Discordance Between Angiographic Assessment and Fractional Flow Reserve or Intravascular Ultrasound in Intermediate Coronary Lesions: A Post-hoc Analysis of the FLAVOUR Trial.

BACKGROUND AND OBJECTIVES: Angiographic assessment of coronary stenosis severity using quantitative coronary angiography (QCA) is often inconsistent with that based on fractional flow reserve (FFR) or intravascular ultrasound (IVUS). We investigated the incidence of discrepancies between QCA and FFR or IVUS, and the outcomes of FFR- and IVUS-guided strategies in discordant coronary lesions. METHODS: This study was a post-hoc analysis of the FLAVOUR study. We used a QCA-derived diameter stenosis (DS) of 60% or greater, the highest tertile, to classify coronary lesions as concordant or discordant with FFR or IVUS criteria for percutaneous coronary intervention (PCI). The patient-oriented composite outcome (POCO) was defined as a composite of death, myocardial infarction, or revascularization at 24 months. RESULTS: The discordance rate between QCA and FFR or IVUS was 30.2% (n=551). The QCA-FFR discordance rate was numerically lower than the QCA-IVUS discordance rate (28.2% vs. 32.4%, p=0.050). In 200 patients with ≥60% DS, PCI was deferred according to negative FFR (n=141) and negative IVUS (n=59) (15.3% vs. 6.5%, p<0.001). The POCO incidence was comparable between the FFR- and IVUS-guided deferral strategies (5.9% vs. 3.4%, p=0.479). Conversely, 351 patients with DS <60% underwent PCI according to positive FFR (n=118) and positive IVUS (n=233) (12.8% vs. 25.9%, p<0.001). FFR- and IVUS-guided PCI did not differ in the incidence of POCO (9.5% vs. 6.5%, p=0.294). CONCLUSIONS: The proportion of QCA-FFR or IVUS discordance was approximately one third for intermediate coronary lesions. FFR- or IVUS-guided strategies for these lesions were comparable with respect to POCO at 24 months. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02673424.

Biogenic Mn Oxide Generation and Mn(II) Removal by a Manganese Oxidizing Bacterium Bacillus sp. Strain M2.

Mn(II)-oxidizing bacteria (MOB) are widely distributed in natural environments and can convert soluble Mn(II) into insoluble Mn(III) and Mn(IV). The biogenic manganese oxides (BioMnOx) produced by MOB have been considered for remediating heavy metal pollution and degrading organic pollutants in an eco-friendly manner. In this study, a manganese-oxidizing bacterium was isolated from Mn-polluted rivulet sediment and identified as Bacillus sp. strain M2 by PCR, phylogenetic tree construction, transmission electron microscopy (TEM), and physiological and biochemical indices. Strain M2 grew well under Mn(II) stress. BioMnOx with nanosized irregular geometric shapes and loose structures generated by strain M2 were found on the surface of the bacterial cells. The content of Mn in the bacteria was as high as 5.36%. Approximately 71.24% and 47.52% of Mn(II) was oxidized to Mn(III/IV) in the cell and in the deposits, respectively, within 3 d of cultivation with Mn(II). Extracellular enzymes contributed to the Mn removal and oxidation. In conclusion, Bacillus sp. strain M2 has a high potential for use in the remediation of Mn-contaminated sites.

Identification and verification of circRNA biomarkers for coronary artery disease based on WGCNA and the LASSO algorithm.

