ObjectiveTo evaluate the efficacy of a multimodal endovascular approach integrating excimer laser atherectomy (ELA), percutaneous transluminal angioplasty (PTA), and drug-eluting stent (DES) implantation for managing complex aortic occlusion in Takayasu arteritis (TA).MethodsA 24-year-old female with TA presented with progressively debilitating clinical manifestations, including severe hypertension (217/126 mmHg) and bilateral lower limb claudication that significantly impaired daily function despite medical management. Imaging confirmed a chronic infra-renal aortic occlusion. Given the lesion complexity and the patient's young age, a multidisciplinary team decision prioritized a minimally invasive approach to avoid the higher risks of open surgery. The selected strategy sequentially integrated ELA for controlled debulking of the fibrotic occlusion and DES implantation to mitigate long-term restenosis risk.ResultsAt 6-month follow-up, ankle-brachial indices improved bilaterally, with normalized systolic blood pressure and absence of claudication. Postoperative contrast-enhanced computed tomography angiography (CTA) confirmed sustained aortic artery patency without restenosis or collateral formation.ConclusionThis case demonstrates the feasibility of ELA and DES integration as a minimally invasive strategy for TA-related aortic lesions, achieving durable hemodynamic and clinical outcomes.

BACKGROUND:Determining the age and composition of deep vein thrombosis (DVT) is essential for optimizing thrombus removal strategies, yet clinical decision-making remains restrained by the subjectivity of symptom-based assessment. We applied non-contrast T1/T2 weighted MRI radiomics with habitat clustering to quantify thrombus evolution, validating MRI habitats against histopathology with translational clinical potential. METHODS:Venous thrombosis was induced in BALB/c mice using a refined inferior vena cava ligation model to ensure consistent thrombus development. Longitudinal and cross-sectional cohorts were imaged at 7 T MRI with T1- and T2-weighted sequences on post-ligation days 2, 7, and 14. Thrombus regions were delineated using a hybrid approach and voxel-level radiomic features were extracted. Unsupervised K-Means clustering defined MRI-based habitats. Imaging signatures were correlated with an artificial neural network pixel classifier and tile-based histomics clustering to quantify red blood cells (RBC), fibrin, and collagen. RESULTS:Radiomic analysis showed a decline in Energy and TotalEnergy and a similar trend in GrayLevelNonUniformity, reflecting a transition from acute to more uniform chronic thrombi. A two habitats strategy could differentiate acute RBC-rich regions from fibrotic components. Histology confirmed RBC-rich areas fell from 88.22% to 6.52% over 14 days, while collagen-rich areas rose from 0.16% to 79.67%. MRI habitat proportions correlated strongly with histological tile clusters (Spearman r = 0.74, p = 0.0005). CONCLUSION:Multiparametric MRI radiomics combined with habitat analysis captures thrombus composition and temporal evolution, with unsupervised histomics providing biological validation. These findings support the translational potential of MRI habitat analysis as a non-invasive biomarker of thrombus heterogeneity.

Here, we report the case of a 30-year-old male who presented with acute right calf muscle pain. Computed tomography angiography revealed a popliteal artery aneurysm in the midsection. Popliteal fossa muscle tissue evaluation revealed that the popliteal artery aneurysm was located beneath an anomalous muscle bundle. Thus, the patient was diagnosed with type III popliteal artery entrapment syndrome and treated surgically. The patient was asymptomatic at rest and during physical activity 4 months after surgery with unobstructed bloodstream in the right popliteal artery. Popliteal artery entrapment syndrome should be considered in young male patients with popliteal artery pseudoaneurysms without atherosclerosis, hereditary diseases, or infections and treated surgically.

The objective of this article is to summarize the research progress and discuss the current difficulties of gene-based therapeutic angiogenesis in lower limb ischemic diseases, so as to provide new research directions for the non-invasive treatment of lower limb ischemia. The basic and clinical trials of gene-based therapeutic angiogenesis in lower limb ischemia in recent years were read and reviewed. Growth factors such as vascular endothelial growth factor, hepatocyte growth factor, and fibroblast growth factor have been extensively studied for their application in lower limb ischemic diseases. However, clinical studies across various phases have shown inconsistent efficacy endpoints. The efficacy of gene therapy remains questionable. Before exploring efficient methods of delivering pro-angiogenic genes to ischemic tissues, clarification is needed regarding whether the goal of gene therapy is to simply promote collateral circulation or create a conducive tissue microenvironment for angiogenesis. In conclusion, pre-clinical and clinical studies have demonstrated the potential of therapeutic angiogenesis, but more systematic and comprehensive research is needed to explore safer, more effective, and cost-effective treatment methods.

