China has a large number of patients but a low rate of medical advice-seeking in oral diseases, leading to difficulties in the prevention and treatment of oral diseases. This situation calls for basic oral health examinations, which would increase the public awareness of oral health and fundamentally enhance the effectiveness of comprehensive prevention and control of oral diseases. As a risk-driven primary care service, oral health examination achieves early war-ning, comorbidity management, and resource optimization through standardized protocols. This program enables the early detection and diagnosis of oral diseases, facilitating timely intervention and improving the oral health status of the public. To standardize the flowchart of oral health examinations and ensure the technical results of the examinations conducted by different examination institutions, this study forms an expert consensus on the technical specification of routine oral health examinations for adults. This consensus, which includes oral examination items, oral examination elements, management of abnormal results and follow-up dental cares, provides standardized guidelines for dentists and dental medical institutions, the keystones in the development of prevention and control network for oral diseases, to conduct routine oral health examinations. 口腔疾病防治面临患者基数大、就诊率低的问题，亟须从基础口腔诊疗入手，提高居民对口腔健康水平的认识，从根源上改善口腔疾病综合防控成效。口腔健康体检作为风险驱动型基础诊疗服务，通过标准化流程实现早期预警、共病管理、资源优化，可以实现对口腔疾病的早发现、早诊断，促进口腔疾病早治疗，是提升人群口腔健康水平的重要环节。本文从健康体检的角度出发，总结了成人口腔健康体检流程以及在此过程中体检医师应密切关注的各类常见口腔疾病和检查要点，对成人口腔健康体检的项目、内容、注意事项、检后随访和重要异常结果管理等进行了规范并形成专家共识，旨在达到规范成人口腔健康体检医疗行为的目的，尽可能保障受检者口腔健康，也使开展健康体检服务的医疗卫生机构能够充分发挥建设口腔疾病防治卫生服务网络的重要作用。.
Polydopamine (PDA) is a mussel-inspired polymeric material that has attracted increasing attention in oral medicine owing to its universal adhesion, favorable biocompatibility, redox activity, photothermal conversion, and versatile surface functionalization. This narrative review summarizes recent advances in PDA-based materials and discusses their potential applications, current limitations, and translational prospects in oral medicine. PDA can be prepared through oxidative self-polymerization, electrochemical polymerization, or enzymatic oxidation, and its morphology, coating thickness, and interfacial properties can be regulated by reaction conditions such as pH, dopamine concentration, temperature, and oxidation environment. In oral hard tissue applications, PDA is widely used to modify titanium, zirconia, magnesium alloys, and bone-repair scaffolds, where it improves surface hydrophilicity, enhances protein adsorption and cell adhesion, promotes osteogenic differentiation, facilitates hydroxyapatite mineralization, and supports osseointegration. PDA-based coatings and hydrogels also show promise in oral soft tissue repair by improving wet adhesion, providing antioxidative protection, regulating local inflammation, and enabling sustained delivery of bioactive molecules. In drug delivery, antibacterial/anti-inflammatory systems, and oral tumor therapy, PDA serves as a multifunctional platform for loading therapeutic agents, metal ions, antimicrobial peptides, or nanoparticles, thereby enabling responsive release, biofilm inhibition, reactive oxygen species regulation, and photothermal or photodynamic antibacterial effects. In addition, PDA-based sensing interfaces have been explored for salivary biomarker detection and oral disease diagnosis through electrochemical, fluorescence, colorimetric, and surface-enhanced Raman strategies. Despite these advantages, most PDA-related studies in oral medicine remain at the preclinical stage. Key unresolved issues include unclear polymerization mechanisms, limited long-term stability data under dynamic oral conditions, incomplete degradation and biosafety evaluation, manufacturing reproducibility, and insufficient clinical evidence. Future studies should emphasize standardized preparation, evidence-weighted evaluation, long-term oral-environment simulation, large-animal validation, and well-designed translational studies.
The extensive use of pesticides in modern agriculture has raised increasing concerns regarding the potential biological effects of repeated exposure to pesticide residues and commercial formulations. Mancozeb is a widely used ethylene-bis-dithiocarbamate fungicide; however, information on its hematological and genotoxic effects following repeated oral exposure remains limited, particularly in female models. In this study, we investigated the hematological, genotoxic, welfare-related, and morphometric effects of subchronic oral exposure to the commercial mancozeb-based formulation Dithane NT in female Swiss mice. The experimental dose of 200 mg/kg/day was defined as a subchronic oral exposure level for the mammalian assay and was interpreted in relation to available mammalian toxicological and regulatory benchmarks. The Artemia salina assay was used only as a preliminary ecotoxicological screening tool for the commercial formulation and was not applied as a direct interspecies dose-conversion model. Animals were orally exposed to mancozeb for 30 consecutive days, followed by evaluation of hematological parameters, erythrocyte osmotic fragility, micronucleus frequency in bone marrow erythrocytes, body parameters, and welfare monitoring. Subchronic oral exposure to mancozeb induced a significant increase in micronucleus frequency in bone marrow erythrocytes, indicating a genotoxic response. Hematological evaluation indicated preservation of erythrocyte-related parameters, leukocyte counts, and erythrocyte membrane stability. Morphometric assessment showed a selective increase in gastrocnemius muscle weight in exposed animals, whereas the remaining evaluated body parameters were not significantly altered. Welfare monitoring identified clinical impairment in a subset of exposed animals, including one euthanasia event before terminal sample collection. Overall, these findings demonstrate that subchronic oral exposure to a mancozeb-based formulation induces genotoxic damage and a selective morphometric alteration in female mice, even in the absence of overt hematological toxicity.
