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Background Extramammary Paget disease (EMPD) is a rare malignant dermatosis with poorly defined outcomes. We investigated clinical characteristics of invasive EMPD at different anatomic sites and by subject demographics to determine prognostic factors for overall survival (OS). Methods All patient data were collected from the Surveillance, Epidemiology, and End Results (SEER) program, 1973–2013, of the U.S. National Cancer Institute. Patients with invasive EMPD of skin, vulva/labia, vagina, scrotum/penis, or other sites were included. After excluding patients with unknown radiation status, data of 2001 patients were analyzed. Primary endpoint was EMPD mortality by anatomic sites. Independent variables included patients’ demographic data, concurrent malignancy (ie, non-EMPD related cancers), tumor size, distant metastasis, and surgery and/or radiation or not. Results Multivariate regression analysis showed that mortality was significantly higher in patients with vaginal EMPD than in patients with vulvar/labial EMPD (adjusted hazard ratio [aHR] = 3.26, p  < 0.001). Patients with distant metastasis had higher mortality than those without (aHR = 3.36, p  < 0.001). Patients who received surgery had significantly lower mortality than those who did not receive surgery (aHR = 0.77, p  = 0.030), and those treated with radiation had significantly higher mortality than those who did not receive radiation (aHR = 1.60, p  = 0.002). Older age was associated with significantly increased mortality (aHR = 1.09, p  < 0.001), and mortality was significantly higher in males than in females (aHR = 1.42, p  = 0.008). Conclusions In conclusion, among EMPD patients, mortality is higher in patients with vaginal EMPD than in those with vulvar/labial EMPD and higher in those who are older, those with concurrent malignancy or distant metastasis. Mortality is also higher in males than in females. Surgery is a protective factor and radiation is a risk factor for OS. Greater understanding of EMPD clinical characteristics, and considering EMPD in differential diagnosis of chronic genital and perianal dermatoses may provide support for early EMPD diagnosis and definitive surgical treatment.

The importance of BET protein BRD4 in gene transcription is well recognized through the study of chemical modulation of its characteristic tandem bromodomain (BrD) binding to lysine-acetylated histones and transcription factors. However, while monovalent inhibition of BRD4 by BET BrD inhibitors such as JQ1 blocks growth of hematopoietic cancers, it is much less effective generally in solid tumors. Here, we report a thienodiazepine-based bivalent BrD inhibitor, MS645, that affords spatially constrained tandem BrD inhibition and consequently sustained repression of BRD4 transcriptional activity in blocking proliferation of solid-tumor cells including a panel of triple-negative breast cancer (TNBC) cells. MS645 blocks BRD4 binding to transcription enhancer/mediator proteins MED1 and YY1 with potency superior to monovalent BET inhibitors, resulting in down-regulation of proinflammatory cytokines and genes for cell-cycle control and DNA damage repair that are largely unaffected by monovalent BrD inhibition. Our study suggests a therapeutic strategy to maximally control BRD4 activity for rapid growth of solid-tumor TNBC cells.

Optical detection equipment (ODE) is subjected to vibrations that hamper the quality of imaging. In this paper, an active vibration isolation and compensation system (VICS) for the ODE is developed and systematically studied to improve the optical imaging quality. An active vibration isolator for cameras is designed, employing a dual-loop control strategy with position compensation and integral force feedback (IFF) control, and establishing the mapping relationship between vibration and image quality. A performance metric for evaluating images is also proposed. Finally, an experimental platform is constructed to verify its effectiveness. Based on the experimental results, it can be concluded that the proposed VICS effectively isolates vibrations, resulting in a reduction of 13.95 dB in the peak at the natural frequency and an 11.76 Hz widening of the isolation bandwidth compared with the system without it. At the same time, the experiments demonstrate that the image performance metric value increases by 46.03% near the natural frequency.

