κ-Opioid receptor activation attenuates osteoarthritis synovitis by regulating macrophage polarization through the NF-κB pathway.

Osteoarthritis (OA) is a prevalent and chronic joint disease that affects the aging population, causing pain and disability. Macrophages in synovium are important mediators of synovial inflammatory activity and pathological joint pain. Previous studies have demonstrated the significant involvement of κ-opioid receptor (KOR) in the regulation of pain and inflammation. Our study reveals a significant reduction in synovial KOR expression among patients and mice with OA. Here, we find that KOR activation effectively inhibits the expressions of the LPS-induced-inflammatory cytokines TNF-α and IL-6 by inhibiting macrophage M1 phenotype. Mechanistically, KOR activation effectively suppresses the proinflammatory factor secretion of macrophages by inhibiting the translocation of NF-κB into the nucleus. Our animal experiments reveal that activation of KOR effectively alleviates knee pain and prevents synovitis progression in OA mice. Consistently, KOR administration suppresses the expressions of M1 macrophage markers and the NF-κB pathway in the synovium of the knee. Collectively, our study suggests that targeting KOR may be a viable strategy for treating OA by inhibiting synovitis and improving joint pain in affected patients.

Plaque burden estimated from optical coherence tomography with deep learning: In vivo validation using co-registered intravascular ultrasound.

OBJECTIVES: The objective of the present study was to compare plaque burden (PB) calculated from optical coherence tomography (OCT) using deep learning (DL) with PB derived from co-registered intravascular ultrasound (IVUS). BACKGROUND: A DL algorithm was developed for automated plaque characterization and PB quantification from OCT images. However, the performance of this algorithm for PB quantification has not been validated. METHODS: Five-year follow-up OCT and IVUS images from 15 patients implanted with bioresorbable vascular scaffold (BVS) at baseline were analyzed. Precise co-registration for 72 anatomical slices was achieved utilizing unique BVS radiopaque markers. PB derived from OCT DL and IVUS were compared. OCT cross-sections were divided into four subgroups with different media visibility level. The impact of media visibility on the numerical difference between OCT-derived and IVUS-derived PB was investigated. The stent sizes selected by OCT DL and IVUS were compared. RESULTS: Sixty-four paired OCT and IVUS cross-sections were compared. OCT DL showed good concordance with IVUS for PB assessment (ICC = 0.81, difference = -3.53 ± 6.17%, p < 0.001). The numerical difference between OCT DL-derived PB and IVUS-derived PB was not substantially impacted by missing segments of media visualization (p = 0.21). OCT DL showed a diagnostic accuracy of 92% in identifying PB > 65%. The stent sizes selected by OCT DL were smaller compared to the ones selected by IVUS (difference = 0.30 ± 0.34 mm, p < 0.001). CONCLUSIONS: The DL algorithm provides a feasible and reliable method for automated PB estimation from OCT, irrespective of media visibility. OCT DL showed good diagnostic accuracy in identifying PB > 65%, revealing its potential to complement conventional OCT imaging.

Local Flow Patterns After Implantation of Bioresorbable Vascular Scaffold in Coronary Bifurcations　- Novel Findings by Computational Fluid Dynamics.

BACKGROUND: Development of methods for accurate reconstruction of bioresorbable scaffolds (BRS) and assessing local hemodynamics is crucial for investigation of vascular healing after BRS implantation.Methods and Results:Patients with BRS that crossed over in a coronary bifurcation were included for analysis. Reconstructions of the coronary lumen and BRS were performed by fusion of optical coherence tomography and coronary angiography generating a tree model (TM) and a hybrid model with BRS (TM-BRS). A virtual BRS model with thinner struts was created and all 3 models were analyzed using computational fluid dynamics to derive: (1) time-average shear stress (TASS), (2) TASS gradient (TASSG), which represents SS heterogeneity, and (3) fractional flow reserve (FFR). Reconstruction of the BRS was successful in all 10 patients. TASS and TASSG were both higher by TM-BRS than by TM in main vessels (difference 0.27±4.30 Pa and 10.18±27.28 Pa/mm, P<0.001), with a remarkable difference at side branch ostia (difference 13.51±17.40 Pa and 81.65±105.19 Pa/mm, P<0.001). With thinner struts, TASS was lower on the strut surface but higher at the inter-strut zones, whereas TASSG was lower in both regions (P<0.001 for all). Computational FFR was lower by TM-BRS than by TM for both main vessels and side branches (P<0.001). CONCLUSIONS: Neglecting BRS reconstruction leads to significantly lower SS and SS heterogeneity, which is most pronounced at side branch ostia. Thinner struts can marginally reduce SS heterogeneity.