Oral tissue repair faces challenges, including complex types of defects, a harsh local microenvironment, and limitations of conventional therapies. Common diseases, such as periodontitis, maxillofacial tumors, trauma, and congenital deformities, cause defects in the alveolar bone and periodontal tissues, affecting a large population. The demand for tissue repair is increasing with accelerating population aging. Defect sites often exhibit a complex microenvironment accompanied with infection, inflammation, ischemia, and immune imbalance, severely impairing the viability and regene-ration of stem cells. Smart delivery materials function as drug delivery platforms and can respond to endogenous and exo-genous stimuli to achieve the spatiotemporally controlled release of drugs and bioactive factors, enabling targeted and precise therapy. Some of these materials also possess tissue-inductive regenerative properties. Smart delivery materials show important application potential in maxillofacial bone repair, periodontal regeneration, pulp reconstruction, and oral mucosal repair. This review summarizes the design strategies, response mechanisms, and cutting-edge applications of intelligent delivery materials in oral tissue repair. Moreover, it analyzes the critical breakthroughs for their clinical translation from the perspectives of mechanical adaptation and controllable degradation, precise responsive release under complex oral microenvironments, synergistic immunomodulation and anti-infective regeneration, and personalized manufacturing. It thereby provides insights for precision therapy and functional reconstruction in oral tissue repair. 口腔组织修复面临缺损类型复杂、局部微环境恶劣及传统治疗手段局限等挑战。牙周炎、颌面部肿瘤、外伤及先天性畸形等口腔常见疾病可导致颌骨及牙周等组织的缺损，患者基数庞大，组织修复治疗需求日益增长。缺损区常存在感染、炎症、缺血及免疫失衡并存的复杂微环境，严重影响组织再生效果。智能递送材料不仅可作为药物递送平台，响应内外源刺激，实现药物与活性因子的时空可控释放，达到靶向递送及精准治疗的目的，而且往往兼具组织诱导再生功能，在颌面骨修复、牙周再生、牙髓重建及口腔黏膜修复中显示出重要的应用价值。本文总结了智能递送材料在口腔组织修复应用中的设计策略、响应机制及前沿应用，并从力学适配与可控降解、复杂口腔微环境下的精准响应释放、免疫调控与抗感染再生协同及个性化制造等方面分析其临床转化的关键突破点，为口腔组织修复的精准治疗与功能重建提供参考。.
Automation technologies and devices are becoming an increasingly important component of the digital and intelligent transformation of oral healthcare. With on-going advances in artificial intelligence, robotics, and advanced manufacturing, their applications have expanded across oral diagnosis, surgery and treatment, prosthodontics, and orthodontics, as well as oral care and maintenance. These technologies have shown considerable potential for improving diagnostic and therapeutic accuracy, efficiency, consistency, and reproducibility. Importantly, automation in oral healthcare should not be understood simply as the replacement of manual procedures by standalone devices. Rather, it represents the optimization of clinical workflows based on standar-dized data acquisition, algorithm- or rule-based decision-making, and dedicated execution platforms. This review summarizes the current research progress and clinical applications of automation technologies and devices in major oral healthcare scenarios and discusses the characteristics, application scope, and practical challenges of different technical routes. Future directions are also outlined to provide a reference for clinical workflow optimization, technology translation, and device development in oral healthcare. 口腔自动化技术与装置正逐步成为口腔医学数字化与智能化发展的重要组成部分。近年来，随着人工智能、机器人和先进制造等技术的持续进步，相关技术在口腔诊断、手术与治疗、口腔修复与正畸以及口腔护理与维护等领域的应用不断拓展，并在提高诊疗的精度、效率、一致性和可重复性方面显示出重要潜力。口腔诊疗自动化并非单一设备对人工操作的简单替代，而是建立在标准化数据采集、算法/规则决策与执行终端基础上的临床工作流优化过程。本文围绕口腔诊疗自动化技术与装置的主要应用场景，系统综述其研究与应用现状，分析不同技术路径的特点、适用范围及现实挑战，并对未来发展方向进行展望，以期为临床诊疗流程优化、相关技术转化与装备发展提供参考。.
