Background Venous Thromboembolism (VTE) is influenced by clinical and genetic factors. The Caprini score is widely used but does not account for population-specific genetic susceptibility in Chinese individuals. We previously developed a Chinese-specific 15-variant polygenic risk score (PRS-15) for VTE; however, its clinical performance and added value when combined with the Caprini score remain unclear. Methods We conducted a multicenter prospective case–control study at 18 hospitals in China (February 2023–March 2025), enrolling 1,013 postoperative VTE cases and 1,025 controls. Blood samples were genotyped for PRS-15, and clinical variables and outcomes were analyzed. Discrimination and calibration were assessed using AUC and the Hosmer–Lemeshow test. Two integrated models were constructed: Model 1, PRS-15T (tertiles: high/intermediate/low) plus Caprini; and Model 2, PRS-15B (binary: high/low) plus Caprini. K-means clustering identified optimal PRS-15 thresholds and integration strategies. Model performance was evaluated by sensitivity, specificity, and net reclassification improvement (NRI), with internal validation by bootstrap resampling. Results The PRS-15 model achieved an AUC of 0.702 (95% CI, 0.680–0.725; P < 0.001). For ternary classification (PRS-15T), the optimal thresholds were 2.230 and 1.730, while the optimal threshold for binary classification (PRS-15B) was 2.335. The sensitivities of Model 1 and Model 2 were 93.88% and 90.52%, respectively, both exceeding that of the Caprini score alone (87.36%). Model 2 demonstrated the highest specificity (33.85%), outperforming Model 1 (26.73%) and the Caprini score (21.37%), and achieved an NRI of 15.65%. Conclusion PRS-15 accurately discriminated VTE cases from controls and remained robust across age and sex subgroups. Adding PRS-15 to the Caprini score significantly improved risk assessment accuracy, supporting its clinical use for VTE risk evaluation in Chinese orthopedic surgical patients.

Renal ischemia-reperfusion injury (RIRI) refers to kidney damage following blood flow restoration, with limited effective treatments available. Bone mesenchymal stem cell (BMSC) derived exosomes exhibit therapeutic potential via targeted molecular delivery, though limited by isolation challenges and transient retention, while curcumin demonstrates multi-organ protective capacities in RIRI. In vivo, RIRI mice received tail vein injections of BMSC exosomes (exo) or curcumin preconditioned BMSC exosomes (cur-exo). Biodistribution was tracked via bioluminescence/immunofluorescence, while therapeutic efficacy was evaluated through renal function parameters, histopathology, and ferroptosis biomarkers. In vitro, ferroptosis-induced renal tubular epithelial cells were treated with exo and cur-exo, with subsequent quantification of Fe²⁺, lipid peroxidation, glutathione, mitochondrial ultrastructure, ROS levels, and ferroptosis-related protein/mRNA expression. Mechanistic studies integrated transcriptomics, siRNA/overexpression systems, ChIP, dual-luciferase assays, SPR, Co-IP and bioinformatics to delineate anti-ferroptosis pathways of cur-exo and the effect of curcumin on miR-16-5p. Curcumin preconditioning can enhance the targeted delivery capability of BMSC exosomes to injured kidneys and improves the restoration of renal function and tissue damage in mice with ischemia-reperfusion injury by inhibiting ferroptosis. In vitro, TCMK-1 cells can take up both exo and cur-exo, with cur-exo significantly enhancing the survival rate of TCMK-1 cells induced by ferroptosis compared to exo. This is achieved by downregulating lipid peroxidation levels, improving iron overload and ROS accumulation, and restoring mitochondrial structure to exert anti-ferroptosis effects. Mechanistically, curcumin increases the expression of miR-16-5p in cur-exo by regulating the activity of CYP1B1, and cur-exo inhibits the translation of Smad3 by delivering miR-16-5p that targets the 3’UTR of Smad3, leading to the downregulation of myoglobin (Mb) transcriptional activity and thereby antagonizing ferroptosis in TCMK-1 cells. Our research indicates that curcumin preconditioned BMSC exosomes can exert a therapeutic effect on RIRI by inhibiting cellular ferroptosis. The primary mechanism behind this effect involves curcumin increasing the expression of miR-16-5p by modulating CYP1B1 activity, and cur-exo promoting the alleviation of ferroptosis in TCMK-1 cells through the miR-16-5p/Smad3/Mb axis. This study provides a new strategy for enhancing the biological functions of exosomes and presents new targets and ideas for the treatment of RIRI.

