Objective Resin-dentin bond long-term stability suffers impairment from collagen degradation, bacterial acidogenesis, and interfacial microleakage. Guided dentin biomimetic remineralization mitig such impairment. We prepared carboxymethyl chitosan (CMC)-bioactive glass (BAG) composite mineralizing film (CB). We used 20 wt% citric acid (CA) as dental etchant to construct integrated CA@CB system. This study evaluated system capacity to promote dentin biomimetic remineralization, enhance resin-dentin interfacial stability, and deliver antibacterial activity. Methods Three CB mineralizing films with different CMC-BAG mass ratios were synthesized and characterized; the etching effect of 20 wt% CA was compared with clinically used etchants. 2D and 3D collagen and demineralized dentin models were used to evaluate the biomimetic mineralization, mechanical properties and resin-dentin bonding durability of the CA@CB system. Antibacterial activity of CA@CB was tested via agar plating, inhibition zone assays and live/dead staining. Results Compared with clinical CPP-ACP, CB mineralizing films release negatively charged ACP nanoparticles steadily and perform better in dentin remineralization and tubule occlusion. 20 wt% CA presents similar etching effects to clinical etchants and improves dentin wettability. This film raises dentin microhardness and modulus, lowers microleakage, and strengthens resin-dentin bonding. The CA@CB system also shows potent antibacterial activity against Streptococcus mutans (S. mutans). Significance CB mineralizing films overcome the drawbacks of traditional liquid remineralizers via their solid form, allowing sustained release of amorphous calcium phosphate (ACP). Meanwhile, the CA@CB system effectively promotes rapid biomimetic mineralization of dentin. It not only improves the stability and durability of the adhesive hybrid layer but also shows strong antibacterial activity.
Artificial intelligence (AI) emerged as the transformative technology in biomedical imaging to improve the accuracy, efficiency and reproducibility of disease diagnosis. Integration of multimodal imaging data for the automated anatomical assessment in preclinical disease models remains insufficiently explored. This study aimed to develop and validate an AI-assisted framework integrating the magnetic resonance imaging (MRI) and computed tomography (CT) for comprehensive anatomical evaluation of the experimental rat disease models. Count of 180 Sprague-Dawley rats were allocated into healthy control and disease-induced groups representing neurological, pulmonary, hepatic and musculoskeletal disorders. High-resolution MRI and CT datasets were acquired longitudinally and processed using the deep-learning architectures for image segmentation, feature extraction, lesion detection and disease classification. Multimodal imaging repository constitutes 4,320 MRI and 3,960 CT image volumes, 96.8% met predefined quality criteria for analysis. Quantitative imaging revealed the significant increases in lesion volume, edema burden, tissue heterogeneity, structural distortion and tissue density across disease groups compared with controls (p < 0.001). Automated segmentation achieved Dice similarity coefficients ranging from 0.91 to 0.94, indicating excellent agreement with the expert annotations. Integrated MRI-CT AI model demonstrated superior diagnostic performance, achieving accuracy of 96.8%, sensitivity of 95.4%, specificity of 97.6% and area under the curve of 0.987, outperforming MRI-only and CT-only models. Strong correlations were observed between the AI-derived imaging biomarkers and histopathological severity scores (r = 0.86-0.93, p < 0.001). The findings demonstrated that AI-assisted multimodal MRI-CT integration provides highly accurate, reproducible and biologically relevant anatomical characterization of experimental disease models and supporting potential application in advanced preclinical imaging, translational research and future precision diagnostic systems.