Oral mucosal administration (OMA) can circumvent hepatic first-pass metabolism and avoid gastrointestinal degradation while offering advantages, such as a rapid onset of action, noninvasiveness, and convenience, positioning it as an important complementary and alternative route to conventional oral and parenteral administration. How-ever, the dynamic and moist environment of the oral cavity leads to inadequate formulation adhesion, substantial drug permeation barriers across the mucosa, and suboptimal controlled-release precision. These limitations have driven the development of oral mucosal drug delivery systems (OMDDSs). This paper systematically summarizes the structural and physiological characteristics of the oral mucosa and dissects the core advantages and major challenges of OMA. It further comments on the research progress and application status of various OMDDSs, including tablets, nanoparticles, hydrogels, patches/films, and microneedles, as well as their clinical application in the management of local oral diseases and systemic disorders. Finally, it discusses future directions, such as artificial intelligence-assisted design, breakthroughs in macromolecular delivery, standardized evaluation systems, and theranostic integration, to provide theoretical references and innovative insights for the rational design and clinical translation of novel OMDDSs. 口腔黏膜给药（OMA）可规避肝脏首过代谢与胃肠道降解，具有起效迅速、无创、便捷等优势，是传统口服与注射给药的重要补充与替代途径。但口腔的动态湿润环境，导致给药制剂黏附性不足、药物跨黏膜渗透屏障显著、控释精准性欠佳等问题，反而推动了口腔黏膜给药系统（OMDDS）的发展。本文系统梳理口腔黏膜的结构与生理特性，剖析OMA的核心优势与主要挑战;评述片剂、纳米粒、水凝胶、贴片/膜剂、微针等OMDDS的研发进展与应用现状，并总结其在口腔局部疾病及全身系统性疾病管理中的临床应用。此外，本文围绕人工智能辅助设计、大分子递送突破、标准化评价体系及诊疗一体化等方向，展望OMDDS的未来发展趋势，为新型OMDDS的创新设计与临床转化提供理论参考与研究思路。.
Iron deficiency anemia (IDA) is common among women of reproductive age and is frequently associated with abnormal uterine bleeding (AUB). Although oral iron is first-line therapy, the optimal dosing schedule remains uncertain. This study compared daily and alternate-day oral iron in real-world practice. We conducted a prospective observational cohort study of women aged 18-70 years with confirmed IDA treated with oral ferrous sulfate at a tertiary referral center between January 2023 and June 2024. Patients received oral iron every 24 h or every 48 h according to physician prescription. AUB etiology was classified using the PALM-COEIN system. Outcomes included hemoglobin change, World Health Organization anemia severity, hemoglobin normalization (≥12 g/dL), adherence, adverse-event-related discontinuation, and intravenous iron escalation. A total of 171 women were included. Leiomyomas were the most frequent PALM-COEIN category (106 patients, 62.0%). Mean baseline hemoglobin was 9.02 ± 1.45 g/dL. At 6 weeks, mean hemoglobin was 10.91 ± 1.76 g/dL in the 24-h group and 11.26 ± 1.86 g/dL in the 48-h group (p = 0.255). At 3 months, final hemoglobin was available in 147 patients; mean values were 12.79 ± 1.68 g/dL and 12.68 ± 1.62 g/dL, respectively (p = 0.692). Hemoglobin normalization occurred in 75.2 and 71.7% of patients, respectively (p = 0.687). Adherence was high, and discontinuation due to adverse events was uncommon. Intravenous iron escalation was numerically more frequent with alternate-day therapy (26.8% vs. 13.9%; p = 0.056), although escalation decisions were based on clinical judgment without standardized criteria. Both regimens were associated with hematologic improvement. However, because allocation was non-randomized, baseline differences were present, and intravenous iron escalation was not based on standardized criteria, equivalence cannot be inferred. Oral iron dosing should be individualized.
Oral stromal and epithelial cells contribute to mucosal inflammation through cytokine-induced chemokine production. Essential oil-containing mouth rinses are widely used as adjuncts to oral hygiene, but whether zinc-containing formulations directly modulate host inflammatory signaling remains unclear. This study investigated the effects of a zinc-containing Listerine® formulation on IL-1β/TNF-α-induced inflammatory responses in human oral cells. Primary human gingival fibroblasts were stimulated with IL-1β/TNF-α in the presence or absence of Listerine®. Transcriptional responses were analyzed by RNA sequencing and validated by quantitative PCR and immunoassays. HSC2 epithelial cells were used to assess selected responses across oral cell types. Phospho-STAT1 immunostaining evaluated canonical STAT1 activation, and ICP-MS determined trace-element composition. IL-1β/TNF-α induced a broad inflammatory transcriptional program characterized by chemokines, NF-κB-associated mediators, and interferon-associated genes. Listerine® attenuated this response, with strongest effects on CXCL10, CXCL11, IFIT family members, GBP family members, and OASL, whereas classical NF-κB-associated chemokines such as CXCL1, CXCL2, and CXCL8 were less affected. Listerine® also induced a zinc-responsive stress-adaptation signature dominated by metallothioneins. ICP-MS analysis confirmed the presence of zinc in Listerine®, and zinc alone partially reproduced the suppression of CXCL10. In contrast, individual essential oil constituents failed to recapitulate the anti-inflammatory effects of the complete formulation. Notably, Listerine® did not prevent IFN-γ-induced STAT1 phosphorylation, indicating that suppression of interferon-associated genes was not due to general blockade of canonical STAT1 activation. These findings identify a previously unrecognized host-modulatory activity of a zinc-containing Listerine® formulation characterized by selective attenuation of interferon-associated inflammatory transcription together with induction of a zinc-responsive metallothionein program.
