Aberrant activation of glycolysis represents a key metabolic mechanism underlying the initiation and progression of nasal inflammation. Allergic rhinitis, chronic rhinosinusitis, and vasomotor rhinitis exhibit distinct etiologies, yet all are characterized by inflammatory responses, impaired epithelial barrier function, and neurovascular dysregulation, in which glycolytic metabolic reprogramming acts as a central hub connecting immunometabolism and inflammatory regulation.Recent evidence indicates that glycolysis-dependent activation of immune cells provides the essential energy basis for inflammatory onset. In dendritic cells, eosinophils, mast cells, and Th2 cells, the expression of key glycolytic enzymes including HK2, PKM2, and LDHA is upregulated, thereby promoting cellular activation and proinflammatory cytokine release via the mTOR-HIF-1α signaling axis. Notably, the metabolic reprogramming of eosinophils prolongs their survival and enhances the release of cytotoxic granules, while in mast cells, enhanced glycolysis facilitates IgE-mediated degranulation and histamine release. Furthermore, glycolysis also influences the Th17/Treg balance, with enhanced glycolytic flux promoting Th17 differentiation and contributing to the heterogeneous inflammatory profiles observed across different rhinitis subtypes.As a central metabolite, lactate contributes to the formation of a metabolism-inflammation vicious cycle through multiple mechanisms. Lactate acidifies the local microenvironment to activate TRPV1 channels and facilitate neuropeptide release, mediates immune cell chemotaxis through GPR81, and regulates gene expression via histone lactylation, thereby sustaining proinflammatory gene transcription. These lactate-mediated processes collectively amplify local inflammation and contribute to the persistence of nasal symptoms.Glycolytic reprogramming in epithelial cells is modulated by the EGF/EGFR pathway, and its dysregulation may result in disrupted tight junctions, abnormal goblet cell hyperplasia, and subsequent tissue remodeling. Substance P and calcitonin gene-related peptide released from sensory neurons, in conjunction with metabolic products, synergistically maintain persistent inflammatory stimulation by activating mast cells, forming a neuro-immune-metabolic regulatory network that drives disease chronicity.From a therapeutic perspective, glycolytic inhibitors such as 2-deoxyglucose, FX11, and 3-bromopyruvate exert anti-inflammatory effects by targeting key enzymes including HK2 and LDHA, each with distinct mechanisms: 2-DG competitively inhibits hexokinase, FX11 selectively targets LDHA to reduce lactate production, and 3-BrPA modulates multiple glycolytic enzymes. Moreover, traditional Chinese medicine formulas, monomeric active components, and small-molecule compounds have shown promising potential in alleviating nasal inflammation by regulating the mTOR-HIF-1α axis, exerting antioxidant effects, and modulating endoplasmic reticulum stress pathways. The multi-target characteristics of these natural products offer advantages in addressing the complex pathophysiology of nasal inflammatory diseases.Despite these advances, several challenges remain. The non-selective inhibition of glycolysis may interfere with epithelial repair and mucosal regeneration, leading to delayed wound healing. Technical limitations in dynamic metabolic monitoring and sampling precision hinder the accurate assessment of local nasal metabolism. Furthermore, current animal models, which predominantly rely on acute stimulation protocols, inadequately recapitulate the chronic tissue remodeling processes characteristic of human rhinitis.This review systematically summarizes glycolysis as a common metabolic node shared by different rhinitis subtypes, offering a novel theoretical basis for the development of precision therapeutic strategies targeting metabolic reprogramming.

