BACKGROUND:Early diagnosis and treatment of carotid artery stenosis (CAS) are crucial for preventing related cerebral ischemic events, making the identification of safe, non-invasive biomarkers highly necessary. AIM:To explore the expression and diagnostic value of miR-7110-5p and miR-4484 in CAS, and to clarify their mechanism of action. METHODS:The expression levels of miR-7110-5p and miR-4484 were detected by RT-qPCR. The receiver operating characteristic (ROC) curves for diagnosing different degrees of CAS were constructed for miR-7110-5p and miR-4484. The target genes and common target genes of miR-7110-5p and miR-4484 were predicted using TargetScan Human, miRTarbase and miRDB databases and confirmed by dual-luciferase reporter gene assays. The activity and apoptosis rate of human carotid artery endothelial cells (HCAECs) were detected by CCK-8 assay and flow cytometry. RESULTS:Both miR-7110-5p and miR-4484 were found to be downregulated in the serum of CAS patients and in ox-LDL-induced HCAECs. The combined diagnostic performance of miR-7110-5p and miR-4484 was superior to that of either alone. IL16 was identified as a common target gene of miR-7110-5p and miR-4484. The miR-7110-5p and miR-4484 mimics significantly reduced the luciferase activity of HCAECs transfected with the wild-type IL16 vector. Both miR-7110-5p and miR-4484 mimics increased the cell viability and decreased the apoptosis rate of ox-LDL-induced HCAECs, while overexpressing IL16 reversed these effects. CONCLUSION:miR-7110-5p and miR-4484 have good diagnostic value in CAS and they mediate ox-LDL-induced HCAECs injury by negatively regulating IL16.

Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE -/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.

Background: This study aimed to explore risk factors leading to asymptomatic penetrating aortic ulcer (PAU) progression. Methods: This retrospective study reviewed the clinical data of patients who were diagnosed with asymptomatic PAU through incidental imaging findings and underwent imaging follow-up between August 2018 and July 2022. Patients were grouped according to ulcer progression. The risk factors for PAU progression were also analyzed. Results: Among 60 patients with PAU, 32 (53.33%) experienced PAU progression. The mean follow-up time was 555.72 +/- 407.60 days. Although there was no statistically significant difference in cancer incidence between the PAU progression group and nonprogression group (24 [75%] vs. 18 [64.28%], P- 0.409), the difference in antineoplastic therapy use between the progression and nonprogression groups was significant (19 [59.38%] vs. 7 [25.00%], P- 0.010). There was no difference in the aortic diameter at the PAU (20.68 +/- 4.16 mm vs. 20.70 +/- 5.28 mm, P- 0.990), PAU width (7.32 +/- 2.53 mm vs. 7.11 +/- 2.29 mm, P- 0.741), and PAU depth (4.13 +/- 1.26 mm vs. 4.08 +/- 1.41 mm, P- 0.880) between the 2 groups. In the progression group, the progression rates of aortic diameter at PAU, PAU width, and PAU depth were 2.16 +/- 4.28 mm/year, 5.91 +/- 14.49 mm/year and 2.87 +/- 5.87 mm/year, respectively. Binary logistic regression analysis showed that antineoplastic therapy was an independent predictor of PAU progression (P- 0.017; odds ratio, 4.144; 95% confidence interval, 1.290e 13.316). Conclusions: Antineoplastic therapy may contribute to the progression of asymptomatic PAU in this retrospective study with small number of patients. Patients with asymptomatic PAU who are receiving or have completed antineoplastic therapy should be more vigilant regarding PAU progression.

This study investigated the impact of maternal high-fat diet on vascular function and endothelial homeostasis in offspring. We found that offspring exposed to maternal high-fat diet exhibited elevated blood pressure, impaired abdominal aortic vascular function, and endothelial homeostasis imbalance. These changes were accompanied by increased levels of reactive oxygen species (ROS) and upregulation of pro-inflammatory cytokines (including IL-1β, TNF-α, IL-6, and IL-10). Treatment with NLRP3 or IL-1β inhibitors prevented the deterioration in vascular function, reduced endothelial NO production, and inflammation induced by maternal high-fat diet exposure compared to the control group. The findings suggest that during pregnancy, mitigating the vascular impairments in offspring induced by maternal high-fat diet can be achieved by inhibiting the NLRP3/IL-1β pathway.