What do osteoporosis and osteoarthritis have in common? An integrated study of overlapping differentially expressed genes in bone mesenchymal stem cells of osteoporosis and osteoarthritis.

OBJECTIVE: For identification of aberrantly expressed genes in mesenchymal stem cells of osteoporosis (OP) and osteoarthritis (OA), Gene Expression Omnibus (GEO) datasets were integrated to investigate the intersection point. METHODS: GSE35958 (osteoporosis) and GSE19664 (osteoarthritis) datasets were obtained from GEO database. The abnormally expressed genes were analyzed by GEO2R. Functional enrichment was explored by Metascape database and R software. The String database and Cytoscape software were used to build the protein-protein interaction network and identify hub genes. GSE35957 and GSE116925 were used as verification datasets. Single-cell analysis and pseudotime analysis were undertaken. CTDbase, Network Analyst, HPA database, HERB database and MIRW database were used to research the information, tissue and cell distribution, regulation, interaction and ingredients targeting the hub genes. Additionally, in vitro experiments such as RT-PCR, ALP staining and immunofluorescence were undertaken as verification tests. RESULTS: Ten hub genes were identified in this study. All these genes play an important role in bone or cartilage generation. They have diagnostic values and therapeutic potential for OA and OP. Single-cell analysis visualized the cell distribution and pseudotime distribution of these genes. Some potential therapeutic ingredients of these genes were identified, such as curcumin, wogonin and glycerin. In vitro experiments, RT-PCR results showed that COL9A3 and MMP3 were downregulated and PTH1R was upregulated during osteogenic induction of BMSC. Immunohistochemical results showed the expression trend of MMP3 and COL2A1. CONCLUSION: Ten abnormal hub genes of osteoporosis and osteoarthritis were identified successfully by this study. They were important regulatory genes for healthy bone and cartilage. These genes could be the common connections between osteoporosis and osteoarthritis as well as treatment targets. Further study of the regulatory mechanism and treatment effects of these genes would be valuable. The results of this study could contribute to further research.

Heme oxygenase 1 linked to inactivation of subchondral osteoclasts in osteoarthritis. / è¡€çº¢ç´ åŠ æ°§é ¶1ä¸Žéª¨å ³èŠ‚ç‚Žè½¯éª¨ä¸‹ç ´éª¨ç»†èƒžå¤±æ´»çš„ç›¸å ³ç ”ç©¶.

Osteoarthritis (OA) is a chronic progressive osteoarthropathy in the elderly. Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA. However, the specific mechanism of osteoclast differentiation in OA remains unclear. In our study, gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus (GEO) repository. GEO2R and Funrich analysis tools were employed to find differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses demonstrated that chemical carcinogenesis, reactive oxygen species (ROS), and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone. Furthermore, fourteen DEGs that are associated with oxidative stress were identified. The first ranked differential gene, heme oxygenase 1 (HMOX1), was selected for further validation. Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of HMOX1. Carnosol was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in vitro. Meanwhile, carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo. Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA. Targeting HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.

TRPA1 aggravates osteoclastogenesis and osteoporosis through activating endoplasmic reticulum stress mediated by SRXN1.

