Cu Single-Atom Nanozyme-Mediated Electrochemiluminescence Biosensor for Highly Sensitive Detection of MicroRNA-622.

MicroRNA (miRNA) detection is a critical aspect of disease diagnosis, and recent studies indicate that miRNA-622 could be a potential target for lung cancer. Herein, Cu single atoms were anchored on graphitic carbon nitride (Cu SAs@CN) as a coreaction accelerator applied in luminol-H2O2 system, thereby establishing an efficient and sensitive electrochemiluminescence (ECL) biosensor for miRNA-622 detection. Cu SAs@CN was explored to possess excellent enzyme-like activities that promote the generation of abundant reactive oxygen species, which amplified ECL emission. Meanwhile, in order to improve the accuracy and sensitivity for miRNA-622 detection, the highly specific trans-cleavage ability of CRISPR/Cas12a was combined with a catalytic hairpin assembly strategy. Therefore, an ECL biosensor for miRNA-622 detection was systematically constructed as a proof of concept, achieving an ultralow limit of detection of 1.09 fM, and the feasibility was demonstrated in human serum samples. The findings of this research provide a promising strategy to enhance the ECL response using versatile single-atom catalysts, thus advancing the development of ECL biosensing applications.

Effectiveness of patient decision aids in patients with advanced kidney disease: a meta-analysis based on randomized controlled trials.

PURPOSE: To systematically evaluate the decision effectiveness of patient decision aids (PtDAs) on the decision-making effect of patients with advanced chronic kidney disease. METHOD: Two authors independently searched ten electronic databases [Web of science, PubMed, the Cochrane Library, Embase, CINAHL, EBSCO, CBM, CNKI, WanFang DATA and Vip database], to include randomized controlled trials of interventions through PtDAs in patients with advanced chronic kidney disease published from the inception of the database until April 2024. Two authors conducted a comprehensive quality evaluation (Cochrane 5.1.0) before independently extracting and analyzing the data with RevMan 5.2. RESULTS: The study included 11 randomized controlled trials with a total of 1613 patients. According to the results, PtDAs can improve the decision knowledge [SMD = 0.53, 95% CI (0.26, 0.80), P = 0.0002] and decision preparation [SMD = 2.34, 95% CI (2.04, 2.65), P < 0.00001] of patients with advanced chronic kidney disease. Additionally, there was a substantial decrease in the levels of decision regret [SMD = - 1.33, 95% CI (- 2.11, - 0.55), P < 0.05] and decision conflict [SMD = - 0.88, 95% CI (- 1.47, - 0.28), P = 0.004]. CONCLUSION: The current available evidence indicates that PtDAs can significantly enhance the decision knowledge and decision preparation of patients with advanced chronic kidney disease. Additionally, PtDAs can reduce the levels of decision regret and decision conflict. TRIAL REGISTRY: CRD42023433798.

Risk Prediction Models for Sarcopenia in Dialysis Patients: A Systematic Review.

Nowadays, numerous studies have developed risk prediction models for sarcopenia in dialysis patients. However, the quality and performance of these models have not been integrated. The purpose of our study is to provide a comprehensive overview of the current risk prediction models for sarcopenia in dialysis patients and to offer a reference for the development of high-quality prediction models. Ten electronic databases were searched from inception to March 8, 2024. Two researchers independently assessed the risk of bias and applicability of the studies, and used Revman, 5.4, software to conduct a meta-analysis of common predictors in the models. A total of 12 studies described 13 risk prediction models for dialysis patients with sarcopenia. In dialysis patients, the prevalence of sarcopenia ranged from 6.60% to 63.73%. The area under curve (AUC) of the 13 models ranged from 0.776 to 0.945. Only six models (AUC ranging from 0.73 to 0.832) were internally validated, while two were externally evaluated (AUC ranging from 0.913 to 0.955). Most studies had a high risk of bias. The most common effective predictors in the models were age, body mass index, muscle circumference, and C-reactive protein. Our study suggests that developing a prediction model for the onset of sarcopenia in dialysis patients requires a rigorous design scheme, and future verification methods will necessitate multicenter external validation.