The hydrodynamic theory suggests that the multidirectional flow of fluids within demineralized dentinal tubules (DTs) in response to external stimuli excites pulpal nerve fibers to produce nociception, causing dentin hypersensitivity (DH). Meanwhile, demineralized dentin's collagen fibers are susceptible to attack by endogenous enzymes and disintegration, continuously decreasing the resistance of the dentin surface and dentin's mechanical properties. Recross-linking and mineralizing damaged collagen fibers, closing DTs, and integrating antienzymatic functions remain significant challenges in dental regenerative medicine. To address these challenges, this study designed a tannic acid synergistic polyaspartic acid-nanohydroxyapatite system (TA@PN), evaluated its cross-linking effect on dentin collagen fibers and the intrafibrillar mineralization and antienzymatic ability, and verified its effect on dentin permeability. Finally, its biocompatibility and ability to induce osteogenic differentiation and biomineralization of MC3T3-E1 were assessed. TA@PN can help develop the next generation of multifunctional desensitizers and remineralizers.
Bioactive glass (BAG) is a widely researched biomaterial in medical science. Renowned for its exceptional biocompatibility and excellent biosafety profile, it has been extensively utilized in clinical practice, especially in the repair and regeneration of bone and soft tissue. In recent years, biomaterials researchers have intensified their exploration of BAG within dental medicine, spanning prosthodontics, oral and maxillofacial surgery, and periodontology. Consequently, BAG has found increasing applications in oral medical products, including pulp capping agents, periodontal restoration, root canal filling agents, coating of dental instruments and implants, etc Notably, remarkable progress has been made in the remineralization of dental hard tissues. A careful survey of the existing literature reveals that most review articles only focus on the application of BAG in root canal treatment, endodontic treatment, implant restoration, and bone regeneration, and there is a conspicuous scarcity of comprehensive reviews dedicated to the application of BAG in the remineralization of dental hard tissue. This paper aims to comprehensively review the remineralization application of BAG in enamel, dentin and cementum. By doing so, it endeavors to furnish a theoretical basis for the treatment of enamel demineralization, dentin demineralization and allergies, and the enhancement of bond durability.
BackgroundAirway allergic disease (AAD) is a class of autoimmune diseases with predominantly Th2-type inflammation, mainly including allergic rhinitis (AR), allergic asthma (AS), and chronic sinusitis (CRS). There are very complex regulatory mechanisms between immune cells and AAD; however, previous reports found that the functions of the same immune cells in AAD are not identical.ObjectiveThe aim of this study was to explore the causal relationship between different phenotypic immune cells and their association with AAD.MethodUtilizing the publicly available Genome-Wide Association Studies (GWAS) database, this study conducted a bidirectional Mendelian randomization (MR) to assess the causal relationship between immune cells of 731 different immunophenotypes and AAD. The primary assessment methods included inverse variance weighting, weighted median, and MR Egger. Additionally, sensitivity analyses such as MR-PRESSO, leave-one-out, and scatter plots were employed to eliminate the interference of heterogeneity and pleiotropy, ensuring the stability of the causal inference.ResultA total of 38 immune cells with different immunophenotypes were found to be positively and causally associated with AR, of which 26 were protective factors and 12 were risk factors. Positive associations were found between 33 immune cells and AS, of which 14 were protective factors and 19 were risk factors, as well as between 39 immune cells and CRS, of which 22 were protective factors and 17 were risk factors. Finally, the results of all relevant immune cells for the three diseases were taken and intersected, and it was found that CD3 on CD39+-activated Treg (IVWAR = 0.001, IVWCRS = 0.043, IVWAS = 0.027) may be the key immune cell that inhibits the development of AAD (ORAR = 0.940, ORAS = 0.967, ORCRS = 0.976).ConclusionThis study reveals that different immune phenotypes of immune cells are closely related to AAD at the genetic level, which provides a theoretical basis for future clinical studies.
Renal metastasis of breast angiosarcoma is rare. This article reports the medical records of a patient diagnosed with breast angiosarcoma who underwent radical mastectomy and was found to have multiple lung metastases 3 years after surgery and renal pelvic metastasis 4 years after surgery. The patient underwent robot-assisted laparoscopic radical nephroureterectomy and sleeve resection of the intramural segment of the ureter, and postoperative pathology and immunohistochemical staining confirmed the diagnosis of renal pelvic metastasis of breast angiosarcoma. The patient received anlotinib for lung metastases following surgery and was followed up for 4 months after surgery. Currently, the patient has symptoms of coughing and hemoptysis but no other discomfort. The diagnosis and treatment of this rare malignant tumor remain challenging.