Osteoporosis (OP) is a disorder of bone remodeling caused by an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Therefore, inhibiting excessive osteoclast activity is one of the promising strategies for treating OP. A major transient receptor potential cation channel, known as transient receptor potential ankyrin 1 (TRPA1), was found to alleviate joint pain and cartilage degeneration in osteoarthritis. However, little research has focused on TRPA1 function in OP. As a result, this study aimed to explore the TRPA1 characteristics and its potential therapeutic function during osteoclastogenesis. The TRPA1 expression gradually increased in the osteoclast differentiation process; however, its suppression with small interfering RNA and an inhibitor (HC030031) significantly controlled the osteoclast count and the expression of osteoclast characteristic genes. Its suppression also inhibited endoplasmic reticulum (ER) stress-related pancreatic ER kinase (PERK) pathways. An ER stress inhibitor (thapsigargin) reversed the down-regulated levels of ER stress and osteoclast differentiation by suppressing TRPA1. Transcriptome sequencing results demonstrated that TRPA1 negatively regulated reactive oxygen species (ROS) and significantly increased the expression of an antioxidant gene, SRXN1. The osteoclast differentiation and the levels of ER stress were enhanced with SRXN1 inhibition. Finally, TRPA1 knockdown targeting macrophages by adeno-associated virus-9 could relieve osteoclast differentiation and osteopenia in ovariectomized mice. In summary, silencing TRPA1 restrained osteoclast differentiation through ROS-mediated down-regulation of ER stress via inhibiting PERK pathways. The study also indicated that TRPA1 might become a prospective treatment target for OP.

Byakangelicol suppresses TiPs-stimulated osteoclastogenesis and bone destruction via COX-2/NF-κB signaling pathway.

Aseptic loosening (AL) is considered a significant cause of prosthesis revision after arthroplasty and a crucial factor in the longevity of an artificial joint prosthesis. The development of AL is primarily attributed to a series of biological reactions, such as peri-prosthetic osteolysis (PPO) induced by wear particles around the prosthesis. Chronic inflammation of the peri-prosthetic border tissue and hyperactivation of osteoclasts are key factors in this process, which are induced by metallic wear particles like Ti particles (TiPs). In our in vitro study, we observed that TiPs significantly enhanced the expression of inflammation-related genes, including COX-2, IL-1ß and IL-6. Through screening a traditional Chinese medicine database, we identified byakangelicol, a traditional Chinese medicine molecule that targets COX-2. Our results demonstrated that byakangelicol effectively inhibited TiPs-stimulated osteoclast activation. Mechanistically, we found that byakangelicol suppressed the expression of COX-2 and related pro-inflammatory factors by modulating macrophage polarization status and NF-κB signaling pathway. The in vivo results also demonstrated that byakangelicol effectively inhibited the expression of inflammation-related factors, thereby significantly alleviating TiPs-induced cranial osteolysis. These findings suggested that byakangelicol could potentially be a promising therapeutic approach for preventing PPO.

ADAM8 silencing suppresses the migration and invasion of fibroblast-like synoviocytes via FSCN1/MAPK cascade in osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a degenerative joint disease that affects elderly populations worldwide, causing pain and disability. Alteration of the fibroblast-like synoviocytes (FLSs) phenotype leads to an imbalance in the synovial inflammatory microenvironment, which accelerates the progression of OA. Despite this knowledge, the specific molecular mechanisms of the synovium that affect OA are still unclear. METHODS: Both in vitro and in vivo experiments were undertaken to explore the role of ADAM8 playing in the synovial inflammatory of OA. A small interfering RNA (siRNA) was targeting ADAM8 to intervene. High-throughput sequencing was also used. RESULTS: Our sequencing analysis revealed significant upregulation of the MAPK signaling cascade and ADAM8 gene expression in IL-1ß-induced FLSs. The in vitro results demonstrated that ADAM8 blockade inhibited the invasion and migration of IL-1ß-induced FLSs, while also suppressing the expression of related matrix metallomatrix proteinases (MMPs). Furthermore, our study revealed that inhibiting ADAM8 weakened the inflammatory protein secretion and MAPK signaling networks in FLSs. Mechanically, it revealed that inhibiting ADAM8 had a significant effect on the expression of migration-related signaling proteins, specifically FSCN1. When siADAM8 was combined with BDP-13176, a FSCN1 inhibitor, the migration and invasion of FLSs was further inhibited. These results suggest that FSCN1 is a crucial downstream factor of ADAM8 in regulating the biological phenotypes of FLSs. The in vivo experiments demonstrated that ADAM8 inhibition effectively reduced synoviocytes inflammation and alleviated the progression of OA in rats. CONCLUSIONS: ADAM8 could be a promising therapeutic target for treating OA by targeting synovial inflammation.

Treatment and Care of Patients with ST-Segment Elevation Myocardial Infarction-What Challenges Remain after Three Decades of Primary Percutaneous Coronary Intervention?