Aptamer responsive DNA Functionalized hydrogels electrochemiluminescence biosensor for the detection of adenosine triphosphate.

DNA hydrogel represents a noteworthy biomaterial. The preparation of biosensors by combining DNA hydrogel with electrochemiluminescence can simplify the modification process and raise the experimental efficiency. In this study, an electrochemiluminescence (ECL) biosensor based on DNA hydrogel was fabricated to detect adenosine triphosphate (ATP) simply and quickly. CdTe-Ru@SiO2 nanospheres capable of ECL resonance energy transfer (RET) were synthesized and encapsulated CdTe-Ru@SiO2 in the DNA hydrogel to provide strong and stable ECL signals. DNA hydrogel avoided the labeling of ECL signal molecules. The aptamer of ATP as the linker of the hydrogel for the specificity of ATP detection. The cross-linked structure of the aptamer and the polymer chains was opened by ATP, and then the decomposition of the DNA hydrogel initiated the escape of CdTe-Ru@SiO2 to generate an ECL signal. The designed biosensor detected ATP without too much modification and complex experimental steps on the electrode surface, with good specificity and stability, and a wide linear range. The detection range was 10-5000 nM, and the detection limit was 6.68 nM (S/N = 3). The combination of DNA hydrogel and ECL biosensor provided a new way for clinical detection of ATP and other biomolecule.

Preventing of nonunion in congenital pseudarthrosis of the tibia cases of Crawford Type I and II through the use of allograft bypass and a brace: Midterm findings.

Background: Congenital pseudarthrosis of the tibia is a limb deformity, which can be distressing for the affected patients and the pediatric orthopedic surgeons involved. We hypothesized that the modified McFarland procedure would avoid fractures and even have a corrective effect on the affected tibia in congenital pseudarthrosis of the tibia patients. Toward this end, we evaluated the midterm results of treating congenital pseudarthrosis of the tibia patients of Crawford Type I and II with allograft bypass combined with long-term bracing. Methods: This study retrospectively evaluated 7 patients with congenital pseudarthrosis of the tibia who were treated with allograft bypass combined with long-term bracing between 2009 and 2018. The median follow-up was 7.0 years (range 3.8-10.0 years). The medical records and radiographs were reviewed for demographic data, clinical characteristics, outcomes, and complications. Results: At the time of the last follow-up, all allografts revealed complete consolidation in the patients' tibiae at both ends. All patients presented no functional restriction of the lower limbs and no amputation or non-union has occurred. Most of the obvious deformities of the tibia diaphysis or ankle joint were corrected. Two complications occurred that required successful revision surgery. Conclusion: In this series of seven congenital pseudarthrosis of the tibia patients, the allograft bypass technique showed satisfactory midterm results and validated our hypothesis. For congenital pseudarthrosis of the tibia patients of Crawford Type I and II, this procedure combined with long-term bracing, which involves the affected leg only, can delay or possibly prevent fractures, decrease tibial malalignment, and preserve leg length. Level of evidence: level IV.

Research on the electromyography-based pattern recognition for inter-limb coordination in human crawling motion.

Aiming to provide a feasible crawling motion analysis method for clinical application, this study introduced electromyography (EMG)-based motion intention recognition technology into the pattern recognition of inter-limb coordination during human crawling for the first time. Eight inter-limb coordination modes (ILCMs) were defined. Ten adult participants were recruited, and each participant performed hands-knees crawling at low, medium, and fast speeds in self-selected ILCMs and the eight predefined ILCMs, respectively. EMG signals for pattern recognition were collected from 30 limbs and trunk muscles, and pressure signals for crawling cycle segmentation were collected from the left palm. The pattern recognition experiments were conducted in participant-specific, multi-participant, and participant-independent ways, respectively, adopting three different classifiers, including bidirectional long short-term memory (BiLSTM) network, support vector machine (SVM), and k-nearest neighbor (KNN). The experimental results show that EMG-based pattern recognition schemes could classify the eight ILCMs with high recognition rates, thereby confirming the feasibility of providing an EMG-based crawling motion analysis method for clinical doctors. Furthermore, based on the classification results of self-selected ILCMs at different speeds and the statistical results of stance duration, swing duration, and the duty factors of stance phase, the possible reasons why humans chose various ILCMs at different crawling speeds were discussed. The research results have potential application value for evaluating crawling function, understanding abnormal crawling control mechanisms, and designing rehabilitation robots.