Ischemia-reperfusion (I/R) injury is a critical contributor to adverse outcomes following stroke. During I/R injury, excessive production of reactive oxygen species (ROS) leads to various forms of neuronal cell death. Moreover, the blood-brain barrier (BBB) significantly hinders the delivery and efficacy of many neuroprotective agents. Given selenium’s crucial role in mitigating brain ischemia, we developed a selenium-based nanozyme encapsulated in glutathione (GSH)-conjugated liposomes to overcome these challenges. Specifically, we encapsulated selenium-doped carbon dot nanozymes (Se-CDs) within GSH-conjugated liposomes (Se-CD@LP-GSH) to enable targeted delivery and enhance therapeutic efficacy in ischemic stroke. This system demonstrates effective ROS scavenging capabilities both in vitro and in vivo, while also enhancing the biocompatibility of Se-CDs and their ability to cross the BBB. In the tMCAo model, Se-CD@LP-GSH reduces the neuronal death and infarct area following cerebral I/R injury, and promotes improvements in spatial learning ability and sensorimotor function. Mechanistically, Se-CD@LP-GSH promoted the upregulation of GPX4, an essential selenoprotein, thereby preserving mitochondrial function and suppressing ROS generation Consequently, the reduced ROS levels inhibit NLRP3/GSDMD-mediated neuronal pyroptosis during cerebral I/R injury. By improving the brain-targeting ability of Se-CDs via GSH-functionalized liposomal delivery, our work elucidates their neuroprotective efficacy and mechanistic basis, thus providing a translationally relevant strategy for ischemic stroke therapy.

Cerebral ischemia–reperfusion (I/R) injury is exacerbated by the infiltration of splenic monocytes/macrophages (Mo/Mϕ) via the spleen–brain axis, where splenic-derived Mo/Mϕ migrate to cerebral lesions through C–C chemokine ligand 2/receptor 2 (CCL2/CCR2) chemotaxis, thereby amplifying oxidative stress and the neuroinflammatory cascade. Building on this endogenous pathway, we devised a delivery strategy that utilizes splenic Mo/Mϕ as “living vehicles” for targeted drug delivery. To this end, we developed a spleen-targeted magnolol liposome (Mag-PEG5K) through optimized PEGylation, ensuring its spleen-specific accumulation and uptake by splenic Mo/Mϕ. After cerebral I/R injury, these nanoparticle-laden cells migrate to the ischemic brain via the CCR2/CCL2 axis to remodel the immunomodulatory microenvironment. This targeted system orchestrates dual therapeutic mechanisms within the lesion: mitochondria-directed reactive oxygen species (ROS) scavenging mitigates oxidative stress and peroxisome proliferator-activated receptor gamma (PPARγ) activation reprograms macrophage polarization, suppressing pro-inflammatory M1 differentiation and curtailing tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) secretion. The attenuated cytokine release suppresses neuronal inflammatory cascades, thereby reducing apoptosis. In vivo, Mag-PEG5K showed superior efficacy to free magnolol, effectively reducing infarct volume and improving long-term neurological outcomes. Supported by favorable biosafety, this work proposes spleen-targeted nanotherapy as an innovative strategy for reprogramming peripheral immunity via the spleen–brain axis, highlighting the translational potential of Mag-PEG5K for addressing neuroinflammation and oxidative damage in ischemic stroke.