Primary percutaneous coronary intervention (pPCI) has revolutionized the prognosis of ST-segment elevation myocardial infarction (STEMI) and is the gold standard treatment. As a result of its success, the number of pPCI centres has expanded worldwide. Despite decades of advancements, clinical outcomes in STEMI patients have plateaued. Out-of-hospital cardiac arrest and cardiogenic shock remain a major cause of high in-hospital mortality, whilst the growing burden of heart failure in long-term STEMI survivors presents a growing problem. Many elements aiming to optimize STEMI treatment are still subject to debate or lack sufficient evidence. This review provides an overview of the most contentious current issues in pPCI in STEMI patients, with an emphasis on unresolved questions and persistent challenges.

DCCAT: Dual-Coordinate Cross-Attention Transformer for thrombus segmentation on coronary OCT.

Acute coronary syndromes (ACS) are one of the leading causes of mortality worldwide, with atherosclerotic plaque rupture and subsequent thrombus formation as the main underlying substrate. Thrombus burden evaluation is important for tailoring treatment therapy and predicting prognosis. Coronary optical coherence tomography (OCT) enables in-vivo visualization of thrombus that cannot otherwise be achieved by other image modalities. However, automatic quantification of thrombus on OCT has not been implemented. The main challenges are due to the variation in location, size and irregularities of thrombus in addition to the small data set. In this paper, we propose a novel dual-coordinate cross-attention transformer network, termed DCCAT, to overcome the above challenges and achieve the first automatic segmentation of thrombus on OCT. Imaging features from both Cartesian and polar coordinates are encoded and fused based on long-range correspondence via multi-head cross-attention mechanism. The dual-coordinate cross-attention block is hierarchically stacked amid convolutional layers at multiple levels, allowing comprehensive feature enhancement. The model was developed based on 5,649 OCT frames from 339 patients and tested using independent external OCT data from 548 frames of 52 patients. DCCAT achieved Dice similarity score (DSC) of 0.706 in segmenting thrombus, which is significantly higher than the CNN-based (0.656) and Transformer-based (0.584) models. We prove that the additional input of polar image not only leverages discriminative features from another coordinate but also improves model robustness for geometrical transformation.Experiment results show that DCCAT achieves competitive performance with only 10% of the total data, highlighting its data efficiency. The proposed dual-coordinate cross-attention design can be easily integrated into other developed Transformer models to boost performance.

Development and validation of a novel angiography-derived index of absolute coronary blood flow and resistance.

Intracoronary continuous thermodilution has been recently proposed as an invasive method to quantify absolute coronary flow (Qabs) and resistance (Rabs) in vivo. The aim of the present study is to develop and validate of a novel pressure-wire- and microcatheter-free surrogate of coronary flow and resistance derived from a standard coronary angiogram. Angiography derived coronary flow (Qangio) and resistance (Rangio) was prospectively validated in a two-center cohort of patients from Oxford Heart Centre and the Essex Cardiothoracic Centre. Qabs and Rabs were measured during resting and hyperemic conditions with continuous thermodilution using the Rayflow microcatheter. Qangio and Rangio were computed from the diagnostic coronary angiogram in a blinded fashion in resting and hyperemic conditions. A total of 62 patients and 115 vessels were included in the present analysis. The median Qabs at rest was 75 ml/min (53-95) and 151 ml/min (105-203) during hyperemia; Qangio at rest was 84 ml/min (66-108) and 154 ml/min (115-195) during hyperemia. There was a strong correlation between Qabs and Qangio (R = 0,72; p < 0.001, R = 0,86; p < 0.001 respectively) with satisfactory interclass correlation (0.841, 95% CI 0.509-0.957; p = 0.0003). The median Rabs was 1111 mmHg/(L/min) (830-1581.4) at rest and 454 mmHg/(L/min) (348-610) during hyperemia; angiographic resistance (Rangio) was 937.4 mmHg/(L/min) (695.4-1261.9) at rest and 492.4 mmHg/(L/min) (406-697) during hyperemia. There was a strong correlation between Rabs and Rangio in both conditions (R = 0,81; p < 0.001 and R = 0,78; p < 0.001 respectively). The was a good correlation between absolute coronary flow reserve (CFR) and angiography-derived CFR (R = 0,61; p < 0.001) and between absolute microvascular resistance reserve (MRR) and angiography-derived MRR (R = 0,49; p < 0.001).

