Postoperative stability reconstruction following spinal tumor resection is a critical step to ensure functional recovery and quality of life for patients. This article systematically reviews the current status of anterior and posterior column reconstruction techniques after spinal tumor resection, including strategies such as bone cement augmentation, titanium mesh cage and artificial vertebral body implantation, and three-dimensional-printed personalized prostheses. It emphasizes the need for individualized treatment plans based on tumor type, anatomical location, and the patient's overall condition. The article also highlights the importance of restoring sagittal balance, multidisciplinary collaboration, and complication prevention for long-term outcomes. In the future, innovations in biomaterials, along with the minimally invasive and intelligent evolution of surgical techniques, will further advance the goal of achieving stable, pain-free, and functionally effective spinal reconstruction for each patient, ultimately enhancing their quality of life.

Intraplaque hemorrhage (IPH) is a key driver of carotid plaque rupture and ischemic events. However, the molecular mechanisms linking immune infiltration to pathological neovascularization in the IPH microenvironment remain poorly defined. This study aimed to elucidate the critical role of the ADAM8-SPP1-ITGB1 signaling axis in driving this ischemic phenotype. Transcriptomic analyses were performed on bulk (n = 230) and single-cell (n = 15) RNA-seq datasets and included weighted gene coexpression network analysis (WGCNA), survival analysis, cell clustering, virtual knockout, and cell–cell communication. In vivo, ApoE knockout mice fed a high-fat diet were evaluated using ultrasound, H E staining, immunofluorescence, and ELISA. In vitro, following siRNA-mediated ADAM8 knockdown, the lipid accumulation, oxidative stress, and apoptosis of ox-LDL-stimulated RAW264.7 macrophages were assessed. HUVECs were subjected to lentivirus-mediated ITGB1 knockdown and treated with recombinant SPP1 to assess cellular proliferation, migration, and angiogenesis. ADAM8 was identified as a robust diagnostic (AUC = 0.935) and prognostic (HR = 2.659) biomarker for the ischemic phenotype of IPH. Single-cell clustering and metabolic analysis revealed a distinct ADAM8+SPP1+ macrophage subset characterized by active glycolysis and a hypoxic state. Virtual knockout analyses, corroborated by in vitro knockdown experiments, confirmed that ADAM8 drives SPP1 expression. Cell-cell communication analysis indicated that this macrophage subpopulation is linked to angiogenic endothelial cells via the SPP1-ITGB1 axis. In vivo, carotid atherosclerotic mice exhibited enrichment of ADAM8+SPP1+ macrophages and elevated serum SPP1 levels. In vitro, ADAM8 downregulation in RAW264.7 macrophages alleviated lipid accumulation, ROS generation, apoptosis, and inflammation. Furthermore, recombinant SPP1 significantly promoted HUVEC proliferation, migration, and angiogenesis. Importantly, these proangiogenic effects were completely abolished by lentivirus-mediated ITGB1 knockdown. ADAM8+SPP1+ macrophages promote IPH and plaque instability via the SPP1-ITGB1 angiogenic axis and are potential therapeutic targets for high-risk atherosclerosis.

Background: The aim of this study was to construct a model by combining routine laboratory biomarkers and clinical characteristics to distinguish acute aortic dissection (AAD) patients from other sudden chest pain patients with AMI, APE and AAA. Methods and Results: Qualified patients were randomly divided into training and validation cohorts. Independent predictive factors for differentiating AAD were filtered out via backward stepwise logistic regression. A nomogram containing the included factors was constructed. The discrimination and calibration abilities were verified via receiver operating characteristic (ROC) curves and calibration curves. The clinical use of the nomogram was evaluated via DCA. A total of 860 eligible patients were randomly allocated to the training (602) and validation (258) cohorts. The WBC count, Baso%, NLR, age, DD and alcohol status were established as independent factors for patients with AAD after multiple logistic regression analysis. A nomogram was constructed. The AUC values were 0.775 (0.733--0.817) and 0.709 (0.637--0.781) for the training and validation cohorts, respectively. The Hosmer–Lemeshow test revealed no significant difference (P>0.05), indicating that the nomogram was reliable. DCA showed favorable clinical benefit. Conclusion. This study constructed a prediction model for AAD. Validation revealed excellent discrimination and calibration, indicating that the nomograms may provide clinical reference information and increase the diagnostic efficiency of AAD.