Cardiovascular diseases (CVDs), the primary cause of global mortality, face persistent therapeutic challenges due to poor drug targeting and systemic side effects. While innovative nanotherapeutic approaches offer improved drug delivery through targeting and stimulus-responsive release mechanisms, clinical translation is limited by poor tissue specificity and manufacturing limitations. We present a universal therapeutic hypothermia (TH, i.e., 32 to 35 °C)-enhanced strategy that amplifies nanocarrier targeting across multiple CVD models. Both hard and soft nanocarriers showed 1.6- to 3-fold increased pathological tissue accumulation under TH versus normothermia, correlating with enhanced therapeutic efficacy in multiple murine models of CVDs, including heart failure, myocardial hypertrophy, ventricular fibrillation, ischemic stroke, atherosclerosis, and deep vein thrombosis. Mechanistically, TH induces temperature-dependent enrichment of apolipoproteins C1 (ApoC1) and C4 in the protein corona of nanoparticle surface, enabling receptor-mediated targeting through upregulated lipoprotein receptors in injured cardiovascular tissues. Notably, ApoC1-mediated targeting outperformed established cardiac-targeting peptides in directing nanoparticles to diseased hearts. The TH-driven approach and direct ApoC1 functionalization provide a straightforward, scalable, and cost-effective approach to enhance nanotherapy precision for CVD treatment, potentially addressing critical barriers in clinical translation.

Hepatocellular carcinoma (HCC) is one of the most lethal forms of cancer globally. HCC cells frequently undergo macroautophagy, also known as autophagy, which can lead to tumor progression and chemotherapy resistance. Annexin A2 (ANXA2) has been identified as a potential therapeutic target in HCC and is involved in the regulation of autophagic process. Here, we for the first time showed that ANXA2 deacetylation plays a crucial role in donafenib-induced autophagy. Mechanistically, donafenib increased SIRT2 activity via triggering both SIRT2 dephosphorylation and deacetylation by respectively downregulating cyclin E/CDK and p300. Moreover, elevation of SIRT2 activity by donafenib caused ANXA2 deacetylation at K81/K206 sites, leading to a reduction of the binding between ANXA2 and mTOR, which resulted in a decrease of mTOR phosphorylation and activity, and ultimately promoted protective autophagy and donafenib insensitivity in HCC cells. Additionally, ANXA2 deacetylation at K81/K206 sites was positively correlated with poor prognosis in HCC patients. Meanwhile, we found that selective inhibition of SIRT2 increased the sensitivity of donafenib in HCC cells by strengthening ANXA2 acetylation. In summary, this study reveals that donafenib induces protective autophagy and decreases its sensitivity in HCC cells through enhancing SIRT2-mediated ANXA2 deacetylation, which suggest that targeting ANXA2 acetylation/deacetylation may be a promising strategy for improving the sensitivity of donafenib in HCC treatment.

Purpose This study analyzed 18F-FDG PET-CT imaging characteristics of penetrating aortic ulcers (PAUs) and evaluating its feasibility and diagnostic efficacy in clinical assessment. Methods In this retrospective study, patients diagnosed with PAUs by CTA between August 2018 and July 2023 who underwent PET-CT within 180 days of CTA were enrolled as the ulcer cohort. Age-, sex-, and hypertension-matched controls (1:1 ratio) served as controls. Statistical analysis was performed on clinical and imaging parameters. Results Thirty-seven PAU patients and thirty-seven matched controls were included. Only two PAU cases (5.41%) showed positive 18F-FDG uptake (SUVmax > 2.5). No statistically significant differences were found in SUVmax or target-to-background ratio (TBR) between groups. While no significant correlations were found between aortic diameter or PAU width and metabolic parameters, Pearson correlation analysis found that PAU had significant positive correlations with both SUVmax (r = 0.437, p = 0.007) and TBR (r = 0.461, p = 0.005); and spearman correlation analysis demonstrated that the PAU depth is positively correlated with TBR (ρ = 0.386, p = 0.018). The positive correlation between PAU depth and TBR remains statistically significant (r = 0.354, p = 0.037) after excluding the two PET-CT-positive outliers. Conclusions Although PAUs demonstrate low rates of hypermetabolism on 18F-FDG PET-CT imaging, ulcer depth exhibits significant positive correlations with TBR values, suggesting 18F-FDG PET-CT may serve as a complementary imaging modality for PAU patients with high-risk features for disease progression.