BACKGROUND: The role of circular RNAs (circRNAs) as biomarkers of coronary artery disease (CAD) remains poorly explored. This study aimed to identify and validate potential circulating circRNAs as biomarkers for the diagnosis of CAD. METHODS: The expression profile of circRNAs associated with CAD was obtained from Gene Expression Omnibus (GEO) database. Differential expression analysis, weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operation (LASSO) were employed to identify CAD-related hub circRNAs. The expression levels of these hub circRNAs were validated using qRT-PCR in blood samples from 100 CAD patients and 100 controls. The diagnostic performance of these circRNAs was evaluated through logistic regression analysis, receiver operator characteristic (ROC) analysis, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Functional enrichment analyses were performed to predict the possible mechanisms of circRNAs in CAD. RESULTS: A total of ten CAD-related hub circRNAs were identified through WGCNA and LASSO analysis. Among them, hsa_circ_0069972 and hsa_circ_0021509 were highly expressed in blood samples of CAD patients, and they were identified as independent predictors after adjustment for relevant confounders. The area under the ROC curve for hsa_circ_0069972 and hsa_circ_0021509 was 0.760 and 0.717, respectively. The classification of patients was improved with the incorporation of circRNAs into the clinical model composed of conventional cardiovascular risk factors, showing an IDI of 0.131 and NRI of 0.170 for hsa_circ_0069972, and an IDI of 0.111 and NRI of 0.150 for hsa_circ_0021509. Functional enrichment analyses revealed that the hsa_circ_0069972-miRNA-mRNA network was enriched in TGF-ß、FoxO and Hippo signaling pathways, while the hsa_circ_0021509-miRNA-mRNA network was enriched in PI3K/Akt and MAPK signaling pathways. CONCLUSION: Hsa_circ_0069972 and hsa_circ_0021509 were identified by integrated analysis, and they are highly expressed in CAD patients. They may serve as novel biomarkers for CAD.

Mild phototherapy mediated by IR780-Gd-OPN nanomicelles suppresses atherosclerotic plaque progression through the activation of the HSP27-regulated NF-κB pathway.

Reducing plaque lipid content and enhancing plaque stability without causing extensive apoptosis of foam cells are ideal requirements for developing a safe and effective treatment of atherosclerosis. In this study, we synthesized IR780-Gd-OPN nanomicelles by conjugating osteopontin (OPN) and loading a gadolinium-macrocyclic ligand (Gd-DOTA) onto near-infrared dye IR780-polyethylene glycol polymer. The nanomicelles were employed for mild phototherapy of atherosclerotic plaques and dual-mode imaging with near-infrared fluorescence and magnetic resonance. In vitro results reveal that the mild phototherapy mediated by IR780-Gd-OPN nanomicelles not only activates heat shock protein (HSP) 27 to protect foam cells against apoptosis but also inhibits the nuclear factor kappa-B (NF-κB) pathway to regulate lipid metabolism and macrophage polarization, thereby diminishing the inflammatory response. In vivo results further validate that mild phototherapy effectively reduces plaque lipid content and size while simultaneously enhancing plaque stability by regulating the ratio of M1 and M2-type macrophages. In summary, this study presents a promising approach for developing a safe and highly efficient method for the precise therapeutic visualization of atherosclerosis. STATEMENT OF SIGNIFICANCE: The rupture of unstable atherosclerotic plaques is a major cause of high mortality rates in cardiovascular diseases. Therefore, the ideal outcome of atherosclerosis treatment is to reduce plaque size while enhancing plaque stability. To address this challenge, we designed IR780-Gd-OPN nanomicelles for mild phototherapy of atherosclerosis. This treatment can effectively reduce plaque size while significantly improving plaque stability by increasing collagen fiber content and elevating the ratio of M2/M1 macrophages, which is mainly attributed to the inhibition of the NF-κB signaling pathway by mild phototherapy-activated HSP27. In summary, our proposed mild phototherapy strategy provides a promising approach for safe and effective treatment of atherosclerosis.

Coronary hemodynamic simulation study.

In this paper, a two-way fluid-structure coupling model is developed to simulate and analyze the hemodynamic process based on dynamic coronary angiography, and examine the influence of different hemodynamic parameters on coronary arteries in typical coronary stenosis lesions. Using the measured FFR pressure data of a patient, the pressure-time function curve is fitted to ensure the accuracy of the boundary conditions. The average error of the simulation pressure results compared to the test data is 6.74%. In addition, the results related to blood flow, pressure contour and wall shear stress contour in a typical cardiac cycle are obtained by simulation analysis. These results are found to be in good agreement with the laws of the real cardiac cycle, which verifies the rationality of the simulation. In conclusion, based on the modeling and hemodynamic simulation analysis process of dynamic coronary angiography, this paper proposes a method to assist the analysis and evaluation of coronary hemodynamic and functional parameters, which has certain practical significance.

Prognostic Implications of Quantitative Flow Ratio and Plaque Characteristics in Intravascular Ultrasound-Guided Treatment Strategy.

