介入技术在下肢动脉硬化闭塞症合并血栓形成中的应用

目的:探讨导管接触性溶栓(catheter-directed thrombolysis,CDT)联合球囊及支架成形术治疗下肢动脉硬化闭塞症合并血栓形成的临床疗效及安全性。方法:选择2011年1月~2014年12月收治的36例下肢动脉硬化闭塞症合并血栓形成性病变患者,先行置管溶栓治疗,再联合球囊及支架成形术治疗,观察其溶栓效果及血管再通情况。结果:本组溶栓总有效率为86.1%,尿激酶用量(75.5±34.6)万单位,溶栓后31例下肢缺血症状改善,下肢疼痛症状有不同程度减轻,下肢跛行距离明显延长,无垃圾脚发生。球囊及支架成形术后踝肱指数(ABI)由术前的0.39±0.11升高至术后的0.79±0.19,差异有统计学意义(P0.01)。随访1~48月,无死亡病例,9例出现支架内膜增生血管再狭窄,5例出现糖尿病膝下动脉狭窄闭塞,给予球囊扩张及支架成形术后下肢缺血症状减轻,其中1例患者于术后3年行下肢截肢治疗。结论:CDT联合球囊及支架成形术治疗下肢动脉硬化闭塞症合并血栓形成具有较高的临床价值,可以为PTA血管成形或支架置入赢得时机,改善下肢缺血,该方式创伤小,并发症少。     

Airway secretory cell fate conversion via YAP‐mTORC1‐dependent essential amino acid metabolism

Tissue homeostasis requires lineage fidelity of stem cells. Dysregulation of cell fate specification and differentiation leads to various diseases, yet the cellular and molecular mechanisms governing these processes remain elusive. We demonstrate that YAP/TAZ activation reprograms airway secretory cells, which subsequently lose their cellular identity and acquire squamous alveolar type 1 (AT1) fate in the lung. This cell fate conversion is mediated via distinctive transitional cell states of damage‐associated transient progenitors (DATPs), recently shown to emerge during injury repair in mouse and human lungs. We further describe a YAP/TAZ signaling cascade to be integral for the fate conversion of secretory cells into AT1 fate, by modulating mTORC1/ATF4‐mediated amino acid metabolism in vivo. Importantly, we observed aberrant activation of the YAP/TAZ‐mTORC1‐ATF4 axis in the altered airway epithelium of bronchiolitis obliterans syndrome, including substantial emergence of DATPs and AT1 cells with severe pulmonary fibrosis. Genetic and pharmacologic inhibition of mTORC1 activity suppresses lineage alteration and subepithelial fibrosis driven by YAP/TAZ activation, proposing a potential therapeutic target for human fibrotic lung diseases.     

Development of Obliterative Bronchiolitis in a Murine Model of Orthotopic Lung Transplantation

Orthotopic lung transplantation in rats was first reported by Asimacopoulos and colleagues in 1971 ¹. Currently, this method is well accepted and standardized not only for the study of allo-rejection but also between syngeneic strains for examining mechanisms of ischemia-reperfusion injury after lung transplantation. Although the application of the rat and other large animal model ² contributed significantly to the elucidation of these studies, the scope of those investigations is limited by the scarcity of knockout and transgenic rats. Due to no effective therapies for obliterative bronchiolitis, the leading cause of death in lung transplant patients, there has been an intensive search for pre-clinical models that replicate obliterative bronchiolitis. The tracheal allograft model is the most widely used and may reproduce some of the histopathologic features of obliterative bronchiolitis ³. However, the lack of an intact vasculature with no connection to the recipient''s conducting airways, and incomplete pathologic features of obliterative bronchiolitis limit the utility of this model ⁴. Unlike transplantation of other solid organs, vascularized mouse lung transplants have only recently been reported by Okazaki and colleagues for the first time in 2007 ⁵. Applying the basic principles of the rat lung transplant, our lab initiated the obliterative bronchiolitis model using minor histoincompatible antigen murine orthotopic single-left lung transplants which allows the further study of obliterative bronchiolitis immunopathogenesis⁶.     