Therapeutic angiogenesis offers a promising strategy for patients with critical limb-threatening ischemia (CLTI) who are unsuitable candidates for revascularization. However, the optimal administration sites for gene therapy agents, such as pCK-HGF-X7, remains undefined. Clinical trials commonly employ multiple intramuscular injections at sites of arterial occlusion; yet the necessity and efficacy of such extensive and repetitive protocols remains unclear. Targeted injections into ischemic tissues or their margins may improve therapeutic outcomes. Moreover, the molecular mechanisms by which hepatocyte growth factor (HGF)/c-Met signaling regulates hypoxia-inducible factor-1α (HIF-1α) expression under hypoxic conditions are not fully understood. This study aims to elucidate these molecular mechanisms in endothelial cells under hypoxic conditions and to identify the most effective injection sites for therapeutic angiogenesis agents. The effects of various HGF isoforms/complexes on human aortic endothelial cells (HAECs) were evaluated under normoxic and hypoxic conditions, focusing on proliferation, migration, and tube formation. Pathway inhibitors were used to explore the underlying mechanisms in hypoxic HAECs, and the findings were validated in a rat hindlimb ischemia model. Results demonstrated that HGF723 and HGF728 activated the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways, regulating HIF expression and significantly enhanced endothelial cell proliferation, migration, and tube formation, particularly under hypoxia. Despite these cellular effects, HGF treatment did not significantly improve tissue perfusion or neovascularization in normal rat hindlimbs. However, in ischemic rat hindlimbs, it markedly promoted angiogenesis and improved tissue perfusion in the gastrocnemius muscle. These findings indicate that therapeutic angiogenesis agents should primarily target hypoxic tissues, extending to the interface between normoxic and hypoxic regions, to optimize treatment efficacy.

Intramuscular injection of donaperminogene seltoplasmid (recombinant human hepatocyte growth factor plasmids) represents a gene therapy that treats patients with chronic limb-threatening ischemia (CLTI). The HOPE CLTI-2 trial was a phase 3, multicenter, double-blind, placebo-controlled study aimed to evaluate the efficacy and safety of seltoplasmid in patients with Rutherford class 5 CLTI. This study did not require participants to be ineligible for revascularization, allowing enrollment of patients with CLTI caused by either atherosclerosis (ASO) or Buerger disease (or thromboangiitis obliterans [TAO]). The primary endpoint was the complete ulcer healing rate at 6 months. A total of 242 participants (53.3% ASO versus 46.7% TAO) were enrolled, with 161 receiving seltoplasmid and 81 receiving placebo. Complete ulcer healing was achieved in 70 patients in the seltoplasmid group compared to 15 patients in the placebo group, resulting in an adjusted healing rate difference of 26.1% (95% confidence interval [CI]: 15.1%-37.0%; p < 0.001). The hazard ratio for healing was 2.31 (95% CI: 1.32-4.05; p = 0.004). The benefits of seltoplasmid on ulcer healing persisted in both TAO and ASO subgroups. Serious adverse events were rare. Our study demonstrated that seltoplasmid significantly improved ulcer healing rates in patients with Rutherford class 5 CLTI compared to placebo.

Therapeutic angiogenesis has garnered significant attention as a potential treatment strategy for lower limb ischemic diseases. Although hepatocyte growth factor (HGF) has been identified as a key promoter of therapeutic angiogenesis, its clinical application is limited due to its short half-life. In this study, we successfully developed and characterized platelet membrane-coated HGF-poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). These nanoparticles demonstrated enhanced capabilities to promote endothelial cell (EC) proliferation, migration, and tube formation in vitro. Additionally, their efficacy in improving tissue perfusion and promoting angiogenesis was confirmed in a hindlimb ischemia rat model. Our findings suggest that platelet membrane-coated HGF-PLGA-NPs could serve as a promising therapeutic approach for enhancing angiogenesis and restoring tissue perfusion in ischemic conditions.

Renovascular hypertension (RVH) is a primary cause of secondary hypertension, primarily driven by the activation of the renin-angiotensin-aldosterone system activation. Recently, growing studies suggested accessory renal artery (ARA) might also contribute to RVH. However, the treatment of ARA-related hypertension and whether to take interventional treatment lack consensus. Herein, we report two cases of ARA-related hypertension in our hospital. Imaging studies of both patients showed ARA stenosis. One patient had ARA occlusion well-compensated through tortuous collateral branches, achieving normal blood pressure by medical treatment alone. The other patient had ARA stenosis coexisted with main renal artery stenosis, and revascularization of both arteries led to a significant postoperative reduction in blood pressure. A literature review was conducted to summarize overall treatment strategies for ARA-related hypertension and clarify the relationship between ARA and hypertension. Recent research supported an association between ARA and hypertension. While medical therapy remains the first-line treatment for ARA-related hypertension, interventional procedures should be considered for patients whose blood pressure remains uncontrolled despite conservative management.

