1.Secondary stent placement for sealing distal tears in aortic intramural hematoma and enhancing distal aortic remodeling: A retrospective study in a single center
Bailang CHEN ; Zanxin WANG ; Xianmian ZHUANG ; Haibing LIU ; Minxin WEI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(06):944-951
Objective To evaluate the clinical efficacy of second-stage endovascular therapy for patients with aortic intramural hematoma (IMH) who developed progression of the distal hematoma into dissection-like changes after an initial procedure. Methods A retrospective analysis was conducted on patients at the University of Hong Kong-Shenzhen Hospital from July 2020 to December 2022. These patients had previously undergone a first-stage procedure to treat the proximal lesion of an IMH. However, follow-up examinations revealed a persistent distal hematoma, the presence of a distal entry tear, and progression of the hematoma into localized or extensive dissection-like changes, which could be accompanied by localized contrast enhancement. These patients then underwent a second-stage stent-graft intervention. The initial procedures included open surgery with total aortic arch replacement or endovascular stent-graft placement to seal the proximal entry tear. In the second-stage procedure, the aorta was divided into three zones based on its anatomy, and zonal stent-graft placement was performed to seal the entry tear and promote thrombosis of the false lumen. Results A total of 18 patients (15 males, 3 females) were included, with a mean age of (53.5±10.6) years (range, 39 to 76 years). The median operation time was 38.0 (29.5, 58.5) min, and the median intraoperative blood loss was 20.0 (20.0, 30.0) mL. The technical success rate was 100.0%. Intraoperative and postoperative imaging confirmed successful exclusion of the distal entry tear of the IMH, with no endoleak, stenosis or occlusion of visceral branches. There were no major perioperative complications, such as death, paraplegia, or visceral ischemia. During follow-up, complete thrombosis or resolution of the false lumen was observed in all patients. Conclusion For patients with residual entry tears and new-onset dissection-like changes in the distal aorta after the first-stage procedure for IMH, second-stage stent-graft placement can effectively seal the entry tear, promote false lumen thrombosis and hematoma resolution, and improve distal aortic remodeling, demonstrating favorable short- to mid-term outcomes.
3.Associations between Metabolic Syndrome Indicators and Colon Polyps: A Mendelian Randomization Study
Dongya CHEN ; Hong XU ; Zhaolin ZHANG ; Fang CHEN ; Qingqing LU ; Feng PAN
Endocrinology and Metabolism 2026;41(2):256-266
Background:
While observational studies have suggested a potential link between metabolic syndrome (MetS) and an increased risk of colon polyps, the causal nature of this association remains uncertain. This study used a two-sample Mendelian randomization (MR) approach to evaluate the relationship between MetS and colon polyps.
Methods:
A two-sample MR analysis was performed using data on MetS, its indicators, and colon polyps obtained from publicly available genome-wide association studies in the Integrative Epidemiology Unit (IEU) and MAGIC databases. Outliers were removed using Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), followed by MR calculations and false discovery rate (FDR) correction. The primary analysis was conducted with the inverse variance-weighted (IVW) method.
Results:
The IVW results indicated no association between hypertension, hyperlipidemia, or diabetes and the risk of colon polyps. High-density lipoprotein cholesterol (HDL-C) (P=0.005), 2-hour glucose (P=0.004), glycated hemoglobin A1c (P=0.004), and the ratio of omega-6 to omega-3 fatty acids (P<0.001) were negatively associated with colon polyps. Conversely, body mass index (BMI) (P<0.001), body fat percentage (P=0.002), waist-to-hip ratio adjusted for BMI (P=0.001), total cholesterol (TC) (P=0.002), triglycerides (TG) (P<0.001), and both omega-3 (P<0.001) and omega-6 fatty acid levels (P=0.02) were positively associated with colon polyps. The relationships between these metabolic indicators and colon polyps remained significant after FDR correction.
Conclusion
Obesity-related traits, TC, and TG may increase the risk of colon polyps, while HDL-C may have a protective effect.