This study aimed to develop a preclinical model in which reinforcement and reward can be measured in the same subject. To this end, we combined the power of drug self-administration and place conditioning paradigms and determined whether voluntary oral oxycodone self-administration would induce conditioned place preference (CPP) and whether this response could be extinguished and reinstated. To assess the face validity of the model, we also evaluated the role of the mu-opioid receptor (MOP) in this process. Male and female C57BL/6 mice, as well as male MOP knockout mice and their wild-type littermates, were initially conditioned with sucrose (4%) in both conditioning chambers for 1 h daily for 2 weeks (4 days a week). Mice were then tested for basal place preference and then underwent alternate-day conditioning (1 h daily) with sucrose (4%) in one chamber and oxycodone in a 4% sucrose solution in the opposite chamber the following day for four consecutive days, followed by a CPP test. The following week, another set of conditioning and testing for CPP was repeated. Subsequently, mice were exposed to the sucrose (45) solution alone for 4 days each week, and a test for extinction of the CPP response at the end of each week. After extinction, mice were challenged with oxycodone (5 mg/kg) and tested for the reinstatement of CPP. Both male and female mice demonstrated robust voluntary oral oxycodone self-administration in a 4% sucrose solution, but it was lower in females than in males. Oxycodone self-administration was associated with CPP in male and female mice. This response was extinguished and reinstated. Unlike wild-type mice, the CPP response was not observed in mice lacking MOP, suggesting that MOP is involved in this response. This is the first study providing evidence for the development of a translational mouse model of reward utilizing oral oxycodone self-administration in a sweetened solution.
In patients on long-term oral anticoagulation (OAC), the optimal antithrombotic strategy in the setting of concomitant chronic coronary syndrome (CCS) remains unclear. We therefore performed a systematic review and meta-analysis of randomized controlled trials comparing OAC monotherapy versus OAC plus single antiplatelet therapy (combination therapy) in patients with CCS and any indication for long-term OAC.. We systematically searched PubMed/MEDLINE and Embase through February 2026 to identify trials randomizing CCS patients with an indication for long-term OAC to OAC monotherapy vs. combination therapy. Net adverse clinical events (NACE) were defined as primary composite endpoint. Key secondary outcomes included major adverse cardiovascular events (MACE), major bleeding, and major or clinically relevant non-major bleeding. Hazard ratios (HRs) were pooled using Bayesian random-effects models. Six (6) randomized trials met the inclusion criteria. Five (5) contributed to quantitative synthesis of primary and main secondary outcome measures (5,777 participants). OAC monotherapy significantly reduced NACE (HR 0.61, 95% CrI 0.43-0.85), major bleeding (HR 0.47, 95% CrI 0.30-0.71) and major or clinically relevant non-major bleeding (HR 0.47, 95% CrI 0.31-0.66) compared to combination therapy. No significant differences were observed for MACE (HR 0.83, 95% CrI 0.60-1.18), cardiovascular death (HR 0.70, 95% CrI 0.44-1.13), all-cause death, unplanned revascularisation, myocardial infarction and ischemic stroke. Prespecified subgroup analyses for NACE and MACE outcomes detected a signal of lower risk of MACE with direct oral anticoagulant monotherapy compared to monotherapy with vitamin K antagonists (p=0.02). In CCS patients on OAC, OAC monotherapy reduces bleeding events compared to combination therapy, without clear evidence of a concomitant increase in ischemic risk. For people with stable coronary artery disease who need long-term treatment with blood thinners, using one blood thinner alone was linked to less bleeding than combining it with aspirin or another anti-clotting medicine, without a clear increase in serious heart-related problems. This study combined data from randomized clinical trials and found that one blood thinner treatment instead of a combination reduced overall harmful events.The two treatment strategies showed no clear difference in major heart problems or heart-related death, suggesting that blood thinner treatment alone may be the safer long-term option.