Aberrant activation of glycolysis represents a key metabolic mechanism underlying the initiation and progression of nasal inflammation. Allergic rhinitis, chronic rhinosinusitis, and vasomotor rhinitis exhibit distinct etiologies, yet all are characterized by inflammatory responses, impaired epithelial barrier function, and neurovascular dysregulation, in which glycolytic metabolic reprogramming acts as a central hub connecting immunometabolism and inflammatory regulation.Recent evidence indicates that glycolysis-dependent activation of immune cells provides the essential energy basis for inflammatory onset. In dendritic cells, eosinophils, mast cells, and Th2 cells, the expression of key glycolytic enzymes including HK2, PKM2, and LDHA is upregulated, thereby promoting cellular activation and proinflammatory cytokine release via the mTOR-HIF-1α signaling axis. Notably, the metabolic reprogramming of eosinophils prolongs their survival and enhances the release of cytotoxic granules, while in mast cells, enhanced glycolysis facilitates IgE-mediated degranulation and histamine release. Furthermore, glycolysis also influences the Th17/Treg balance, with enhanced glycolytic flux promoting Th17 differentiation and contributing to the heterogeneous inflammatory profiles observed across different rhinitis subtypes.As a central metabolite, lactate contributes to the formation of a metabolism-inflammation vicious cycle through multiple mechanisms. Lactate acidifies the local microenvironment to activate TRPV1 channels and facilitate neuropeptide release, mediates immune cell chemotaxis through GPR81, and regulates gene expression via histone lactylation, thereby sustaining proinflammatory gene transcription. These lactate-mediated processes collectively amplify local inflammation and contribute to the persistence of nasal symptoms.Glycolytic reprogramming in epithelial cells is modulated by the EGF/EGFR pathway, and its dysregulation may result in disrupted tight junctions, abnormal goblet cell hyperplasia, and subsequent tissue remodeling. Substance P and calcitonin gene-related peptide released from sensory neurons, in conjunction with metabolic products, synergistically maintain persistent inflammatory stimulation by activating mast cells, forming a neuro-immune-metabolic regulatory network that drives disease chronicity.From a therapeutic perspective, glycolytic inhibitors such as 2-deoxyglucose, FX11, and 3-bromopyruvate exert anti-inflammatory effects by targeting key enzymes including HK2 and LDHA, each with distinct mechanisms: 2-DG competitively inhibits hexokinase, FX11 selectively targets LDHA to reduce lactate production, and 3-BrPA modulates multiple glycolytic enzymes. Moreover, traditional Chinese medicine formulas, monomeric active components, and small-molecule compounds have shown promising potential in alleviating nasal inflammation by regulating the mTOR-HIF-1α axis, exerting antioxidant effects, and modulating endoplasmic reticulum stress pathways. The multi-target characteristics of these natural products offer advantages in addressing the complex pathophysiology of nasal inflammatory diseases.Despite these advances, several challenges remain. The non-selective inhibition of glycolysis may interfere with epithelial repair and mucosal regeneration, leading to delayed wound healing. Technical limitations in dynamic metabolic monitoring and sampling precision hinder the accurate assessment of local nasal metabolism. Furthermore, current animal models, which predominantly rely on acute stimulation protocols, inadequately recapitulate the chronic tissue remodeling processes characteristic of human rhinitis.This review systematically summarizes glycolysis as a common metabolic node shared by different rhinitis subtypes, offering a novel theoretical basis for the development of precision therapeutic strategies targeting metabolic reprogramming.

INTRODUCTION: We aimed to understand the awareness and attitudes of elderly Southeast Asians towards telehealth services during the coronavirus disease 2019 (COVID-19) pandemic in this study. METHODS: In this qualitative study, 78 individuals from Singapore (51.3% female, mean age 73.0 ± 7.6 years) were interviewed via telephone between 13 May 2020 and 9 June 2020 during Singapore's first COVID-19 'circuit breaker'. Participants were asked to describe their understanding of telehealth, their experience of and willingness to utilise these services, and the barriers and facilitators underlying their decision. Transcripts were analysed using thematic analysis, guided by the United Theory of Acceptance Use of Technology framework. RESULTS: Of the 78 participants, 24 (30.8%) were able to describe the range of telehealth services available and 15 (19.2%) had previously utilised these services. Conversely, 14 (17.9%) participants thought that telehealth comprised solely home medication delivery and 50 (51.3%) participants did not know about telehealth. Despite the advantages offered by telehealth services, participants preferred in-person consultations due to a perceived lack of human interaction and accuracy of diagnoses, poor digital literacy and a lack of access to telehealth-capable devices. CONCLUSION Our results showed poor overall awareness of the range of telehealth services available among elderly Asian individuals, with many harbouring erroneous views regarding their use. These data suggest that public health education campaigns are needed to improve awareness of and correct negative perceptions towards telehealth services in elderly Asians.
Humans ; COVID-19/epidemiology* ; Female ; Telemedicine ; Aged ; Male ; Singapore/epidemiology* ; Qualitative Research ; Health Knowledge, Attitudes, Practice ; SARS-CoV-2 ; Aged, 80 and over ; Middle Aged ; Pandemics ; Awareness ; Asian People ; Southeast Asian People