下肢动脉硬化闭塞症血管成形术的疗效观察

目的:探讨血管成形术治疗下肢动脉硬化闭塞症的临床应用价值。方法:对我院78例下肢动脉硬化闭塞患者的临床资料进行回顾性分析。78例患者(98条血管)术前经CTA诊断后,行腔内血管成形术(PTA)和血管支架植入术治疗,治疗后随访1~18个月,分析踝/肱指数(ABI)、血管内径、皮温及足背动脉搏动的变化。结果:成功完成77例(98.7%)患者、97条(99.0%)患肢的PTA和支架植入术,除1例下肢动脉完全闭塞患者导丝未能成功通过病变导致介入失败外,其余病例经介入治疗后均开通,术中所有病例均未发生血肿、血管壁破裂、穿孔或内支架移位,远端血管血栓栓塞等并发症。术后,患者下肢缺血症状消失或明显减轻,踝/肱指数(ABI)由术前(0.39±0.23)恢复至(0.86±0.26),下肢血管内径及足背动脉搏动均明显改善。结论:PTA和血管支架植入术是一种治疗下肢动脉硬化闭塞症安全有效的方法,成功率高,并发症少,再狭窄率低。     

沙格雷酯治疗2型糖尿病伴下肢动脉硬化闭塞症患者的疗效评估

目的:探讨沙格雷酯治疗2型糖尿病伴下肢动脉硬化闭塞症(ASO)患者的临床疗效。方法:选择2014年4月~2015年5月我院2型糖尿病伴下肢ASO患者80例,给予口服沙格雷酯100 mg,3次/日,连续8周,监测治疗前后患肢的症状与体征、双下肢动脉峰值血流速度、血糖、血脂及血液流变学等指标的变化。结果:口服沙格雷酯8周后,患者疼痛感、冷感、间歇性踱行、麻木感及下肢溃疡等主观症状有效率均大于91%,临床总有效率为93.75%。治疗后患者左、右下肢动脉血管直径与治疗前比较,差异无统计学意义(P0.05),但左、右下肢动脉峰值血流速度比治疗前显著降低,差异有统计学意义(P0.05)。治疗后患者的甘油三酯、总胆固醇、低密度脂蛋白、全血高切黏度及全血低切黏度比治疗前降低,差异有统计学意义(P0.05)。结论:沙格雷酯可改善2型糖尿病伴下肢ASO患者的症状,降低双下肢动脉峰值血流速度,临床疗效确切,值得临床推广应用。     

NLRP3炎性小体及其下游产物在TAO和ASO患者动脉中的表达及意义

目的:探讨NLRP3炎性小体及其下游产物在血栓闭塞性脉管炎(TAO)和动脉粥样硬化闭塞症(ASO)患者动脉中的表达及意义。方法:选择8例TAO患者截肢后的下肢动脉,13例ASO患者截肢后的下肢动脉,5例因窒息死亡的新生儿主动脉,将三组动脉分别进行HE染色及免疫组化分析,半定量的测量3组动脉中NLRP3、Caspase-1、IL-1β和IL-18的累积光密度值(IOD)并进行组间比较。结果:3组动脉组织的HE染色结果均符合其特征。TAO组和ASO组动脉组织中NLRP3、Caspase-1、IL-1β和IL-18的表达与对照组相比均显著升高,差异具有统计学意义(P0.05)。结论:NLRP3、Caspase-1、IL-1β和IL-18在TAO和ASO患者动脉组织中的表达明显升高,NLRP3炎性小体及其下游产物可能参与了TAO和ASO的发病过程。     

股动脉注射蝮蛇抗栓酶等治疗血栓闭塞性脉管炎67例

６７例血栓闭塞性脉管炎患者从股动脉注射药物,观察其疗效。方法采用蝮蛇抗拴酶０．７５ＩＵ、６５４－２１０ｍｇ,妥拉苏林２５ｍｇ、１％普鲁卡因２０ｍｌ行患侧股动脉注射治疗１５天,治疗前后对患侧足背动脉、胫后动脉、月国动脉、股动脉共２７６条血管分别用经颅多普勒血流仪（ＴＣＤ）检查。结果治疗后患肢动脉血流峰值明显增高,搏动指数（ＰＩ）和阻力指数（ＲＩ）明显降低,临床表现明显好转。     