Synovial sarcoma: the misdiagnosed sarcoma.

Synovial sarcoma is a rare and highly malignant soft tissue sarcoma. The inconspicuous and diversity of its early symptoms make it a highly misdiagnosed disease. The management of synovial sarcomas is challenging as they are rare and have a poor prognosis. Early and correct diagnosis and treatment are critical for clinical outcomes. Misdiagnosis or delayed diagnosis can have devastating consequences for the patient. The detection of SS18 gene rearrangement is considered a powerful tool in establishing the diagnosis of synovial sarcomas. Biopsies and testing for gene rearrangements are recommended for all patients in whom SS cannot be excluded. Surgery is the mainstay of treatment for synovial sarcomas. Neoadjuvant/adjuvant radiotherapy is recommended for patients with big tumors (>5 cm) or positive resection margins, and neoadjuvant/adjuvant chemotherapy is recommended for patients with high-risk tumors or advanced diseases. This article reviews synovial sarcomas from the perspectives of clinical and radiological presentation, histological and cytogenetic analysis, differential diagnosis, treatment, and prognosis.

Neurological prognosis in surgically treated acute aortic dissection with brain computed tomography perfusion.

OBJECTIVES: The aim of this study was to explore the prognostic value of brain computed tomography perfusion (CTP) for postoperative new stroke in acute type A aortic dissection (ATAAD) patients. METHODS: Patients with ATAAD and suspected cerebral malperfusion who underwent brain CTP and surgical repair were retrospectively analysed. Brain perfusion was quantified mainly with the averaged cerebral blood flow. Significant clinical and imaging findings were identified through univariable and multivariable regression analysis. Furthermore, the added prognostic benefit of perfusion parameters was confirmed with the receiver operating characteristic curves in the entire cohort and subgroup analysis. RESULTS: The incidence of postoperative new stroke was 30.8% (44/143). The independent adjusted predictors of postoperative new stroke included an impaired averaged cerebral blood flow (ml/100 ml/min) (odds ratio: 0.889; P < 0.001), severe stenosis (odds ratio: 5.218; P = 0.011) or occlusion (odds ratio: 14.697; P = 0.048) of the true lumen in common carotid artery (CCA), hypotension on admission (odds ratio: 9.644; P = 0.016) and a longer surgery time (odds ratio: 1.593; P = 0.021). The area under the receiver operating characteristic curves significantly improved after adding perfusion parameters to clinical and computed tomography angiography characteristics (P = 0.048). This benefit was more pronounced in patients with severe stenosis or occlusion in CCA true lumen (P = 0.004). CONCLUSIONS: Brain CTP could be a useful prognostic tool for surgically treated ATAAD patients and especially beneficial in patients with severe stenosis or occlusion of the CCA true lumen.

Comparative genomic analyses reveal the genetic basis of the yellow-seed trait in Brassica napus.

Yellow-seed trait is a desirable breeding characteristic of rapeseed (Brassica napus) that could greatly improve seed oil yield and quality. However, the underlying mechanisms controlling this phenotype in B. napus plants are difficult to discern because of their complexity. Here, we assemble high-quality genomes of yellow-seeded (GH06) and black-seeded (ZY821). Combining in-depth fine mapping of a quantitative trait locus (QTL) for seed color with other omics data reveal BnA09MYB47a, encoding an R2R3-MYB-type transcription factor, as the causal gene of a major QTL controlling the yellow-seed trait. Functional studies show that sequence variation of BnA09MYB47a underlies the functional divergence between the yellow- and black-seeded B. napus. The black-seed allele BnA09MYB47aZY821, but not the yellow-seed allele BnA09MYB47aGH06, promotes flavonoid biosynthesis by directly activating the expression of BnTT18. Our discovery suggests a possible approach to breeding B. napus for improved commercial value and facilitates flavonoid biosynthesis studies in Brassica crops.