BACKGROUND: Quantitative flow ratio (QFR) is a method for evaluating fractional flow reserve without the use of an invasive coronary pressure wire or pharmacological hyperemic agent. OBJECTIVES: The aim of this study was to investigate the prognostic implications of QFR and plaque characteristics in patients who underwent intravascular ultrasound (IVUS)-guided treatment for intermediate lesions. METHODS: Among the IVUS-guided strategy group in the FLAVOUR (Fractional Flow Reserve and Intravascular Ultrasound for Clinical Outcomes in Patients with Intermediate Stenosis) trial, vessels suitable for QFR analysis were included in this study. High-risk features were defined as low QFR (≤0.90), quantitative high-risk plaque characteristics (qn-HRPCs) (minimal lumen area ≤3.5 mm2, or plaque burden ≥70%), and qualitative high-risk plaque characteristics (ql-HRPCs) (attenuated plaque, positive remodeling, or plaque rupture) assessed using IVUS. The primary clinical endpoint was target vessel failure (TVF), defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization. RESULTS: A total of 415 (46.1%) vessels could be analyzable for QFR. The numbers of qn-HRPCs and ql-HRPCs increased with decreasing QFR. Among deferred vessels, those with 3 high-risk features exhibits a significantly higher risk of TVF compared with those with ≤2 high-risk features (12.0% vs 2.7%; HR: 4.54; 95% CI: 1.02-20.29). CONCLUSIONS: Among the IVUS-guided deferred group, vessels with qn-HRPC and ql-HRPC with low QFR (≤0.90) exhibited a significantly higher risk for TVF compared with those with ≤2 features. Integrative assessment of angiography-derived fractional flow reserve and anatomical and morphological plaque characteristics is recommended to improve clinical outcomes in patients undergoing IVUS-guided deferred treatment.

Physiology- or Imaging-Guided Strategies for Intermediate Coronary Stenosis.

Importance: Treatment strategies for intermediate coronary lesions guided by fractional flow reserve (FFR) and intravascular ultrasonography (IVUS) have shown comparable outcomes. Identifying low-risk deferred vessels to ensure the safe deferral of percutaneous coronary intervention (PCI) and high-risk revascularized vessels that necessitate thorough follow-up can help determine optimal treatment strategies. Objectives: To investigate outcomes according to treatment types and FFR and IVUS parameters after FFR- or IVUS-guided treatment. Design, Setting, and Participants: This cohort study included patients with intermediate coronary stenosis from the Fractional Flow Reserve and Intravascular Ultrasound-Guided Intervention Strategy for Clinical Outcomes in Patients With Intermediate Stenosis (FLAVOUR) trial, an investigator-initiated, prospective, open-label, multicenter randomized clinical trial that assigned patients into an IVUS-guided strategy (which recommended PCI for minimum lumen area [MLA] ≤3 mm2 or 3 mm2 to 4 mm2 with plaque burden [PB] ≥70%) or an FFR-guided strategy (which recommended PCI for FFR ≤0.80). Data were analyzed from November to December 2022. Exposures: FFR or IVUS parameters within the deferred and revascularized vessels. Main Outcomes and Measures: The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, and revascularization at 2 years. Results: A total of 1619 patients (mean [SD] age, 65.1 [9.6] years; 1137 [70.2%] male) with 1753 vessels were included in analysis. In 950 vessels for which revascularization was deferred, incidence of TVF was comparable between IVUS and FFR groups (3.8% vs 4.1%; P = .72). Vessels with FFR greater than 0.92 in the FFR group and MLA greater than 4.5 mm2 or PB of 58% or less in the IVUS group were identified as low-risk deferred vessels, with a decreased risk of TVF (hazard ratio [HR], 0.25 [95% CI, 0.09-0.71]; P = .009). In 803 revascularized vessels, the incidence of TVF was comparable between IVUS and FFR groups (3.6% vs 3.7%; P = .95), which was similar in the revascularized vessels undergoing PCI optimization (4.2% vs 2.5%; P = .31). Vessels with post-PCI FFR of 0.80 or less in the FFR group or minimum stent area of 6.0 mm2 or less or with PB at stent edge greater than 58% in the IVUS group had an increased risk for TVF (HR, 7.20 [95% CI, 3.20-16.21]; P < .001). Conclusions and Relevance: In this cohort study of patients with intermediate coronary stenosis, FFR- and IVUS-guided strategies showed comparable outcomes in both deferred and revascularized vessels. Binary FFR and IVUS parameters could further define low-risk deferred vessels and high-risk revascularized vessels.