Value of Combined Optical Coherence Tomography and Optical Flow Ratio Measurements After Percutaneous Coronary Intervention.

BACKGROUND: Optical flow ratio (OFR) is a novel computational fractional flow reserve derived from optical coherence tomography (OCT). However, the impact of combining post-stenting morphology (OCT) and physiology (OFR) remains largely unknown. METHODS: OCT and OFR were analysed at an independent core laboratory. Target lesion failure (TLF) was defined as the composite of cardiac death, target lesion myocardial infarction, and target lesion revascularisation. Suboptimal stent deployment was identified with at least 1 TLF-related OCT or OFR characteristic. RESULTS: A total of 448 patients with acute coronary syndrome (459 vessels) were assessed. Stent expansion < 80%, minimal stent area < 4.5 mm2, and stent edge lipid-rich plaque and OFR < 0.90 were independent predictors of TLF (all P < 0.001). Patients with OCT-suboptimal (adjusted hazard ratio [aHR] 7.88, 95% CI 2.73-22.72,-P < 0.001) or OFR-suboptimal (aHR 5.78, 95% CI 2.54-13.14; P < 0.001) stent deployment showed significantly higher risk of TLF compared with those with optimal stent deployment, with a significant interaction (Pinteraction < 0.001). OCT and OFR both-suboptimal stent deployment was confirmed as an independent predictor of TLF (aHR 9.39, 95% CI 4.25-20.76; P < 0.001). CONCLUSIONS: Combined OCT and OFR conferred an optimal reclassification of stent deployment, which may aid in decision making regarding a tailored PCI strategy for optimal stent deployment.

[Efficacy and safety of multiple-dose intravenous tranexamic acid for reducing blood loss in complex tibial plateau fractures: A prospective randomized controlled trial].

Objective: To investigate the efficacy and safety of multiple-dose intravenous tranexamic acid (TXA) for reducing blood loss in complex tibial plateau fractures with open reduction internal fixation by a prospective randomized controlled trial. Methods: A study was conducted on patients with Schatzker type Ⅳ-Ⅵ tibial plateau fractures admitted between August 2020 and December 2022. Among them, 88 patients met the selection criteria and were included in the study. They were randomly allocated into 3 groups, the control group (28 cases), single-dose TXA group (31 cases), and multiple-dose TXA group (29 cases), using a random number table method. There was no significant difference ( P>0.05) in terms of age, gender, body mass index, the Schatzker type and side of fracture, laboratory examinations [hemoglobin (Hb), activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (Fib), international normalized ratio (INR), D-dimer, and interleukin 6 (IL-6)], and preoperative blood volume. The control group received intravenous infusion of 100 mL saline at 15 minutes before operation and 3, 6, and 24 hours after the first administration. The single-dose TXA group received intravenous infusion of 1 g TXA (dissolved in 100 mL saline) at 15 minutes before operation, followed by an equal amount of saline at each time point after the first administration. The multiple-dose TXA group received intravenous infusion of 1 g TXA (dissolved in 100 mL saline) at each time point. The relevant indicators were recorded and compared between groups to evaluate the effectiveness and safety of TXA, including hospital stays, operation time, occurrence of infection; the occurrence of lower extremity deep vein thrombosis, intermuscular vein thrombosis, and pulmonary embolism at 1 week after operation; the lowest postoperative Hb value and Hb reduction rate, the difference (change value) between pre- and post-operative APTT, PT, Fib, and INR; D-dimer and IL-6 at 24 and 72 hours after operation; total blood loss, intraoperative blood loss, hidden blood loss, drainage flow during 48 hours after operation, and postoperative blood transfusion. Results: ① TXA efficacy evaluation: the lowest Hb value in the control group was significantly lower than that in the other two groups ( P<0.05), and there was no significant difference between the single- and multiple-dose TXA groups ( P>0.05). The Hb reduction rate, total blood loss, intraoperative blood loss, drainage flow during 48 hours after operation, and hidden blood loss showed a gradual decrease trend in the control group, single-dose TXA group, and multiple-dose TXA group. And differences were significant ( P<0.05) in the Hb reduction rate and drainage flow during 48 hours after operation between groups, and the total blood loss and hidden blood loss between control group and other two groups. ② TXA safety evaluation: no lower extremity deep vein thrombosis or pulmonary embolism occurred in the three groups after operation, but 3, 4, and 2 cases of intermuscular vein thrombosis occurred in the control group, single-dose TXA group, and multiple-dose TXA group, respectively, and the differences in the incidences between groups were not significant ( P>0.05). There was no significant difference in the operation time between groups ( P>0.05). But the length of hospital stay was significantly longer in the control group than in the other groups ( P<0.05); there was no significant difference between the single- and multiple-dose TXA groups ( P>0.05). ③ Effect of TXA on blood coagulation and inflammatory response: the incisions of the 3 groups healed by first intention, and no infections occurred. The differences in the changes of APTT, PT, Fib, and INR between groups were not significant ( P>0.05). The D-dimer and IL-6 in the three groups showed a trend of first increasing and then decreasing over time, and there was a significant difference between different time points in the three groups ( P<0.05). At 24 and 72 hours after operation, there was no significant difference in D-dimer between groups ( P>0.05), while there was a significant difference in IL-6 between groups ( P<0.05). Conclusion: Multiple intravenous applications of TXA can reduce perioperative blood loss and shorten hospital stays in patients undergoing open reduction and internal fixation of complex tibial plateau fractures, provide additional fibrinolysis control and ameliorate postoperative inflammatory response.