Epitope-Directed Antibody Elicitation by Genetically Encoded Chemical Cross-Linking Reactivity in the Antigen.

No current methods can selectively elicit an antibody response to a specific conformational epitope in a whole antigen in vivo. Here, we incorporated Nε-acryloyl-l-lysine (AcrK) or Nε-crotonyl-l-lysine (Kcr) with cross-linking activities into the specific epitopes of antigens and immunized mice to generate antibodies that can covalently cross-link with the antigens. By taking advantage of antibody clonal selection and evolution in vivo, an orthogonal antibody-antigen cross-linking reaction can be generated. With this mechanism, we developed a new approach for facile elicitation of antibodies binding to specific epitopes of the antigen in vivo. Antibody responses were directed and enriched to the target epitopes on protein antigens or peptide-KLH conjugates after mouse immunization with the AcrK or Kcr-incorporated immunogens. The effect is so prominent that the majority of selected hits bind to the target epitope. Furthermore, the epitope-specific antibodies effectively block IL-1ß from activating its receptor, indicating its potential for the development of protein subunit vaccines.

A novel biodegradable polymer-coated sirolimus-eluting stent: 1-year results of the HELIOS registry.

BACKGROUND: The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer. The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting. METHODS: The HELIOS registry is a prospective, multicenter, cohort study conducted at 38 centers across China between November 2018 and December 2019. A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, non-fatal target vessel myocardial infarction (MI), and clinically indicated target lesion revascularization (TLR) at 1-year follow-up. Kaplan-Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves. RESULTS: A total of 2998 (98.0%) patients completed the 1-year follow-up. The 1-year incidence of TLF was 3.10% (94/2998, 95% closed interval: 2.54-3.78%). The rates of cardiac death, non-fatal target vessel MI and clinically indicated TLR were 2.33% (70/2998), 0.20% (6/2998), and 0.70% (21/2998), respectively. The rate of stent thrombosis was 0.33% (10/2998). Age ≥60 years, diabetes mellitus, family history of coronary artery disease, acute myocardial infarction at admission, and device success were independent predictors of TLF at 1 year. CONCLUSION: The 1-year incidence rates of TLF and stent thrombosis were 3.10% and 0.33%, respectively, in patients treated with HELIOS stents. Our results provide clinical evidence for interventional cardiologists and policymakers to evaluate HELIOS stent. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03916432.

Muscle synergy analysis of eight inter-limb coordination modes during human hands-knees crawling movement.

In order to reveal in-depth the neuromuscular control mechanism of human crawling, this study carries out muscle synergy extraction and analysis on human hands-knees crawling under eight specific inter-limb coordination modes, which are defined according to the swing sequence of limbs and includes two-limb swing crawling modes and six single-limb swing crawling modes. Ten healthy adults participate in crawling data collection, and surface electromyography (sEMG) signals are recorded from 30 muscles of limbs and trunk. Non-negative matrix factorization (NNMF) algorithm is adopted for muscle synergy extraction, and a three-step muscle synergy analysis scheme is implemented by using the hierarchical clustering method. Based on results of muscle synergy extraction, 4 to 7 synergies are extracted from each participant in each inter-limb coordination mode, which supports the muscle synergy hypothesis to some extent, namely, central nervous system (CNS) controls the inter-limb coordination modes during crawling movement by recruiting a certain amount of muscle synergies, rather than a single muscle. In addition, when different participants crawl in the same inter-limb coordination mode, they share more temporal features in recruiting muscle synergies. Further, by extracting and analyzing intra-mode shared synergies among participants and inter-mode shared synergies among the eight inter-limb coordination modes, the CNS is found to realize single-limb swing crawling modes by recruiting the four inter-mode shared synergy structures related to the swing function of each limb in different orders, and realize the two-limb swing crawling modes by recruiting synchronously two intra-mode shared synergy structures. The research results of the muscle synergy analysis on the eight specific inter-limb coordination modes, on the one hand, provide a basis for muscle synergy hypothesis from the perspective of crawling motion, on the other hand, also provide a possible explanation for the choice of the inter-limb coordination mode in human crawling.

