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In relieving local pains, lidocaine, one of ester-type local anesthetics, has been used. To develop the lidocaine membranes of enhanced local anesthetic effects, we have designed to establish the composition of wound dressings based on lidocaine chloride (LCH) (anesthetic drug)-loaded chitosan (CS)/polymyxin B sulfate (PMB). The LCH membranes (LCH-CS/PMB) was fabricated by the LCH oxide solutions within the CS/PMB matrix. The influences of different experimental limitations on CS/PMB membrane formations were examined. The double membrane particle sizes were evaluated by scanning electron microscopy (HR-SEM). Additionally, antibacterial efficacy was developed for gram-positive and negative microorganisms. Moreover, we examined healing of skin wounds formed in mouse models over 16 days. In contrast to the untreated wounds, rapid healing was perceived in the LCH-CS/PMB-treated wound with less damaging. These findings indicate that LCH-CS/PMB-based bandaging materials could be a potential innovative biomaterial for tissue repair and regeneration for wound healing applications in an animal model.

Insomnia (ISM) is one of the non-traditional drivers of atherosclerosis (AS) and an important risk factor for AS-related cardiovascular disease. Our study aimed to explore the shared pathways and diagnostic biomarkers of ISM-related AS using integrated bioinformatics analysis. We download the datasets from the Gene Expression Omnibus database and the GeneCards database. Weighted gene co-expression network analysis and gene differential expression analysis were applied to screen the AS-related gene set. The shared genes of ISM and AS were obtained by intersecting with ISM-related genes. Subsequently, candidate diagnostic biomarkers were identified by constructing protein-protein interaction networks and machine learning algorithms, and a nomogram was constructed. Moreover, to explore potential mechanisms, a comprehensive analysis of shared genes was carried out, including enrichment analysis, protein interactions, immune cell infiltration, and single-cell sequencing analysis. We successfully screened 61 genes shared by ISM and AS, of which 3 genes ( , , and ) were identified as diagnostic biomarkers. A nomogram with excellent predictive value was constructed (the area under curve of the model constructed by the biomarkers was 0.931, and the validation set was 0.745). In addition, the shared genes were mainly enriched in immune and inflammatory response regulation pathways. The biomarkers were associated with a variety of immune cells, especially myeloid immune cells. We constructed a diagnostic nomogram based on , , and and explored the inflammatory-immune mechanisms, which indicated new insights for early diagnosis and treatment of ISM-related AS.

A single injection of low-dose human umbilical cord-derived mesenchymal stem cells (UC-MSCs) has been previously demonstrated to relieve synovitis and bone erosion in animal models of arthritis, but whether frequent injections of high-dose UC-MSCs relieve arthritis and inhibit loss of muscle mass has remained elusive. In the present study, DBA/1 mice were randomly divided into three groups: Normal (wild-type mice; n=11), collagen-induced arthritis (CIA; n=12) and CIA treated with UC-MSCs (n=11; 5x106 UC-MSCs per week for 3 weeks). Arthritis and skeletal muscle cachexia were evaluated until the end of the experiment on day 84. It was indicated that both the CIA and UC-MSC groups had lower body weights compared with the normal mice. Clinical arthritis scores, hind ankle diameters, synovitis and bone erosion progressively increased and were similar between the CIA and UC-MSC groups. Although there was no difference in food intake among the three groups, the normalized food intake of normal group was significantly higher than CIA group and UC-MSC group from day 42 onwards; there was no significance on day 77 but this could be neglected. Furthermore, gastrocnemius muscle weight in the UC-MSC group was significantly reduced compared with that in the CIA and normal groups. The UC-MSC group had higher levels of proinflammatory cytokines, such as TNF-α, IL-6 and IL-1β than those in the CIA group. However, the other cytokines assessed and the fibrosis indices in the CIA and UC-MSC groups were not different from those in the control group and there was no inflammatory cell infiltration. Thus, frequent injections of high-dose UC-MSCs slightly aggravated synovitis and muscle cachexia in the murine CIA model and should therefore be avoided in the treatment of arthritis.

Myocardial ischemia remains one of the principal causes of mortality and morbidity worldwide, necessitating novel approaches to facilitate early diagnosis and subsequent risk evaluation following reperfusion. Although advancements in wearables capable of ECG (electrocardiogram) monitoring have been initiated, these devices have encountered barriers due to limited capacities to encapsulate the temporally complex nature of ischemic events, notably in risk stratifying reperfusion injury. In this paper, we describe a framework that leverages bionic, wearable ECG sensor technologies along with multimodal large language models using a coherent temporal modeling effort to address the intertwining of fine-grained temporal dependencies, heterogeneous biomedical modalities, and interpretable risk stratification. Our temporally hierarchical fusion transformer utilizes a cross-granularity attention mechanism to model intrabeat, interbeat, and long-term dependencies all simultaneously. The validation of our system was carried out using 4 datasets across n = 108,778 patients, 17,173 of whom were ischemia-positive cases (4,627 from PTB-XL, 5,243 from MIMIC-IV, 6,891 from CODE-15%, and 412 in the wearable cohort). The area under receiver operating characteristic curve (AUROC) for the model for ischemia was 0.947, and the C-index for post-reperfusion risk stratification was 0.923, with a relative AUROC improvement of 4.8% to 9.5% over the best baseline in each dataset. Importantly, we achieved an average lead time of 18.4 min prior to the ischemic event to allow the clinician to enact interventions. Ultimately, this research demonstrates a prototype of an intelligent cardiovascular care monitoring system that couples advanced sensing with clinical decision support.