INTRODUCTION:Body mass index (BMI) has been implicated in various cardiovascular conditions, but its association with peripheral artery disease (PAD) in both real-world and genetic studies have been contentious and debated. METHODS:This study enrolled 6707 individuals from the National Health and Nutrition Examination Survey database to investigate the association between BMI and the risk of PAD. The weighted logistic regression, restricted cubic spline, and subgroup analysis were performed using real-world data. Mendelian randomization study was conducted using genetic data from the Genome-Wide Association Study. The inverse variance weighted method was used as the primary analysis approach, and a sensitivity analysis was conducted to identify pleiotropy and heterogeneity bias. RESULTS:Individuals with PAD had higher mean BMI values compared to those without PAD (28.82 ± 5.87 and 28.31 ± 5.42, P = 0.007). For the categorical variable of BMI, individuals in obesity class 2 (odds ratio [OR] = 1.532, 95% CI = 1.082-2.169; P = 0.013) and obesity class 3 (OR = 2.479, 95% CI = 1.515-4.056; P < 0.001) had a higher risk of PAD analyzed by weighted logistic regression. Subgroup analysis revealed that the association between BMI and PAD persisted. Given that a higher BMI is associated with PAD, we selected obesity for Mendelian randomization analysis and observed that obesity had a relationship with PAD (inverse variance weight: OR = 1.194, 95% CI = 1.099-1.296; P < 0.001). The reliable findings were validated by sensitive analysis (all P > 0.05). CONCLUSIONS:BMI is a robust risk factor for PAD. A higher BMI (especially ≥35 kg/m2) is associated with an increased risk of developing PAD. Meanwhile, there is a causal relationship between obesity and PAD. Interventions are necessary for targeted obesity prevention and management strategies for PAD.

Background:Lynch syndrome (LS) is an autosomal dominant disorder caused by germline mutations in mismatch repair (MMR) genes or EpCAM, leading to various cancers, particularly colorectal cancer (CRC). EpCAM mutations account for approximately 1%-3% of LS cases, while co-mutations involving EpCAM and MSH2 are exceedingly rare. To date, co-mutations of EpCAM, MSH2 and PMS2 have not been reported in the literature. Case Presentation:This case reports a 25-year-old male diagnosed with adenocarcinoma of the ascending colon. His family history revealed eight cancer cases among 30 relatives across five generations, consistent with LS. Immunohistochemistry (IHC) of the tumor showed loss of EpCAM, MSH2 and MSH6 protein expression. Genetic testing of the proband's tumor identified a novel large deletion affecting EpCAM exons 8-9 and MSH2 exons 1-16, likely pathogenic mutations disrupting MMR gene function. Whole-exome sequencing (WES) of peripheral blood from six family members, including the proband and his son, revealed co-mutations of EpCAM (c.344T>C), MSH2 (c.2744A>G), PMS2 (c.1408 C>T) and APC (c.5465T>A). Although public databases suggested these variants are benign or of uncertain significance (VUS), several in silico prediction tools and prior literature suggest potential pathogenicity. Notably, WES of the proband's son's peripheral blood also detected the same large deletions in EpCAM and MSH2, implying the presence of germline mosaicism and a possibly heightened early-onset cancer risk. Conclusion:This rare subtype of LS emphasizes the need for comprehensive genetic screening and may inform future strategies for early detection and management in LS families. Further studies are required to confirm these findings.