OBJECTIVE:Recombinant human hepatocyte growth factor (HGF) plasmids are novel alternatives to salvage limbs in patients with chronic limb threatening ischaemia (CLTI). A systematic review and meta-analysis of data was conducted to assess the therapeutic efficacy of HGF plasmids in patients with CLTI. DATA SOURCES:Randomised controlled studies evaluating HGF plasmid efficacy in patients with CLTI were identified using MEDLINE, Embase, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov databases. REVIEW METHODS:Meta-analyses of the reported relative risk (RR) or mean difference (MD) were conducted. Subgroup analyses were performed to determine the efficacy of HGF plasmids in cohorts excluding Buerger's disease. Certainty of evidence for each outcome was assessed. RESULTS:Seven studies (n = 655 participants) were included. Based on low certainty evidence, patients treated with HGF had a significantly higher complete ulcer healing rate (RR 1.99, 95% confidence interval [CI] 1.30 - 3.04; p = .002) than patients treated with placebo. HGF treatment was associated with reduced visual analogue scale (VAS) scores of pain severity (MD -1.56, 95% CI -2.12 - -1.00; p < .001) vs. placebo in patients with CLTI assessed at three month follow up (low certainty evidence); no significant differences were observed in major amputation (RR 0.91, 95% CI 0.48 - 1.73; p = .77) (low certainty evidence) or all cause mortality rate (RR 0.93, 95% CI 0.38 - 2.27; p = .87) (low certainty evidence) between patients treated with HGF and placebo. Low certainty evidence suggested no significant differences in change in ankle brachial index at six months (MD 0.00, 95% CI -0.09 - 0.09; p = 1.0) between patients treated with HGF and placebo. The complete ulcer healing rate and improved three month VAS scores of pain severity benefits persisted in subgroup analyses (low certainty evidence). CONCLUSION:Low certainty evidence suggested that HGF treatment is associated with an increased complete ulcer healing rate and reduced ischaemic pain in patients with CLTI.

Abstract This paper reports a phase I dose-escalation clinical trial for the treatment of peripheral arterial disease (PAD) with BF30, a recombinant Sendai virus vector carrying the human native fibroblast growth factor 2 (hFGF2) gene. Our goal was to evaluate the safety and tolerability of BF30 at varying doses while assessing its preliminary therapeutic effect. Twelve male patients with PAD unsuitable for revascularization procedures that met the enrollment criteria were recruited. Each patient received a BF30 injection on one side of the ischemic lower limb. No deaths occurred prior to the 6-month follow-up. No severe adverse events or Grade 3/4 adverse events related to the BF30 injections were noted. Furthermore, the viral genome level was below the quantization limit after 6 months, and hemagglutination activity was undetectable in seven of the 12 cases. Abnormal changes in hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and proinflammatory factor serum levels were not observed. None of the cases exhibited a positive anti-drug antibody signal. In addition, a positive therapeutic effect was demonstrated by the reduction in rest pain and Rutherford classification and improvement of the ankle-brachial index. While a higher dose triggered a stronger immune response, it was more effective in improving the Rutherford classification and quality of life.

颈动脉内膜剥脱术(CEA)是治疗颅外段颈动脉狭窄、预防缺血性脑卒中发生的重要手术方式.经过70年的发展,CEA的有效性和安全性已通过多项大型临床随机对照试验验证,并衍生出多种手术方式.传统CEA的颈动脉切口为颈总动脉至颈内动脉的纵向切口,由于直接原位缝合术后易发生再狭窄,因而通常需使用补片.目前,临床主要应用的术式是补片成形CEA和外翻式CEA,各有优劣,关于其手术经验和改良方案已有研究报道.颈动脉内膜剥脱改良根治术(分叉上移术)是结合CEA的手术原理及临床经验而提出的手术方式,其特点在于无需使用补片,术后的融合管腔直径大,具备临床研究价值,但较难处理高位颈动脉病变,其有效性、安全性及适用人群尚需进一步进行临床试验的探索.由于重建颈动脉分叉,该术式也具有推广至其他累及颈动脉分叉的颈部病变(如颈动脉体瘤)的潜在价值.本文主要针对其应用背景、临床应用现状及技术要点加以述评,以期能够为临床工作和研究提供参考.

