自体块状皮质骨修复种植区颌骨缺损

背景:自体骨有骨传导、骨诱导及骨生成的特性,同时具有良好的生物相容性,移植后无排斥反应。但关于自体骨块移植后的骨块是完全被吸收替代?还是能保留细胞活性长期存留?仍存在争议。目的:观察皮质骨移植后改建再生过程中的组织学变化。方法:6只健康比格犬麻醉后拔除两侧上颌前磨牙,并去除颊侧宽约10 mm、长约15 mm、厚度约2 mm的骨板,建立上颌骨缺损模型,在双侧下颌骨体颊侧切取相应大小的块状皮质骨并修整边缘。在上颌骨缺损区移植皮质骨块,一侧为单纯块状皮质骨移植,另一侧在块状皮质骨移植同期植入种植体。分别于骨移植后3,6个月取材,进行大体观测和组织学观察,分析移植骨块的吸收率、移植骨中的细胞存活率。实验方案经大连医科大学动物实验伦理委员会批准。结果与结论:①大体观察可见移植骨块体积逐渐缩小,边缘圆钝,与基骨结合稳固;②6个月时全部种植体脱落;硬组织磨片可见移植骨块与基骨间存在新生骨连接;6个月时移植骨骨陷窝孔隙率明显低于3个月,移植骨吸收率显著高于3个月(均P<0.05);③结果说明,块状皮质骨移植后,能够与受植区基骨发生骨结合,其内部的骨细胞部分保持活力,随着愈合期延长,新生骨细胞的比例增加,移植骨块的体积逐渐变小。皮质骨移植同期种植后移植物吸收明显,种植体骨结合不良。     

3D打印结合虚拟手术设计治疗复杂Pilon骨折

文题释义：Pilon骨折：为发生于胫骨远端1/3波及胫骨远端关节面的粉碎性或压缩骨折,治疗关键在于有效复位骨折、恢复踝关节面正常解剖关系。目前临床上主要包括切开复位内固定、外固定术等治疗术式。 3D打印结合虚拟手术设计：是以3D打印技术与虚拟手术设计相结合,全面、直观、准确地显示骨折的立体形态和各部位解剖结构的空间关系。通过3D Objects窗口中的Move和Rotate对骨折块进行虚拟移动并复位,根据虚拟操作情况,制定虚拟骨折块复位方式、移动距离及旋转角度,可以缩短手术时间、减少手术创伤及出血量、获得更好的骨折复位及功能恢复的一种方法。 背景：Pilon骨折主要是垂直压缩暴力累及胫骨远端关节面的骨折,尤其是高能量损伤的Pilon骨折,其骨折移位明显,干骺端不同程度的压缩、粉碎,高度不稳定、关节软骨原发性损伤以及关节面不平整是Pilion骨折的特征,因其治疗难度大、并发症多、致残率高,已成为骨科最具挑战性的难题之一。良好的术前规划与设计可减少并发症的发生,获得更好的修复效果。 目的：探讨3D打印技术结合虚拟手术设计在复杂Pilon骨折治疗中的应用效果。 方法：选择2017年8月至2018年11月玉林市中西医结合骨科医院收治的88例复杂Pilon骨折患者,按随机数字表法分为2组,3D打印组38例,对照组50例。3D打印组采用3D技术结合虚拟手术设计辅助进行手术治疗,对照组采用传统常规手术。记录2组手术时间、手术出血量、手术切口长度、钢板一次性成功放置率、术后踝关节功能恢复情况及术口愈合情况。 结果与结论：①3D打印组在手术时间、手术出血量、手术切口长度、钢板一次性成功放置率、复位满意度(Burwell-Charnley骨折复位放射学评价)、术后12个月随访功能恢复程度(Mazur踝关节评分)、术口愈合情况方面均优于对照组,差异均有显著性意义(P < 0.05);②提示与传统常规手术相比,使用3D打印结合虚拟手术设计治疗复杂Pilon骨折可以缩短手术时间、减少手术创伤及出血量,获得更好的骨折复位及功能恢复。 ORCID: 0000-0002-7553-7254(梁周) 中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