Background Peripheral artery disease (PAD) caused by atherosclerotic stenosis or occlusion of the arteries of the lower extremities is a major global health concern. Despite advances in endovascular therapies, treating complex lesions such as heavily calcified segments and chronic total occlusions remains challenging, which limits procedural success and long-term patency. The novel 355-nm cold laser atherectomy (CLA) system offers a photochemical, low-thermal approach to plaque ablation, with potential advantages in safety and efficacy. Objectives The aim of this study was to evaluate the safety and efficacy of a 355-nm CLA system for treating lower limb atherosclerotic stenosis and occlusion in a prospective, multicenter, randomized controlled trial. Methods This trial enrolled 110 patients with symptomatic lower extremity PAD (Rutherford classes 2-5) and ≥70% stenosis or occlusion. Patients were randomly assigned to the CLA and excimer laser atherectomy (ELA) groups. The primary endpoint was improvement in vessel diameter stenosis (DS%) prior to any adjunctive therapy. Secondary endpoints included primary patency, target lesion revascularization (TLR), Rutherford classification improvement, and ankle-brachial index values at 30 days and 6 months postoperatively, as well as a device-oriented composite endpoint. Results A total of 109 patients (CLA, n = 58; ELA, n = 51) were included in the analysis. Baseline demographics and comorbidities were well balanced between the groups. Postprocedural DS% improved significantly in both groups, with no significant intergroup differences (CLA, 59.92% ± 15.02%; ELA, 57.52% ± 17.22%; P = 0.438). The mean improvement in DS% (CLA, 34.28%; ELA, 34.35%) met the noninferiority threshold. At 30 days, the primary patency rates were 85.1% (CLA) and 87.8% (ELA), with TLR rates of 0.0% and 1.9%, respectively. At 6 months, patency decreased to 71.7% (CLA) and 61.5% (ELA), and TLR occurred in 6.5% and 10.2% of patients, respectively (P = 0.698). Ankle-brachial index values and Rutherford classification improved similarly in the 2 groups. Subgroup analyses revealed that for TASC (Trans-Atlantic Inter-Society Consensus) C/D and long lesions (≥10 cm), CLA had lower TLR rates at 6 months (P < 0.05), suggesting potential advantages for complex lesions. Conclusions The 355-nm CLA system showed similar safety and efficacy to the excimer laser, with a trend toward reducing TLR in complex PAD lesions. These findings highlight its potential as a next-generation endovascular tool that could refine revascularization strategies and improve patient outcomes in clinical practice. (DCB for Dialysis Access Stent Graft Restenosis; NCT03360279)

BACKGROUND:Endovenous microwave ablation (EMA) is an emerging minimally invasive therapy for varicose veins; however, robust evidence comparing EMA to established endovenous laser ablation (EVLA) remains limited. This multicenter randomized controlled trial aimed to evaluate the non-inferiority of EMA versus EVLA for the treatment of great saphenous vein (GSV) insufficiency. MATERIALS AND METHODS:A total of 180 patients with GSV reflux were randomized 1:1 to either EMA or EVLA. The primary outcome was GSV occlusion rate at 6 months postoperatively (non-inferiority margin, 10%). Secondary outcomes included occlusion rates at 1 week, 3 months, and 12 months postoperatively; changes in Venous Clinical Severity Score (VCSS) and Aberdeen Varicose Vein Questionnaire (AVVQ) scores; procedural metrics; and safety outcomes. RESULTS:EMA demonstrated non-inferiority to EVLA at 6 months postoperative GSV occlusion rates (full analysis set: 94.32% vs. 90.00%, risk difference [RD] 4.32%, 95% confidence interval [CI]: -4.00% to 13.06%; per-protocol set: 97.65% vs. 95.29%, RD 2.35%, 95% CI: -4.08% to 9.47%, P < 0.001 for both analyses). Both groups exhibited comparable and significant reductions in VCSS (EMA: 4.18 ± 2.24-1.10 ± 1.18; EVLA: 4.13 ± 2.50-0.93 ± 1.0) and AVVQ scores (EMA: 6.03 ± 3.21-1.54 ± 2.28; EVLA: 6.30 ± 3.68-1.12 ± 1.72) over 12 months (time effect P < 0.001; group-by-time interaction P > 0.05), indicating equivalent symptom relief. Kaplan-Meier analysis revealed no significant difference in the time to GSV recanalization between the groups during long-term follow-up (log-rank test, P = 0.15). Device-related adverse events were rare (EMA, 2.27% vs. EVLA, 2.22%; P = 1.00), with no device deficiencies or serious adverse events related to the surgery or device. CONCLUSION:EMA is non-inferior to EVLA for GSV closure at 6 months, with similar safety profiles and quality-of-life outcomes. These findings support EMA as a viable alternative to EVLA, warranting further investigation of its long-term durability.