Effects of macrolides on airway microbiome and cytokine of children with bronchiolitis: A systematic review and meta‐analysis of randomized controlled trials

Macrolides may attenuate airway inflammation of bronchiolitis with anti‐inflammatory and antiviral effects. However, the potential mechanisms of action underlying the efficiency of macrolides in treating bronchiolitis are limited. Therefore, we performed a meta‐analysis to assess the effects of macrolides on airway microbiome and cytokine of children with bronchiolitis. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched until May 2018. The reference lists of included studies and pertinent reviews were investigated for supplementing our search. Randomized controlled trials (RCTs) that compared macrolides with placebo assessing the change of microbiome in airway and cytokine were included. A total of four RCTs were included in this review. Data analysis showed no significant reduction of viruses at 48 hr after azithromycin treatment (p = 0.41). There were significant reductions in Streptococcus pneumoniae (risk ratio [RR] 0.28, 95% confidence interval (CI) 0.14 to 0.6, p < 0.01), Haemophilus influenza (RR 0.35, 95% CI 0.2 to 0.62, p < 0.01), and Moraxella catarrhalis (RR 0.29, 95% CI 0.17 to 0.5, p < 0.01), but no significant reduction of Staphylococcus aureus (p = 0.28) following treatment with macrolides. There was a significant decrease in the serum interleukin‐8(IL‐8), interleukin‐4(IL‐4), and eotaxin levels following 3 weeks of clarithromycin therapy. There was no significant difference in the serum IL‐8 level at Day 15 after the intervention between the azithromycin and control groups; however, a significant reduction of nasal lavage IL‐8 level was found. The macrolides may reduce the IL‐8 levels in the airway and plasma, but failed to demonstrate an antiviral effect in children with bronchiolitis.     

64层螺旋CT三维重建技术对下肢动脉粥样硬化病变的显示

目的探讨64层螺旋CT三维重建技术对下肢动脉病变的显示。方法103例下肢动脉粥样硬化的患者行64层螺旋CT血管造影检查资料在工作站进行多种三维重建,分析其影像表现。结果103例患者均获得了成功的造影图像,2459根下肢动脉血管得到了显示。其中845根(34.4%)下肢动脉血管正常;672根(27.3%)轻度狭窄;327根(13.3%)中度狭窄;292根(11.9%)重度狭窄,323根(13.1%)下肢动脉血管闭塞。结论64层螺旋CT三维重建是又一种无创性的、可靠的、简便的检查下肢动脉粥样硬化的方法,具有较高的临床价值。     

置管溶栓联合自体外周血干细胞移植治疗血栓闭塞性脉管炎

目的观察置管溶栓联合自体外周血干细胞移植治疗血栓闭塞性脉管炎（TAO）的疗效。方法回顾性分析昆明医科大学第四附属医院血管外科2009年4月至2013年4月期间收治的64例TAO患者（68条患肢）,随机均分为两组,其中32例行置管溶栓联合自体外周血干细胞移植术（A组）,32例单纯采用自体外周血干细胞移植术（B组）,采用主观指标包括患肢疼痛、冷感以及客观指标包括跛行距离、踝肱指数、足部溃疡变化、皮温、截肢率进行疗效评价。采用t检验和Х^2检验分析两组疗效指标的差异。结果移植1个月后,两组64例患者（68条患肢）小腿疼痛均不同程度缓解,小腿冷、凉感觉消失;干细胞移植3个月后,A、B组两组间歇性跛行距离[（311.24±124.56）m,220.38±45.53）m,t=6.01,P=0.01],下肢皮温[（30.29±0.42）℃,（29.50±0.46）℃,t=28.05,P=0.00]、ABI（0.64±0.02,0.51±0.02,t=26.00,P=0.00）差异均具有统计学意义。A组中2例（2条患肢）,B组中4例（4条患肢）术后3个月由于小腿中段以下出现坏死导致膝下截肢,截肢率A组为：5.9﹪（2/34）;B组为：11.8﹪（4/34）;所有患者经肿瘤标记物、B超或CTA检查,均未发现恶性肿瘤、视网膜增生、动脉瘤等并发症。结论置管溶栓联合自体外周血干细胞移植治疗TAO是一种可供选择的新的治疗途径。