Integrin alpha 4 beta 1 and alpha 4 beta 7 are overexpressed in macrophages and leukocytes and play important roles in mediating cell homing and recruitment to inflammatory tissues. Herein, to enhance the targeting ability of nanotherapeutics for inflammatory bowel disease (IBD) treatment, cyclosporine A-loaded nanoparticles (CsA NPs) were coated with macrophage membranes (MM-CsA NPs) or leukocyte membranes (LM-CsA NPs). In vitro experiments demonstrated that the physicochemical properties of the nanotherapeutics (e.g., size, zeta potential, polymer dispersity index, and drug release profiles) did not obviously change after cell membrane coating. However, integrin alpha 4 beta 1 and alpha 4 beta 7 were expressed in MM-CsA NPs and LM-CsA NPs, respectively, which significantly inhibited normal macrophage phagocytosis and obviously increased uptake by proinflammatory macrophages and endothelial cells. In vivo experiments verified that cell membrane-coated nanotherapeutics have longer retention times in inflammatory intestinal tissues. Importantly, LM-CsA NPs significantly mitigated weight loss, alleviated colon shortening, decreased disease activity indices (DAIs), and promoted colon tissue repair in acute and chronic colitis model mice. Furthermore, LM-CsA NPs significantly decreased the expression of inflammatory factors such as TNF-alpha and IL-6 and increased the expression of gut barrier-related proteins such as E-cadherin, ZO-1, and occludin protein in colitis mice.

本研究回顾性分析国内首例行达芬奇机器人手术系统辅助下腹主动脉瘤切除人工血管重建术患者的临床资料，该患者为39岁女性，因检查发现腹主动脉瘤1个月入院，结合患者对微创治疗及远期疗效的综合要求行达芬奇机器人手术系统辅助下腹主动脉瘤切除人工血管重建术。手术时间506 min，术中出血量约为1 200 ml，其中800 ml以自体血回收后回输，完成腹主动脉瘤切除人工血管重建后，腹主动脉人工血管充盈良好，近心端及远心端吻合口吻合良好，无明显渗血，远端髂动脉搏动良好，双侧足背动脉可触及搏动，无术中并发症发生。患者术后住院时间为8 d。患者术后随访半年，患者腹部切口及各戳卡孔愈合良好，腹部搏动性包块消失，生存良好。本研究提示达芬奇机器人手术系统辅助下腹主动脉瘤切除人工血管重建安全可行，近期疗效较好。

This study compared the efficacy and safety of distal transradial access (dTRA) and common femoral artery access (CFA) for endovascular treatment of non-coronary arterial disease. 102 interventions were divided into dTRA ( n = 51) and CFA ( n = 51) groups; the puncture success rate was 100% in both groups. The mean number of punctures and puncture time were greater in the dTRA than CFA group (1.86 vs 1.04 and 3.96 vs ≤1.00 min, p < .001 for both), whereas the access-related complication rate was comparable. The surgical success rate was higher in the CFA than dTRA group (98.0 vs 84.3, p = .036), and the operative time was longer in the dTRA than CFA group (99.09 vs 84.10 min, p = .017). The postoperative adverse event rate was not different between the dTRA and CFA groups. dTRA is a safe and feasible access for non-coronary arterial disease and is comparable to CFA in terms of puncture success, access-related complications, and major adverse events. The dTRA is inferior to CFA in the treatment of lower extremity arterial disease. Due to the increase in the operation time and the contrast medium volume in the dTRA, it is necessary to be vigilant about contrast nephropathy and late radiological random side effects.

双下腔静脉畸形是指肾静脉以下左右2条对称的下腔静脉均出现畸形,其在下腔静脉变异中少见,占0. 2％～3％,变异的主要原因是在胚胎期发育过程中双侧上主静脉持续存在而未退化[1],通常无明显临床症状或体征,导致漏诊误诊.双下腔静脉畸形合并下腔静脉滤器内血栓形成的发生更是罕见.现结合我院的1例特殊病例和相关文献,探讨双下腔静脉畸形合并滤器内血栓形成的临床特征,为双下腔静脉畸形和滤器内血栓形成的早期识别和诊治策略提供参考,现报告如下.

目的 探讨个体化微创栓塞方案治疗头面部动静脉畸形的疗效.方法 收集陆军军医大学第一附属医院2019年1月至2021年10月收治的13例复杂头面部动静脉畸形患者的临床资料,并对手术策略、栓塞材料选择、治疗效果、术后并发症、随访结果等进行总结.结果 本研究中13例患者均顺利出院,手术有效率为100%,其中8例完全治愈,术前搏动,疼痛消失,皮温恢复正常;有5例术后出现不同程度并发症,经积极处理后完全缓解.结论 头面部动静脉畸形供血动脉复杂,临床表现多样,手术处理方法不同,应根据畸形血管的特点和患者一般情况采取个体化治疗.

