RATIONALE AND OBJECTIVES:Sarcopenia is a significant predictor of adverse outcomes in cardiovascular diseases. However, most prior studies have focused on lumbar muscle indices and have overlooked the prognostic relevance of site-specific muscle loss in peripheral artery disease (PAD). This study aimed to evaluate whether machine learning (ML) models incorporating the lower-leg muscle index (LMI) provide superior prediction of long-term mortality in PAD patients undergoing revascularization. MATERIALS AND METHODS:A retrospective cohort of 208 consecutive PAD patients hospitalized for planned lower-extremity revascularization was analyzed. Preoperative clinical data and CT angiography-derived muscle indices were collected. Feature selection employed LASSO, mRMR, random forest, and gradient boosting; the number of variables was limited by the 10 events per variable rule. Multivariate Cox regression assessed associations between muscle indices and all-cause mortality. Eight ML models were validated, and performance was evaluated with C-index and AUC. Calibration and decision curve analysis were also performed. RESULTS:During a mean follow-up of 29.5 ± 15.5 months, 44 deaths were recorded. Non-survivors had more comorbidities, inflammation, and lower-limb muscle loss. Among muscle indices, LMI showed the highest discrimination for mortality (AUC 0.71), outperforming abdominal indices. Higher LMI was associated with lower mortality risk (HR = 0.94, 95 % CI 0.92-0.97, p = 0.004) across all subgroups. Gradient boosting yielded the best predictive performance, with C-indexes of 0.847, 0.809, and 0.823 at 1, 3, and 5 years, respectively. Calibration and decision curve analysis demonstrated model robustness and clinical utility. CONCLUSIONS:Lower-leg muscle index is a superior and accessible predictor of long-term mortality in PAD, exceeding conventional abdominal muscle indices. ML models using LMI enable individualized risk stratification and may improve post-revascularization management.

BACKGORUND:Peripheral arterial disease (PAD) is a chronic vascular disease with high morbidity, often accompanied by sarcopenia. However, the prognostic value and mechanistic relevance of computed tomography (CT)-defined sarcopenia in PAD remain unclear. This study aims to assess the independent impact of sarcopenia on all-cause mortality and major adverse cardiovascular events in PAD patients, and to determine optimal third lumbar vertebra skeletal muscle index (L3-SMI) cutoffs for risk stratification. METHODS:In this retrospective cohort study, 208 PAD patients were grouped by L3-SMI into sarcopenia (n = 110) and nonsarcopenia (n = 98). Multivariate Cox regression evaluated associations with mortality and major adverse cardiovascular events (MACE), while restricted cubic spline (RCS) models explored dose-response patterns. Kaplan-Meier and log-rank tests compared survival, and Spearman correlation analyzed functional and metabolic associations. RESULTS:The sarcopenia group exhibited significantly higher age (71.5 ± 9.38 vs. 65.81 ± 10.25 years, P < 0.001), while lower L3-SMI (36.48 ± 5.67 vs. 47.31 ± 7.88 cm2/m2, P < 0.001), lower body mass index (22.31 ± 2.96 vs. 25.77 ± 2.72 kg/m2, P < 0.001), lower albumin (37 vs. 39 g/L, P = 0.005), and lower serum phosphate (1.14 vs. 1.23 mmol/L, P = 0.009). Over a 36-month median follow-up, sarcopenia was associated with increased all-cause death (27% vs. 14%, P = 0.034) and MACE incidence (28% vs. 14%, P = 0.024). Multivariate Cox regression revealed that each 1-unit decrease in L3-SMI elevated death risk by 7% (adjusted hazard ratio [HR] = 0.93, 95% confidence interval [CI]: 0.88-0.98, P = 0.009) and MACE risk by 9% (adjusted HR = 0.92, 95% CI: 0.86-0.96, P = 0.008). RCS analysis identified nonlinear dose-response relationships: L3-SMI <40.97 cm2/m2 sharply increased death risk (HR = 3.3), while L3-SMI <48.78 cm2/m2 significantly amplified MACE risk (HR = 7.89). Correlations between L3-SMI and Barthel index (r = 0.56, P < 0.001), serum phosphate (r = 0.53, P = 0.002), and Fontaine stage (r = -0.39, P = 0.007) suggested sarcopenia might exacerbate disease progression via metabolic dysregulation, immune suppression, and functional decline. CONCLUSION:CT-defined sarcopenia independently predicts poor outcomes in PAD. L3-SMI thresholds enable early risk stratification and support targeted interventions to improve prognosis. These findings underscore the importance of incorporating body composition assessment into routine risk evaluation for PAD patients.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the cellular images shown in Fig. 7A on p. 995 were strikingly similar to data in a paper that had previously been published in the journal Molecular Cancer that was written by different authors at different research institutes. Furthermore, an independent analysis of the data in this paper performed by the Editorial Office revealed that flow cytometric data in Fig. 2A, the cell migration and invasion assay data in Fig. 3A and D and the control western blot data in Fig. 5A were also strikingly similar to data that had either previously been published in articles written by different authors at different research institutes, or which were submitted for publication at around the same time. Given that the abovementioned data had already been published before the receipt of this paper at International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 42: 988‑997, 2018; DOI: 10.3892/ijmm.2018.3685].