Bioengineering of small-diameter blood vessels offers a promising approach to reduce the morbidity associated with coronary artery and peripheral vascular disease. The aim of this study was to construct a two-layered small-diameter blood vessel using smooth muscle cells (SMCs) and endothelial cells (ECs) differentiated from human adipose-derived stem cells (hASCs). The outer layer was constructed with biodegradable polycaprolactone (PCL)-gelatin mesh seeded with SMCs, and this complex was then rolled around a silicone tube under pulsatile stimulation. After incubation for 6 to 8 weeks, the PCL-gelatin degraded and the luminal supporting silicone tube was removed. The smooth muscle layer was subsequently lined with ECs differentiated from hASCs after stimulation with VEGF and BMP4 in combination hypoxia. The phenotype of differentiated SMCs and ECs, and the cytotoxicity of the scaffold and biomechanical assessment were analyzed. Our results demonstrated that the two-layered bioengineered vessels exhibited biomechanical properties similar to normal human saphenous veins (HSV). Therefore, hASCs provide SMCs and ECs for bioengineering of small-diameter blood vessels.

Background: Treatment of diabetic wounds is a major challenge in clinical practice. Extracellular vesicles (EVs) from adipose-derived stem cells have shown effectiveness in diabetic wound models. However, obtaining ADSC-EVs requires culturing vast numbers of cells, which is hampered by the need for expensive equipment and reagents, extended time cost, and complicated procedures before commercialization. Therefore, methods to extract EVs from discarded tissue need to be developed, for immediate application during surgery. For this reason, mechanical, collagenase-digestive, and constant in-vitro -collective methods were designed and compared for preparing therapy-grade EVs directly from adipose tissue. Methods: Characteristics and quantities of EVs were detected by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting firstly. To investigate the biological effects of EVs on diabetic wound healing, angiogenesis, proliferation, migration, and inflammation-regulation assays were then evaluated in vitro , along with a diabetic wound healing mouse model in vivo . To further explore the potential therapeutic mechanism of EVs, miRNA expression profile of EVs were also identified and analyzed. Results: The adipose tissue derived EVs (AT-EVs) were showed to qualify ISEV identification by nanoparticle tracking analysis and Western blotting and the AT-EVs yield from three methods was equal. EVs also showed promoting effects on biological processes related to diabetic wound healing, which depend on fibroblasts, keratinocytes, endothelial cells, and macrophages both in vitro and in vivo . We also observed enrichment of overlapping or unique miRNAs originate from different types of AT-EVs associated with diabetic wound healing for further investigation. Conclusion: After comparative analyses, a mechanical method was proposed for preparing immediate clinical applicable EVs from adipose tissue that would result in reduced preparation time and lower cost, which could have promising application potential in treating diabetic wounds.

Persistence of γ-H2AX after ionizing radiation (IR) or drug therapy is a robust reporter of unrepaired DNA double strand breaks in treated cells. DU-145 prostate cancer cells were treated with a chemical library ±IR and assayed for persistence of γ-H2AX using an automated 96-well immunocytochemistry assay at 4 hours after treatment. Hits that resulted in persistence of γ-H2AX foci were tested for effects on cell survival. The molecular targets of hits were validated by molecular, genetic and biochemical assays and in vivo activity was tested in a validated Drosophila cancer model. We identified 2 compounds, MS0019266 and MS0017509, which markedly increased persistence of γ-H2AX, apoptosis and radiosensitization in DU-145 cells. Chemical evaluation demonstrated that both compounds exhibited structurally similar and biochemical assays confirmed that these compounds inhibit ribonucleotide reductase. DNA microarray analysis and immunoblotting demonstrates that MS0019266 significantly decreased polo-like kinase 1 gene and protein expression. MS0019266 demonstrated in vivo antitumor activity without significant whole organism toxicity. MS0019266 and MS0017509 are promising compounds that may be candidates for further development as radiosensitizing compounds as inhibitors of ribonucleotide reductase.