Dysfunctional immune regulation plays a crucial role in the pathogenesis of airway allergies. Macrophages are one of the components of the immune regulation cells. The aim of this study is to elucidate the role of lysine demethylase 5 A (KDM5A) in maintaining macrophages’ immune regulatory ability. DNA was extracted from Lactobacillus rhamnosus GG to be designated as LgDNA. LgDNA was administered to the mice through nasal instillations. M2 macrophages (M2 cells) were isolated from the airway tissues using flow cytometry. We found that airway M2 cells of mice with airway Th2 polarization had reduced amounts of IL-10 and KDM5A. Mice with Kdm5a deficiency in M2 cells showed the airway Th2 polarization. The expression of Kdm5a in airway M2 cells was enhanced by nasal instillations containing LgDNA. KDM5A mediated the effects of LgDNA on inducing the Il10 expression in airway M2 cells. Administration of LgDNA mitigated experimental airway allergy. M2 macrophages in the airway tissues of mice with airway allergy show low levels of KDM5A. By upregulating KDM5A expression, LgDNA can increase Il10 expression and reconcile airway Th2 polarization.
Glioma has a high malignant degree and poor prognosis, which seriously affects the prognosis of patients. Traditional treatment methods mainly include craniotomy tumor resection, postoperative radiotherapy and chemotherapy. Although above methods have achieved remarkable curative effect, they still have certain limitations and adverse reactions. With the introduction of the concept of minimally invasive surgery and its clinical application as well as the development and progress of imaging technology, minimally invasive treatment of glioma has become a research hotspot in the field of neuromedicine, including photothermal treatment, photodynamic therapy, laser-induced thermal theraphy and TT-Fields of tumor. These therapeutic methods possess the advantages of precision, minimally invasive, quick recovery and significant curative effect, and have been widely used in clinical practice. The purpose of this review is to introduce the progress of minimally invasive treatment of glioma in recent years and the achievements and prospects for the future.
BACKGROUND Gigantic epidermal cysts (GECs) are rare benign skin appendicular tumours also known as keratinocysts. GECs have a high incidence and their wall is made up of epidermis. Epidermal cysts can occur in any part of the skin; clinical manifestations include skin colour hemispherical swelling; cystic; mobile; 0.5 cm to several centimetres in diameter; and slow growth. CASE SUMMARY Herein, we report a case involving a 56-year-old female with a GEC in the occipitalia. On July 25, 2023, a patient with a GEC was admitted to the neurosurgery Department of the Second Affiliated Hospital of Xi'an Medical University. The phyma was shown to be a solid mass during the operation and was confirmed to be a GEC based on pathological examination. CONCLUSION Epidermal cysts are common cystic nodules on the surface of the body, the aetiology is unclear, the clinical manifestations can vary, and the misdiagnosis rate is high. However, giant epidermal cysts are rare. In most cases, however, the prognosis is satisfactory. This paper analyses and summarizes the population, location, clinical and pathological characteristics and pathogenesis of the disease to strengthen the understanding of this disease and improve the accuracy of clinical diagnosis.