Background: This systematic review/meta-analysis investigated the risks of fluoroquinolones (FQs) for aortic aneurysms (thoracic/abdominal) and Stanford A/B dissections. Methods: We searched EMBASE, Ovid, PubMed, Web of Science, and Scopus databases in February 2024. Eligible observational studies were those that presented adjusted risk estimates for aortic aneurysm or dissection (AAD) incidence, aortic-specific mortality, or all-cause mortality in FQ-treated versus untreated unexposed populations. Results: A total of 13 studies were included (36,224,419 participants), eight of which were cohort studies, two were nested case-control studies, and three were case-crossover designs. FQ exposure was associated with significantly elevated de novo AAD risk within 30 days (relative risk (RR) = 3.40, 95% confidence interval (CI) = [2.72, 4.24]; heterogeneity: I2 = 41.5%, p = 0.11) and 60 days (RR = 3.53, 95% CI = [2.78, 4.49]; heterogeneity: I2 = 87.0%, p < 0.0001). The analysis also revealed a higher all-cause mortality risk for FQs versus non-exposed controls (odds ratio (OR) = 1.44, 95% CI = [1.08, 1.93]; heterogeneity: I2 = 0%, p = 0.80). Subgroup analysis demonstrated comparable aortic dissection (AD) and aortic aneurysm (AA) risks, except for a significantly increased de novo AA risk at 30 days (RR = 9.13, 95% CI = [6.05, 13.78]; heterogeneity: I2 = 68.7%, p = 0.07) and 60 days (OR = 1.69, 95% CI = [1.27, 2.26]; heterogeneity: I2 = 52%, p = 0.10). Conclusion: This meta-analysis found a significant association between FQ use and short-term AAD risk. These results suggest that clinicians should weigh the risks of AAD before prescribing FQs, especially in patients with aortic vulnerability or pre-existing aortic pathology, considering alternative treatments when feasible. The PROSPERO Registration: CRD42024509853 (https://www.crd.york.ac.uk/PROSPERO/view/CRD42024509853).