4.Influence of Footwear on Foot Comfort of Workers Engaged in Prolonged Standing Occupations: A Systematic Review
Lu-ping KANG ; Tai-sheng GONG ; Xiao-hong QUAN ; Chen ZHANG
Safety and Health at Work 2026;17(1):24-32
Prolonged standing work can lead to various lower limb health issues. Footwear, as a convenient and noninvasive intervention, plays a key role in foot protection. The purpose of this review was to evaluate the impact of footwear characteristics on foot comfort among workers engaged in prolonged standing occupations. A systematic search of PubMed, Web of Science, Scopus, and the Cochrane Library was conducted until March 2025 for experimental and observational studies; the review is registered in International Prospective Register of Systematic Reviews (CRD420251003253).Given the diversity of study designs, participant characteristics, and outcome measures, results were synthesized narratively, organizing findings by footwear design factors. The synthesis indicated that soft soles reduce foot impact and fatigue but offer limited support, whereas hard soles enhance stability but may cause localized pressure and discomfort. Sole hardness should balance cushioning and support based on activity: hard soles for standing and soft soles for walking. Insole hardness must be carefully considered as semirigid arch supports can cause discomfort. Most insoles improve pressure distribution by adjusting arch loading, and some enhance intrinsic foot muscles by promoting toe engagement, reducing leg swelling. Custom orthotic insoles outperform standard ones in comfort and balance. Future research should promote interdisciplinary collaboration with footwear designers to explore key design parameters and establish a scientific framework for protective footwear.
5.Engineered Bacteriophages for The Treatment of Multidrug-resistant Bacterial Infections
Yu-Ying CHEN ; Chun-Mei HUANG ; Jin-Zhi PAN ; De-Liang LIU ; Yang ZHOU ; Gui-Qin DAI ; Peng-Fei ZHAO ; Hong-Zhou LU ; Ming-Bin ZHENG
Progress in Biochemistry and Biophysics 2026;53(6):1581-1596
Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.
6.Reactive and Enzyme-activated Probe Strategies for Imaging Acute Kidney Injury
Ru-Long CHEN ; Ting-Fei XIE ; Jin-Xin ZHANG ; Jia-Ting CHEN ; Jie LI ; Peng-Fei ZHANG ; Ji-Hong CHEN ; Lin-Tao CAI
Progress in Biochemistry and Biophysics 2026;53(6):1622-1637
Acute kidney injury (AKI) is a prevalent and life-threatening clinical syndrome characterised by a rapid decline in renal function and diverse pathological etiologies. The condition has been demonstrated to be associated with elevated mortality rates and an increased risk of progression to chronic kidney disease. At present, clinicians depend heavily on conventional functional markers, such as serum creatinine and urine output, for the diagnosis and staging of the disease. It is evident that these conventional indicators characteristically manifest a considerable temporal delay and only undergo modification subsequent to considerable tissue damage. This severely restricts the timeframe for early detection and timely therapeutic intervention. Furthermore, standard markers fail to provide specific biological information regarding the underlying cellular injury mechanisms. The utilisation of advanced probe technologies in molecular imaging offers a robust alternative to overcome these inherent diagnostic limitations.This comprehensive review systematically evaluates recent progress in the design and application of two primary categories of molecular imaging tools for acute kidney disease, specifically reactive probes and enzyme-activated probes. Reactive probes are engineered to specifically interact with redox-active chemical species, including hydrogen peroxide, peroxynitrite, hypochlorous acid, and sulfur dioxide. Because oxidative stress constitutes a primary early event in acute renal tubular damage, these probes enable researchers and clinicians to visualize early cellular injury and radical accumulation well before global renal functional decline becomes evident. We discuss the application of these reactive probes across multiple imaging modalities including fluorescence imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), and photoacoustic techniques. Photoacoustic imaging combines high spatial resolution with deep tissue penetration and has successfully demonstrated the ability to provide diagnostic alerts up to 12 h before any detectable rise in serum creatinine levels. Additionally, specific reactive probes have shown promising translational potential when tested by high-throughput screening in clinical human urine samples. Enzyme-activated probes target the specific catalytic activity of disease-relevant enzymes. These include well-documented renal tubular structural biomarkers such as NAG, GGT, and ALP, along with apoptosis-related caspases and specific nitroreductases. By responding only to enzymatic cleavage, these tools provide highly specific and pathology-directed imaging readouts. Recent structural design strategies in this field have advanced significantly beyond single-enzyme detection. Researchers are now focusing on sophisticated dual-target recognition to minimize background noise, multimodal integration to cross-validate imaging signals, and theranostic applications where probes simultaneously deliver diagnostic feedback and therapeutic agents to injured tissues. Nanotechnology serves as a fundamental enabler for realizing these advanced probe functions. By precisely optimizing nanoparticle parameters such as hydrodynamic size, surface charge, and targeting ligands, researchers can achieve amplified signal output, highly precise kidney delivery, and protection against premature degradation in the systemic circulation. For example, modifying surface charges can significantly enhance the active uptake of nanoprobes by damaged renal tubular epithelial cells.While preclinical probe development has progressed rapidly, moving these technologies into routine clinical practice remains a major challenge. We analyze the translational feasibility and current obstacles from biological, technological, and regulatory perspectives. Although biological targets such as KIM-1, FAP, and ALP have been validated in extensive patient cohorts, practical barriers severely limit their immediate clinical application. These obstacles involve complex changes in in vivo pharmacokinetics. During an acute injury episode, the extreme drop in the glomerular filtration rate alters probe clearance and can cause unwanted systemic accumulation or confusing background imaging signals. Other major hurdles include a lack of comprehensive long-term toxicity data and the absence of standardized manufacturing protocols to ensure batch-to-batch consistency. Future successful translation will require rigorous multi-center clinical studies to confirm the true diagnostic value of these probes over traditional markers. Researchers must also establish strict standardization of imaging procedures and comprehensive safety evaluations. Ultimately, this review provides a thorough reference framework for designing clinically translatable molecular probes and building a precision diagnostic imaging system for acute kidney injury.