We assessed protein biomarkers expressed in oral leukoplakia (OL) that are associated with the risk of transformation into oral squamous cell carcinoma (OSCC). Tissue sections of OL transforming into OSCC (leuko-ca), the corresponding OSCC and OL that did not progress to OSCC (leuko-nonca) were analyzed with global relative quantification to compare proteome profiles. Immunohistochemistry was performed to validate the expression of identified biomarkers. The top enriched biological pathways in OL transforming into OSCC within 5-26 months after diagnosis (short duration [SD]-leuko-ca) compared with leuko-nonca were pathways regulating remodeling of the extracellular matrix (ECM) and lipid and cholesterol metabolism/transport. Kininogen-1, apolipoprotein E (ApoE), collagen alpha-1 (XVIII) chain (COL18A1), sortilin, and perlecan were the most downregulated proteins, whereas EEF1D was the most upregulated in SD-leuko-ca compared with leuko-nonca. Immunohistochemistry confirmed the expression of kininogen-1, ApoE, perlecan, and EEF1D in OL and OSCC. In OSCC compared with leuko-ca, enriched biological pathways involved keratinocyte and epithelial differentiation and immune response regulation. We identified biomarkers in OL that were associated with the risk of malignant transformation. Our study gives further support for the importance of the immune system, ECM remodeling, and lipoproteins and cholesterol metabolism in the progression of OL to OSCC.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have traditionally been central to pharmacological pain management in Japan, but population aging and increased use of mechanism-based analgesics may be changing prescribing patterns. We compared oral analgesic prescribing between fiscal year (FY) 2014 and FY2022 using nationwide claims-based open data, focusing on age and sex differences. We analyzed aggregated prescription volumes from the 1st and 9th editions of the National Database of Health Insurance Claims and Specific Health Checkups of Japan Open Data for FY2014 (April 2014-March 2015) and FY2022 (April 2022-March 2023). Analgesics were grouped as acetaminophen, NSAIDs, cyclooxygenase-2 selective inhibitors, weak opioids, duloxetine, neuropathic pain medications, and neurotropin. We calculated population-based prescription volume rates (per 1,000 population) using official population estimates and summarized patterns by sex and age group (<20, 20-64, ≥65 years). We also calculated within-age-group composition (percent share). Poisson regression with log(population) offset estimated incidence rate ratios (IRRs) comparing FY2022 versus FY2014 using robust standard errors; NSAID IRRs were further examined by age-sex strata. Total prescription volume increased from 3.69 × 109 in FY2014 to 6.09 × 109 in FY2022. Rates per 1,000 population increased in all age groups, with the largest absolute increase among adults aged ≥65 years. NSAIDs remained the most frequently prescribed class by rate in adults aged 20-64 years, but composition shifted away from NSAIDs toward acetaminophen and neuropathic pain medications, most notably in older adults. Overall IRR was 1.55, with large increases for acetaminophen (2.51), neuropathic pain medications (2.14), duloxetine (2.29), and weak opioids (1.88), while NSAIDs changed modestly (1.15). NSAID rates decreased in older female strata (IRR <1 from ages 70-74 years). Oral analgesic prescribing in Japan increased substantially between FY2014 and FY2022, alongside age-specific shifts away from NSAIDs toward acetaminophen and neuropathic pain medications, particularly among older adults.
To investigate the current medi-cation adherence status and analyze its influencing factors in patients with oral lichen planus (OLP) and thus provide a reference for developing interventions to improve medication adherence in this population. A cross-sectional survey was conducted among patients with OLP who attended the Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, between February 2023 and September 2024. Data were collected by using a general information questionnaire, a patient medication questionnaire, and the Morisky medication adherence scale (MMAS-8). Univariate analysis was first performed, and variables with P<0.1 were included in a multiple linear regression model to adjust for interactions and potential confounding effects, assessing the effect of demographic characteristics, disease status, disease cognition, and medication behavior on medication adherence. A total of 388 patients with OLP were included. The mean MMAS-8 score was 5.37, with a median of 5.75 (Q₁, Q₃: 4.00, 7.00). Medication adherence was categorized as low (MMAS-8<6) in 202 patients (52.1%), medium (6≤MMAS-8<8) in 147 patients (37.9%), and high (MMAS-8=8) in 39 patients (10.1%). Univariate analysis and multiple regression model adjustment revealed that educational level and anxiety related to long-term medication were independent negative influen-cing factors for medication adherence. By contrast, awareness of the drug abuse harm and the experience of adverse drug reactions were independent positive influencing factors. Medication adherence among patients with OLP is generally suboptimal. A high educational level and medication-related anxiety are risk factors for low adherence, whereas sufficient awareness of the harm of drug abuse and the actual experience of adverse drug reactions are associa-ted with good adherence. This situation suggests that differentiated patient education and increased attention to psychological intervention during treatment are necessary in clinical practice to improve medication adherence in patients OLP specifically. 目的: 调查口腔扁平苔藓（OLP）患者用药依从性现状，并分析其影响因素，以期为制定改善OLP患者用药依从性的干预措施提供参考。方法: 采用横断面调查法，通过一般资料调查表、患者用药情况调查问卷和Morisky用药依从性量表（MMAS-8），对2023年2月—2024年9月就诊于四川大学华西口腔医院口腔黏膜病科的OLP患者进行横断面调查。采用多元回归模型评估OLP患者的人口学、疾病状态、疾病认知、用药行为对用药依从性的影响。通过单因素分析纳入P<0.1的因子，然后通过多元回归模型分析校正交互作用及潜在的混杂影响。结果: 共纳入388名OLP患者，其MMAS-8平均得分为5.37分，中位数为5.75分（Q1，Q3:4.00，7.00），依从性低（MMAS-8<6分）202例（52.1%），依从性中（6≤MMAS-8<8）147例（37.9%），依从性高（MMAS-8=8）39例（10.1%）。通过单因素分析及多元回归模型校正后发现:文化程度、用药焦虑为独立负向因素;对滥用药物危害的认知、药物不良反应为独立正向因素。结论: 文化程度高、用药焦虑会降低OLP患者的用药依从性;而对滥用药物危害的认知充分、经历过药物不良反应，则会增强其用药依从性。在临床实践中，应实施差异化的患者教育，重视治疗过程中的心理干预，以针对性地改善用药依从性。.