Because of the low incidence rate, spontaneous isolated superior mesenteric artery dissection (SISMAD) is once considered as a rare disease. In recent years, with the widespread application of enhanced computed tomography (CT), reports of SISMAD have increased. At present, there is no consensus on the optimal treatment of SISMAD, and there are various imaging classifica-tions based on CT. However, clinical management strategy for SISMAD according to any imaging classification based on CT has not yet been acknowledged. Foreign scholars believe that conservative treatment can improve symptoms in most SISMAD patients, while Chinese scholars prefer endo-vascular intervention. The authors review the research progress of treatment options on SISMAD based on computed tomography imaging classification.

目的 探讨经解剖鼻烟壶区远端桡动脉入路在下肢动脉疾病腔内治疗中的疗效.方法 回顾性分析我院因下肢动脉疾病行腔内治疗的11例患者的临床资料,统计患者穿刺及手术相关指标.结果 所有患者均成功穿刺远端桡动脉,穿刺成功时间(2.8±1.5)min,穿刺次数(1.6±0.6)次,仅1例穿刺点周围淤青,无穿刺部位相关的严重并发症发生;患者手术均成功进行,手术成功率100%,其中机械吸栓3例,球囊扩张3例,球囊扩张+支架置入4例,股动脉假性动脉瘤硬化治疗1例;干预血管总数16根,平均(1.45±0.52)根,手术时间(114.3±58.4)min,X射线照射时间(45.3±23.6)min,造影剂用量(147.3±54.6)mL,围术期未发生重大并发症.结论 远端桡动脉入路是一种安全可行的下肢动脉疾病腔内治疗的手术入路,有较高的穿刺成功率和较低的并发症并发生率.但由于导管长度限制,远端桡动脉入路在处理膝下动脉病变时有一定局限性.

目的 分析经颈静脉肝内门体分流术(TIPS)治疗急性和慢性门静脉血栓(PVT)的安全性和有效性.方法 回顾性分析我院12例行TIPS治疗的PVT患者的临床资料,观察手术成功率、血栓负荷减少程度、门静脉压力变化、门静脉通畅、腹痛腹胀缓解、围术期并发症等情况.结果 12例患者TIPS手术均成功,手术成功率100%;围术期均未发生消化道及腹腔出血、肝性脑病等并发症.1例急性PVT患者置管溶栓后血栓消退明显,未行后续支架治疗;其余11例慢性PVT患者均一期行支架植入及胃冠状静脉栓塞术.术后复查,门静脉系统超声或CT血管成像检査示门静脉主干及TIPS分流支架血流通畅.结论 TIPS治疗急性和慢性PVT安全可行,其可减轻急性PVT患者血栓负荷,避免肝及肠道坏死;对于慢性PVT,TIPS能有效重塑门静脉通路,同时降低门静脉压力,减少门静脉高压引起的消化道出血、腹腔积液等并发症.

目的 探讨经血管介入手术在治疗复杂医源性血管腔内异物中的临床效果.方法 回顾性分析2019年3月至2022年3月在我院接受介入治疗的3例复杂医源性血管腔内异物患者的临床资料,其中导丝碎裂、刺破血管及穿透周围脏器、局部血栓机化包裹导丝并血管闭塞1例,植入性导管周围血栓形成、粘连血管及心脏瓣膜1例,导丝脱入血管并发静脉血栓形成伴血管狭窄、局部血栓机化包裹导丝1例.经静脉采用钳夹、圈套、绞缠、拖拽、套取等血管腔内介入技术治疗,观察异物取出率及手术相关并发症.结果 3例患者的异物取出率为100%,其中完全取出2例,部分取出1例(残留约5%).出现血管损伤1例,其余2例无其他严重并发症.结论 介入术创伤小,并发症少,异物取出率高,效果显著,可作为复杂医源性血管腔内异物取出的治疗方式.

目的 分析腔内导管搅拌溶栓治疗伴下腔静脉及肝静脉新鲜血栓的布-加综合征(BCS)的安全性和有效性.方法 回顾分析我院22例BCS伴下腔静脉及肝静脉新鲜血栓患者的临床资料,患者均接受经导管搅栓溶栓、血栓抽吸及经皮血管成形术等腔内介入治疗.统计患者治疗后血栓清除及并发症发生情况.结果 21例患者下腔静脉及肝静脉新鲜血栓完全清除,1例患者溶栓后消化道出血,终止治疗,且随访期间失访.22例患者围术期均未出现肺栓塞症状.随访期间,21例患者下腔静脉及肝静脉血流通畅,无血栓形成、明显狭窄及肺动脉栓塞发生,患者临床症状及体征完全消失,11例植入支架的患者支架无明显移位或断裂.结论 腔内导管搅拌溶栓治疗BCS合并下腔静脉及肝静脉新鲜血栓安全有效,可有效清除下腔静脉及肝静脉新鲜血栓,避免肺动脉栓塞的发生.