Dentin biomineralization is a gene-regulated, cytokine-mediated, programmed process by mineralized cells to form highly ordered hydroxyapatite (HAP) crystals encapsulating dentin matrix, ultimately creating a stable dentin interface. Repairing dentin damage caused by irreversible demineralization has been a significant challenge in dental regenerative medicine due to dentin's limited biomineralization capacity. It is well established that non-collagenous proteins (NCPs)-collagen interactions and NCPs-crystal interactions influence the nucleation, deposition, arrangement, and assembly of HAP crystals during the biomineralization process. Inspired by this process, NCP analogs can be used as a biomimetic template to stabilize the intermediate mineral phases of biomineralization to achieve collagen fibrils' hierarchical mineralization in dentin. In addition, specific functional groups can be introduced to achieve antimicrobial, anti-enzymatic, cross-linking and tissue regeneration functions to restore the microstructure and mechanical properties of demineralized dentin. Therefore, designing and developing NCP analogs are currently a hot topic in dentin biomimetic restorations. However, most existing reviews have only focused on the mineralizing effect of NCP analogs and have rarely summarized their additional functions and applications at the dentin interface. This review first summarizes the basic principles of dentin biomineralization and biomimetic mineralization and then focuses on the common classifications of NCP analogs and newly introduced functional properties. It finally discusses the applications and limitations of NCP analogs in dentin interface, providing a theoretical basis for applying NCP analogs in the minimally invasive treatment of demineralized dentin.
Neuroendocrine carcinoma (NEC) is a rare yet potentially perilous neoplasm. The objective of this study was to develop prognostic models for the survival of NEC patients in the genitourinary system and subsequently validate these models. A total of 7125 neuroendocrine neoplasm (NEN) patients were extracted. Comparison of survival in patients with different types of NEN before and after propensity score-matching (PSM). A total of 3057 patients with NEC, whose information was complete, were extracted. The NEC influencing factors were chosen through the utilization of the least absolute shrinkage and selection operator regression model (LASSO) and the Fine & Gary model (FGM). Furthermore, nomograms were built. To validate the accuracy of the prediction, the efficiency was verified using bootstrap self-sampling techniques and receiver operating characteristic curves. LASSO and FGM were utilized to construct three models. Confirmation of validation was achieved by conducting analyses of the area under the curve and decision curve. Moreover, the FGS (DSS analysis using FGM) model produced higher net benefits. To maximize the advantages for patients, the FGS model disregarded the influence of additional occurrences. Patients are expected to experience advantages in terms of treatment options and survival assessment through the utilization of these models.
Resin-bonded restorations are the most important caries treatment method in clinical practice. Thus, improving the durability of dentin bonding remains a pressing issue. As a promising solution, guided tissue remineralization can induce the formation of apatite nanocrystals to repair defects in the dentin bonding interface. In this study, we present an experimental 20 wt % citric acid (CA) dental etching agent that removes the smear layer. After CA-etching, approximately 3.55 wt % residual CA formed a strong bond with collagen fibrils, reducing the interfacial energy between the remineralizing solution and dentin. CA helped achieve almost complete intrafibrillar and extrafibrillar mineralization after 24 h of mineralization. CA also significantly promoted poly(amidoamine)-induced dentin biomimetic mineralization. The elastic modulus and microhardness of remineralized dentin were restored to that of sound dentin. The remineralized interface reduced microleakage and provided a stronger, longer-lasting bond than conventional phosphate acid-etching. The newly developed CA dental etching agents promoted rapid dentin biomimetic mineralization and improved bonding efficacy through interfacial control, representing a new approach with clinical practice implications.
Numerous studies establish a significant correlation between autoimmune disorders (AIDs) and prostate cancer (PCa). Our Mendelian randomization (MR) analysis investigates the potential connection between rheumatoid arthritis (RA) and PCa, aiming to confirm causal links between systemic lupus erythematosus (SLE), hyperthyroidism, and PCa. Summary statistics from genome-wide association studies provided data on PCa and three AIDs. MR analysis, using IVW as the main approach, assessed causal relationships, validated by sensitivity analysis. IVW revealed a correlation between genetically anticipated RA and PCa, notably in Europeans (OR = 1.03; 95% CI 1.01–1.04, p = 2*10−5). Evidence supported a lower PCa risk in individuals with SLE (OR = 0.94; 95% CI 0.91–0.97, p = 2*10−4) and hyperthyroidism (OR = 0.02; 95% CI 0.001–0.2, p = 2*10−3). Weighted mode and median confirmed these findings. No pleiotropic effects were observed, and MR heterogeneity tests indicated dataset homogeneity. Our study establishes a causal link between RA, SLE, hyperthyroidism, and PCa.
