对象,采用自体外周血单核细胞移植联合多孔髓芯减压治疗,治疗后进行疼痛、髋关节功能、患者满意度评估,并进行X射线片、CT及MRI等检查。结果与结论：所有患者均获得随访,随访时间11-14个月,平均随访(12.5±0.6)个月,在随访期间未发生并发症与严重不良反应。治疗后疼痛评分、Harris评分较治疗前均有明显改善,差异有显著性意义(P <0.05)。治疗后12个月患者满意度优良率为92%。MRI检查低信号区所占股骨头体积的百分比：治疗前为(40.1±7.34)%,治疗后6个月为(20.23±5.4)%,治疗前后差异有显著性意义(P <0.05)。结果表明自体外周血单核细胞移植联合多孔髓芯减压治疗股骨头坏死的早期临床疗效显著,可明显减轻关节疼痛,改善并恢复髋关节功能,延缓病情发展恶化。     

CEUS观察兔肝VX2肿瘤坏死演变

目的应用CEUS技术观察兔肝VX2肿瘤坏死过程,探讨VX2肿瘤生长坏死规律及其对实验产生的影响。方法应用超声引导下经皮穿刺种植法成功建立24只兔VX2肝肿瘤模型,并通过CEUS技术分别在肿瘤种植后10、14、21、28天动态观察肝肿瘤演变过程,测量肿瘤体积及坏死体积,计算瘤内坏死率。结果在肿瘤种植后10、14、21、28天兔肝VX2肿瘤体积、坏死灶体积和坏死率比较,差异均有统计学意义(P均0.05);肿瘤种植后10、14、21、28天的CEUS表现能反映出肿瘤的病理学特征。实验依据CEUS和病理特点将肿瘤生长过程细分为5个时期,0~10天为肿瘤实质前期;11~14天为肿瘤实质后期;15~21天为肿瘤坏死初期;22~28天为加速坏死期;28天后为肿瘤囊变期。结论 CEUS可准确判断肝肿瘤实质及坏死范围;VX2肿瘤的生长演变及肿瘤坏死具有规律性,可根据不同实验要求选择适宜的研究时间段。     

Cell death and autophagy in tuberculosis

Mycobacterium tuberculosis has succeeded in infecting one-third of the human race though inhibition or evasion of innate and adaptive immunity. The pathogen is a facultative intracellular parasite that uses the niche provided by mononuclear phagocytes for its advantage. Complex interactions determine whether the bacillus will or will not be delivered to acidified lysosomes, whether the host phagocyte will survive infection or die, and whether the timing and mode of cell death works to the advantage of the host or the pathogen. Here we discuss cell death and autophagy in TB. These fundamental processes of cell biology feature in all aspects of TB pathogenesis and may be exploited to the treatment or prevention of TB disease.     

重组人肿瘤坏死因子相关弱凋亡诱导因子对小鼠主动脉内皮舒张功能及凝血相关因子的影响

目的 采用重组人肿瘤坏死因子相关弱凋亡诱导因子（rhTWEAK）经腹腔注射,诱导血管内皮损伤模型,观察rhTWEAK对小鼠主动脉内皮舒张功能和凝血相关因子的影响。方法 3～4周龄C57BL小鼠32只,随机分成4组,每组8只,腹腔注射各药物：①rhTWEAK组：rhTWEAK按5 μg/（kg·d）的量溶于生理盐水,共0.3 mL,腹腔注射,连续注射7天;②rhTWEAK＋抗rhTWEAK组：先给予抗rhTWEAK腹腔注射,15 min后再给予rhTWEAK注射;③IgG组：给予小鼠非特异性IgG腹腔注射;④对照组：给予0.3 mL生理盐水注射。分别在干预1周后眼球取血,分离上清;取小鼠胸主动脉段进行血管舒张功能的检测。酶联免疫吸附法检测血浆中内皮型一氧化氮合酶（eNOS）、高敏C反应蛋白（hs-CRP）、一氧化氮（NO）、组织因子（TF）、组织因子途径抑制物（TFPI）含量。结果 ①与对照组、rhTWEAK＋抗rhTWEAK组、IgG组相比,rhTWEAK组内皮依赖性血管舒张功能、血浆中eNOS、NO、TFPI水平明显降低,TF水平明显升高,均有统计学意义（均P<0.05）;血浆中hs-CRP含量未见明显改变（P>0.05）;②rhTWEAK组、IgG组与对照组相比,血管内皮舒张功能、血浆中NO、TF、TFPI、eNOS、hs-CRP含量变化均无统计学差异（均P>0.05）。结论 rhTWEAK可诱导内皮功能紊乱和凝血相关因子含量的改变,这可能是TWEAK参与动脉粥样硬化早期血管内皮损害的机制。     

Updated developments on molecular imaging and therapeutic strategies directed against necrosis

Cell death plays important roles in living organisms and is a hallmark of numerous disorders such as cardiovascular diseases, sepsis and acute pancreatitis. Moreover, cell death also plays a pivotal role in the treatment of certain diseases, for example, cancer. Noninvasive visualization of cell death contributes to gained insight into diseases, development of individualized treatment plans, evaluation of treatment responses, and prediction of patient prognosis. On the other hand, cell death can also be targeted for the treatment of diseases. Although there are many ways for a cell to die, only apoptosis and necrosis have been extensively studied in terms of cell death related theranostics. This review mainly focuses on molecular imaging and therapeutic strategies directed against necrosis. Necrosis shares common morphological characteristics including the rupture of cell membrane integrity and release of cellular contents, which provide potential biomarkers for visualization of necrosis and necrosis targeted therapy. In the present review, we summarize the updated joint efforts to develop molecular imaging probes and therapeutic strategies targeting the biomarkers exposed by necrotic cells. Moreover, we also discuss the challenges in developing necrosis imaging probes and propose several biomarkers of necrosis that deserve to be explored in future imaging and therapy research.     

Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

OBJECTIVE:

It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage.

METHODS:

We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student''s t-test.

RESULTS:

The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group.

CONCLUSION:

For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion.     

Eritoran对蛛网膜下腔出血兔基底动脉IL-1β、TNF-α和IFN-β mRNA表达的影响

目的 探讨eritora对蛛网膜下腔出血(subarachnoid hemorrhage,SAH)兔基底动脉炎性细胞因子白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和干扰素-β(interferon-β,IFN-β)mRNA表达的影响.方法 36只健康成年雄性新西兰兔随机分为SAH组(n=12)、生理盐水组(n=12)和eritoran组(n=12).采用枕大池自体动脉血二次注血法建立SAH模型,生理盐水组用生理盐水等量置换脑脊液,SAH组置换脑脊液后立即注入等量自体非肝素化动脉血,eritoran组在每次经枕大池注血后立即静脉注射eritoran( 1.5 mg/kg).进行摄食情况和神经功能缺损评分.实时荧光定量聚合酶链反应检测基底动脉IL-1β、TNF-α和IFN-β mRNA表达.结果 Eritoran组进食评分[(1.20 ±0.41)分对(2.20±0.61)分;t=53.073,P=0.002]、神经功能缺损评分[(1.46±0.32)分对(2.60±0.08)分;t=306.431,P=0.001]、IL-1β [(1.22±0.48)对(2.38±0.06);P=0.000]、TNF-α[(1.39±0.07)对(3.32±0.21),P=0.000]和IFN-β[(1.51±0.08)对(2.18±0.05),P=0.000] mRNA表达均显著低于SAH组.结论 Eritoran可下调SAH兔基底动脉炎性细胞因子IL-1β、TNF-α和IFN-β mRNA表达,增加摄食量,减轻神经功能缺损.