Causal associations of plasma omega-3 polyunsaturated fatty acids with sarcopenia-related traits: a two-sample Mendelian randomization study.

OBJECTIVE: To evaluate the causal effect of plasma omega-3 polyunsaturated fatty acids (PUFAs) on sarcopenia-related traits (lean mass, grip strength and walking pace) utilizing two-sample Mendelian randomization (MR) approach. METHODS: Based on genome-wide association study (GWAS) summary statistics, we performed two-sample MR applying the inverse variance weighted (IVW) as the primary method, supplemented with four additional sensitivity analyses. Furthermore, multivariable MR (MVMR) was applied to assess these associations independent of alcohol drinking, type 2 diabetes (T2D), triglycerides (TG), estimated glomerular filtration rate (eGFR) and C-reactive protein (CRP). RESULTS: In univariable MR, the IVW analysis suggested no significant causal effect of genetically determined plasma omega-3 PUFAs on fat-free mass (right leg: ß = 0.01, 95% CI = -0.02 to 0.05, P = 0.375; left leg: ß = 0.01, 95% CI = -0.02 to 0.04, P = 0.446; right arm: ß = 0.01, 95% CI = -0.02 to 0.05, P = 0.376; left arm: ß = 0.01, 95% CI = -0.02 to 0.04, P = 0.384; trunk:ß = 0.02, 95% CI = -0.02 to 0.06, P = 0.283; whole: ß = 0.01, 95% CI = -0.03 to 0.04, P = 0.631), grip strength (right hand: ß = -0.01, 95% CI = -0.03 to 0.01, P = 0.387; left hand: ß = -0.01, 95% CI = -0.02 to 0.01, P = 0.553) and walking pace (ß = 0.00, 95% CI = -0.01 to 0.02, P = 0.575), and sensitive analysis generated similar non-significant results. Furthermore, the MVMR revealed no independent causal association. CONCLUSIONS: Genetically determined plasma omega-3 PUFAs have no causal effect on sarcopenia-related traits.

Rationale and design of a comparison of angiography-derived fractional flow reserve-guided and intravascular ultrasound-guided intervention strategy for clinical outcomes in patients with coronary artery disease: a randomised controlled trial (FLAVOUR II).

INTRODUCTION: Percutaneous coronary intervention (PCI) guided by coronary angiography-derived fractional flow reserve (FFR) or intravascular ultrasound (IVUS) has shown improved clinical outcomes compared with angiography-only-guided PCI. In patients with intermediate stenoses, FFR resulted in fewer coronary interventions and was non-inferior to IVUS with respect to clinical outcomes. However, whether this finding can be applied to angiography-derived FFR in significant coronary artery disease (CAD) remains unclear. METHOD AND ANALYSIS: The comparison of angiography-derived FFR-guided and IVUS-guided intervention strategies for clinical outcomes in patients with coronary artery disease (FLAVOUR II) trial is a multicentre, prospective, randomised controlled trial. A total of 1872 patients with angiographically significant CAD (stenoses of at least 50% as estimated visually through angiography) in a major epicardial coronary artery will be randomised 1:1 to receive either angiography-derived FFR-guided or IVUS-guided PCI. Patients will be treated with second-generation drug-eluting stent according to the predefined criteria for revascularisation: angiography-derived FFR≤0.8 and minimal lumen area (MLA)≤3 mm2 or 3 mm270%. The primary endpoint is a composite of all-cause death, myocardial infarction and revascularisation at 12 months after randomisation. We will test the non-inferiority of the angiography-derived FFR-guided strategy compared with the IVUS-guided decision for PCI and the stent optimisation strategy.The FLAVOUR II trial will provide new insights into optimal evaluation and treatment strategies for patients with CAD. ETHICS AND DISSEMINATION: FLAVOUR II was approved by the institutional review board at each participating site (The Second Affiliated Hospital of Zhejiang University School of Medicine Approval No: 2020LSYD410) and will be conducted in line with the Declaration of Helsinki. Informed consent would be obtained from each patient before their participation. The study results will be submitted to a scientific journal. TRIAL REGISTRATION NUMBER: NCT04397211.