This study aims to integrate network pharmacology, machine learning, and survival analysis to preliminarily explore the molecular mechanisms underlying the inhibitory effects of thalidomide on the malignant transformation of oral leukoplakia (OLK). First, multisource databases and an OLK transcriptomic cohort (GSE26549) were integrated to identify the intersecting feature genes between thalidomide and OLK with epithelial dysplasia, followed by pathway enrichment analysis. Subsequently, a protein-protein interaction (PPI) network was constructed, and ensemble machine learning algorithms were applied to screen for core biomarkers. Kaplan-Meier curves and multivariate Cox proportional hazard regression models were utilized to evaluate the clinical prognostic efficacy of these core biomarkers. Finally, molecular docking was employed to validate the physical binding potential between thalidomide and the core biomarkers of OLK. A total of 16 intersecting target genes between thalidomide and OLK with epithelial dysplasia were identified. These genes were primarily enriched in the signaling pathways of the cell cycle, phosphatidylinositol 3-kinase/protein kinase B (PI3K-Akt), and microRNAs in cancer. PPI network analysis combined with ensemble algorithms ultimately identified four core biomarkers: MET proto-oncogene, receptor tyrosine kinase (MET), Aurora kinase A (AURKA), DNA methyltransferase 1 (DNMT1), and poly(ADP-ribose) polymerase 1 (PARP1). Survival analysis revealed that high expression levels of MET (P=0.004) and AURKA (P=0.029) increased the risk of malignant transformation in OLK. Furthermore, MET exhibited crucial independent prognostic value in the multivariate Cox proportional hazard regression model (hazard ratio=2.58, P=0.051). Molecular docking demonstrated that thalidomide could stably bind to the MET receptor (binding energy=-38.178 kJ/mol). Thalidomide may exert its inhibitory effects against the malignant progression of OLK by primarily targeting MET and synergistically ac-ting on key biomarkers, including AURKA, DNMT1, and PARP1, thereby suppressing downstream PI3K-Akt and cell cycle signaling pathways. This study not only provides robust computational biology evidence for the "drug repurpo-sing" of thalidomide but also highlights a promising pharmacological option for the clinical intervention of OLK's malignant transformation. 目的: 本研究旨在整合网络药理学、机器学习与生存分析，初步解析沙利度胺抑制口腔白斑病（OLK）恶变的分子机制。方法: 首先联合多源数据库与OLK转录组队列（GSE26549），获得沙利度胺与OLK伴有上皮异常增生的交集特征基因集并进行通路富集分析;继而构建蛋白质-蛋白质相互作用（PPI）网络，联合集成机器学习算法筛选核心标志物;然后利用Kaplan-Meier曲线及多因素Cox比例风险回归模型评估核心标志物的临床预后效能;最后借助分子对接技术验证沙利度胺与OLK核心标志物的物理结合潜能。结果: 共获得16个沙利度胺与OLK伴有上皮异常增生的交集靶点基因，主要富集于细胞周期信号通路、磷脂酰肌醇-3-激酶/蛋白激酶B信号通路（PI3K-Akt）和癌症中的微小RNA信号通路。拓扑网络分析联合机器学习算法最终筛选出MET原癌基因（MET）、极光激酶A（AURKA）、DNA甲基转移酶 1（DNMT1）及聚（ADP-核糖）聚合酶1（PARP1）为四大核心标志物。生存分析显示，MET（P=0.004）和AURKA（P=0.029）的高表达可增加OLK恶变风险，且MET在多因素Cox比例风险回归模型中表现出关键的独立预后潜能（风险比=2.58，P=0.051）。分子对接显示:沙利度胺能够与MET受体稳定结合（结合能为 -38.178 kJ/mol）。结论: 沙利度胺可能以MET为核心干预靶点，协同AURKA、DNMT1及PARP1等关键分子，通过抑制下游PI3K-Akt及细胞周期等信号通路，进而抑制OLK的恶性转变进程。本研究不仅为沙利度胺的“老药新用”提供坚实的计算生物学依据，也为OLK的临床恶变干预提供具有潜力的药物选择。.