BACKGROUND:To evaluate differential expression of matrilin-2/transforming growth factor (TGF)-β/Smad signaling pathway components and downstream targets in primary atherosclerotic plaques versus in-stent restenosis (ISR) lesions of femoropopliteal arteries in lower extremity arteriosclerosis obliterans (LEASO) patients and to explore the mechanistic role of this pathway in regulating vascular smooth muscle cell (VSMC) phenotypic modulation for preventing postinterventional restenosis. METHODS:Femoropopliteal intimal tissues were collected from 20 primary LEASO patients and 20 ISR patients with matched baseline characteristics. Western blot quantified matrilin-2, TGF-β, contractile (TAGLN) versus synthetic (MYH10) VSMC markers, and Smad phosphorylation levels. Lentiviral transduction was used to overexpress matrilin-2 in human aortic VSMCs. Subsequent analyses included TGF-β/p-Smad signaling activation, VSMC phenotypic marker expression, and functional assessments of proliferation/migration. RESULTS:ISR lesions exhibited significantly reduced matrilin-2, TGF-β, and p-Smad levels compared to primary lesions, alongside elevated MYH10 and reduced TAGLN expression. Matrilin-2 overexpression upregulated TGF-β, TAGLN, and p-Smad, while suppressing VSMC proliferation and migration. Smad inhibition reversed these effects, increasing MYH10 and enhancing proliferative/migratory capacities. CONCLUSION:ISR lesions demonstrate predominant synthetic VSMC phenotypes compared to primary LEASO plaques. Matrilin-2 inhibits the phenotypic transition from contractile to synthetic VSMC by upregulating TGF-β/Smad signaling, thereby attenuating postinterventional restenosis in LEASO.

STUDY DESIGN:Retrospective single-institution cohort study. OBJECTIVE:To evaluate the efficacy of combined intermittent pneumatic compression (IPC) and graduated compression stockings (GCS) versus GCS alone for preventing deep venous thrombosis (DVT) in patients undergoing separation surgery for thoracolumbar metastases. SUMMARY OF BACKGROUND DATA:DVT is a significant perioperative complication in spinal metastasis surgery. Mechanical prophylaxis is preferred over chemoprophylaxis due to bleeding risks, but evidence supporting the combined use of IPC and GCS over GCS alone is lacking. METHODS:From 2018 to 2023, 385 patients undergoing separation surgery were included. Group A (n=184) received GCS alone; group B (n=201) received combined IPC and GCS. All patients underwent compression duplex ultrasound preoperatively and on postoperative day 7 to detect DVT. Demographic, surgical, and neurological data were collected and compared. RESULTS:Overall DVT incidence was 7.6% in group A and 6.5% in group B, with no significant difference ( P  > 0.05). No symptomatic pulmonary embolism occurred. Subgroup analysis of patients with preoperative Frankel A-C scores (severe neurological impairment) showed a significantly lower DVT rate in the combined therapy group (4.8% vs. 8.6%, P  < 0.05). No difference was found in patients with Frankel D-E scores. CONCLUSIONS:Combined IPC and GCS significantly reduced DVT incidence in patients with severe preoperative neurological impairment (Frankel A-C) but not in those with milder deficits (Frankel D-E). Preoperative neurological status should guide the DVT prophylaxis strategy in spinal metastasis surgery.

Background: The clinical characteristics and predictors for aortic adverse events (AAEs) after thoracic endovascular aortic repair (TEVAR) of non-hypertensive aortic dissection (AD) patients remain unclear. This study sought to clarify the clinical features of non-hypertensive AD and its incidence of AAEs after TEVAR. Methods: Clinical data were collected from the electronic medical records, imaging databases and followup. Baseline characteristics were balanced by propensity score matching (PSM). Kaplan-Meier analysis and Cox proportional hazards regression analysis were performed to asses postoperative AAEs and risk factors. Results: Eight hundred and eighty-eight eligible AD patients who had received TEVAR were included. The proportion of males (72.2% vs. 80.6%, P=0.006) and the mean age of onset (55.17 +/- 14.95 vs. 59.08 +/- 13.34 years, P=0.001) were lower in the non-hypertension group. Type A dissection still accounted for a higher proportion in the non-hypertensive group than the hypertensive group (38.2% vs. 28.3%, P=0.02) after matching. Non-hypertensive AD showed alower mean survive time (36.65 +/- 2.08 vs. 42.74 +/- 1.41 months, P=0.01) with a higher 5-year adverse event ratio (37.4% vs. 29.0%, P=0.05). Hazard ratio (HR) of type A dissection, international normalized ratio (INR), prothrombin time (PT), aortic root diameter (AoRoot) and left ventricular volume associated with AAEs after TEVAR were 3.348 [95% confidence interval (CI): 2.313- 4.846], 269.197 (95% CI: 3.46-20,946.462), 0.595 (95% CI: 0.369-0.959), 2.446 (95% CI: 1.542-3.880), 1.008 (95% CI: 1.004-1.012), respectively. Conclusions: Non-hypertensive patients presented a higher proportion of female and type A classification, and a younger mean age of TEVAR treatment. Preoperative indicators including Stanford classification, PT, activated partial thromboplastin time (APTT), AoRoot and left ventricular volume were major risk factors for adverse events after TEVAR, which deserve to be further explored and evaluated for its predictive value for better management of AD.