In modern restorative dentistry, adhesive resin materials are vital for achieving minimally invasive, esthetic, and tooth-preserving restorations. However, exposed collagen fibers are found in the hybrid layer of the resin-dentin bonding interface due to incomplete resin penetration. As a result, the hybrid layer is susceptible to attack by internal and external factors such as hydrolysis and enzymatic degradation, and the durability of dentin bonding remains limited. Therefore, efforts have been made to improve the stability of the resin-dentin interface and achieve long-term clinical success. New ion-releasing adhesive resin materials are synthesized by introducing remineralizing ions such as calcium and phosphorus, which continuously release mineral ions into the bonding interface in resin-bonded restorations to achieve dentin biomimetic remineralization and improve bond durability. As an adhesive resin material capable of biomimetic mineralization, maintaining excellent bond strength and restoring the mechanical properties of demineralized dentin is the key to its function. This paper reviews whether ion-releasing dental adhesive materials can maintain the mechanical properties of the resin-dentin bonding interface by supplementing the various active ingredients required for dentin remineralization from three aspects: phosphate, silicate, and bioactive glass.
While it is known that accurate evaluation of overall survival (OS) and disease-specific survival (DSS) for patients with primary adrenal lymphoma (PAL) can affect their prognosis, no stable and effective prediction model exists. This study aimed to develop prediction models to evaluate survival. This study enrolled 5448 patients with adrenal masses from the SEER Program. The influencing factors were selected using the least absolute shrinkage and selection operator regression model (LASSO) and Fine and Gray model (FGM). In addition, nomograms were constructed. Receiver operating characteristic curves and bootstrap self-sampling methods were used to verify the discrimination and consistency of the nomograms. The independent influencing factors for PAL survival were selected by LASSO and FGM, and three models were built: the OS, DSS, and FGS (DSS analysis by FGM) model. The areas under the curve and decision curve analyses indicated that the models were valid. This study developed survival prediction models to predict OS and DSS of patients with PAL. The FGS model was more accurate than the DSS model in the short term. Above all, these models should offer benefits to patients with PAL in terms of the treatment modality choice and survival evaluation.
ObjectiveThe aim is to construct machine learning (ML) prediction models for the difficulty of retroperitoneal laparoscopic adrenalectomy (RPLA) based on clinical and radiomic characteristics and to validate the models.MethodsPatients who had undergone RPLA at Shanxi Bethune Hospital between August 2014 and December 2020 were retrospectively gathered. They were then randomly split into a training set and a validation set, maintaining a ratio of 7:3. The model was constructed using the training set and validated using the validation set. Furthermore, a total of 117 patients were gathered between January and December 2021 to form a prospective set for validation. Radiomic features were extracted by drawing the region of interest using the 3D slicer image computing platform and Python. Key features were selected through LASSO, and the radiomics score (Rad-score) was calculated. Various ML models were constructed by combining Rad-score with clinical characteristics. The optimal models were selected based on precision, recall, the area under the curve, F1 score, calibration curve, receiver operating characteristic curve, and decision curve analysis in the training, validation, and prospective sets. Shapley Additive exPlanations (SHAP) was used to demonstrate the impact of each variable in the respective models.ResultsAfter comparing the performance of 7 ML models in the training, validation, and prospective sets, it was found that the RF model had a more stable predictive performance, while xGBoost can significantly benefit patients. According to SHAP, the variable importance of the two models is similar, and both can reflect that the Rad-score has the most significant impact. At the same time, clinical characteristics such as hemoglobin, age, body mass index, gender, and diabetes mellitus also influenced the difficulty.ConclusionThis study constructed ML models for predicting the difficulty of RPLA by combining clinical and radiomic characteristics. The models can help surgeons evaluate surgical difficulty, reduce risks, and improve patient benefits.