黄芩苷调控自噬保护肠黏膜屏障干预肠道急性移植物抗宿主病

文题释义：移植物抗宿主病：是由于移植后异体供者移植物中的T淋巴细胞,经受者发动的一系列“细胞因子风暴”刺激,显著增强了其对受者抗原的免疫反应,以受者靶细胞为目标发动细胞毒攻击,其中皮肤、肝及肠道是主要的靶目标。根据移植物抗宿主病在移植后发生的时间,如在100 d内发生者称为急性移植物抗宿主病,在100 d后发生者称为慢性移植物抗宿主病。黄芩苷：黄芩汤的君药黄芩,《神农本草经》谓可治“肠辟泄利”,性苦寒,可清肺胃胆及大肠经之湿热,黄芩苷是黄芩中提取的一种黄酮类化合物,具有抑菌、清除氧自由基等作用,减轻蛋白酶与炎性因子对组织的损害。 摘要背景：急性移植物抗宿主病是造血干细胞移植后早期最容易致死的并发症之一,如何干预急性移植物抗宿主病病程是个热点问题。目的：探讨黄芩苷调控自噬干预肠道急性移植物抗宿主病的机制。方法：⁶⁰Co照射CB6F1小鼠4 h,立即尾静脉输注Balb/c小鼠单个核细胞悬液(骨髓+脾),建立单倍体造血干细胞移植模型。造模后当天开始模型组灌胃生理盐水,治疗组灌胃黄芩苷,剂量为30 mg/(kg·d),共14 d。治疗后进行小鼠急性移植物抗宿主病临床评分、小肠黏膜急性移植物抗宿主病病理评级,透射电镜观察小肠黏膜自噬泡结构,流式细胞仪检测小肠黏膜上皮细胞活性氧水平,Western blot检测自噬相关蛋白LC3Ⅱ、LC3-Ⅰ、Beclin1的表达。结果与结论：①治疗组临床急性移植物抗宿主病评分、小肠黏膜病理评级明显优于模型组;②透射电镜下模型组存在自噬泡但线粒体结构毁坏严重,治疗组自噬泡增多且线粒体结构相对完整;③治疗组小鼠小肠黏膜上皮细胞活性氧水平低于模型组(P < 0.01),治疗组LC3Ⅱ/Ⅰ、Beclin1的表达水平明显高于模型组(P < 0.01);④结果表明,黄芩苷可以通过降低活性氧的产生,提高小肠黏膜细胞的自噬水平,保护肠黏膜屏障,进而降低移植后肠道急性移植物抗宿主病的发病率。ORCID: 0000-0002-8771-5898(崔兴) 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

Notch3信号介导小胶质细胞活化在慢性前列腺炎疼痛中的作用

目的观察Notch3介导L5~S2脊段背角小胶质细胞活化在慢性前列腺炎疼痛中的作用。方法大鼠分为实验组(慢性前列腺炎组)和对照组,实验组通过完全弗氏佐剂(CFA)注射前列腺来制作大鼠慢性前列腺炎疼痛模型,对照组注射生理盐水,采用热辐射甩尾痛阈测定和前列腺组织病理学检查鉴定疼痛模型,分别在注射CFA后0、4、12、24 d,采用qRT-PCR检测L5~S2脊段后角小胶质细胞活化标志物IBA-1和受体Notch3 mRNA的表达,采用ELISA检测小胶质细胞炎症因子TNF-α和IL-1β的分泌,并在鞘内注射小胶质细胞和Notch3抑制剂后检测小胶质细胞TNF-α和IL-1β蛋白的表达。结果前列腺组织病理和热痛域实验证实慢性前列腺炎疼痛模型建立成功。实验组大鼠Notch3、IBA-1、TNF-α及IL-1β的表达在第4天开始增加,第12天达到最高水平,第24天开始下降,均显著高于对照组,差异有极显著性统计学意义(P<0.01)。抑制小胶质细胞和Notch3受体后,TNF-α和IL-1β的分泌明显减少(P<0.05)。结论慢性前列腺炎疼痛中Notch3介导L5~S2脊段中枢小胶质细胞活化,炎症因子分泌增加,与慢性前列腺炎呈现的持续顽固神经炎性疼痛有关。     

Generating functional CD8+ T cell memory response under transient CD4+ T cell deficiency: implications for vaccination of immunocompromised individuals

Studies based on either MHC class II-knockout or CD4+ T cell-depleted murine models have demonstrated a critical role for CD4+ T cells in the generation of CD8+ T cell memory. However, it is difficult to extend these findings to immunocompromised humans where a complete loss of CD4+ T cells is rarely observed. Here, we have developed a model setting, which allows studies on the generation of CD8+ T cell memory responses in a transient CD4+ T cell-deficient setting similar to that seen in immunocompromised patients. Immunisation with an adenoviral vaccine under transient helpless or help-deficient conditions showed varying degrees of impact on the priming of CD8+ T cell responses. Antigen-specific T cells generated under normal CD4+ T cell help and transient help-deficient conditions showed similar effector phenotype and were capable of proliferation upon secondary antigen encounter. Most importantly, in spite of CD4+ T cell deficiency, the long-term CD8+ T cell memory response remained functionally stable and showed comparable cytotoxic effector function as seen in CD8+ T cells generated with normal CD4+ T cell numbers. These findings provide evidence that in spite of partially impaired activation of a primary CD8+ T cell response, a fully functional and stable memory CTL response can be induced under conditions of severe transient CD4+ T cell deficiency.     