Complete blood counts are central to clinical practice but require invasive sampling and centralized laboratory analysis. Optical-resolution photoacoustic microscopy provides intrinsic specificity to red blood cells (RBCs) through hemoglobin absorption. However, conventional implementations typically depend on bulky acoustic coupling schemes that hinder clinical translation. Here, we present a compact and integrable, label-free optoacoustic platform that combines optical-resolution excitation in an epi-illumination geometry with a transparent silicon-photonics acoustic detector (SPADE) featuring a wide acoustic acceptance angle that enables detection without strict optical-acoustic co-alignment. System performance was first characterized using optoacoustic point sources and subsequently evaluated in controlled RBC flow experiments within a tapered glass-capillary microfluidic phantom, as well as in vivo measurements of superficial inner-lip capillaries in human volunteers. The transparent SPADE preserved tight optical focusing (≤ 4 µm) and provided an acoustic bandwidth exceeding 100 MHz with a noise-equivalent pressure of approximately 2.3 mPa/Hz¹ ᐟ². Single-RBC transients were robustly detected in the phantom across varying flow conditions, while in vivo measurements at multiple capillary sites yielded reproducible transient signals consistent with individual RBC passages. These results establish a practical framework for stable, fixed-position optoacoustic detection of individual RBCs in superficial human capillaries, demonstrating the potential of transparent SPADE-based systems for non-invasive blood analysis.
Cancer remains a major global health challenge, and quercetin, a widely distributed dietary flavonoid, has attracted increasing attention for its anti-inflammatory, antioxidant, and neuroprotective properties in oncology research. This narrative review synthesizes recent preclinical and clinical evidence on quercetin for cancer prevention and treatment, with an emphasis on its adjuvant role, toxicity-modulating effects, and formulation strategies designed to improve delivery. Quercetin has been reported to enhance the activity of several chemotherapeutic agents by modulating apoptosis, drug-resistance mechanisms, and key signaling pathways; moreover, it may reduce treatment-related nephrotoxicity, cardiotoxicity, reproductive toxicity, and neurotoxicity. Nevertheless, clinical translation remains limited by poor aqueous solubility, reduced stability, rapid metabolism, and low bioavailability. In addition, clinical trial data remain sparse, and many completed studies have not yet reported outcomes. Consequently, advances in delivery systems, including nanoformulations, liposomes, and micelles, may improve quercetin stability, absorption, and tumor targeting. Overall, quercetin appears to be a promising adjunct in oncology; however, stronger clinical evidence and optimized delivery strategies are required to define its therapeutic value.
口腔药物学是口腔医学与现代药物学深度交叉融合产生的重要学科，主要研究口腔疾病预防、诊治和康复中应用药物的药理学、药剂学及治疗学的特点和规律，从而安全、有效、合理地使用药物，并为安全合理使用药物提供指导。近年来，随着分子生物学、材料科学、临床药学的快速发展，口腔药物学领域正经历着从经验用药向精准药物治疗、从传统剂型向智能递送系统的深刻转变。新理论、新技术、新剂型、新药物层出不穷，为口腔疾病的药物治疗带来了前所未有的机遇与挑战。为了更好地推动口腔药物学的发展和进步，我们依托《华西口腔医学杂志》 平台组织搭建“口腔药物前沿”专栏，邀请全国口腔临床、口腔基础研究和口腔药学领域的专家和团队，系统梳理口腔药物学领域的最新进展，涵盖核心用药机制、合理治疗策略、新型给药系统、智能材料与组织工程等前沿议题，从不同维度呈现了当前口腔药物学研究的活跃图景，从而推动该领域的学术交流和学科交叉创新，为行业提供权威参考。.
Optimised oral mesalazine therapy (4 or 4.8 g/day depending on the formulation) has been associated with better outcomes than lower doses in mild-to-moderate ulcerative colitis (UC). The aim of this post-hoc analysis of the IMPACT study was to provide a greater understanding of the influence of disease severity on the outcomes in patients with mild-to-moderate UC receiving oral mesalazine. IMPACT was a Dutch, phase 4, non-interventional, observational, 12-month prospective study that enrolled 151 adult patients with mild-to-moderate UC who received oral prolonged-release mesalazine de novo or had a dose escalation for an active episode (NCT02261636). The current analysis compared the outcomes in patients receiving mesalazine 4 g/day versus 2-3 g/day. Of 147 patients (median age = 46 years, 47.6% women), 139 (94.6%) received 4 g/day, mostly as prolonged-release mesalazine granules (74.2%). Recurrence was significantly reduced for patients on 4 g/day versus 2-3 g/day (26.6% vs. 62.5%, p = 0.03). There was a trend towards a longer disease-free interval for those on the optimised dose over the 12-month period (mean = 16.8 vs. 12.8 months, p = 0.49). Time to recurrence was similar (p = 0.241) for patients with milder [Ulcerative Colitis Disease Activity Index (UCDAI) scores ≤3] versus more moderately active disease (scores ≥4), with a significantly higher rate of combined oral plus topical therapy in the latter (23.2% vs. 46.1%, p = 0.004). Patients' preferred formulation was granules (68.0%) given once daily (78.7%), with good adherence to all formulations (≥8.5/10, high = 10) irrespective of regimen (p = 0.873). Optimised mesalazine treatment improved the clinical outcomes in patients across the spectrum of mild-to-moderate UC.