7.Electroacupuncture Ameliorates NLRP3-mediated Pyroptosis in Spinal Cord Injury Rats by Reshaping The Gut Microbiota
Yin-Jie CUI ; Hong-Ru LI ; Jing-Yi LIU ; Hai-Lin DU ; Shu-Wen LIU ; Yuan YANG ; Chen-Guang ZHENG ; Jian-Qin XIANG ; Xiao-Juan SONG
Progress in Biochemistry and Biophysics 2026;53(5):1132-1153
ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.
8.Noninvasive Screening for Chronic Atrophic Gastritis Using Photoplethysmography-derived Meridian-labelled Harmonic Parameters
Yun-Qing LE ; Jian-Xin CHEN ; Ai-Ping CHEN ; Zhi-Hong LI
Progress in Biochemistry and Biophysics 2026;53(5):1178-1194
ObjectiveChronic atrophic gastritis (CAG) is usually diagnosed by gastroscopy and histopathological biopsy. These procedures remain the reference standard, but their invasive nature and resource requirements may limit their use in large-scale population screening and repeated follow-up. A convenient and reproducible method for noninvasive auxiliary screening may help identify individuals who require further endoscopic assessment. Fingertip photoplethysmography (PPG) provides a noninvasive recording of peripheral pulse waves and allows harmonic features to be extracted from the signal. In this study, the so-called meridian-related variables were defined as PPG-derived harmonic parameters labelled according to meridian nomenclature, rather than as direct measurements of meridian physiology. This study aimed to compare these harmonic parameters between patients with CAG and non-CAG controls, identify parameters that remained different after age adjustment, and develop a multivariable model for noninvasive auxiliary screening and pre-endoscopic risk stratification of CAG. MethodsA total of 343 participants were included, comprising 171 patients with CAG and 172 non-CAG controls. CAG diagnosis was established using gastroscopy and histopathology as the reference standard. Fingertip PPG signals were collected using a PPG-based pulse acquisition device. Eight PPG-derived harmonic parameters labelled according to meridian nomenclature were extracted for analysis. Between-group differences were first assessed using nonparametric tests. Age-adjusted analyses were then performed to reduce potential confounding by age. The false discovery rate (FDR) method was applied for multiple-comparison correction. A multivariable logistic regression model integrating age and multiple harmonic parameters was constructed. Model performance was evaluated using receiver operating characteristic (ROC) analysis and the area under the curve (AUC). Internal validation performance was assessed using stratified five-fold cross-validation and bootstrap optimism correction. Threshold performance was examined using both a high-specificity strategy and a Youden index-based cutoff. Decision curve analysis was used to evaluate the model’s net clinical benefit across a range of threshold probabilities. ResultsAll eight harmonic parameters were non-normally distributed. In the univariate analysis, the stomach-labelled harmonic parameter (ST), bladder-labelled harmonic parameter (BL), and liver-labelled harmonic parameter (LR) differed between the CAG and non-CAG groups. After age adjustment and FDR correction, only ST and BL remained statistically significant. Compared with non-CAG controls, patients with CAG showed higher ST values and lower BL values. This finding indicates an associated differential harmonic pattern that was not fully explained by age distribution. However, the discriminative ability of a single harmonic parameter was limited. The best-performing single indicator was ST, with an AUC of 0.652 (95% CI: 0.595-0.707). The multivariable model integrating age and multiple harmonic parameters achieved an AUC of 0.791 (95% CI: 0.743-0.835), representing an improvement of 0.139 over ST alone. In internal validation, stratified five-fold cross-validation yielded a mean AUC of 0.753 (95% CI: 0.715-0.781), and the bootstrap optimism-corrected AUC was 0.748. These results suggest that the model retained moderate discriminative performance after internal validation.At a specificity of at least 95%, the model achieved a sensitivity of only 40.4% (95% CI: 25.7%-49.7%). This high-specificity cutoff may be suboptimal as the preferred threshold for an initial screening setting because of the potential risk of missed CAG cases. The Youden index-based optimal cutoff was 0.419, corresponding to a sensitivity of 80.7% and a specificity of 62.8%. This threshold may better match the practical aim of noninvasive auxiliary screening, where sensitivity is usually prioritized to reduce missed cases. Decision curve analysis showed that, within a threshold probability range of 10%-55%, the model provided higher net clinical benefit than the reference strategies of recommending gastroscopy for all participants or for none. ConclusionPatients with CAG showed associated harmonic differences in fingertip PPG-derived features, mainly characterized by higher ST and lower BL values after age adjustment and FDR correction. Compared with a single harmonic parameter, the multivariable model showed better overall discrimination and retained moderate internal validation performance. These findings suggest that PPG-derived harmonic parameters labelled according to meridian nomenclature may provide auxiliary information for noninvasive auxiliary screening and front-line triage before gastroscopic confirmation in CAG. The present results support further validation rather than immediate clinical implementation. External validation in independent, multicenter, and preferably prospective screening cohorts is needed to assess the model’s generalizability, screening performance, and potential clinical utility.