Risk prediction of preoperative acute ischemic stroke in acute type A aortic dissection.

OBJECTIVES: To predict preoperative acute ischemic stroke (AIS) in acute type A aortic dissection (ATAAD). METHODS: In this multi-center retrospective study, 508 consecutive patients diagnosed as ATAAD between April 2020 and March 2021 were considered for inclusion. The patients were divided into a development cohort and two validation cohorts based on time periods and centers. Clinical data and imaging findings obtained were analyzed. Univariable and multivariable logistic regression analyses were performed to identify predictors associated with preoperative AIS. The performance of resulting nomogram was evaluated in discrimination and calibration on all cohorts. RESULTS: A total of 224 patients were in the development cohort, 94 in the temporal validation cohort, and 118 in the geographical validation cohort. Six predictors were identified: age, syncope, D-dimer, moderate to severe aortic valve insufficiency, diameter ratio of true lumen in ascending aorta < 0.33, and common carotid artery dissection. The nomogram established showed good discrimination (area under the receiver operating characteristic curve [AUC], 0.803; 95% CI: 0.742, 0.864) and calibration (Hosmer-Lemeshow test p = 0.300) in the development cohort. External validation showed good discrimination and calibration abilities in both temporal (AUC, 0.778; 95% CI: 0.671, 0.885; Hosmer-Lemeshow test p = 0.161) and geographical cohort (AUC, 0.806; 95% CI: 0.717, 0.895; Hosmer-Lemeshow test p = 0.100). CONCLUSIONS: A nomogram, based on simple imaging and clinical variables collected on admission, showed good discrimination and calibration abilities in predicting preoperative AIS for ATAAD patients. KEY POINTS: • A nomogram based on simple imaging and clinical findings may predict preoperative acute ischemic stroke in patients with acute type A aortic dissection in emergencies. • The nomogram showed good discrimination and calibration abilities in validation cohorts.

Improvement of Symptoms and Quality of Life After Successful Percutaneous Coronary Intervention for Chronic Total Occlusion in Elderly Patients.

Background Data regarding the impact of successful chronic total occlusion treated with percutaneous coronary intervention (CTO-PCI) on symptoms and quality of life (QOL) in elderly patients (≥75 years) are unknown. This prospective study aimed to assess whether successful CTO-PCI could improve the symptoms and QOL in elderly patients (≥75 years). Methods and Results Consecutive patients who underwent elective CTO-PCI were prospectively enrolled and subdivided into 3 groups based on age: age<65 years, 65 years≤age<75 years, and age≥75 years. The primary outcomes included symptoms, as assessed with the New York Heart Association functional class and Seattle Angina Questionnaire, and QOL, as assessed with the 12-Item Short-Form Health Survey questionnaire, at baseline, 1 month, and 1 year after successful CTO-PCI. Of 1076 patients with CTO, 101 were age≥75 years (9.39%). Hemoglobin, estimated glomerular filtration rate, and left ventricular ejection fraction levels all decreased with increasing age, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) increased. The proportion of dyspnea and coronary lesions, including multivessel disease, multi-CTO lesion, and calcification were higher in elderly patients. Procedural success rate, intraprocedural complications, and in-hospital major adverse cardiac events were not statistically different in the 3 groups. Importantly, symptoms, including dyspnea and angina, were markedly improved regardless of age at 1-month and 1-year follow-up (P<0.05). Likewise, successful CTO-PCI significantly improved QOL at 1-month and 1-year follow-up (P<0.01). Additionally, the incidence of major adverse cardiac events and all-cause mortality at 1-month and 1-year follow-up was not statistically different in the 3 groups. Conclusions Successful PCI was beneficial and feasible to improve symptoms and QOL in patients ≥75 years of age with CTO.