Vascular smooth muscle cells (VSMCs) play an important role in the pathogenesis of vascular remolding, such as atherosclerosis and restenosis. Solute carrier family 6 member 6 (SLC6A6) is a transmembrane transporter that maintains a variety of physiological functions and is highly expressed in VSMCs. However, its role on VSMCs during neointimal formation remains unknown. In this study, mRNA and protein levels of SLC6A6 were examined using models of VSMC phenotype switching in vivo and in vitro and human artery samples with or without atherosclerosis. SLC6A6 gain- and loss-of-function approaches were performed by adenovirus infection or small interfering RNA (siRNA) transfection, respectively. Reactive oxygen species (ROS), proliferation, migration, and phenotype-related proteins of VSMCs were measured. Vascular stenosis rate and related genes were assessed in a rat vascular balloon injury model overexpressing SLC6A6. SLC6A6 was downregulated in dedifferentiated VSMCs, atherosclerotic vascular tissues, and injured vascular tissues. SLC6A6 suppressed VSMC proliferation and migration, while increasing contractile VSMC proteins. Mechanistically, SLC6A6 overexpression reduced ROS production and inhibited the Wnt/β-catenin pathway. Furthermore, SLC6A6 overexpression suppressed neointimal formation in vivo. Collectively, overexpression of SLC6A6 suppresses neointimal formation by inhibiting VSMC proliferation and migration via Wnt/β-catenin signaling and maintaining the VSMC contractile phenotype.

Introduction Renal artery stenosis (RAS) is a significant reason for secondary hypertension. Impaired renal function and subsequent cardiopulmonary dysfunction could also occur. Patients of non-atherosclerotic RAS has a relatively young age and long life expectancy. Revascularization with percutaneous transluminal angioplasty (PTA) is a viable treatment option. However, restenosis is unavoidable which limits its use. Drug-coated balloon (DCB) has been proven to be effective in restenosis prevention in femoropopliteal arterial diseases and in patients with renal artery stenosis. And PTA for Renal artery fibromuscular dysplasia is safe and clinically successful. Therefore, we could speculate that DCB might have potential efficacy in non-atherosclerotic RAS treatment. Methods and analysis This will be a randomized multi-center-controlled trial. Eighty-four eligible participants will be assigned randomly in a 1:1 ratio to the control group (plain old balloon, POB) and the experimental group (DCB). Subjects in the former group will receive balloon dilatation alone, and in the latter group will undergo the DCB angioplasty. The DCB used in this study will be a paclitaxel-coated balloon (Orchid, Acotec Scientific Holdings Limited, Beijing, China). Follow-up visits will be scheduled 1, 3, 6, 9, and 12 months after the intervention. Primary outcomes will include controlled blood pressure and primary patency in the 9-month follow-up. Secondary outcomes will include technical success rate, complication rate, and bail-out stenting rate. Trial registration ClinicalTrials.gov (number NCT 05858190). Protocol version V.4 (3 May 2023).

本文报道1例38岁女性患者，因“血压升高5年，面容改变2年，憋喘6个月”于2019年3月就诊于北京协和医院内科。外院诊断“高血压性心脏病、心功能不全、高血压性肾损害”，本院检查患者随机生长激素（GH）、胰岛素样生长因子1（IGF1）水平明显升高，葡萄糖生长激素抑制试验不被抑制，垂体MRI可见大腺瘤，考虑肢端肥大症、垂体GH大腺瘤，同时合并心力衰竭、全心增大、中-重度三尖瓣关闭不全、心功能Ⅱ级（NYHA分级），重度肺动脉高压、恶性高血压、高血压性肾损害（CKD5期）、肾性贫血、高血压视网膜病变。先给予生长抑素类似物降低GH水平，改善临床症状，待心功能改善后再次评估手术风险，择期行垂体瘤手术。药物治疗方面，给予醋酸奥曲肽0.1 mg/次，每8小时1次皮下注射，溴隐亭2.5 mg/次，1次/d。2019年7月在全麻下行经鼻蝶窦入路垂体腺瘤切除术+鞍底重建术，术前及术后行血透治疗，术后复查GH 2.4 μg/L。符合垂体腺瘤。所以对于起病较早的难治性高血压，应特别注意筛查继发性高血压的病因，达到早期诊断、早期治疗的目的。