INTRODUCTION:Most oncogenic genes contribute to cancer progression, but their role and regulatory mechanisms are not yet fully understood in hepatocellular carcinoma (HCC). This study aimed to explore the role of miR-328-3p and the regulatory relationship between miR-328-3p and HMOX1 in HCC. METHODS:We utilized Cox and LASSO regression to identify a panel of oncogenic genes associated with hepatocellular carcinoma (HCC) progression within the TCGA-LIHC cohort and the GSE104580 dataset. The expression levels of the hub gene, HMOX1, were assessed in HCC cell lines using qPCR. The functional roles of miR-328-3p and HMOX1 were evaluated through a series of in vitro assays, including CCK-8 for proliferation, colony formation, wound healing, and Transwell assays for migration and invasion. The direct interaction between miR-328-3p and HMOX1 was explored using a luciferase reporter assay, Western blot (WB) for protein expression analysis, and functional assays to determine the impact on cell proliferation and migration. RESULTS:Eight candidate genes (BIRC5, TNSF4, SPP1, HMOX1, ADM, RBP2, IGF1, and LECT2) were screen out. The hub gene HMOX1 among had high expression level in HCC cell lines. High HMOX1 expressing cell line had significantly increased proliferation and migration capacities. Moreover, HMOX1 was identified as a target of miR-328-3p, which regulated the HMOX1 expression in qPCR and WB assays. High miR-328-3p expressing HCC cell had diminished capacities for proliferation and migration. However, concurrent upregulation of HMOX1 expression resulted in enhanced proliferative and migratory abilities in these cells. CONCLUSION:Our study has advanced our understanding of the roles of miR-328-3p and HMOX1 in HCC, demonstrating the inhibitory effect of miR-328-3p on the oncogenic activity of HMOX1. Hence, these results revealed the function of miR-328-3p and a novel mechanistic pathway for HCC and suggested the potential therapeutic targeting of miR-328-3p and HMOX1 for HCC intervention strategies.

Vascular diseases constitute a significant contributor to worldwide mortality rates, placing a substantial strain on healthcare systems and socio-economic aspects. They are closely associated with inflammatory responses, as sustained inflammation could impact endothelial function, the release of inflammatory mediators, and platelet activation, thus accelerating the progression of vascular diseases. Consequently, directing therapeutic efforts towards mitigating inflammation represents a crucial approach in the management of vascular diseases. Traditional anti-inflammatory medications may have extensive effects on multiple tissues and organs when absorbed through the bloodstream. Conversely, treatments targeting inflammatory vascular diseases, such as monoclonal antibodies, drug-eluting stents, and nano-drugs, can achieve more precise effects, including precise intervention, minimal non-specific effects, and prolonged efficacy. In addition, personalized therapy is an important development trend in targeted therapy for inflammatory vascular diseases. Leveraging advanced simulation algorithms and clinical trial data, treatment strategies are gradually being personalized based on patients' genetic, biomarker, and clinical profiles. It is expected that the application of precision medicine in the field of vascular diseases will have a broader future. In conclusion, targeting therapies offer enhanced safety and efficacy compared to conventional medications; investigating novel targeting therapies and promoting clinical transformation may be a promising direction in improving the prognosis of patients with inflammatory vascular diseases. This article reviews the pathogenesis of inflammatory vascular diseases and presents a comprehensive overview of the potential for targeted therapies in managing this condition.

