Loss of GRB2 associated binding protein 1 in arteriosclerosis obliterans promotes host autophagy

Background:Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy.Methods:In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1.Results:The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t = 6.43, P < 0.05). The expression level of GAB1 mRNA (1.00 vs. 0.24, t = 7.41, P < 0.05) and protein (0.72 vs. 0.21, t = 5.97, P < 0.05) was significantly decreased in ASO group as compared with the control group. Loss of GAB1 led to a remarkable decrease in LC3II (1.19 vs. 0.68, t = 5.99, P < 0.05), whereas overexpression of GAB1 significantly led to a decrease in LC3II level (0.41 vs. 0.93, t = 7.12, P < 0.05). Phosphorylation levels of JNK and p38 were significantly associated with gain- and loss-of-function of GAB1 protein.Conclusion:Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.     

药物涂层球囊治疗膝下动脉硬化性狭窄或闭塞致严重下肢缺血

目的 观察药物涂层球囊(DCB)治疗膝下动脉硬化性狭窄或闭塞致严重下肢缺血(CLI)的效果。方法 回顾性分析96例膝下动脉硬化性狭窄或闭塞致CLI患者,其中50例接受DCB治疗(DCB组)、46例接受普通球囊治疗(对照组),比较2组治疗效果、安全性及预后。结果 96例球囊均到达病变部位并成功完成扩张,未植入补救性支架。组间术前及术后即刻踝肱指数(ABI)、Rutherford分级及Wagner分级差异均无统计学意义(P均＞0.05);术后6、12个月DCB组ABI高于、Rutherford分级及Wagner分级均低于对照组(P均＜0.05)。术后6、12个月,DCB组一期通畅率均高于、管腔丢失均少于对照组(P均＜0.05),组间截肢率差异均无统计学意义(P均＞0.05)。Kaplan-Meier分析结果显示,术后12个月,DCB组免于临床驱动的靶病变血运重建率(CD-TLR)为89.81%,高于对照组的67.39%(P=0.008 8)。结论 DCB治疗膝下动脉硬化性狭窄或闭塞致CLI效果较好。     

DSA引导下血管腔内成形术治疗下肢动脉硬化闭塞症的临床研究

目的:探讨DSA引导下血管腔内成形术(TA)治疗下肢动脉硬化闭塞症(ASO-LE)的临床效果。方法:2017年3月至2019年4月,手术治疗的ASO-LE患者93例,依据治疗方式的不同分为A组(行TA,n=49)和B组[行下肢动脉旁路移植术(LEABG),n=44],两组患者均在数字减影血管造影(DSA)引导下进行。对比两组患者手术成功率;两组患者术前即刻(T1)、术后1 d(T2)、术后3 d(T3)及术后1周(T4)时刻视觉模拟疼痛评分(VAS);对比术前(T1')、术后1个月(T2')及术后3个月(T3')时刻两组患者下肢缺血程度[患者踝肱指数(ABI)、趾肱指数(TBI)];对比T1'、T2'及T3'时刻两组患者足背动脉血流动力学[足背动脉内径(D)、血流峰速(PV)、血流量(BF)];对比T1'、T2'及T3'时刻两组患者下肢感觉神经传导速度(SNCV)和运动神经传导速度(MNCV);术后6个月,对比两组患者并发症发生率。结果:两组患者手术成功率无显著差异(P>0.05);患者VAS评分组间、时间、交互对比差异均有统计学意义(P<0.05),与T1相比,T2、T3及T4时两组患者VAS评分均降低(P<0.05),与T2相比较,T3及T4时两组患者VAS评分均降低(P<0.05),与T3相比较,T4时两组患者VAS评分均降低(P<0.05),A组T2、T3及T4时刻VAS评分均低于B组(P<0.05);ABI、TBI、D、PV、BF、SNCV和MNCV组间、时间、交互对比差异均有统计学意义(P<0.05);与T1'相比,T2'及T3'时两组患者ABI、TBI、D、PV、BF、SNCV和MNCV均升高(P<0.05);与T2'相比较,T3'时2组患者ABI、TBI、下肢SNCV和MNCV均升高(P<0.05),A组T2'及T3'时刻ABI、TBI、D、PV、BF、SNCV和MNCV均高于B组(P<0.05);A组患者并发症发生率显著低于B组(P<0.05)。结论:相比LEABG,DSA引导下对ASO-LE患者进行TA治疗能够减轻疼痛,改善下肢缺血及足背动脉血流动力学,提高下肢SNCV和MNCV,降低并发症的发生率。     