Clinical Outcomes of Deferred Lesions by IVUS Versus FFR-Guided Treatment Decision.

BACKGROUND: There are limited data regarding the safety of deferral of percutaneous coronary intervention based on intravascular ultrasound (IVUS) findings. The current study sought to compare the prognosis between deferred lesions based on IVUS and fractional flow reserve (FFR)-guided treatment decision. METHODS: This study is a post hoc analysis of the FLAVOUR randomized trial (Fractional Flow Reserve and Intravascular Ultrasound for Clinical Outcomes in Patients With Intermediate Stenosis) that compared 2-year clinical outcomes between IVUS- and FFR-guided treatment decision on intermediate coronary artery lesions using predefined criteria. In both IVUS and FFR groups, vessels were classified into deferred or revascularized vessels, and patients were classified as those with or without deferred lesions. Vessel-oriented composite outcomes (cardiac death, target vessel myocardial infarction, or target vessel revascularization) in deferred vessels and patient-oriented composite outcomes (death, myocardial infarction, or any revascularization) in patients with deferred lesions were compared between the IVUS and FFR groups. RESULTS: A total of 1682 patients and 1820 vessels were analyzed, of which 922 patients and 989 vessels were deferred. At 2 years, there was no difference in the cumulative incidence of vessel-oriented composite outcomes in deferred vessels between IVUS (n=375) and FFR (n=614) groups (3.8% versus 4.1%; hazard ratio, 0.91 [95% CI, 0.47-1.75]; P=0.77). The risk of vessel-oriented composite outcomes was comparable between deferred and revascularized vessels following treatment decision by IVUS (3.8% versus 3.5%; hazard ratio, 1.09 [95% CI, 0.54-2.19]; P=0.81) and FFR (4.1% versus 3.6%; hazard ratio, 1.14 [95% CI, 0.56-2.32]; P=0.72). In comparison of patient-oriented composite outcomes in patients with deferred lesions, there was no significant difference between the IVUS (n=357) and FFR (n=565) groups (6.2% versus 5.9%; hazard ratio, 1.05 [95% CI, 0.61-1.80]; P=0.86). CONCLUSIONS: In patients with intermediate coronary artery stenosis, deferral of percutaneous coronary intervention based on IVUS-guided treatment decision showed comparable risk of clinical events with FFR-guided treatment decision. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02673424.

Prediction of fractional flow reserve with enhanced ant lion optimized support vector machine.

The evaluation of coronary morphology provides important guidance for the treatment of coronary heart disease (CHD). A chaotic Gaussian mutation antlion optimizer algorithm (CGALO) is proposed in the paper, and it is combined with SVM to construct a classification prediction model for Fractional flow reserve (FFR). To overcome the limitations of the original antlion optimizer (ALO) algorithm, the chaotic Gaussian mutation strategy is introduced, which leads to an improvement in its convergence speed and accuracy. To evaluate the proposed algorithm's performance, comparative experiments were conducted on 23 benchmark functions alongside 12 other cutting-edge optimization algorithms. The experimental outcomes demonstrate that the proposed algorithm achieves superior convergence accuracy and speed compared to the alternative comparison algorithms. Additionally, it is combined with SVM and FS to construct a hierarchical FFR classification model, which is utilized to make effective predictions for 84 patients at the affiliated hospital of medical school, Ningbo university. The experimental results demonstrate that the proposed model achieves an average accuracy of 92%. Moreover, it concludes that smoking history, number of lesion vessels, lesion location, diffuse lesions and ST segment changes, and other factors are the most critical indicators for FFR. Therefore, the model that has been established is a new FFR intelligent classification prediction technology that can effectively assist doctors in making corresponding decisions and evaluation plans.

Sex Differences in Fractional Flow Reserve- or Intravascular Ultrasound-Guided Percutaneous Coronary Intervention.