Background:Researches on Marfan syndrome and Ehlers-Danlos syndrome leading to early-onset aortic dissection (AD) emphasize the importance of gene variants, but the genetic pathogenesis, clinical characteristics and outcomes of early-onset isolated Stanford type B aortic dissection (iTBAD) patients remain unclear and need to be further elucidated. Methods:Isolated type B AD patients with an onset age of less than 50 years were enrolled in this study. Whole exome sequencing (WES) was performed to detect 11 known thoracic aortic aneurysm and dissection (TAAD) gene variants. Clinical characteristics and outcomes were compared between patients with and without gene variants. Multivariate Cox regression analysis was performed to identify independent risk factors for aortic-related adverse events (ARAEs) after endovascular aortic repair. Results:A total of 37 patients were included. Ten patients carried 10 variants in five TAAD genes, four of whom carried pathogenic or likely pathogenic variants. Compared to patients without the variants, patients with variants had a lower incidence of hypertension (50.0% vs. 88.9%, P=0.021), a higher incidence of other vascular abnormalities (60.0% vs. 18.5%, P=0.038), all-cause mortality (40.0% vs. 3.7%, P=0.014) and aortic related mortality (30.0% vs. 3.7%, P=0.052). Multivariate analysis confirmed the presence of TAAD gene variants as the only independent risk factor for ARAEs [hazard ratio (HR) =4.00; 95% confidence interval (CI): 1.26-12.74; P=0.019]. Conclusions:Routine genetic testing is necessary for early-onset iTBAD patients. Individuals with a high risk of ARAEs can be identified by detecting TAAD gene variants, which is important for risk stratification and proper management.

The leaf of Perilla frutescens (L.) Britt (PF) has been reported to negatively affect adipocyte formation, inhibit body-fat formation, and lower body weight. However, its effect on adipocyte browning remains unknown. Thus, the mechanism of PF in promoting adipocyte browning was investigated. The ingredients of PF were acquired from the online database and filtered with oral bioavailability and drug-likeness criteria. The browning-related target genes were obtained from the Gene Card database. A Venn diagram was employed to obtain the overlapped genes that may play a part in PF promoting adipocyte browning, and an enrichment was analysis conducted based on these overlapped genes. A total of 17 active ingredients of PF were filtered, which may regulate intracellular receptor-signaling pathways, the activation of protein kinase activity, and other pathways through 56 targets. In vitro validation showed that PF promotes mitochondrial biogenesis and upregulates brite adipocyte-related gene expression. The browning effect of PF can be mediated by the p38 MAPK pathway as well as PI3K-AKT pathway. The study revealed that PF could promote adipocyte browning through multitargets and multipathways. An in vitro study validated that the browning effect of PF can be mediated by both the P38 MAPK pathway and the PI3K-AKT pathway.

Chemotherapy remains as the first-choice treatment option for triple-negative breast cancer (TNBC). However, the limited tumor penetration and low cellular internalization efficiency of current nanocarrier-based systems impede the access of anticancer drugs to TNBC with dense stroma and thereby greatly restricts clinical therapeutic efficacy, especially for TNBC bone metastasis. In this work, biomimetic head/hollow tail nanorobots were designed through a site-selective superassembly strategy. We show that nanorobots enable efficient remodeling of the dense tumor stromal microenvironments (TSM) for deep tumor penetration. Furthermore, the self-movement ability and spiky head markedly promote interfacial cellular uptake efficacy, transvascular extravasation, and intratumoral penetration. These nanorobots, which integrate deep tumor penetration, active cellular internalization, near-infrared (NIR) light-responsive release, and photothermal therapy capacities into a single nanodevice efficiently suppress tumor growth in a bone metastasis female mouse model of TNBC and also demonstrate potent antitumor efficacy in three different subcutaneous tumor models.

Low responsiveness to anti-programmed death-1/programmed death-ligand 1 (anti-PD-1/PD-L1) for solid tumors indicates the presence of other immunosuppressive pathways. Siglec15, a newly discovered immune checkpoint, has been reported to repress immune responses in the tumor microenvironment (TME) and regulate osteoclast differentiation. However, the role of Siglec15 in the treatment for bone metastasis remains unclear. Herein, Siglec15 shows significantly higher expression in lung adenocarcinoma spinal metastasis (LUAD-SM) than in para-cancerous spinal tissues and primary LUAD. Subsequently, a TME-responsive hollow MnO2 nanoplatform (H-M) loaded with Siglec15 siRNA and cisplatin (H-M@siS15/Cis) is developed, and the surface is modified with an aspartic acid octapeptide (Asp(8)), thus allowing H-M to target spinal metastasis. High drug-loading capacity, good biocompatibility, effective tumor accumulation, and efficient Siglec15 silencing are demonstrated. Furthermore, the nanoparticles could reverse immunosuppression caused by tumor cells and tumor-associated macrophages (TAMs) and inhibit osteoclast differentiation via Siglec15 downregulation in vitro. In a LUAD-SM mouse model, H-M@siS15/Cis-Asp(8) exhibits superior therapeutic efficacy via synergetic immunochemotherapy and osteolysis inhibition. Taken together, this single nanoplatform reveals the therapeutic potential of the new immune checkpoint Siglec15 in LUAD-SM and provides a strategy to treat this disease.