Specific metabolic aberrations of cancer cells rapidly generate energy with a minuscule but detectable temperature variation, which is a typical characteristic providing insight into cancer pathogenesis. However, to date, intracellular temperature mapping of cancer cell metabolism with high temporal and spatial resolution has not been realized. In this study, we mapped and monitored in real-time the intracellular temperature variations of mitochondria and cytoplasm at a subcellular scale via a single-molecule coherent modulation microscopy coupling targeted molecule labeling technique. According to the variation of the decoherence processes of targeted molecules as a function of intracellular temperature, we achieved a high temperature resolution (<0.1 K) and proved that this technique could eliminate interference from fluorescence intensity disturbance and external pH change. Furthermore, we showed a positive correlation between the determined temperature and the adenosine triphosphate production rate of mitochondrial metabolism in combination with a cell energy metabolic analyzer. This technology enables accurate real-time temporal and spatial visualization of cancer metabolism and establishes diagnoses and therapies for cancer.
With the deepening of research on condensed matter chemistry, artificially guided demineralized dentin remineralization has changed from a classical remineralization pathway of the thermodynamic deposition mode to a biomimetic mineralization mode. This new mode is more consistent with the biological mineralization process. The biomimetic mineralization model can successfully simulate natural mineralization and restore the microstructure and mechanical properties of demineralized dentin. Therefore, it has a good application value in the treatment of caries and dentin hypersensitivity and adhesive restorations. This paper analyzes the principles of guided tissue remineralization and describes new research findings related to the classical mineralization model and the novel biomaterials developed using the biomimetic mineralization mode in detail. It also describes the application of these principles to improve the dentin bonding system. It thus shares the new findings in guided tissue remineralization applied to dentin bonding systems. Finally, the existing problems in this field and future development directions are proposed.
生命科学的发展一直伴随着显微技术的创新.基于超快光学的单分子相干调制显微成像技术在量子力学的理论基础上,通过结合超快光学和显微技术使观测生物的微观量子现象成为可能.这篇综述首先介绍了该技术利用飞秒激光脉冲对实现了单分子量子相干态的操控,并通过调制解调技术获得单分子周围相干信息的基本原理.然后分别介绍了其在生物方面的两个应用:(1)通过降低生物自荧光和背景噪声,实现了生物成像对比度两个数量级的提高;(2)通过提取相干可视度V获得了单分子周围微观的量子信息,为生物体微环境的观察提供了有效手段.最后文章对基于单分子相干调制显微成像在癌症研究方面做了展望,该方法将为癌症的早期诊断和预后评估提供新的途径.
Objectives To investigate the effects of livin on the Th2 immune response in airway allergic diseases (AAD) and explore the interaction among livin, GATA3, IL-4 in peripheral blood CD4(+) T cells of AAD patients. Methods WT mice and livin KO mice were developed for model of AAD. Th2 cell levels in the lung tissues and spleen were assessed by flow cytometry. Also, it was assessed in the culture after exposing to livin inhibitor (Lp-15); the protein and mRNA levels of livin, GATA3 and IL-4 in peripheral blood CD4(+) T cells isolated from patients with or without AAD were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. Finally, Co-immunoprecipitation (Co-IP) was employed to identify the interaction between livin and GATA3. Results Compared with WT mouse, Th2 cell frequency in lung tissues and spleen was significantly decreased in livin KO mouse; after adding Lp-15, the differentiation from Naive CD4(+)T cells in spleen to Th2 cells was blocked; the protein and mRNA levels of livin, GATA3 and IL-4 in AAD group were higher than that in control group. The levels of livin were positively correlated with IL-4, and GATA3 was also positively correlated with IL-4 and livin. GATA3 was detected in the protein complex co-precipitated with livin antibody, and livin was also detected in the protein complex co-precipitated by GATA3 antibody. Conclusion Livin increases the expression of IL-4 and facilitates naive CD4(+) T cells to differentiate into Th2 cells, which triggers airway allergy.