In the myocardial infarction microenvironment, the effect of macrophages on the function of bone marrow mesenchymal stem cells (BMSCs) is unclear. In this study, we investigated the role of hypoxia/serum deprivation (H/SD)-induced M1-type macrophage-derived exosomes on BMSC viability, migration, and apoptosis. We found that H/SD reduced BMSC viability and migration, increased BMSC apoptosis, and induced macrophage polarization toward the M1 phenotype. BMSCs were cultured by the supernatant of H/SD-induced THP-1 cells (M1-type macrophages) with or without exosome inhibitor treatment. The results show that BMSC apoptosis is increased in the H/SD-induced THP-1 cell supernatant group and is decreased by GM4869 treatment, indicating that M1-type macrophages induce BMSC apoptosis through exosomes. In addition, we confirm that miR-222 plays an important role in promoting BMSC apoptosis by targeting B-cell lymphoma (Bcl)-2. M1-type macrophage-derived exosomes significantly decrease BMSC viability and migration and increase BMSC apoptosis, and these effects are partly abolished by a miR-222 inhibitor. Our findings suggest that under H/SD conditions, exosomes derived from M1-type macrophages can induce BMSC apoptosis by delivering miR-222 to BMSCs. Under conditions of hypoxia and serum deprivation, M1 macrophages secrete exosomes and transfer miR-222 to bone marrow mesenchymal stem cells (BMSC), which inhibits the expression of the antiapoptotic gene Bcl-2. This results in BMSC apoptosis and inhibition of mesenchymal stem cell proliferation and migration, which may affect the efficacy of BMSC in the treatment of acute myocardial infarction.

In the myocardial infarction microenvironment, the effect of macrophages on the function of bone marrow mesenchymal stem cells (BMSCs) is unclear. In this study, we investigated the role of hypoxia/serum deprivation (H/SD)-induced M1-type macrophage-derived exosomes on BMSC viability, migration, and apoptosis. We found that H/SD reduced BMSC viability and migration, increased BMSC apoptosis, and induced macrophage polarization toward the M1 phenotype. BMSCs were cultured by the supernatant of H/SD-induced THP-1 cells (M1-type macrophages) with or without exosome inhibitor treatment. The results show that BMSC apoptosis is increased in the H/SD-induced THP-1 cell supernatant group and is decreased by GM4869 treatment, indicating that M1-type macrophages induce BMSC apoptosis through exosomes. In addition, we confirm that miR-222 plays an important role in promoting BMSC apoptosis by targeting B-cell lymphoma (Bcl)-2. M1-type macrophage-derived exosomes significantly decrease BMSC viability and migration and increase BMSC apoptosis, and these effects are partly abolished by a miR-222 inhibitor. Our findings suggest that under H/SD conditions, exosomes derived from M1-type macrophages can induce BMSC apoptosis by delivering miR-222 to BMSCs. Under conditions of hypoxia and serum deprivation, M1 macrophages secrete exosomes and transfer miR-222 to bone marrow mesenchymal stem cells (BMSC), which inhibits the expression of the antiapoptotic gene Bcl-2. This results in BMSC apoptosis and inhibition of mesenchymal stem cell proliferation and migration, which may affect the efficacy of BMSC in the treatment of acute myocardial infarction.

A lack of standardization in heart team implementation potentially leads to suboptimal decision-making quality, and we previously established a modified heart team protocol to improve the decision-making quality. The present trial was to validate the effect of the modified heart team implementation protocol on improving the decision-making quality versus the conventional protocol in complex coronary artery disease (CAD). Eligible interventional cardiologists, cardiac surgeons and non-interventional cardiologists were randomly allocated to the intervention or control arm and established 12 heart teams in each arm. The 12 heart teams in each arm were randomly divided into 6 pairs, and 480 historic cases with complex CAD into 6 sets of 80 cases. In each arm, each set of 80 cases was discussed independently by one pair of heart teams, with each case finally receiving two heart team decisions ('pairwise decisions'). The intervention arm conducted heart team decision-making according to the previously established protocol and the control arm based on guideline recommendations. The primary outcome was the overall percent agreement of the inter-team pairwise decisions. Decision-making appropriateness was further analysed. A total of 36 cardiac surgeons, 36 interventional cardiologists and 12 non-interventional cardiologists from 26 centres were enrolled. The overall percent agreement was significantly higher in the intervention arm than the control arm (72.1% vs 65.8%, P = 0.04; kappa 0.51 vs 0.37). Both team-level (19.4% vs 33.0%; P < 0.001) and specialist-level (interventional cardiologists, 19.8% vs 37.7%, P < 0.001; cardiac surgeons, 19.8% vs 28.7%, P < 0.001) inappropriateness rate of decision-making was significantly lower in the intervention arm than the control arm. The modified heart team implementation protocol improved the decision-making quality and appropriateness compared with the guideline-based protocol.

Introduction: We sought to determine the effects of brief exposures to low concentrations of tobacco secondhand smoke (SHS) on arterial flow-mediated dilation (FMD, a nitric oxide-dependent measure of vascular endothelial function), in a controlled animal model never before exposed to smoke. In humans, SHS exposure for 30min impairs FMD. It is important to gain a better understanding of the acute effects of exposure to SHS at low concentrations and for brief periods of time. Methods: We measured changes in FMD in rats exposed to a range of real-world levels of SHS for durations of 30min, 10min, 1min, and 4 breaths (roughly 15 s). Results: We observed a dose-response relationship between SHS particle concentration over 30min and post-exposure impairment of FMD, which was linear through the range typically encountered in smoky restaurants and then saturated at higher concentrations. One min of exposure to SHS at moderate concentrations was sufficient to impair FMD. Conclusions: Brief SHS exposure at real-world levels reversibly impairs FMD. Even 1min of SHS exposure can cause reduction of endothelial function.