As an institutional framework for technology-based entrepreneurs, entrepreneurial support organizations (ESOs) have experienced significant growth driven by various stakeholders, including governments, universities, and enterprises. At present, ESOs are undergoing a critical transition toward market-oriented operations. Investigating and enhancing the entrepreneurial incubation mechanisms within ESOs to strengthen their core competitiveness are crucial. This study employs a range of research methodologies, including participatory research, to identify the key tasks and core business functions of ESOs through a comparative analysis of different ESO models. Drawing on uncertainty and entrepreneurship theories, this article proposes a comprehensive framework for ESO entrepreneurship incubation from a macro perspective, aiming to effectively address the uncertainties inherent in the market. It develops a model of the ESO business incubation mechanism at the micro level, offering a detailed analysis of the internal logic and operational processes involved. Furthermore, to address the challenges related to mentorship during the incubation process, this article introduces an innovative “project + coaching” synergistic development mechanism, which provides valuable theoretical insights and practical guidance for ESOs seeking to increase their core competitiveness.

Background Considering the limited data on the feasibility of virtual reality (VR) in lumbar puncture (LP) training, we aimed to evaluate the effectiveness of VR combined with conventional training (instructional videos and high-fidelity LP simulation) on LP proficiency. Methods In this single-blind randomized controlled trial, 88 medical students were randomly assigned to the purely conventional training (CT) group (undergoing 30 min of conventional training) and the virtual reality training (VRT) group (undergoing 20 min of conventional training and 10 min of VR training). After the 30-min intervention, all participants were asked to perform the entire LP procedure independently to check for their proficiency level. After 3 months, they will be reconvened for a follow-up to check their retention of LP skills. The 12 key points of lumbar puncture (maximum total score: 12) were used as the primary assessment parameters. Results The proficiency in LP performance was not different between the CT and VRT groups (8.29 vs. 7.79, respectively, P  > 0.05). Each training modality demonstrated specific strengths at the procedural step level. The participants in CT group displayed higher success rates in preparation, administration of anesthesia, and completion of the procedure, whereas those in the VRT group performed better in measuring cerebrospinal fluid pressure. Meanwhile, the performance of LP in the two groups exhibited no significant differences in the follow-up after 3 months (CT group vs VRT group: 5.04 vs 4.74, P  > 0.05). Furthermore, the participants who introduced VR into their training demonstrated a higher level of interest in clinical skills (CT group vs. VRT group: 60.5% vs 75.6%) and satisfaction with their training (CT group vs VRT group: 41.9% vs 51.2%). Conclusions Training mode combined with VR and conventional training was comparable with CT training in terms of overall proficiency of LP performance. Nonetheless, it was associated with higher self-reported interest and satisfaction among medical students and could be used as a supplement to CT. The efficacy of VR training can be enhanced by further optimizing its programming settings. Trial registration The study was approved by the China Clinical Trial Registry (ChiCTR2200057109) on 28 February 2022 before initiation.

Purpose To evaluate the clinical efficacy of ultrasound-guided local anesthetic injection combined with myofascial trigger point mini-needle knife therapy for acute lumbar sprain management. Methods In this prospective study, 60 patients (January–July 2024) received ultrasound-guided injections at the third lumbar ( L 3) transverse process attachment and posterior medial spinal nerve branch, combined with miniscalpel-needle release of MTrPs. Visual analog scale (VAS), modified Oswestry disability index (MODI), and lumbar range of motion (ROM) were assessed pre-treatment and on days 3 and 7 post-treatment. Results VAS scores, modified ODI scores, and ROM scores on days 3 and 7 post-treatment were significantly reduced compared to baseline (all P  < 0.001). Further pairwise comparisons revealed statistically significant improvements in VAS scores (MD − 1.25; 98.33% CI − 1.50 to − 0.75; P  < 0.001) and modified ODI scores (MD − 2.50; 98.33% CI − 3.00 to − 2.00; P  < 0.001) from day 3 to day 5. However, no significant change in ROM scores was observed between days 3 and 7, indicating rapid stabilization of mobility metrics. Conclusions The integration of ultrasound-guided anesthesia and miniscalpel-needle therapy provides rapid pain relief, functional recovery, and mobility restoration in acute lumbar sprain. This multimodal approach demonstrates clinical efficacy with minimized invasiveness, aligning with evidence supporting ultrasound-guided precision and MTrP-targeted interventions.