Peripheral artery disease (PAD) is a progressive ischemic condition with limited therapeutic options at advanced stages. Current treatments predominantly target revascularization, often neglecting the metabolic dysregulation underlying this condition. Emerging evidence positions lactate not merely as a glycolytic byproduct but as a critical signaling metabolite that orchestrates neovascularization, vascular remodeling, and immune modulation. Furthermore, lactate-induced histone and nonhistone lactylation dynamically regulate gene expression in ischemic tissues, exerting stage- and cell type-specific effects that may be protective or deleterious. This duality underscores the complexity of lactate signaling and its context-dependent influence on PAD progression. Importantly, lactate and lactylation profoundly affect key vascular cell functions, including endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages, modulating neovascularization and remodeling. This review summarizes recent advances in the understanding of lactate and lactylation, focusing on their regulatory roles in PAD-associated neovascularization and therapeutic potential for PAD.

Matrine, a natural alkaloid, has a wide range of pharmacological effects, such as antibacterial, anti-inflammatory, anti-oxidation, and anti-tumor. However, the molecular mechanism of matrine in the treatment of atherosclerosis (AS) is not fully understood. Human umbilical vein endothelial cells (HUVECs) were treated with 100 mu g/mL ox-LDL to construct an AS cell model in vitro, and the cells were treated with matrine at different concentrations. Our results showed that matrine alleviated the decrease of HUVEC viability and the increase of ferroptosis induced by ox-LDL treatment. Subsequently, we found that matrine targeted regenerating family member 1 alpha (REG1A) and inhibited the expression level of REG1A in ox-LDL treated HUVECs. Overexpression of REG1A attenuated the improvement of matrine on activation of the PI3K/Akt/mTOR pathway and ferroptosis in ox-LDL treated HUVECs. In addition, both LY294002 (an inhibitor of the PI3K signaling) and Erastin (an inducer of ferroptosis) reversed the alleviation of matrine treatment on ferroptosis in ox-LDL treated HUVECs. The results in vivo showed that matrine treatment inhibited high-fat diet-induced aortic ferroptosis in ApoE-/- mice and alleviated arterial tissue lesions. In summary, matrine inhibits ferroptosis by targeting REG1A to activate PI3K/Akt/mTOR pathway, thereby alleviating aortic endothelial injury and lipid plaque formation in AS mice, suggesting that matrine has potential value for the treatment of AS.

Forces on the linker of the nucleoskeleton and cytoskeleton (LINC) complex control nuclear mechano-sensing and mechano-adaptation. However, the force transmission dynamics across the LINC complex are not fully understood, mainly because of the lack of imaging tools. We developed a set of genetically-encoded fluorescence resonance energy transfer (FRET)-based nuclear tension sensors (NuTS) that measure tension forces across SUN1/2 proteins in living cells with high sensitivity. SUN2-based NuTS (NuTS2) responded rapidly to mechanical changes in cell contractility and matrix stiffness. Notably, NuTS2 dynamically showed force transmission with high spatiotemporal resolution during cell adhesion, migration and squeeze. We also used NuTS2 to monitor tension force changes as the notochord matures in zebrafish development. NuTS2 detected a gradient tension force that increased from the posterior tail buds to the anterior as vacuoles expanded in notochord cells. Force reduction affected notochord maturation and zebrafish embryo development. Our results provide a biophysical cue for dissecting how force transmission on SUN2 protein regulates embryo development. ### Competing Interest Statement Q.P. has filed a patent application (202411578009.0, substantive examination) to China National Intellectual Property Administration for NuTS technology through the Shenzhen Bay Laboratory on 6 November 2024. JW and JQ are co-inventors on the patent. The other authors declare no competing interests.