Single-nucleus sequencing deciphers developmental trajectories in rice pistils.

Angiosperms possess a life cycle with an alternation of sporophyte and gametophyte generations, which happens in plant organs like pistils. Rice pistils contain ovules and receive pollen for successful fertilization to produce grains. The cellular expression profile in rice pistils is largely unknown. Here, we show a cell census of rice pistils before fertilization through the use of droplet-based single-nucleus RNA sequencing. The ab initio marker identification validated by in situ hybridization assists with cell-type annotation, revealing cell heterogeneity between ovule- and carpel-originated cells. A comparison of 1N (gametophyte) and 2N (sporophyte) nuclei identifies the developmental path of germ cells in ovules with typical resetting of pluripotency before the sporophyte-gametophyte transition, while trajectory analysis of carpel-originated cells suggests previously neglected features of epidermis specification and style function. These findings gain a systems-level view of cellular differentiation and development of rice pistils before flowering and lay a foundation for understanding female reproductive development in plants.

Elevated branched-chain amino acid promotes atherosclerosis progression by enhancing mitochondrial-to-nuclear H2O2-disulfide HMGB1 in macrophages.

As the essential amino acids, branched-chain amino acid (BCAA) from diets is indispensable for health. BCAA supplementation is often recommended for patients with consumptive diseases or healthy people who exercise regularly. Latest studies and ours reported that elevated BCAA level was positively correlated with metabolic syndrome, diabetes, thrombosis and heart failure. However, the adverse effect of BCAA in atherosclerosis (AS) and its underlying mechanism remain unknown. Here, we found elevated plasma BCAA level was an independent risk factor for CHD patients by a human cohort study. By employing the HCD-fed ApoE-/- mice of AS model, ingestion of BCAA significantly increased plaque volume, instability and inflammation in AS. Elevated BCAA due to high dietary BCAA intake or BCAA catabolic defects promoted AS progression. Furthermore, BCAA catabolic defects were found in the monocytes of patients with CHD and abdominal macrophages in AS mice. Improvement of BCAA catabolism in macrophages alleviated AS burden in mice. The protein screening assay revealed HMGB1 as a potential molecular target of BCAA in activating proinflammatory macrophages. Excessive BCAA induced the formation and secretion of disulfide HMGB1 as well as subsequent inflammatory cascade of macrophages in a mitochondrial-nuclear H2O2 dependent manner. Scavenging nuclear H2O2 by overexpression of nucleus-targeting catalase (nCAT) effectively inhibited BCAA-induced inflammation in macrophages. All of the results above illustrate that elevated BCAA promotes AS progression by inducing redox-regulated HMGB1 translocation and further proinflammatory macrophage activation. Our findings provide novel insights into the role of animo acids as the daily dietary nutrients in AS development, and also suggest that restricting excessive dietary BCAA consuming and promoting BCAA catabolism may serve as promising strategies to alleviate and prevent AS and its subsequent CHD.

The effects of qigong intervention based on the Internet on quality of life and physical fitness in Chinese postoperative breast cancer patients: a protocol of randomized controlled trial.

BACKGROUND: The purpose of this study is to verify the improvement of remote qigong intervention on the quality of life and physical fitness of breast cancer patients after surgery by means of a randomized controlled trial and to compare it with the conventional exercise combination of aerobic exercise and resistance training. METHODS/DESIGN: The research approach applied in this study is a randomized controlled trial. After completing the baseline questionnaire and physical fitness test, participants were randomly assigned to either the qigong group or the combined exercise rehabilitation group. Patients in the qigong group performed Qigong-Baduanjin twice a week for 30 min each time under remote guidance and practiced Baduanjin by themselves at other times. Patients in the combined exercise rehabilitation group were given resistance training twice a week for 30 min under remote guidance, and walking the rest of the time. At the end of the 12-week intervention, outcomes testing and data collection were carried out. The primary outcomes are quality of life, measured using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and the Functional Assessment of Cancer Therapy-Breast (FATC-B). The secondary outcomes include cardiopulmonary endurance, upper limb strength, lower limb strength, and skinfold thickness. DISCUSSION: The importance of postoperative exercise rehabilitation for breast cancer has been gradually accepted by more and more doctors and patients, but further research and development of simple and practical means of exercise rehabilitation are necessary. Remote qigong intervention for breast cancer patients via the Internet will be a great alternative. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027989. Registered on December 7, 2019.