To screen and validate the activity of potential therapeutic substances in wall-broken Ganoderma lucidum spore powder (BGLSP) for promoting ulcer healing. The potential active components of BGLSP were screened through network pharmacology combined with molecular docking and verified via the cell counting kit(CCK)-8 assay, cell scratch assay, and a rat oral ulcer model.​. Network pharmacology revealed that 25 compounds in BGLSP exert prohealing effects through multiple targets and pathways. Molecular docking identified seven compounds with strong binding affinity. On the basis of their relative contents in BGLSP, ganoderic acid A (GAA) and ganoderic acid G (GAG) were identified as the key potential active constituents promoting ulcer healing. At low concentrations, GAA and GAG showed no cytotoxicity. GAA promoted the migration of human primary gingival fibroblasts in a concentration-dependent manner, whereas GAG showed a promotive effect only at 2.5 µmol/L. GAA and GAG enhanced collagen deposition and angiogenesis in rat oral ulcers, accelerating healing. GAA demonstrated a good effect at low concentrations in the early stage of ulcer healing but a superior effect at high concentrations in the later stage of ulcer healing, whereas GAG exhibited a concentration-dependent promotive effect. Conclusion​​ BGLSP promotes ulcer hea-ling through multicomponent, multitarget, and multipathway synergistic effects. GAA and GAG, as potential active constituents of BGLSP, play important roles in the early hea-ling of oral ulcers. 目的: 筛选破壁灵芝孢子粉（BGLSP）促溃疡愈合的潜在药效物质并行活性验证。方法: 结合网络药理学与分子对接筛选BGLSP的潜在活性成分，并通过细胞计数试剂盒（CCK）-8法、细胞划痕实验及大鼠口腔溃疡模型进行活性验证。结果: ​BGLSP中的25种化合物经多靶点、多通路发挥促愈合作用，经分子对接筛选出7种化合物，根据其在BGLSP中的相对含量，​确定灵芝酸A（GAA）与灵芝酸G（GAG）为BGLSP中促进溃疡愈合的潜在药效物质。GAA及GAG低浓度时无细胞毒性，GAA呈浓度依赖性促进人牙龈成纤维细胞（HGFs）迁移，GAG仅在2.5 µmol/L时具有促迁移作用。GAA与GAG均可促进大鼠口腔溃疡胶原沉积与血管生成，加快口腔溃疡愈合;GAA的促愈合作用早期以低浓度为佳，后期以高浓度更优，GAG呈现浓度依赖性的促进作用。结论: BGLSP经多成分-多靶点-多通路协同作用促进溃疡愈合，其中GAA和GAG作为BGLSP的潜在药效物质，在口腔溃疡早期愈合中发挥重要作用。.
Ribonucleotide Reductase (RR) is a pivotal enzyme in DNA synthesis and repair, making it a vital target in cancer therapy. While synthetic RR inhibitors such as gemcitabine and hydroxyurea are used clinically, their long-term efficacy is hampered by drug resistance and systemic toxicity. This has prompted growing interest in natural compounds with potential anticancer properties and reduced toxicity. This study aims to evaluate the molecular interactions and pharmacokinetic profiles of two naturally derived compounds traditionally used, genistein (Chinese name: , derived from Glycine max) and hematoxylin (Chinese name: , extracted from Caesalpinia sappan), against human RR using molecular docking and in silico pharmacological analyses. The three-dimensional structure of human RR (PDB ID: 6L7L) was retrieved and subjected to docking simulations using AutoDock Vina and Chimera. Genistein and hematoxylin were docked into the RR active site, and their interactions were analyzed in comparison to gemcitabine. Molecular dynamics simulations over 100 ns further confirmed the structural stability and binding persistence of both compounds within the RR active site. Pharmacokinetic and drug-likeness properties were evaluated via SwissADME and Molinspiration platforms. Both genistein and hematoxylin exhibited strong binding affinities (-8.2 kcal/mol, -8.8 kcal/mol), respectively, to the RR active site, interacting with key catalytic residues in a manner comparable to the standard drug gemcitabine (-7.3 kcal/mol). Molecular dynamics simulations over 100 ns further confirmed the structural stability and binding persistence of both compounds within the RR active site. In silico pharmacokinetic predictions indicated good oral bioavailability, compliance with drug-likeness criteria, and low predicted toxicity. Genistein emerges as a good candidate owing to its strong RRM1 binding, favorable physicochemical attributes, clean medicinal chemistry profile, and low predicted toxicity. Hematoxylin offers superior binding affinity but requires refinement to address solubility and PAINS-related concerns. Gemcitabine, while efficacious clinically, suffers from limited oral bioavailability and potential toxicities. Genistein and hematoxylin demonstrate promising molecular interactions and pharmacological profiles as potential natural RR inhibitors. Their dual role in traditional healing and modern molecular pharmacology supports further preclinical development as anticancer agents.