INTRODUCTION: Radiofrequency ablation (RFA) avoids the complications of general anaesthesia, reduces length of hospitalisation and reduces morbidity from surgery. As such, it is a strong alternative treatment for patients with comorbidities who are not surgical candidates. However, to our knowledge, there have only been 1 systematic review and 3 combined systematic review and meta-analyses on this topic to date. This systematic review and meta-analysis seeks to evaluate the efficacy and safety of RFA in the treatment of papillary thyroid carcinoma (PTC) with longer follow-up durations. METHOD: PubMed, Embase and Cochrane databases were searched for relevant studies published from 1990 to 2021; 13 studies with a total of 1366 patients were included. The Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and Sandelowski et al.'s approach1 to "negotiated consensual validation" were used to achieve consensus on the final list of articles to be included. All authors then assessed each study using a rating scheme modified from the Oxford Centre for Evidence-Based Medicine. RESULTS: Pooled volume reduction rates (VRRs) from 1 to 48 months after RFA, complete disappearance rates (CDR) and complications were assessed. Pooled mean VRRs were 96.59 (95% confidence interval [CI] 91.05-102.13, I2=0%) at 12 months2-6 and 99.31 (95% CI 93.74-104.88, I2=not applicable) at 48 months.2,5 Five studies showed an eventual CDR of 100%.2,4,7-9 No life-threatening complications were recorded. The most common complications included pain, transient voice hoarseness, fever and less commonly, first-degree burn. CONCLUSION RFA may be an effective and safe alternative to treating PTC. Larger clinical trials with longer follow-up are needed to further evaluate the effectiveness of RFA in treating PTC.
Humans ; Radiofrequency Ablation/methods* ; Thyroid Cancer, Papillary/surgery* ; Thyroid Neoplasms/surgery* ; Treatment Outcome ; Postoperative Complications/etiology*

INTRODUCTION: Degenerative mitral stenosis (DMS) is frequently cited as increasing in prevalence in the developed world, although comparatively little is known about DMS in comparison to rheumatic mitral stenosis (RMS). METHOD: A retrospective observational study was conducted on 745 cases of native-valve mitral stenosis (MS) with median follow-up time of 7.25 years. Clinical and echocardiographic parameters were compared. Univariate and multivariate Cox regression analyses were performed for a composite of all-cause mortality and heart failure hospitalisation. RESULTS: Patients with DMS compared to RMS were older (age, mean ± standard deviation: 69.6 ± 12.3 versus [vs] 51.6 ± 14.3 years, respectively; P<0.001) and a greater proportion had medical comorbidities such as diabetes mellitus (78 [41.9%] vs 112 [20.0%], P<0.001). The proportion of cases of degenerative aetiology increased from 1.1% in 1991-1995 to 41.0% in 2016-2017. In multivariate analysis for the composite outcome, age (hazard ratio [HR] 95% confidence interval [CI] of 1.032 [1.020-1.044]; P<0.001), diabetes mellitus (HR 1.443, 95% CI 1.068-1.948; P=0.017), chronic kidney disease (HR 2.043, 95% CI 1.470-2.841; P<0.001) and pulmonary artery systolic pressure (HR 1.019, 95% CI 1.010- 1.027; P<0.001) demonstrated significant indepen-dent associations. The aetiology of MS was not independently associated with the composite outcome. CONCLUSION DMS is becoming an increasingly common cause of native-valve MS. Despite numerous clinical differences between RMS and DMS, the aetiology of MS did not independently influence a composite of mortality or heart failure hospitalisation.
Humans ; Mitral Valve Stenosis/etiology* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Rheumatic Heart Disease/mortality* ; Echocardiography ; Hospitalization/statistics & numerical data* ; Heart Failure/epidemiology* ; Singapore/epidemiology* ; Proportional Hazards Models ; Diabetes Mellitus/epidemiology*

INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

Objective:To explore a factor analysis method for job training needs based on "P4 medicine", and to provide evidence-based support for optimizing continuing education systems for medical staff in military rest homes and sanatoriums.Methods:A cross-sectional study was conducted with 95 medical staff from military rest homes and sanatoriums within the support system who participated in job training at Xinqiao Hospital. A structured questionnaire was developed based on the "P4 medicine" framework. After two rounds of Delphi expert consultation, 46 core indicators were selected. A principal component analysis was used to extract common factors, and a model of hierarchical needs was constructed by combining varimax rotation and entropy weight methods.Results:Four common factors were extracted, accounting for 81.564% cumulative variance. The first factor "dynamic updating of geriatric medical knowledge" (31.83%) covered clinical core competencies in managing geriatric comorbidities and recognizing critical values. The second factor "emergency responsiveness and personalized care" (26.05%) focused on military medical regulations, emergency treatment protocols, and tailored interventions. The third factor "multidisciplinary collaboration and leadership development" (12.41%) emphasized team reorganization in combat-ready scenarios. The fourth factor "integration of intelligent technologies" (11.29%) reflected data-driven decision-making needs. Entropy weight analysis highlighted dynamic medical knowledge updates (e.g., emergency skills with a weight of 0.050) and AI applications with a weight of 0.019 among the top 10% high-weight indicators.Conclusions:The "P4 medicine" effectively delineates the multidimensional training needs of grassroots medical personnel. Its four-dimensional structure (predictive, normative, collaborative, and innovative) provides a theoretical framework for curriculum design. We recommend constructing tiered training modules prioritizing technology-enabled mechanisms to enhance the precision and sustainability of geriatric healthcare services.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.