BACKGROUND: A recent randomized trial reported fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) strategy was noninferior to the intracoronary ultrasound (IVUS)-guided PCI strategy with respect to clinical outcomes with fewer revascularizations. OBJECTIVES: This study sought to investigate the sex differences in treatment and clinical outcomes according to physiology- or imaging-guided PCI strategies. METHODS: In this secondary analysis of the FLAVOUR (Fractional Flow Reserve or Intravascular Ultrasonography to Guide PCI) trial, the impact of sex on procedural characteristics, PCI rate, and outcomes according to different strategies and treatment types (PCI vs deferral of PCI) was analyzed. The primary outcome was target vessel failure (TVF) at 24 months, defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization. RESULTS: Of 1,619 patients, 30% were women. Compared with men, women had a smaller minimal lumen area, smaller plaque burden, and higher FFR. They had a lower PCI rate (40.8% vs 47.9%; P = 0.008), which was mainly contributed by FFR guidance. Overall, women showed a lower TVF rate (2.4% vs 4.5%). According to the treatment type, the cumulative incidence of TVF was lower in women than in men among those with the deferral of PCI (1.7% vs 5.2%). However, this trend was not observed in patients who underwent PCI. In both women and men, there were no differences in clinical outcomes between the FFR- and IVUS-guided strategies. CONCLUSIONS: In cases of intermediate stenosis, despite receiving fewer interventions, women had more favorable outcomes than men. The use of FFR led to a lower PCI rate but had a similar prognostic value compared with IVUS in both women and men.

Relationships Between Inflammatory Parameters Derived From Complete Blood Count and Quantitative Flow Ratio in Patients With Stable Coronary Artery Disease.

To investigate the relationships between inflammatory parameters, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII), and quantitative flow ratio (QFR) in stable coronary artery disease (CAD) patients (n = 450) enrolled in this cross-sectional study. Logistic regression was performed to evaluate the associations of NLR, PLR, MLR, and SII evaluated as continuous and binary variables with QFR ≤0.80. When treated as continuous variables, lnNLR was associated with QFR ≤0.80 with borderline significance in univariable (odds ratio (OR) = 1.60, p = .05) and multivariable analysis (OR = 1.72, p = .05), while lnMLR was associated with QFR ≤0.80 significantly in univariable analysis (OR = 1.87, p = .03) and with borderline significance in multivariable analysis (OR = 1.91, p = .05). When treated as binary variables, high levels of MLR and SII were significantly associated with QFR ≤0.80 in univariable (MLR: OR = 1.91, p = .02; SII: OR = 2.42, p = .006) and multivariable analysis (MLR: OR = 1.83, p = .04; SII: OR = 2.19, p = .02). NLR, MLR, and SII, but not PLR, were significantly associated with the severity of coronary physiology in stable CAD patients.

Diet-derived circulating antioxidants and risk of knee osteoarthritis, hip osteoarthritis and rheumatoid arthritis: a two-sample Mendelian randomization study.

Objective: To examine the causal associations of diet-derived circulating antioxidants with knee osteoarthritis (OA), hip OA, and rheumatoid arthritis (RA) within the two-sample Mendelian randomization (MR) framework. Method: Independent single-nucleotide polymorphisms (SNPs) significantly associated with circulating levels of diet-derived antioxidants (retinol, ß-carotene, lycopene, vitamin C and vitamin E) were extracted as genetic instruments. Summary statistics of genetic instruments associated with knee OA, hip OA, and RA were obtained from corresponding genome-wide association studies (GWASs). The inverse-variance weighted (IVW) was applied as the primary analysis method, with four sensitivity analysis approaches employed to evaluate the robustness of the primary results. Results: Genetically determined per unit increment of absolute circulating levels of retinol was significantly associated with a reduced risk of hip OA [odds ratio (OR) = 0.45, 95% confidence interval (CI) 0.26-0.78, p = 4.43 × 10-3], while genetically determined per unit increase in absolute circulating levels of ß-carotene was suggestively associated with increased risk of RA (OR = 1.32, 95% CI 1.07-1.62, p = 9.10 × 10-3). No other causal association was found. Significant evidence for heterogeneity and pleiotropic outlier was only identified when absolute circulating vitamin C was evaluated as the exposure, whereas all sensitive analysis provided consistently non-significant results. Conclusion: Our results demonstrated that genetically determined lifelong higher exposure to absolute circulating levels of retinol is associated with a decreased risk of hip OA. Further MR study with more genetic instruments for absolute circulating levels of antioxidants are needed to confirm our results.