Chronic limb-threatening ischemia (CLTI) is the most severe form of peripheral arterial disease (PAD). Mesenchymal stem cell (MSC) transplantation holds promise as a treatment for CLTI; however, the harsh local environment poses challenges to its effectiveness. Apoptotic vesicles (ApoVs) are extracellular vesicles produced by cells undergoing apoptosis, and they can carry various biomolecules from their parent cells, including proteins, RNA, DNA, lipids, ions, and gas neurotransmitters. ApoVs play significant roles in anti-inflammatory responses, anti-tumor activities, and tissue regeneration through intercellular communication, and they have demonstrated potential as drug carriers. In this study, we investigated the potential of bone marrow stem cell (BMSC)-derived ApoVs for treating CLTI. In vivo, we explored the therapeutic effect of ApoVs on a hindlimb ischemia model through Laser Doppler, matrigel plug assay, and histological analysis. In vitro, we analyzed the effects of ApoVs on the proliferation, migration, and angiogenesis of HUVECs and explored the uptake process of ApoVs. In addition, Proteomic analysis, western blotting, quantitative real-time PCR, shRNA, and siRNA were used to analyze ApoVs-induced HUVECs activation and downstream signaling pathways. BMSCs transplantation showed improvement in a hind limb ischemia model, and this effect still exists after apoptosis of BMSCs. Subsequently, ApoVs of BMSCs were isolated and found to improve mouse hind limb ischemia in vivo. In vitro, ApoVs can be ingested by HUVECs through dynamin-, clathrin-, and caveolin-mediated endocytosis and promote its proliferation, migration, and angiogenesis. Mechanistically, ApoVs transferred NAMPT to HUVECs, therefore activating the NAMPT/SIRT1/FOXO1 axis, influencing the transcriptional activity of FOXO1, and promoting angiogenesis. Our results demonstrate that the transplanted BMSCs can ameliorate hindlimb ischemia by releasing ApoVs during apoptosis. The main mechanism of this effect is promoting the proliferation, migration, and angiogenesis of HUVECs through the NAMPT/SIRT1/FOXO1 axis. This study provides different insights into the therapeutic mechanisms through BMSCs and suggests a promising direction for ApoVs transplantation. Not applicable.

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.

Ischemia-reperfusion (I/R) injury is a critical contributor to adverse outcomes following stroke. During I/R injury, excessive production of reactive oxygen species (ROS) leads to various forms of neuronal cell death. Moreover, the blood-brain barrier (BBB) significantly hinders the delivery and efficacy of many neuroprotective agents. Given selenium’s crucial role in mitigating brain ischemia, we developed a selenium-based nanozyme encapsulated in glutathione (GSH)-conjugated liposomes to overcome these challenges. Specifically, we encapsulated selenium-doped carbon dot nanozymes (Se-CDs) within GSH-conjugated liposomes (Se-CD@LP-GSH) to enable targeted delivery and enhance therapeutic efficacy in ischemic stroke. This system demonstrates effective ROS scavenging capabilities both in vitro and in vivo, while also enhancing the biocompatibility of Se-CDs and their ability to cross the BBB. In the tMCAo model, Se-CD@LP-GSH reduces the neuronal death and infarct area following cerebral I/R injury, and promotes improvements in spatial learning ability and sensorimotor function. Mechanistically, Se-CD@LP-GSH promoted the upregulation of GPX4, an essential selenoprotein, thereby preserving mitochondrial function and suppressing ROS generation Consequently, the reduced ROS levels inhibit NLRP3/GSDMD-mediated neuronal pyroptosis during cerebral I/R injury. By improving the brain-targeting ability of Se-CDs via GSH-functionalized liposomal delivery, our work elucidates their neuroprotective efficacy and mechanistic basis, thus providing a translationally relevant strategy for ischemic stroke therapy.