BACKGROUND:Abdominal aortic endograft infection (AAEI) is a rare but life-threatening complication following endovascular aneurysm repair. This study aimed to report surgical outcomes of AAEI from 2 specialized Chinese vascular centers and analyze prognostic risk factors. METHODS:A dual-center retrospective cohort study enrolled 41 patients who underwent complete infected graft excision and revascularization for AAEI between February 2018 and September 2025. Clinical data were collected and analyzed via Kaplan-Meier survival analysis and univariate COX regression. RESULTS:This cohort included 40 males and 1 female (mean age: 64.22 ± 9.12 years). Complete removal of the infected graft was performed in all cases, with revascularization achieved via extra-anatomical bypass (EAB, n = 39) or in situ reconstruction (n = 2). Median follow-up time was 12 months. All-cause mortality was 29.3%, nonfatal complication rate was 39.0% and reintervention rate was 17.1% (7/41). Elevated white blood cell (WBC) (P = 0.01, hazard ratio [HR] = 3.90) and enteric fistula (P = 0.04, HR = 3.21) worsened survival; advanced age showed a trend toward significance (P = 0.09). C-reactive protein level and renal artery stent coverage had no significant prognostic impact (P > 0.05). CONCLUSION:EAB is a feasible and practical option for high-risk AAEI patients, particularly at centers lacking biological grafts. Enteric fistula, elevated preoperative WBC, and advanced age predict poor survival. Large prospective multicenter trials are needed to refine individualized treatments for AAEI.

BACKGROUND:An increasing number of patients with abdominal aortic aneurysms (AAAs) are opting for endovascular aneurysm repair (EVAR), and predicting postoperative survival is important for patient management. The development of a postoperative prognostic model using machine learning (ML) can be effective in predicting postoperative survival, and research on this issue needs to be further enhanced. This study aims to establish predictive models for prognosis in AAA patients after EVAR. METHODS:Perioperative and follow-up information of 163 AAA patients were collected in Beijing Hospital who underwent EVAR from January 2016 to April 2023. The patients were divided into a training set and a test set in a ratio of 7:3. ML methods such as least absolute shrinkage and selection operator (LASSO) regression, random forests, linear discriminant analysis, naive Bayes, K-nearest neighbor algorithm, support vector machines, and decision trees were selected to build prediction models, and these models were evaluated by the receiver operating characteristic curves (ROC). RESULTS:The study cohort comprised 163 patients with a mean age of 72 ± 8.4 years, 33 (20.2%) patients died during the follow-up period, and the majority were male (88.3%). Patients were categorized into survivors (n = 130) and nonsurvivors (n = 33). LASSO regression selected chronic obstructive pulmonary disease (COPD), maximum diameter of aneurysm to body mass index ratio (DBR), and stroke history. The area under the ROC (AUC) for the training and test sets of nomogram was 0.77 and 0.75, respectively. K-Nearest Neighbors (KNN) was the most effective ML algorithm, with the AUC of 0.85 and 0.81 superlatively for the training and test sets. CONCLUSION:Stroke, DBR, and COPD can predict prognosis after EVAR in AAA patients. KNN is better than other algorithms in the study.

Objective To share the diagnosis and treatment outcomes of brucellar aortoiliac aneurysms (BIAAs) from two large vascular surgery centres in China, and to describe the clinical characteristics and prognosis of different treatment regimens. Methods A retrospective analysis was performed on the demographic, clinical, and follow up data of 15 patients with BIAAs admitted to the Department of Vascular Surgery, Beijing Friendship Hospital, Capital Medical University, and Beijing Hospital between May 2019 and June 2025. Results Among the 15 patients, 14 were men and one was a woman; 12 had a history of contact with sheep or their faeces. Lumbar/abdominal pain and fever were the most common clinical manifestations. The positive rate of Brucella Rose Bengal Test (RBT) was 100% (15 of 15), the positive rate of blood culture was 40% (6 of 15), and the positive rate of intra-operative tissue culture was 11% (1 of 9). All 15 patients completed follow up with a mean follow up duration of 32.93 ± 22.61 months, and the survival rate was 93% (14 of 15). Five patients who received endovascular treatment had a good prognosis, five patients who underwent open surgery achieved satisfactory curative effects, one patient who received conservative treatment remained stable, and four patients who received endovascular treatment developed severe complications and infection recurrence, among whom one died despite rescue efforts. Conclusion BIAAs are clinically rare and highly dangerous. Open surgery based on anti-Brucella therapy remains the preferred radical treatment option in clinical practice, and endovascular treatment can be used as an alternative in specific emergency cases. It should be noted that this study had a small sample size, and the comparison of different treatment methods was mainly descriptive, with certain limitations.

