ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.

Diabetic macular edema(DME)may occur at any stage of diabetic retinopathy(DR)and represents a significant cause of visual impairment in patients with DR. The pathogenesis of DME is complex, involving numerous risk factors. Recent studies have increasingly revealed that the occurrence and development of DME represents an intertwined pathophysiological process involving metabolic disorders, disruption of the blood-retinal barrier, amplified inflammatory responses, hemodynamic alterations, and the formation of hypoxic microenvironments. Multiple risk factors, including hyperglycaemia, dyslipidaemia, and genetic factors, synergistically drive this process. Risk factors and pathogenesis are a dynamic, interactive relationship in the progression of disease. Comprehensive management of risk factors such as blood glucose and blood lipids, along with multi-target interventions on core pathogenic mechanisms—such as combined anti-vascular endothelial growth factor(VEGF)and anti-inflammatory treatments, exploration of gene therapy and regulation of metabolic pathways—are expected to become key strategies for delaying the progression of DME.

Purpose: Maintaining the quality of Single Best Answer (SBA) questions remains a challenge in medical education, especially as artificial intelligence (AI)-generated items become more common. While considerable attention has been paid to AI question generation, the vetting process is under-explored and difficult to scale. Methods: This study investigates the feasibility and reliability of using a large language model to support the vetting of SBA questions. An AI-based reviewer, QA-bot, was developed using custom GPT and embedded with 25 criteria aligned with Bloom’s taxonomy (Levels 1–3). QA-bot and two experienced educators independently evaluated 32 AI-generated SBA questions using the shared evaluation rubric. Results: The rubric showed high internal consistency (Cronbach’s alpha=0.878), and strong inter-rater reliability between human reviewers (intraclass correlation coefficient [ICC]=0.893). QA-bot demonstrated good alignment with human raters (ICC=0.861 and 0.840). While the AI performed well on objective, rule-based criteria, it was less consistent in detecting irrelevant complexity and accurately judging difficulty. Conclusion These findings suggest that AI can function as an efficient first-pass reviewer, improving consistency and reducing workload, with human oversight remaining essential for educational and clinical relevance.

Background and Objectives: Heart failure (HF) imposes a significant global burden, yet awareness and implementation of guideline-directed management remain suboptimal. This study evaluated HF awareness, diagnostic patterns, and therapeutic strategies among physicians in Korea. Methods: A nationwide online survey was conducted from July to August 2019, targeting primary care physicians (PCPs; n=8,000) and hospital-based cardiology specialists (n=1,339) across Korea. The questionnaire comprised 23 items covering baseline characteristics, perceptions of HF prognosis, diagnostic approaches, and treatment practices. Results: A total of 543 physicians responded (209 PCPs and 334 cardiology specialists). While the majority correctly defined HF, a substantial proportion underestimated the lifetime risk and poor prognosis. Cardiology specialists were more likely than PCPs to use objective diagnostic tools, including echocardiography (97% vs. 61%, p<0.001) and natriuretic peptide testing (90% vs. 57%, p<0.001). Among PCPs, 29% reported diagnosing HF based on symptoms and physical findings without objective testing, and 27% reported referring patients to general hospitals for diagnostic evaluation. Prescription rates for guideline-directed medical therapies, including renin-angiotensin system blockers and beta-blockers, were consistently higher among cardiology specialists.PCPs more frequently cited advanced age as a barrier to prescribing evidence-based medications. Conclusions Physicians’ awareness and clinical practices regarding HF in Korea remain suboptimal. Given the growing burden, high mortality, and substantial costs of HF, early detection, appropriate diagnostic evaluation, and timely referral are essential. Targeted education and system-level strategies to improve guideline implementation, particularly in primary care settings, are warranted.

BACKGROUND: The beneficial effects of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on adverse cardiac outcomes in diabetic patients are well-established. However, the effects of SGLT2i against cancer therapy-related cardiotoxicity remain understudied. We investigated the association between SGLT2i and cardiac outcomes in cancer patients. METHODS: PubMed, Embase, and the Cochrane Library were searched from their inception until September 30, 2024 for studies evaluating the effects of SGLT2i in patients with cancer. The primary outcomes included incident heart failure (HF), HF exacerbation, HF hospitalization, atrial fibrillation/atrial flutter (AF/AFL), myocardial infarction, and all-cause mortality. The secondary outcomes included acute kidney injury and sepsis. Odds ratio (OR) with 95% CI was pooled. RESULTS: Thirteen studies with 85,596 patients were included. Compared to non-SGLT2i use, SGLT2i treatment was associated with lower risks of incident HF (OR = 0.51, 95% CI: 0.32-0.79, P = 0.003), HF exacerbation (OR = 0.74, 95% CI: 0.63-0.87, P < 0.001), AF/AFL (OR = 0.67, 95% CI: 0.55-0.82, P < 0.001), myocardial infarction (OR = 0.61, 95% CI: 0.41-0.90, P = 0.01), and all-cause mortality (OR = 0.44, 95% CI: 0.28-0.69, P < 0.001), but not for HF hospitalization (OR = 0.58, 95% CI: 0.22-1.55, P = 0.28). As for safety outcomes, SGLT2i use was associated with lower risks of acute kidney injury (OR = 0.68, 95% CI: 0.57-0.81, P < 0.001) and sepsis (OR = 0.32, 95% CI: 0.23-0.44, P < 0.001). CONCLUSIONS SGLT2i were associated with lower risks of incident HF, HF exacerbation, AF/AFL, myocardial infarction, all-cause mortality, acute kidney injury, and sepsis in cancer patients.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE: The molecular biology of alleles of ABO blood group A_el and B_el subtype from two samples was analyzed to explore the effect of mutations on the structure of glycosyltransferase. METHODS: The ABO phenotypes were identified by serological techniques, then exons 6 and 7 of ABO gene were amplified and sequenced, combined with haplotype analysis to determine the genotypes. Finally, homology modeling of the mutated A/B glycosyltransferase were conducted by Modeller software and the effect of mutations on the spatial structure was analyzed by PyMol software. RESULTS: The serological phenotypes of the two samples were A_el and B_el, and their genotypes were ABO*AW.37/ABO*O.01.01 and ABO*BEL.03/ABO*O.01.01, respectively. The three-dimensional structure modeling of the protein showed that, compared to the wild-type glycosyltransferase, two hydrogen bonds between the side chain of p.Glu314 and surrounding amino acid disappeared in the p.Lys314Glu mutant GTA; the hydrogen bonds between the side chain of p.Trp168 and surrounding amino acid also disappeared, and the hydrogen bond between the main chain of p.Trp168 and p.Gly165 was shortened to 3.3 Å in the p.Arg168Trp mutant GTB. CONCLUSION Mutations in exon 7 of ABO gene c.940A>G and c.502C>T are keys to the formation of AW.37 and BEL.03 alleles, resulting in decreased expression of A and B antigens, respectively.
ABO Blood-Group System/classification* ; Humans ; Genotype ; Mutation ; Alleles ; Glycosyltransferases/genetics* ; Exons ; Haplotypes ; Phenotype ; Models, Molecular

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female