Promoting the establishment of collateral circulation is essential for chronic lower extremity ischemia. However, no effective therapeutic drugs have yet been developed. Recent studies discovered that in the peripheral arteries, there are GABAB1 receptors expressed in endothelial cells and smooth muscle cells, these receptors may have some effects in regulating vascular functions, but the precise mechanism is not yet clear. This study explores the effect of GABAB1 receptor inhibition on angiogenesis and its regulatory mechanism. The expression of GABAB1 in HUVECs was knocked down using shRNA transfection, and effects in HUVECs' proliferation, migration, and tube formation ability were detected. Western blot and RT-PCR were used to verify the signal pathway. The murine hind limb ischemia model was used to verify the effect of CGP35348, an antagonist of GABAB1R, on the recovery of blood flow perfusion and angiogenesis in ischemic tissues. Cell proliferation, migration, and tube formation ability were improved after GABAB1 receptor knockdown in HUVECs. The phosphorylation of the HIPPO/YAP pathway decreased, while the effect of promoting angiogenesis increased. After treating the ischemic hindlimbs of mice with GABAB1 receptor antagonists, the blood flow perfusion recovered, and the angiogenesis increased. These findings demonstrate the effect of GABAB1 receptor inhibition on the HIPPO/YAP pathway in regulating angiogenesis, suggesting that inhibiting GABAB1 receptor levels might be a novel approach for chronic lower extremity ischemia diseases.

Background: Venous thromboembolism (VTE) has both environmental and genetic risk factors. It is regulated by poly-genes and multisites. The polygenic risk score (PRS) has been widely used because any single genetic biomarker failed to accurately predict the genetic risk of VTE. However, no polygenic risk model has been proposed for VTE in the Chinese population. Thus, we aimed to construct a PRS model for the first episode of VTE in the Chinese population.Methods: First, single nucleotide polymorphisms (SNPs) associated with VTE in genome-wide association studies, meta-analyses, and candidate gene studies were screened as variables for the PRS. The logarithm of the odds ratio was used to weight the variables. Second, a training set with simulated data from 1000 cases of VTE and 1000 controls was created with different genotypes and frequencies. Finally, we calculated the area under the receiver operating characteristic curve (AUC) to evaluate the discriminatory ability of the PRS model.Results: We screened 53 SNPs potentially associated with the first episode of VTE in the Chinese population. The AUC of the PRS-53 model (containing 53 SNPs) was 0.748 (95% confidence interval, 0.727-0.770) in the training set. From the largest weight to the smallest weight, SNPs were incrementally added to the model to calculate the AUC for model optimization. The AUC of the PRS-10 model (containing 10 SNPs) was 0.718 (95% confidence interval, 0.696-0.740), with no statistically significant difference from the AUC for the PRS-53 model.Conclusions: The PRS-10 and PRS-53 models showed similar predictive abilities and satisfactory discriminatory power and can be used to predict the genetic risk of the first episode of VTE in the Chinese population. The simplified PRS-10 model is more efficient in clinical practice. (J Vasc Surg Venous Lymphat Disord 2024;12:101666.)

Nei endonuclease VIII-like 3 (NEIL3), a novel tumor-related gene, is differentially expressed and involved in pathophysiological processes in multiple tumors. However, the potential biological functions and molecular mechanisms of NEIL3 in human clear cell renal cell carcinoma (ccRCC) have not been identified. In this research, we demonstrated that NEIL3, transcriptionally activated by E2F1, served as an oncogene to facilitate cell proliferation and cell cycle progression and contribute to tumorigenesis via the cyclin D1-Rb-E2F1 feedback loop in ccRCC. First, we found that NEIL3 expression was upregulated in ccRCC tissues and cell lines compared with matched adjacent nontumor tissues and renal tubular epithelial cells and was also positively correlated with adverse clinicopathological characteristics, such as advanced cancer stages and higher tumor grades, and acted as an independent prognostic marker in ccRCC. Mechanistically, we demonstrated that NEIL3 promoted cell proliferation, DNA replication and cell cycle progression in vitro and tumor growth in vivo. Furthermore, we found that NEIL3 overexpression activated the cyclin D1-Rb-E2F1 pathway, and the E2F1 upregulation transcriptionally activated NEIL3 expression, thus forming a feedback loop. In addition, there was a positive correlation between NEIL3 and E2F1 expression in clinical specimens of ccRCC. Taken together, our results suggest that NEIL3 serves as a proto-oncogene in ccRCC and presents as a novel candidate for ccRCC diagnosis and treatment.