Improvement in the contrast of CEST MRI via intermolecular double quantum coherences

The tremendous potential of chemical exchange saturation transfer (CEST) agents as an emerging class of magnetic resonance imaging contrast media has been demonstrated in recent years. In a CEST experiment, a high CEST contrast is always welcome. However, when the exchange rate is low, which may happen in exchangeable solute protons of low concentration, it is usually hard to obtain an excellent CEST efficiency. Recently, we noted that the intermolecular multiple quantum coherence signal is more sensitive to the changes of the magnetization magnitude than a conventional single quantum coherence signal. Consequently, it may be easier when used in obtaining a CEST contrast. In this note, a modified COSY (two-dimensional correlated spectroscopy) revamped with an asymmetric Z-gradient echo detection (CRAZED) sequence combined with an off-resonance saturation pulse followed by a standard spin-echo imaging sequence was designed to obtain a better CEST contrast image based on the intermolecular double quantum coherence method. An analytical expression was derived from a dipolar field theory. Experiments were performed on an agar-glucose phantom, and the results demonstrate the feasibility of our method.     

新型撑开器结合微创内固定系统内固定治疗胫骨近端骨折

背景:传统手术治疗方法治疗胫骨近端骨折对骨折部位剥离广泛,且影响局部血液循环,增加骨折延迟愈合和不愈合的发生率。近年来兴起的微创内固定系统,可以最大限度地保护局部软组织以及血液循环,为骨折愈合提供更好的条件,而新型撑开器的应用也解决了传统人手牵引复位稳定性、持久性的问题,两者的结合应用逐渐受到关注。目的:探讨新型撑开器辅助复位、微创内固定系统治疗胫骨近端骨折的疗效。方法:以2016年5月至2019年10月收治的22例胫骨近端骨折患者为研究,随机分为对照组和观察组,各11例。对照组采用传统手法复位、常规切口钢板内固定;观察组以新型撑开器辅助复位、微创内固定系统钢板内固定。试验经广州医科大学附属第五医院伦理委员会批准。结果与结论:与对照组相比,观察组患者末次随访时Rasmussen膝关节功能评分较优,术中失血量、手术用时、住院天数、开始负重时间较少,出现关节受限、骨折延迟愈合等术后并发症患者数量较少,但骨折愈合时间与对照组接近,且切口感染、内固定松动断裂等术后并发症患者数量与对照组接近。提示应用新型撑开器结合微创内固定系统内固定治疗胫骨近端骨折,可以减少手术复位时间、降低局部软组织损伤,有利于患者早期功能锻炼,减少手术后并发症。     

Impaired attention network in temporal lobe epilepsy: A resting FMRI study

Attention deficit is a common symptom in the patient with mesial temporal lobe epilepsy (mTLE). Although presumption has been proposed by the previous study that mTLE may have impaired attention networks, no fMRI study has addressed the alteration of the dorsal attention network in mTLE. Twenty-four patients with bilateral mTLE and the same number of gender- and age-matched healthy controls participated in the current fMRI study. The resting-state network corresponding to the dorsal attention network (DAN) was extracted by using independent component analysis (ICA) from each participant. Functional connectivity in the DAN was then compared between the patients and controls. In addition, the scores of Trail Making Test (TMT) in the patients were correlated to the z-score of the voxels showing significant difference between the two groups. Compared with the controls, the patients with mTLE presented decreased functional connectivity in almost all the regions within the DAN. Moreover, there were negative correlations between the TMT scores and the z-scores in the voxels showing decreased or increased functional connectivity in mTLE. Our results suggested that the alteration of DAN might underpin the impairment of top-down attention function in mTLE. Our fMRI study may contribute to the understanding of neuro-pathophysiological mechanism of attention impairments in patients with mTLE.     

Effects of chloride and potassium channel blockers on apoptotic cell shrinkage and apoptosis in cortical neurons

K⁺ and Cl^– homeostasis have been implicated in cell volume regulation and apoptosis. We addressed the hypothesis that K⁺ and Cl^– efflux may contribute to apoptotic cell shrinkage and apoptotic death in cultured cortical neurons. CLC-2 and CLC-3 chloride channels were detected in cultured cortical neurons. The Cl^– channel blockers 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS), 4-acetamido-4-isothiocyanatostilbene-2,2-disulfonic acid (SITS) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) inhibited the outwardly rectifying Cl^– current, prevented apoptotic cell shrinkage, and mildly attenuated cell death induced by staurosporine, C₂-ceramide, or serum deprivation. Cl^– channel blockers, however, at concentrations that prevented cell shrinkage had no significant effects on caspase activation and/or DNA fragmentation. Cell death in the presence of a Cl^– channel blocker was still sensitive to blockade by the caspase inhibitor z-Val-Ala-Asp(OMe)-fluoromethyl ketone (z-VAD-fmk). Electron microscopy revealed that, although DIDS prevented apoptotic cell shrinkage, certain apoptotic ultrastructural alterations still took place in injured neurons. On the other hand, the K⁺ channel blocker tetraethylammonium (TEA), clofilium, or the caspase inhibitor z-VAD-fmk prevented cell shrinkage as well as caspase activation and/or DNA damage, and showed stronger neuroprotection against apoptotic alterations and cell death. The results indicate that neurons may undergo apoptotic process without cell shrinkage and imply distinct roles for Cl^– and K⁺ homeostasis in regulating different apoptotic events.