Computing intracoronary blood flow rate under incomplete boundary conditions: Combing coronary anatomy and fractional flow reserve.

BACKGROUND: Accurate measurement of intracoronary blood flow rate is of great significance for the diagnosis of ischemic heart disease (IHD). Computational fluid dynamic (CFD) method, combining coronary angiography images and fractional flow reserve (FFR), provides a new way to calculate the mean flow rate. However, due to the incomplete boundary conditions obtained by FFR, side branches were ignored which was likely to have a significant impact on the accuracy. In this paper, a novel CFD based method for calculating the mean intracoronary flow rate under incomplete pressure boundary conditions was proposed, in order to improve the accuracy by including the side branches. METHODS: A pressure-flow curve based flow resistance model was employed to model resistance of the epicardial arteries. A series of steady flow simulations were performed to extract the parameters of the flow resistance model, which implicitly specified constraints for splitting flow between branches and thus enabled the mean intracoronary blood flow rate to be calculated in two or more branches under incomplete pressure boundary conditions. Simulation experiments were designed to validate the proposed method in both idealized and reconstructed 3D models of coronary branches, and the impact of the assumed coefficient of the Murray's Law for splitting flow between branches was also investigated. RESULTS: The mean percentage error of the proposed method was +2.05%±0.04% for idealized models and +2.24%±0.01% for reconstructed models, and it was much lower than that of the method ignoring side branches (+38.48%±10.45% for idealized models and +30.54%±6.12% for reconstructed models). When the assumed coefficient of the Murray's Law was inconsistent with the real blood flow condition, the percentage errors still maintained less than about 3.00%. CONCLUSIONS: The proposed method provided an easy and accurate way to measure the mean intracoronary flow rate and would facilitate the accurate diagnosis of IHD.

Adipose mesenchymal stem cells-derived exosomes alleviate osteoarthritis by transporting microRNA -376c-3p and targeting the WNT-beta-catenin signaling axis.

Osteoarthritis (OA), one of the major diseases afflicting the elderly, is a type of degenerative joint disease related to cartilage and synovium. This study aimed to clarify the role and mechanism of adipose mesenchymal stem cell (ADSC)-derived exosomes (Exos) in OA-induced chondrocyte degradation and synovial hyperplasia, thus improving the quality of life of patients. The rat OA model, chondrocytes, synovial fibroblast models and immunofluorescence were applied to observe the in vivo and in vitro functions of human ADSC (hADSC)-derived Exos in OA and its possible regulatory signaling pathways. Bioinformatics software and luciferase reporter assay were carried out to verify the mechanism of microRNA-376c-3p (miR-376c-3p) in hADSC-derived Exos in OA in vitro. Moreover, Safranine O-Fast Green Cartilage staining, Masson staining, immunohistochemistry and immunofluorescence were conducted to verify the role of miR-376c-3p in hADSC-derived Exos in OA in vivo. hADSC-derived Exos mitigated OA-induced chondrocyte degradation and synovial fibrosis both in vivo and in vitro models by repressing the WNT-beta-catenin signaling pathway. For the mechanism exploration in vitro, miR-376c-3p was raised in hADSC-derived Exos and mediated the fibrosis of synovial fibroblasts in OA, and miR-376c-3p targeted the 3'-untranslated region of WNT3 or WNT9a. Meanwhile, the in vivo experiments also corroborated that the miR-376c-3p in hADSC-derived Exos mitigated OA-induced chondrocyte degradation and synovial fibrosis. MiR-376c-3p in hADSC-derived Exos repressed the WNT-beta-catenin pathway by targeting WNT3 or WNT9a, and then mitigating OA-induced chondrocyte degradation and synovial fibrosis, thereby providing theoretical basis for clinical implementation of treatment.