Background In patients with acute aortic dissection (AAD), increased vascular smooth muscle cell (VSMC) apoptosis has been found. Human cytomegalovirus (HCMV)-miR-US33-5p was significantly increased in the plasma of patients with AAD. However, the roles of miR-US33-5p in human aortic VSMC (HA-VSMC) apoptosis remain to be elucidated. Methods In the current study, cell apoptosis was analyzed by flow cytometry, cell proliferation by CCK-8 assay, and differentially expressed genes by RNA sequencing. Luciferase reporter assay was used for binding analysis between miR-US33-5p and endothelial PAS domain protein 1 (EPAS1), and EPAS1 and amino acid transporter heavy chain, member 2 (SLC3A2). The enrichment degree of SLC3A2 promoter DNA was analyzed by chromatin immunoprecipitation assay. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunoblotting were performed for measuring messenger RNA (mRNA) and protein levels, respectively. Results It was found that HCMV infection inhibited proliferation but promoted HA-VSMC apoptosis by upregulating HCMV-miR-US33-5p. Transfection of HCMV-miR-US33-5p mimics the significant effect on several signaling pathways including integrin signaling as shown in the RNA sequencing data. Western blotting analysis confirmed that HCMV-miR-US33-5p mimics suppression of the activity of key factors of the integrin signal pathway including FAK, AKT, CAS, and Rac. Mechanistic study showed that HCMV-miR-US33-5p bound to the 3′-untranslated region of EPAS1 to suppress its expression, leading to suppression of SLC3A2 expression, which ultimately promoted cell apoptosis and inhibited cell proliferation. This was confirmed by the findings that silencing EPAS1 significantly reduced the SLC3A2 expression and inhibited proliferation and key factors of integrin signal pathway. Conclusions HCMV-miR-US33-5p suppressed proliferation, key factors of integrin signal pathway, and EPAS1/SLC3A2 expression, but promoted HA-VSMC apoptosis. These findings highlighted the importance of HCMV-miR-US33-5p/EPAS1/SCL3A2 signaling and may provide new insights into therapeutic strategies for AAD.

Thoracic aortic aneurysms and dissections are precarious conditions that often cannot be diagnosed with fatal outcomes. Over the last few years, pathogenic variants in numerous genes have been identified that predispose to heritable presentations of TAAD. An evidence-based strategy for the selection of genes to test in familial TAAD helps inform family screening and intervention to prevent life-threatening events. Using whole-exome sequencing, four members of three unrelated families clinically diagnosed with TAAD were used to identify the genetic origin of the disorder. Variant evaluation was carried out to detect the pathogenic mutation. Our studies suggest that mutations of COL3A1 and ACTA2 are responsible for familial TAAD. In addition, we highlight FBLN5, FBN1, SLC2A10, FBN2, and NOTCH1 as candidate genes. Future studies of crosstalk among the pathways may provide us a step toward understanding the pathogenic mechanism. This finding indicates the necessity of obtaining family medical history and screening of extended relatives of patients with TAAD for the early identification and treatment of TAAD.