Angiography-based coronary flow reserve: The feasibility of automatic computation by artificial intelligence.

BACKGROUND: Coronary flow reserve (CFR) has prognostic value in patients with coronary artery disease. However, its measurement is complex, and automatic methods for CFR computation are scarcely available. We developed an automatic method for CFR computation based on coronary angiography and assessed its feasibility. METHODS: Coronary angiographies from the Corelab database were annotated by experienced analysts. A convolutional neural network (CNN) model was trained for automatic segmentation of the main coronary arteries during contrast injection. The segmentation performance was evaluated using 5-fold cross-validation. Subsequently, the CNN model was implemented into a prototype software package for automatic computation of the CFR (CFRauto) and applied on a different sample of patients with angiographies performed both at rest and during maximal hyperemia, to assess the feasibility of CFRauto and its agreement with the manual computational method based on frame count (CFRmanual). RESULTS: Altogether, 137,126 images of 5913 angiographic runs from 2407 patients were used to develop and evaluate the CNN model. Good segmentation performance was observed. CFRauto was successfully computed in 136 out of 149 vessels (91.3%). The average analysis time to derive CFRauto was 18.1 ± 10.3 s per vessel. Moderate correlation (r = 0.51, p < 0.001) was observed between CFRauto and CFRmanual, with a mean difference of 0.12 ± 0.53. CONCLUSIONS: Automatic computation of the CFR based on coronary angiography is feasible. This method might facilitate wider adoption of coronary physiology in the catheterization laboratory to assess microcirculatory function.

Reciprocal assistance of intravascular imaging in three-dimensional stent reconstruction: Using cross-modal translation based on disentanglement representation.

BACKGROUND: Accurate and efficient 3-dimension (3D) reconstruction of coronary stents in intravascular imaging of optical coherence tomography (OCT) or intravascular ultrasound (IVUS) is important for optimization of complex percutaneous coronary interventions (PCI). Deep learning has been used to address this technical challenge. However, manual annotation of stent is strenuous, especially for IVUS images. To this end, we aim to explore whether the OCT and IVUS images can assist each other in stent 3D reconstruction when one of them is lack of labeled dataset. METHODS: We firstly performed cross-modal translation between OCT and IVUS images, where disentangled representation was employed to generate synthetic images with good stent consistency. The reciprocal assistance of OCT and IVUS in stent 3D reconstruction was then conducted by applying unsupervised and semi-supervised learning with the aid of synthetic images. Stent consistency in synthetic images and reciprocal effectiveness in stent 3D reconstruction were quantitatively assessed by F1-Score (FS) on two datasets: OCT-High Definition IVUS (HD IVUS) and OCT-Conventional IVUS (IVUS). RESULTS: The employment of disentangled representation achieved higher stent consistency in synthetic images (OCT to HD IVUS: FS=0.789 vs 0.684; HD IVUS to OCT: FS=0.766 vs 0.682; OCT to IVUS: FS=0.806 vs 0.664; IVUS to OCT: FS=0.724 vs 0.673). For stent 3D reconstruction, the assistance from synthetic images significantly promoted unsupervised adaptation across modalities (OCT to HD IVUS: FS=0.776 vs 0.109; HD IVUS to OCT: FS=0.826 vs 0.125; OCT to IVUS: FS=0.782 vs 0.068; IVUS to OCT: FS=0.815 vs 0.123), and improved performance in semi-supervised learning, especially when only limited labeled data was available. CONCLUSION: The intravascular images of OCT and IVUS can provide reciprocal assistance to each other in stent 3D reconstruction by cross-modal translation, where the stent consistency in synthetic images was maintained by disentangled representation.