The prevalence of Peripheral Artery Disease (PAD) is rising globally, yet early risk stratification remains challenging due to the limitations of traditional obesity metrics. TyG–ABSI, an index combining Triglyceride-Glucose (TyG) with A Body Shape Index (ABSI), is a novel marker reflecting both functional insulin resistance and structural visceral adiposity. However, its predictive value for PAD remains unexplored in large prospective cohorts. We included 390,274 adults from the UK Biobank. Baseline characteristics were analyzed across TyG–ABSI quartiles and PAD status. Associations between TyG-related indices and incident PAD were assessed using multivariable-adjusted Cox regression, Kaplan–Meier survival curves, and restricted cubic splines. Robustness was evaluated via Fine-Gray competing risk models, propensity score matching, subgroup analyses, and external validation in the NHANES database. Consensus k-means clustering, integrating biochemical and insulin resistance markers, identified metabolic phenotypes and stratified PAD risk. Feature selection (LASSO, Boruta, and Minimum Redundancy Maximum Relevance [mRMR]) guided the development of six machine learning models (logistic regression, GBM, XGBoost, AdaBoost, LightGBM, and neural network) for PAD prediction, with interpretability assessed via SHAP analysis. Higher TyG–ABSI and related indices were strongly associated with increased PAD incidence (cumulative incidence at 15 years: 4.16

Objective Type V Takayasu arteritis (TAK) is the most extensive form of this large-vessel vasculitis, frequently necessitating complex surgical management due to its multiterritory arterial involvement. This study aims to evaluate the clinical efficacy and safety of 1-stage supra-aortic and aortovisceral artery (SAVA) bypass in patients with Numano type V TAK. Methods We retrospectively reviewed all patients diagnosed with type V TAK undergoing simultaneous SAVA bypass at 6 tertiary centers in China between February 2017 and April 2024. These patients were selected from a multicenter surgical database of 264 patients with TAK. Demographics and characteristics were collected. The primary end point was mortality within 30 days after surgery; secondary end points included graft patency, major surgery-related complications, and overall survival. All patients were prospectively followed, and outcomes were analyzed. Results A total of 12 patients, with 115 SAVA segments affected by TAK, underwent reconstruction of 42 arteries. These reconstructions utilized 14 autologous great saphenous vein grafts and 28 prosthetic grafts with a mean operative time of 514 ± 101 minutes. The 30-day survival rate was 100%. During a mean follow-up duration of 47.4 ± 28.5 months, 4 cases of graft restenosis were detected, of which 1 was successfully resolved via surgical thrombectomy and 3 were managed conservatively. No late mortality or major complications was observed. Postoperatively, systolic blood pressure decreased significantly, and patients achieved sustained symptom relief with improved health-related quality of life. Conclusions With appropriate perioperative management and surgical planning, the simultaneous reconstruction of SAVA in type V TAK can be performed safely and effectively.