Cerebral protection devices (CPDs) often were applied to improve the safety of carotid artery stenting, but the CPD itself may cause fatal complications. We report a case of a retained CPD that was an Emboshield NAV6 device left in situ , which was retrieved successfully with esophageal biopsy forceps.

CHIVA是一种以多普勒超声检查为基础的局部麻醉下静脉曲张微创治疗手段,其打破了下肢静脉曲张的传统治疗理念,将血流动力学概念与血管疾病的诊断、治疗充分结合到一起,在保留浅静脉引流网络同时治疗近端反流点以移除过载血流,从而达到治疗静脉高压的目的.本文从CHIVA的原理、优势及缺点、治疗效果方面进行比较,表明CHIVA是一种可行的治疗静脉曲张的替代手术,与传统大隐静脉剥脱术相比,其主要优点包括保留隐静脉、局部麻醉、低复发率、低成本、低疼痛感、无神经损伤等.同时CHIVA的血流动力学理念可被借鉴于当前任何一种治疗方法,从而达到更精确的治疗.CHIVA主要的缺点是术前需精密的超声评估,学习曲线较长,需要培训静脉血流动力学团队.

Purpose: This study aimed to develop and internally validate nomograms for predicting restenosis after endovascular treatment of lower extremity arterial diseases. Materials and Methods: A total of 181 hospitalized patients with lower extremity arterial disease diagnosed for the first time between 2018 and 2019 were retrospectively collected. Patients were randomly divided into a primary cohort (n=127) and a validation cohort (n=54) at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) regression was used to optimize the feature selection of the prediction model. Combined with the best characteristics of LASSO regression, the prediction model was established by multivariate Cox regression analysis. The predictive models' identification, calibration, and clinical practicability were evaluated by the C index, calibration curve, and decision curve. The prognosis of patients with different grades was compared by survival analysis. Internal validation of the model used data from the validation cohort. Results: The predictive factors included in the nomogram were lesion site, use of antiplatelet drugs, application of drug coating technology, calibration, coronary heart disease, and international normalized ratio (INR). The prediction model demonstrated good calibration ability, and the C index was 0.762 (95% confidence interval: 0.691-0.823). The C index of the validation cohort was 0.864 (95% confidence interval: 0.801-0.927), which also showed good calibration ability. The decision curve shows that when the threshold probability of the prediction model is more significant than 2.5%, the patients benefit significantly from our prediction model, and the maximum net benefit rate is 30.9%. Patients were graded according to the nomogram. Survival analysis found that there was a significant difference in the postoperative primary patency rate between patients of different classifications (log-rank p<0.001) in both the primary cohort and the validation cohort. Conclusion: We developed a nomogram to predict the risk of target vessel restenosis after endovascular treatment by considering information on lesion site, postoperative antiplatelet drugs, calcification, coronary heart disease, drug coating technology, and INR. Clinical Impact Clinicians can grade patients after endovascular procedure according to the scores of the nomograms and apply intervention measures of different intensities for people at different risk levels. During the follow-up process, an individualized follow-up plan can be further formulated according to the risk classification. Identifying and analyzing risk factors is essential for making appropriate clinical decisions to prevent restenosis.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the tumour images shown in Fig. 7A and certain of the cell proliferation assay images shown in Fig. 3B were strikingly similar to data that had already appeared in another article written by different authors at different research institutes [Xiao W Wang, J, Li H, Xia D, Yu G, Yao W, Yang Y, Xiao H, Lang B, Ma X et al: Fibulin‑1 is epigenetically down‑regulated and related with bladder cancer recurrence. BMC Cancer 14: 677, 2014]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, 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. [Oncol Rep 38: 2435‑2443, 2017; DOI: 10.3892/or.2017.5884].