Advances in Diagnosis, Therapy, and Prognosis of Coronary Artery Disease Powered by Deep Learning Algorithms.

Percutaneous coronary intervention has been a standard treatment strategy for patients with coronary artery disease with continuous ebullient progress in technology and techniques. The application of artificial intelligence and deep learning in particular is currently boosting the development of interventional solutions, improving the efficiency and objectivity of diagnosis and treatment. The ever-growing amount of data and computing power together with cutting-edge algorithms pave the way for the integration of deep learning into clinical practice, which has revolutionized the interventional workflow in imaging processing, interpretation, and navigation. This review discusses the development of deep learning algorithms and their corresponding evaluation metrics together with their clinical applications. Advanced deep learning algorithms create new opportunities for precise diagnosis and tailored treatment with a high degree of automation, reduced radiation, and enhanced risk stratification. Generalization, interpretability, and regulatory issues are remaining challenges that need to be addressed through joint efforts from multidisciplinary community.

The Emerging Role of the Mitochondrial Respiratory Chain in Skeletal Aging.

Maintenance of mitochondrial homeostasis is crucial for ensuring healthy mitochondria and normal cellular function. This process is primarily responsible for regulating processes that include mitochondrial OXPHOS, which generates ATP, as well as mitochondrial oxidative stress, apoptosis, calcium homeostasis, and mitophagy. Bone mesenchymal stem cells express factors that aid in bone formation and vascular growth. Positive regulation of hematopoietic stem cells in the bone marrow affects the differentiation of osteoclasts. Furthermore, the metabolic regulation of cells that play fundamental roles in various regions of the bone, as well as interactions within the bone microenvironment, actively participates in regulating bone integrity and aging. The maintenance of cellular homeostasis is dependent on the regulation of intracellular organelles, thus understanding the impact of mitochondrial functional changes on overall bone metabolism is crucially important. Recent studies have revealed that mitochondrial homeostasis can lead to morphological and functional abnormalities in senescent cells, particularly in the context of bone diseases. Mitochondrial dysfunction in skeletal diseases results in abnormal metabolism of bone-associated cells and a secondary dysregulated microenvironment within bone tissue. This imbalance in the oxidative system and immune disruption in the bone microenvironment ultimately leads to bone dysplasia. In this review, we examine the latest developments in mitochondrial respiratory chain regulation and its impacts on maintenance of bone health. Specifically, we explored whether enhancing mitochondrial function can reduce the occurrence of bone cell deterioration and improve bone metabolism. These findings offer prospects for developing bone remodeling biology strategies to treat age-related degenerative diseases.

Comprehensive appraisal of cardiac motion artefact in optical coherence tomography.