OBJECTIVE:Current guidelines recommend postponing surgical intervention in patients with Takayasu's arteritis (TAK) until the disease becomes quiescent, which could exacerbate the incidence of pre-operative adverse events. Considering advances in peri-operative management, the association between pre-operative disease activity and long term prognosis after revascularisation requires re-evaluation. METHODS:This was a multicentre, retrospective cohort study conducted across six tertiary Chinese centres, including patients receiving revascularisation procedures for arterial stenosis or occlusion due to TAK between August 2016 and January 2024. Kaplan-Meier survival analyses, Cox proportional hazards regression, and subgroup analyses were performed to evaluate the relationship between pre-operative disease activity and long term outcomes. Potential prognostic risk factors associated with clinical outcomes were identified using Cox regression analysis and receiver operating characteristic curve analysis. RESULTS:The outcomes of 165 consecutive patients with TAK who underwent 201 surgical interventions, including 94 (46.8%) endovascular revascularisations (EVRs) and 107 (53.2%) open surgical revascularisations (OSRs), were analysed. Interestingly, pre-operative disease activity parameters (active state defined by the 2018 European Alliance of Associations for Rheumatology consensus, Kerr score, and biological inflammation) were of little relevance to the incidence of poor long term outcomes among patients undergoing either EVR or OSR. Moreover, peri-operative immunosuppressive treatment was a prognostic factor for favourable outcomes after EVR (hazard ratio [HR] 3.10, 95% confidence interval [CI] 1.20 - 8.75, p = .009), whereas pre-operative thrombin time showed a statistically significant negative correlation with the risk of poor long term outcomes following OSR over the eight year follow up (HR 0.81, 95% CI 0.70 - 0.94, p = .004; p of non-linearity = .42), with an optimal cutoff value of 13 seconds. CONCLUSION:These data indicated a lack of correlation between pre-operative disease activity and long term prognosis. Peri-operative immunosuppressive treatment and thrombin time should be considered in the clinical decision making and peri-operative management of patients undergoing EVR and OSR, respectively.

BACKGROUND:This study aimed to systematically review the impact of frailty on outcomes following abdominal aortic aneurysm (AAA) surgery. METHODS:MEDLINE, Embase, and Scopus were searched for studies of frailty on AAA surgery. A modified Newcastle-Ottawa scale was used to assess the quality of the included studies. The impact of frailty on outcomes was expressed as odds ratios (ORs) or hazard ratios (HRs) using a random effects model. RESULTS:A total of 12 studies were finally included for analysis. Overall frailty was associated with a significantly increased risk of 30-day mortality in patients who underwent AAA surgery (OR 4.380, 95% confidence interval [CI] 3.590-5.340, I2 = 0%). Functionally dependent patients exhibited a substantial rise in 30-day mortality risk following AAA surgery compared to independent patients (OR 4.690, 95% CI 3.730-5.910 I2 = 0%). Frailty was also associated with a higher risk of long-term all-cause mortality in the included population (HR 2.200, 95% CI 1.750-2.780, I2 = 0%). Central muscle mass was significantly associated with a higher risk of worse long-term survival in patients who underwent AAA surgery (HR 2.130, 95% CI 1.670-2.720, I2 = 0%). Functional dependency was associated with a significantly increased risk of complications in patients undergoing major AAA surgery (OR 2.570, 95% CI 2.020-3.270, I2 = 54%). CONCLUSION:Frailty correlates with both short-term and long-term mortality and survival in AAA patients. Therefore, it is imperative to conduct thorough assessments of functional status or muscle volume preoperatively, followed by appropriate patient stratification to optimize patient outcomes.

BACKGROUND:To summarize the experience of diagnosing and treating of infrarenal infected native abdominal aortic aneurysm (INAA) by reviewing the clinical characteristics, management strategies, and outcomes of patients in a single center. METHODS:The clinical data of 17 patients with INAA admitted to the Department of Vascular Surgery, Beijing Hospital, from April 2017 to October 2024 were retrospectively analyzed. Patient demographics, comorbidities, postoperative complications, long-term survival, reintervention rates, treatment approaches, and follow-up outcomes were reviewed and summarized. RESULTS:Of the 17 patients included (94.1% male, mean age 63.4 ± 7.2 years), 52.9% presented with abdominal pain and 58.8% were threatened with aneurysm rupture or fistula formation. Microbial cultures identified gram-negative bacilli in 82.4% of cases. Four patients received conservative treatment, of whom three died (75%). Thirteen patients underwent surgery: five received open surgical repair (all survived, 100% survival rate), and eight endovascular aneurysm repairs (three died, 62.5% survival rate). The overall mortality rate was 35.3%. The treatment modality may have contributed to the observed differences in survival. CONCLUSION:Our results suggest that OSR may offer favorable outcomes for selected patients with INAA, while EVAR can be considered for high-risk or emergency cases. Individualized treatment strategies, based on multidisciplinary team evaluation and patient characteristics, are essential for optimal care. Given the retrospective design, small sample size, and possible selection bias, these findings are preliminary and hypothesis-generating. Further large-scale, prospective studies are needed to confirm the optimal management of INAA.

