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。     

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。     

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).     

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.     

CD4 T Cells but Not Th17 Cells Are Required for Mouse Lung Transplant Obliterative Bronchiolitis

Lung transplant survival is limited by obliterative bronchiolitis (OB), but the mechanisms of OB development are unknown. Previous studies in a mouse model of orthotopic lung transplantation suggested a requirement for IL‐17. We have used this orthotopic mouse model to investigate the source of IL‐17A and the requirement for T cells producing IL‐17A. The major sources of IL‐17A were CD4⁺ T cells and γδ T cells. Depletion of CD4⁺ T cells led to a significantly decreased frequency and number of IL‐17A⁺ lymphocytes and was sufficient to prevent acute rejection and OB. However, mice with STAT3‐deficient T cells, which are unable to differentiate into Th17 cells, rejected lung allografts and developed OB similar to control mice. The frequency of IL‐17A⁺ cells was not decreased in mice with STAT3‐deficient T cells due mainly to the presence of IL‐17A⁺ γδ T cells. Deficiency of γδ T cells also did not affect the development of airway fibrosis. Our data suggest that CD4⁺ T cells are required for OB development and expansion of IL‐17A responses in the lung, while Th17 and γδ T cells are not absolutely required and may compensate for each other.     

HLA‐G*01:04∼UTR3 Recipient Correlates With Lower Survival and Higher Frequency of Chronic Rejection After Lung Transplantation

Lung transplantation (LTx) is a valid therapeutic option for selected patients with end‐stage lung disease. Soluble HLA‐G (sHLA‐G) has been associated with increased graft survival and decreased rejection episodes in solid organ transplantation. HLA‐G haplotypes named UTRs, defined by SNPs from both the 5′URR and 3′UTR, have been reported to reliably predict sHLA‐G level. The aim of this retrospective study was to determine the impact of HLA‐G alleles and UTR polymorphism from LTx recipients on anti‐HLA allo‐immunization risk, overall survival and chronic rejection (CLAD). HLA‐G SNPs were genotyped in 124 recipients who underwent LTx from 1996 to 2010 in Marseille, 123 healthy individuals and 26 cystic fibrosis patients not requiring LTx. sHLA‐G levels were measured for 38 LTx patients at D0, M3 and M12 and for 123 healthy donors. HLA‐G*01:06～UTR2 was associated with a worse evolution of cystic fibrosis (p = 0.005) but not of long‐term survival post‐LTx. HLA‐G*01:04～UTR3 haplotype was associated with lower levels of sHLA‐G at D0 and M3 (p = 0.03), impaired long‐term survival (p = 0.001), increased CLAD occurrence (p = 0.03) and the production of de novo donor‐specific antibodies (DSA) at M3 (p = 0.01). This study is the first to show the deleterious association of different HLA‐G alleles and UTRs in LTx.     

Mediation Analysis of Aortic Stiffness and Renal Microvascular Function

Aortic stiffening, assessed by carotid-femoral pulse wave velocity, is associated with CKD. Transmission of excessive flow pulsatility into the low-impedance renal microvasculature may mediate this association. However, direct analyses of macrovascular–microvascular relations in the kidney are limited. Using arterial tonometry, iohexol clearance, and magnetic resonance imaging, we related arterial stiffness, GFR, urinary albumin excretion, and potential mediators, including renal artery pulsatility index, renal vascular resistance, and arterial volume in the cortex, in 367 older adults (ages 72–92 years) participating in the Age, Gene/Environment Susceptibility-Reykjavik Study. In a model adjusted for age, sex, heart rate, and body size, aortic stiffness was related to GFR (Slope of regression B=−2.28±0.85 ml/min per SD, P=0.008) but not urine albumin (P=0.09). After accounting for pulsatility index, the relation between aortic stiffness and GFR was no longer significant (P=0.10). Mediation analysis showed that 34% of the relation between aortic stiffness and GFR was mediated by pulsatility index (95% confidence interval of indirect effect, −1.35 to −0.29). An additional 20% or 36% of the relation was mediated by lower arterial volume in the cortex or higher renal vascular resistance, respectively, when offered as mediators downstream from higher pulsatility index (95% confidence interval of indirect effect including arterial volume in the cortex, −2.22 to −0.40; 95% confidence interval of indirect effect including renal vascular resistance, −2.51 to −0.76). These analyses provide the first evidence that aortic stiffness may contribute to lower GFR by transferring excessive flow pulsatility into the susceptible renal microvasculature, leading to dynamic constriction or vessel loss.