Objective: To determine the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) following radical gastrectomy and to identify independent risk factors of CR-POPF. Background: CR-POPF and its sequelae are potential complications following radical gastrectomy. The reported incidence of CR-POPF was quite different across various regions, and no consensus was reached. Methods: Between December 2017 to November 2018, patients who underwent radical gastrectomy from 22 centers across 13 regions in China were prospectively recruited. The primary endpoint was the occurrence of CR-POPF, defined by the International Study Group of Pancreatic Fistula (ISGPF) in 2016. Clinically relevant change and short-term outcomes were recorded to diagnose and grade the POPF. Multivariate regression analyses were performed to identify independent risk factors of clinically relevant postoperative pancreatic fistula (CR-POPF). Results: A total of 2089 cases were analyzed. The incidence of biochemical leakage (BL) and CR-POPF were 19.6% and 1.1% respectively. All CR-POPF patients recovered well after appropriate treatment and no Grade C POPF were recorded. Logistic regression analysis showed pTNM III (OR, 2.940; 95% CI 1.180-7.325; P = 0.021) and LigaSure usage (OR, 6.618; 95% CI 1.847-23.707; P = 0.004) were independent risk factors of CR-POPF. LigaSure usage (OR, 4.817; 95% CI 1.184-19.598; P = 0.028), the drain amylase content (D-AMY) on postoperative day 3 (POD3) =5 times the upper limit of normal amylase (OR, 3.476; 95% CI 1.240-9.744; P = 0.018) and open surgery (OR, 2.463; 95% CI 1.003-6.050; P = 0.049) were independent predictors for identifying CR-POPF from BL. Conclusion: In rich-experienced gastric cancer centers, there is high prevalence of BL secondary to radical gastrectomy without clinical impact. Fewer patients suffered Grade B POPF, and Grade C POPF was less common. The patients with pTNM III or LigaSure usage were prone to suffer CR-POPF. Surgery procedure, LigaSure usage combined with D-AMY measurement on POD3 are promising for early identification of CR-POPF.

Abdominal aortic aneurysm (AAA) is a progressive focal dilatation and weakening of the abdominal aorta, causing 1.3% of all deaths among men aged 65–85 years worldwide. The formation of AAA is a complex process with multiple risk factors. Therefore, this study aimed to determine the relationship of disease severity and physiological factors, and gut microbiota structures in AAA patients. Physiological indicators and fecal 16S rRNA gene sequences from healthy controls and patients with AAA were collected. The correlations between the diameter of the AAA and clinical parameters, and gut microbiota composition were then analyzed separately using multivariable analysis. The diameter of AAA was extremely positively correlated with smoking index, alkaline phosphatase, blood glucose, and blood triglycerides and negatively correlated with prealbumin and Cystatin C. As the diameter of AAA increased, the α-diversity, including Chao 1, Shannon, and Simpson indices, of the gut microbiota decreased and presented a negative linear relationship. Patients with AAA with more severe disease had significantly increased relative abundance of Enterobacteriaceae and decreased relative abundance of Veillonellaceae. A strong correlation was observed between the diameter and physiological data, as well as between diameter and gut microbiota composition. This study could improve the understanding of AAA, and gut microbiota may be a potential target to prevent and treat this deadly disease.

目的 探讨同期与序贯治疗对下肢静脉曲张合并静脉性溃疡的临床疗效.方法 收集陆军军医大学第一附属医院2019年7月至2021年4月间收治的70例下肢静脉曲张合并溃疡患者临床资料,根据治疗方式不同将患者分为观察组(n=35,采用同期治疗)和对照组(n=35,采用序贯治疗).比较两组患者的溃疡愈合时间、抗生素使用时间、换药次数、疼痛情况、炎症指标变化情况.结果 观察组患者溃疡愈合时间、抗生素使用时间、疼痛时间均短于对照组,换药次数少于对照组,差异均有统计学意义(P<0.05).术后1周,两组患者白细胞计数、淋巴细胞百分比、白细胞介素-6比较,差异均无统计学意义(P>0.05).结论 对于合并静脉性溃疡的下肢静脉曲张,先行静脉曲张手术治疗能够明显缩短治疗时间,减轻患者症状,加快溃疡愈合.