Abstract The onset age of acute ischemic stroke (IS) is gradually younger, which brings great challenges and burden to the medical system. For stroke patients, time is the brain cells, so any method contributes to rapid identification or diagnosis of stroke is extremely meaningful. Metabolomics analysis provides us with new means and ideas for discovering potential stroke-related biomarkers and understanding the pathogenesis of youth IS. In this study, fifty-five patients with IS were assigned in two groups(senior or junior) according to the age(60-year-old) and were performed serum metabolomics analysis based on Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS) system. Forty differential metabolites were selected, mainly ceramides, lipids, and amino acids, which are mainly related to aging, cardiovascular and cerebrovascular diseases, and antitumor mechanisms. The pathway analysis showed that the differential metabolites were mainly enriched in sphingolippid metabolism, glycine metabolism, serine and threonine metabolism, glycerol phospholipid metabolism, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and vitamin B6 metabolism. Our study suggests that the mechanism of IS in young adults was most likely associated with elevated plasma lactose ceramide levels and abnormal sphingolipid metabolic pathway.

Abstract Arteriosclerosis obliterans of lower limbs is a common peripheral arterial disease in clinics. With the development of endovascular therapy, the commonly used clinical treatment methods include balloon stent endovascular therapy and plaque resection. However, these treatment methods are often accompanied by high restenosis rate. This study aims to find a new treatment method from the genetic level.

Pyroptosis has been implicated in the pathophysiology of myocardial infarction (MI) in rodents, but its contribution to reperfusion injury in MI patients is unclear. Here, we evaluated pyroptosis in MI patients in vitro and in vivo models of myocardial ischemia/reperfusion (I/R) injury. We also investigated the molecular mechanisms that regulate pyroptosis and myocardial I/R injury in these in vitro and in vivo models. The study showed that MI patients exhibited elevated serum concentrations of the pyroptosis-related pro-inflammatory cytokines IL-1β and IL-18. Increased levels of IL-1β and IL-18 as well as the pyroptosis-related inflammatory caspases (caspase-1 and 11) were detected in cultured cardiomyocytes after anoxia/reoxygenation (A/R) and in cardiac tissues after I/R. Circ-NNT and USP46 were upregulated while miR-33a-5p was downregulated in MI patients, as well as in cultured cardiomyocytes after A/R and cardiac tissues after I/R. Circ-NNT or USP46 knockdown or miR-33a-5p overexpression inhibited the expression of pro-caspase-1, cleaved caspase-1, pro-caspase-11, cleaved caspase-11, IL-1β, and IL-18 in A/R cardiomyocytes and attenuated myocardial infarction in I/R mice. The results from luciferase reporter assays and gene overexpression/knockdown studies indicated that miR-33a-5p directly targets USP46, and circ-NNT regulates USP46 by acting as a miR-33a-5p sponge. Direct association between circ-NNT and miR-33a-5p in cardiomyocytes was confirmed by pull-down assays. In summary, pyroptosis is activated during myocardial I/R and contributes to reperfusion injury. Circ-NNT promotes pyroptosis and myocardial I/R injury by acting as a miR-33a-5p sponge to regulate USP46. This circ-NNT→miR-33a-5p→USP46 signaling axis may serve as a potential target for the development of cardio-protective agents to improve the clinical outcome of reperfusion therapy.

The aim of this study is to detect the diagnosis value of neutrophil lymphocyte ratio (NLR) and fibrinogen (FIB) in type B aortic dissection (TBAD) patients. This retrospective observation study consisted patients with TBAD, aortic aneurysm and physical examination between January 1, 2016 and December 31, 2019. Demographic and clinical information after the first admission were collected. Multivariate logistic regression analysis was performed to explore the correlational relationship between NLR, FIB and TBAD. Receiver Operating Characteristic Curve (ROC) was performed to evaluate the diagnostic implication of NLR and FIB in TBAD patients. Six hundred and six patients who were first diagnosed with TBAD were included. Control groups were 202 aortic aneurysm and 140 physical examination subjects. The level of NLR and FIB in aortic dissection patients was significantly higher than aortic aneurysm patients and healthy group (P < 0.001). According to the results of multivariate logistic regression analysis, NLR and FIB were independent risk factors of aortic dissection, and the odds ratio (OR) and 95% confidence interval (CI) value of NLR and FIB were 1.499 (1.126–1.738) and 1.914 (1.475–2.485), respectively. The area under the curve (AUC) was 0.836 of NLR and 0.756 of FIB. NLR and FIB showed high specificity, 89% and 83% respectively. This is the first study provided information on the diagnosis performance of NLR and FIB in TBAD patients. NLR and FIB showed high specificity, which may be a valuable tool for the diagnosis of TBAD.