Objective This study aimed to evaluate the impact of frailty and inflammation on all-cause mortality in patients with abdominal aortic aneurysm (AAA) who underwent endovascular aneurysm repair (EVAR), and key risk factors were also explored. Methods A retrospective analysis was conducted on 174 patients with AAA who underwent EVAR at Beijing Hospital between 2016 and 2024. Frailty was assessed using the modified five-item Frailty Index (mFI-5). Inflammation was quantified by the red cell distribution width-to-albumin ratio (RAR), a novel inflammatory marker. We examined the associations between frailty, preoperative risk factors, and mortality using Kaplan-Meier survival analysis and Cox proportional hazards models. Mediation analysis was performed to evaluate the role of RAR in the relationship between frailty and mortality. Results Frailty was found to be an independent risk factor for all-cause mortality following EVAR (HR = 1.95, P = 0.048). Preoperative anemia (HR = 0.98, P = 0.032), elevated creatinine levels (HR = 1.01, P = 0.013), and prolonged operation time (HR = 1.01, P = 0.029) were also independent predictors of mortality. Kaplan-Meier survival analysis revealed significantly lower survival rates for frailty patients (P = 0.004). Additionally, RAR mediated 23.8% of the relationship between frailty and mortality (P = 0.012), underscoring its role as a key indicator of chronic inflammation. Conclusions Frailty and chronic inflammation, as measured by the innovative RAR marker, are significant contributors to mortality after EVAR. This study highlights the clinical utility of RAR in identifying high-risk AAA patients and its potential for guiding targeted preoperative interventions. Incorporating frailty assessments and inflammation monitoring into routine preoperative evaluations may improve patient outcomes by enabling personalized approaches such as nutritional optimization and inflammation control.

Background: Clinically useful predictors for risk stratification of long-term survival may assist in selecting patients for endovascular abdominal aortic aneurysm (EVAR) procedures. This study aimed to analyze the prognostic significance of peroperative novel systemic inflammatory markers (SIMs), including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), hemoglobin-to-red cell distribution width ratio (HRR), systemic immune-inflammatory index (SIII), and systemic inflammatory response index (SIRI), for long-term mortality in EVAR. Methods: A retrospective analysis was performed on 147 consecutive patients who underwent their first EVAR procedure at the Department of Vascular Surgery, Beijing Hospital. The patients were divided into the mortality group (n = 37) and the survival group (n = 110). The receiver operating characteristic curves were used to ascertain the threshold value demonstrating the most robust connection with mortality. The Kaplan–Meier survival analysis was performed between each SIM and mortality. The relationship between SIMs and survival was investigated using restricted cubic splines and multivariate Cox regression analysis. Results: The study included 147 patients, with an average follow-up duration of 34.28 ± 22.95 months. Deceased patients showed significantly higher NLR (p < 0.001) and reduced HRR (p < 0.001). The Kaplan–Meier estimates of mortality were considerably greater in the higher-NLR group (NLR >2.77) and lower-HRR group (HRR <10.64). The hazard ratio (HR) of 0.833 (95% confidence interval (95% CI): 0.71–0.97, p < 0.021) was determined to be statistically significant in predicting death in the multivariable analysis. Conclusions: Preoperative higher-NLR and lower-HRR have been associated with a lower long-term survival rate in abdominal aortic aneurysm (AAA) patients undergoing elective EVAR. Multivariate Cox regression showed that decreased preoperative HRR is an independent risk factor that increases mortality risk following EVAR. SIMs, such as the NLR and HRR, could be used in future clinical risk prediction methodologies for AAA patients undergoing EVAR. However, additional prospective cohort studies are needed to identify these findings.