Polydopamine nanoparticle-mediated mild photothermal therapy for inhibiting atherosclerotic plaque progression by regulating lipid metabolism of foam cells.

Since apoptosis of foam, cells can induce plaque instability, reducing intracellular lipid content while protecting foam cells from apoptosis is beneficial for the safe and efficient therapy of atherosclerosis. In this study, osteopontin-coupled polydopamine (PDA-OPN) nanoparticles were synthesized and applied to target mild photothermal therapy (PTT) of atherosclerosis. The results from laser confocal microscopy indicate that PDA-OPN nanoparticles can be specially recognized and absorbed by foam cells. Under near-infrared laser irradiation, the mild photothermal generated by PDA-OPN decreases intracellular lipid accumulation but does not induce cell apoptosis. In vivo treatments demonstrate that mild PTT can substantially reduce plaque area and improve plaque stability by upregulating the expression of plaque fibrosis in ApoE-/- mice. Our findings reinforce that the PDA-OPN nanoparticle-mediated mild PTT can inhibit atherosclerotic progression, which provides new insights for developing safe and effective treatment methods for atherosclerosis.

Association of Circular RNAs levels in blood and Essential Hypertension with Carotid Plaque.

BACKGROUND: As one of the essential hypertension (EH)-mediated target organ damage, carotid plaque is a crucial subclinical precursor for cardiovascular events. Therefore, it is vital to identify the risk factors and pathogenesis for EH with carotid plaque. METHODS: Based on our previous microarray analysis, we selected four circRNAs as the candidate circRNAs and detected their expression levels in blood of 192 subjects (64 healthy controls, 64 EH patients, and 64 EH patients with carotid plaque) by qRT-PCR analysis. The regulatory mechanism of circRNAs involved in carotid plaque was predicted by bioinformatics analysis. RESULTS: The level of hsa_circ_0124782 increased significantly and the levels of hsa_circ_0131618 and hsa_circ_0127342 decreased significantly in the EH group and EH with carotid plaque group compared with the control group (P < .05). Functional enrichment analysis showed that three circRNAs might be implicated in pathogenesis for carotid plaque. CONCLUSION: Our study revealed the relationship between three circRNAs and carotid plaque, suggesting that they may serve as potential biomarkers for EH with carotid plaque.

Serum Leukocyte Cell-Derived Chemotaxin 2 (LECT2) Level Is Associated with Osteoporosis.

OBJECTIVE: The aim of this study was to examine serum leukocyte cell-derived chemotaxin 2 (LECT2) levels in osteoporosis subjects to confirm its association with osteoporosis. METHODS: A total of 204 adult subjects were recruited. Bone mineral densities (BMD) were assessed and blood samples were collected for measurements of biomedical parameters and the bone turnover markers. Serum LECT2 levels were measured by enzyme-linked immunosorbent assay. The relationships between serum LECT2 levels and other parameters were analyzed using the Spearman correlation coefficient. RESULTS: Serum LECT2 levels were significantly increased in osteoporosis subjects over controls. We found a significantly negative correlation of serum LECT2 with BMD, 25-hydroxy-vitamin D, and creatinine and a significantly positive correlation with C-terminal telopeptide of type 1 collagen and total cholesterol. CONCLUSION: Serum LECT2 levels were significantly upregulated in osteoporosis subjects and correlated with the severity of bone loss. Serum LECT2 could be a potential biomarker to assess the risk of bone loss.

Advances in imaging and treatment of atherosclerosis based on organic nanoparticles.