Combination of intramuscular transplantation of autologous mononuclear bone marrow cells with sympathectomy (L2, 3) in patients with peripheral arterial disease(PAD)

BackgroundIn most patients with severe, chronic extremity ischemic diseases, intervention or surgical treatment is often not suitable. Combination of intramuscular transplantation of autologous monocular bone marrow cells (AMBMCs) and sympathectomy (L2, 3) has been proved therapeutically beneficial.MethodsWe studied 170 patients (combined group 80, control group 90) with extremity ischemia (TAO, ASO FontaineⅡ,Ⅲ, Ⅳ) between January 2013 and September 2019.ResultsIn contrast to pre-operation, the walking distance of patients increased significantly (from 61.34 ± 52.23 m to 156.0 ± 32.4 m, p < 0.01), and the ankle-brachial index (ABI) remarkably improved (from 0.28 ± 0.13 to 0.59 ± 0.23, p < 0.05).ConclusionCombined therapy is feasible and effective for patients with peripheral arterial disease (PAD).     

Severe adenovirus pneumonia with hemophagocytic syndrome and respiratory failure

We report the case of an 18-month-old infant with severe serotype 3 adenovirus pneumonia, exceptionally associated with hemophagocytic syndrome. Treatment included cidofovir and mechanical ventilation for 13 days. The child developed chronic respiratory insufficiency due to bronchiectasis and bronchiolitis obliterans.     

抗中性粒细胞胞浆抗体在儿童闭塞性细支气管炎病情评估中的价值

目的 探讨抗中性粒细胞胞浆抗体（ANCA）在儿童闭塞性细支气管炎（BO）病情评估中的临床价值。方法 前瞻性选取2009年6月至2014年10月诊断为BO的患儿59例为研究对象，应用酶联免疫吸附法检测患儿血清中的髓过氧化物酶（MPO）及蛋白酶3（PR3）ANCA的浓度，根据其结果将患儿分为ANCA双阴性组（n=22）、ANCA单阳性组（n=17）及ANCA双阳性组（n=20）。比较入院时各组患儿的BO发生危险因素、临床症状、胸部高分辨CT（HRCT）及肺部病理学评分，以及ANCA表达水平及临床症状、胸部HRCT评分随时间的变化。结果 ANCA双阳性组患儿的BO危险因素评分明显高于ANCA双阴性组（P < 0.05），ANCA单阳性组及双阳性组的临床症状、胸部HRCT及肺部病理学评分均高于ANCA双阴性组（P < 0.05）。患儿出院后随访6个月，MPO-ANCA、PR3-ANCA滴度水平均较入院时和出院时降低（P < 0.05）；其临床症状评分亦低于入院时（P < 0.05），但胸部HRCT评分与入院时比较差异无统计学意义（P > 0.05）；ANCA单阳性组及双阳性组的临床症状评分仍高于ANCA双阴性组（P < 0.05）。结论 ANCA表达水平与BO患儿的病情严重程度具有相关性，对病情评估有一定的临床意义。     

基于中西医临床病症特点血栓闭塞性脉管炎动物模型分析

基于血栓闭塞性脉管炎的临床病症特点,通过查阅相关文献,整理分析并建立血栓闭塞性脉管炎的西医诊断标准与中医辨证标准,总结血栓闭塞性脉管炎动物模型的造模方法、造模对象、模型优缺点。分析其与中西医临床病症特点的吻合度,总结发现血栓闭塞性脉管炎动物模型与西医临床病症吻合度较高,与中医寒湿阻络证和热毒伤阴证吻合度较高,与湿热毒盛证和气血两虚证吻合度较低,没有与血脉淤阻证相吻合的动物模型。患肢病变程度、病理、血液流变学指标(血液黏度、红细胞沉降率)为最常检测指标。现阶段相对于大量临床治疗血栓闭塞性脉管炎的病例报道,实验研究相对薄弱,建立合理的模型判断量化标准,复制与中医证候吻合度更高的动物模型是日后的研究重点。