Background: The operation rate for different involved arteries and the manifestation of vessel involvement of patients with Takayasu arteritis undergoing open or endovascular operations remain unclear. We aimed to investigate the clinical characteristics, vessel involvement, angiographic classification and operations information in a large cohort of patients with Takayasu arteritis undergoing open or endovascular operations at a single centre in China. Methods: From January 2017 to October 2022, a total of 153 consecutive patients undergoing open or endovascular operations were recruited from the Department of Vascular Surgery of Beijing Hospital. The demographic characteristics, clinical presentations, pattern of vascular involvement and operation information were collected and analysed. Results: The majority of patients were female (128/153, 83.7%). The most common vascular finding was hypertension (66.7%). The subclavian (74.2%), carotid (70.1%) and renal (68.9%) arteries were the most commonly involved arteries. Type V (40.5%) was the most common angiographic classification pattern. A total of 296 open or endovascular operations were performed, including 73 percutaneous transluminal angioplasties (PTAs), 50 stent placements and 173 bypass graft operations. Patients with renal (83.3%) or carotid (65.2%) artery involvement had markedly higher rates of undergoing operations. Conclusions: The subclavian and carotid arteries, as well as the type V (40.5%) pattern, exhibited the highest frequency of involvement among patients with Takayasu arteritis who underwent open or endovascular operations. Variations in angiographic features can result in differences in clinical manifestations and significantly impact the possibility and modality of operations.

Gene therapy offers a promising avenue for treating ischemic diseases, yet its clinical efficacy is hindered by the limitations of single gene therapy and the high oxidative stress microenvironment characteristic of such conditions. Lipid-polymer hybrid vectors represent a novel approach to enhance the effectiveness of gene therapy by harnessing the combined advantages of lipids and polymers. In this study, we engineered lipid-polymer hybrid nanocarriers with tailored structural modifications to create a versatile membrane fusion lipid-nuclear targeted polymer nanodelivery system (FLNPs) optimized for gene delivery. Our results demonstrate that FLNPs facilitate efficient cellular uptake and gene transfection via membrane fusion, lysosome avoidance, and nuclear targeting mechanisms. Upon encapsulating Hepatocyte Growth Factor plasmid (pHGF) and Catalase plasmid (pCAT), HGF/CAT-FLNPs were prepared, which significantly enhanced the resistance of C2C12 cells to H2O2-induced injury in vitro. In vivo studies further revealed that HGF/CAT-FLNPs effectively alleviated hindlimb ischemia-induced gangrene, restored motor function, and promoted blood perfusion recovery in mice. Metabolomics analysis indicated that FLNPs didn’t induce metabolic disturbances during gene transfection. In conclusion, FLNPs represent a versatile platform for multi-dimensional assisted gene delivery, significantly improving the efficiency of gene delivery and holding promise for effective synergistic treatment of lower limb ischemia using pHGF and pCAT.

Pulmonary embolism (PE) is one of the leading causes of cardiovascular death, resulting in a significant socioeconomic burden. Although current treatments primarily focus on anticoagulation and thrombolysis, there is an urgent need for a better understanding of its pathophysiology and the development of new treatment strategies. Animal models play a crucial role in understanding PE and developing new therapies for the disease, with rodents commonly used due to ethical and cost considerations. However, existing rodent models for PE are limited by a lack of standardized procedures, which hampers reproducibility and cross-study comparisons. This study aims to establish a minimally invasive rat model of PE using autologous blood clots. The model features a minimally invasive blood sampling technique, a standardized thrombus generation procedure, and minimally invasive vein access. Additionally, protocols for quantifying infarcted areas and visualizing the pulmonary arterial tree are provided. These procedures aim to improve the reliability of rodent models for studying PE progression and facilitate the development of novel treatments.