Atherosclerosis, a systemic chronic inflammatory disease, can lead to thrombosis and vascular occlusion, thereby inducing a series of serious vascular diseases. Currently, distinguishing unstable plaques early and achieving more effective treatment are the two main clinical concerns in atherosclerosis. Organic nanoparticles have great potential in atherosclerotic imaging and treatment, showing superior biocompatibility, drug-loading capacity, and synthesis. This article illustrates the process of atherosclerosis onset and the key targeted cells, then systematically summarizes recent progress made in organic nanoparticle-based imaging of different types of targeted cells and therapeutic methods for atherosclerosis, including optical and acoustic-induced therapy, drug delivery, gene therapy, and immunotherapy. Finally, we discuss the major impediments that need to be addressed in future clinical practice. We believe this article will help readers to develop a comprehensive and in-depth understanding of organic nanoparticle-based atherosclerotic imaging and treatment, thus advancing further development of anti-atherosclerosis therapies.

Characteristics of Soil Erodibility in the Yinna Mountainous Area, Eastern Guangdong Province, China.

Soil erodibility research is of theoretical and practical significance to the prediction and prevention of regional soil erosion. At present, the study on soil erodibility in the lateritic red soil area of eastern Guangdong province is relatively lacking. Taking the forest land soil of the Yinna mountainous area as the research object, the physical and chemical properties (organic matter mass fraction, texture, moisture, bulk density, pH, aggregate content) of soil samples at different altitudes were measured with field survey sampling and indoor analysis. Soil erodibility K values were simulated with different models (the EPIC model, the Torri model, and the Shirazi model) and the regional applicability of the K simulation models was discussed. The influence of soil properties on soil erodibility was analyzed. The results showed that: (1) K values in the Yinna mountainous area are between 0.0250 and 0.0331 t·hm2·h/MJ·mm·hm2, and the K value in the subsoil layer (20-40 cm) is higher than that of the topsoil layer (0-20 cm). These values decreased significantly with the increase of altitude. The soil in the study area belongs to low-medium to medium erodible soil types. (2) The three models have certain applicability in the Yinna mountainous area, but the simulation results still lack validation. (3) Soil particle size composition is the most important factor affecting the K value in the study area. As far as the topsoil is concerned, K values increase with the increase of clay and silt content and decrease with the increase of sand content and aggregate stability. Soil erodibility has no significant correlation with pH and bulk density and has no clear relationship with the content of soil organic carbon and soil moisture. The research results can provide basic data for regional soil and water conservation and the construction of K value databases of different soil types in China.

Fractional Flow Reserve or Intravascular Ultrasonography to Guide PCI.

BACKGROUND: In patients with coronary artery disease who are being evaluated for percutaneous coronary intervention (PCI), procedures can be guided by fractional flow reserve (FFR) or intravascular ultrasonography (IVUS) for decision making regarding revascularization and stent implantation. However, the differences in clinical outcomes when only one method is used for both purposes are unclear. METHODS: We randomly assigned 1682 patients who were being evaluated for PCI for the treatment of intermediate stenosis (40 to 70% occlusion by visual estimation on coronary angiography) in a 1:1 ratio to undergo either an FFR-guided or IVUS-guided procedure. FFR or IVUS was to be used to determine whether to perform PCI and to assess PCI success. In the FFR group, PCI was to be performed if the FFR was 0.80 or less. In the IVUS group, the criteria for PCI were a minimal lumen area measuring either 3 mm2 or less or measuring 3 to 4 mm2 with a plaque burden of more than 70%. The primary outcome was a composite of death, myocardial infarction, or revascularization at 24 months after randomization. We tested the noninferiority of the FFR group as compared with the IVUS group (noninferiority margin, 2.5 percentage points). RESULTS: The frequency of PCI was 44.4% among patients in the FFR group and 65.3% among those in the IVUS group. At 24 months, a primary-outcome event had occurred in 8.1% of the patients in the FFR group and in 8.5% of those in the IVUS group (absolute difference, -0.4 percentage points; upper boundary of the one-sided 97.5% confidence interval, 2.2 percentage points; P = 0.01 for noninferiority). Patient-reported outcomes as reported on the Seattle Angina Questionnaire were similar in the two groups. CONCLUSIONS: In patients with intermediate stenosis who were being evaluated for PCI, FFR guidance was noninferior to IVUS guidance with respect to the composite primary outcome of death, myocardial infarction, or revascularization at 24 months. (Funded by Boston Scientific; FLAVOUR ClinicalTrials.gov number, NCT02673424.).