BACKGROUND: The relation between cardiac motion artefact (CMA) in optical coherence tomography (OCT) and the phases of cardiac cycle is unclear. METHODS: Optical coherence tomography pullbacks containing metallic stents were co-registered with angiography and retrospectively analyzed. The beginning of three phases, namely ejection, rapid-inflow and diastasis, was identified in angiography. Rotation, shortening, elongation and repetition were qualitatively labelled as CMA artefacts. Platforms with coaxial longitudinal connectors (ML8 and Magmaris) entered a quantitative sub-study, consisting of measuring the length of their connector at the beginning of each phase. RESULTS: A total of 261 stents (127 patients) were analyzed, including 105 stents for quantitative sub-study. CMA was detected in 61 (23.4%) stents: rotation in 6 (2.3%), shortening in 50 (19.2%), elongation in 51 (19.5%) and repetition in 12 (4.6%). Shortening was always observed during ejection phase, while elongation and repetition were always observed during rapid-inflow. Rotation occurred in both ejection and rapid-inflow phases, while no artefact was reported during diastasis. Longitudinal connectors measured in early ejection phase and in early rapid-inflow phase were shorter and longer, respectively, than those measured in diastasis, irrespective of the presence of CMA in the qualitative assessment. CONCLUSIONS: Cardiac motion artefact is prevalent in OCT studies, but shortening and elongation of vascular structures occur during early ejection and during early rapid-inflow, respectively, to a greater or lesser extent in all cases. Diastasis is free of CMA and hence the period in which longitudinal measurements can be more accurately quantified.

CB2 regulates oxidative stress and osteoclastogenesis through NOX1-dependent signaling pathway in titanium particle-induced osteolysis.

Periprosthetic osteolysis (PPO) induced by wear particles at the interface between the prosthesis and bone is a crucial issue of periprosthetic bone loss and implant failure. After wear and tear, granular material accumulates around the joint prosthesis, causing a chronic inflammatory response, progressive osteoclast activation and eventual loosening of the prosthesis. Although many studies have been conducted to address bone loss after joint replacement surgeries, they have not fully addressed these issues. Focusing on osteoclast activation induced by particles has important theoretical implications. Cannabinoid type II receptor (CB2) is a seven-transmembrane receptor that is predominantly distributed in the human immune system and has been revealed to be highly expressed in bone-associated cells. Previous studies have shown that modulation of CB2 has a positive effect on bone metabolism. However, the exact mechanism has not yet been elucidated. In our experiments, we found that NOX1-mediated ROS accumulation was involved in titanium particle-stimulated osteoclast differentiation. Furthermore, we confirmed that CB2 blockade alleviated titanium particle-stimulated osteoclast activation by inhibiting the NOX1-mediated oxidative stress pathway. In animal experiments, downregulation of CB2 alleviated the occurrence of titanium particle-induced cranial osteolysis by inhibiting osteoclasts and scavenging intracellular ROS. Collectively, our results suggest that CB2 blockade may be an attractive and promising therapeutic scheme for particle-stimulated osteoclast differentiation and preventing PPO.

Quantitative flow ratio as a continuous predictor of myocardial infarction.

BACKGROUND: The quantitative flow ratio (QFR) identifies functionally ischaemic lesions that may benefit more from percutaneous coronary intervention (PCI) than from medical therapy. AIMS: This study investigated the association between QFR and myocardial infarction (MI) as affected by PCI versus medical therapy. METHODS: All vessels requiring measurement (reference diameter ≥2.5 mm and existence of at least one stenotic lesion with diameter stenosis of 50-90%) in the FAVOR III China (5,564 vessels) and PANDA-III trials (4,471 vessels) were screened and analysed for offline QFR. The present study reported clinical outcomes on a per-vessel level. Interaction between vessel treatment and QFR as a continuous variable was evaluated for the threshold of 2-year MI estimated by Cox proportional hazards model. RESULTS: Compared with medical therapy at 2 years, PCI reduced the MI risk in vessels with a QFR ≤0.80 (3.0% vs 4.6%) but increased the MI risk in vessels with a QFR>0.80 (3.6% vs 1.2%). Additionally, continuous QFR showed an inverse association with spontaneous MI (hazard ratio [HR] 0.89, 95% confidence interval [CI]: 0.79-0.99; p=0.04) that was reduced by PCI compared to medical therapy (HR 0.26, 95% CI: 0.17-0.40; p<0.0001). The interaction indicated a net benefit for PCI over medical therapy to reduce total MI beginning at QFR ≤0.64. CONCLUSIONS: The present study demonstrated a continuous, inverse relationship between the QFR value of a vessel and its subsequent risk for MI, and PCI, compared to medical therapy, reduced this risk beginning at a QFR value of 0.64. These novel findings provide physicians with an angiographic tool for optimising vessel selection for PCI.