Anastomotic healing is an important problem after gastrointestinal surgery. Improper handling can easily lead to anastomotic leakage, further inducing sepsis, septic shock, and even life-threatening. Platelet-rich plasma (PRP) is an autologous blood product composed of concentrated platelets. Its platelet concentration is higher than the baseline level of the whole blood. It contains a variety of growth factors, making it practical for quickly healing complex wounds and reducing the length of hospital stay. Therefore, it is widely used in skin and shoulder joints. In recent years, the application of PRP in gastrointestinal surgery has received extensive attention. However, the current research on improving anastomotic healing by PRP mainly focuses on animal experiments, lacks uniform standards, and the effects are not entirely accordant, which has strained its clinical application. This article takes the improvement of intestinal anastomotic healing by PRP as a point of entry, systematically expounds on the research progress of PRP in improving intestinal anastomotic recovery to provide a reference for promoting its clinical application.

Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine malignancy, accounting for less than 1% of all uterine malignancies. And there is no literature reporting about acute obstruction of inferior vena cava (IVC) caused by LG-ESS. In November 2021, A patient diagnosed with LG-ESS was admitted to our hospital, presenting with pitting edema of the right lower limb, menstrual disturbance, nausea, oliguria andincreased serum creatinine. Imaging suggested complete obstruction of IVC cava. This difficult case was successfully treated with staging surgery combined with endocrine therapy by a cooperative multidisciplinary team (MDT). The important role of MDT in the treatment process of such a difficult and serious case was demonstrated.

Nutcracker syndrome (NCS) is a rare disease that may cause proteinuria, renal dysfunction and varicose of genital veins. Traditional open surgery prefers left renal vein transposition, but this surgical method is more traumatic and patients often have more postoperative short-term and long-term complications affecting the quality of life. This article reports a case of a young male patient with NCS complicated with left varicocele. He was treated with left gonadal vein-inferior vena cava transposition and high ligation of spermatic vein, which achieved good results after surgery. This surgical method provides a new treatment idea for patients with NCS and varicocele, which is worthy of clinical reference.

Endothelial dysfunction is a key accessory to diabetic cardiovascular complications, and the regulatory role of the extracellular vesicles (EVs) from the innate immune system is growing. We tested whether EVs derived from high glucose-induced monocytes could shuttle microRNAs and impair endothelial cells. EVs from high glucose- and basal glucose-treated THP-1 cells (HG-THP-1 EVs and BG-THP-1 EVs) were isolated and identified. After coculture with THP-1 EVs, human umbilical vein endothelial cells (HUVECs) were tested by proliferation, migration, reactive oxygen species (ROS) detection assays, and western blot for Nrf2/NLRP3 signaling. MiR-142-5p was predicted by miRNAs databases and further verified by RT–qPCR and dual-luciferase reporter gene assays that inhibit Nrf2 expression. The regulation of miR-142-5p in HUVECs was further evaluated. A type 1 diabetes mellitus (T1DM) mouse model was developed for miR-142-5p inhibition. Aorta tissue was harvested for hematoxylin-eosin staining and immunohistochemistry of interleukin-1β (IL-1β). Compared to BG-THP-1 EVs, HG-THP-1 EVs significantly reduced migration and increased ROS production in HUVECs but did not affect proliferation. HG-THP-1 EVs induced suppression of Nrf2 signaling and NLRP3 signaling activation. RT–qPCR results showed that HG-THP-1 EVs overexpressed miR-142-5p in HUVECs. The transfection of miR-142-5p mimics into HUVECs exhibited consistent regulatory effects on HG-THP-1 EVs, whereas miR-142-5p inhibitors demonstrated protective effects. The miR-142-5p antagomir significantly reduced the IL-1β level in T1DM aortas despite morphological changes. To conclude, miR-142-5p transferred by high glucose-induced monocyte EVs participates in diabetic endothelial damage. The inhibition of miR-142-5p could be a potential adjuvant to diabetic cardiovascular protection.

Vascular restenosis is the main factor affecting the prognosis of angioplasty in cardiovascular diseases, and inflammation is a central link in the progression of restenosis. Previous research that applies interleukin 10 (IL10) nanoparticles can effectively regulate local inflammation, but their targeted delivery efficacy remains to be improved. In this study, IL10 nanoparticles were successfully prepared and then coated by a preactive platelet membrane. The ability to target and regulate macrophage polarization has been demonstrated, thereby regu-lating smooth muscle cell and endothelial cell functions. In vivo experiments were carried out in a carotid artery injury model and verified the above functions and the effect on inhibiting vascular restenosis. Immune regulation-based platelet membrane coated nanoparticle loaded with IL10 proved to be an excellent candidate for targeting vascular injury and holds promise as an innovative drug delivery system for suppressing vascular restenosis.