9.Subtalar arthroereisis for treatment of pediatric flexible flatfoot:relationship between radiographic indicators and clinical efficacy
Guangtao LIAO ; Ziyu FENG ; Xiaoyong FU ; Qinglan ZHAO ; Chao CHEN ; Jinsong HONG
Chinese Journal of Tissue Engineering Research 2026;30(3):661-670
BACKGROUND:Pediatric flexible flatfoot is a common foot deformity that often leads to foot pain and reduced quality of life.OBJECTIVE:To explore the relationship between radiographic parameters and clinical efficacy of subtalar arthroereisis in the treatment of pediatric flexible flatfoot.METHODS:A retrospective study was conducted on 56 pediatric patients(mean age of 11.8 years)who underwent subtalar arthroereisis at Guangzhou Orthopedic Hospital between January 2022 and May 2023.All patients underwent detailed radiographic examinations and clinical evaluations before and after surgery,including the American Orthopaedic Foot & Ankle Society Ankle-Hindfoot score and Visual Analog Scale score.Paired t-tests and independent t-tests were used to compare changes in radiographic parameters and clinical scores before and after surgery.Correlation analyses were conducted to evaluate the relationship between radiographic parameters and clinical outcomes.RESULTS AND CONCLUSION:(1)All radiographic parameters significantly improved during the 8 to 12-month follow-up after surgery(P<0.001).(2)Clinical evaluation results indicated that the American Orthopaedic Foot & Ankle Society Ankle-Hindfoot score significantly improved from 66.2±6.0 preoperatively to 91.3±5.8 postoperatively,and the Visual Analog Scale score significantly decreased from 3.1±0.8 preoperatively to 1.3±0.8 postoperatively(P<0.001).(3)Independent t-tests showed a significant difference in postoperative the first metatarsal angle and Visual Analog Scale score grades(P=0.043),with a smaller the first metatarsal angle associated with less postoperative pain;preoperative lateral arch angle showed a significant difference between the"excellent"and"good"groups in postoperative American Orthopaedic Foot & Ankle Society Ankle-Hindfoot scores(P=0.033),suggesting that a smaller preoperative posterior arch angle might predict better postoperative foot function recovery.(4)Correlation analysis showed that preoperative posterior arch angle(r=-0.486,P<0.01)and heel pitch angle(r=-0.344,P<0.01)were significantly negatively correlated with postoperative American Orthopaedic Foot & Ankle Society Ankle-Hindfoot,while preoperative medial longitudinal arch angle(r=0.293,P<0.05)was significantly positively correlated with postoperative American Orthopaedic Foot & Ankle Society Ankle-Hindfoot.Postoperative medial longitudinal arch angle(r=0.331,P<0.05)and lateral arch angle(r=0.387,P<0.01)were significantly positively correlated with postoperative American Orthopaedic Foot & Ankle Society Ankle-Hindfoot,whereas postoperative Bohler's angle(r=-0.272,P<0.05),posterior arch angle(r=-0.461,P<0.01),and heel pitch angle(r=-0.318,P<0.01)were significantly negatively correlated with postoperative American Orthopaedic Foot & Ankle Society Ankle-Hindfoot.(5)It is concluded that subtalar arthroereisis is significantly effective in correcting pediatric flexible flatfoot,and improvements in radiographic parameters are closely related to clinical efficacy.Preoperative and postoperative radiographic evaluations can serve as important reference indicators for predicting postoperative clinical outcomes,guiding clinicians to optimize treatment plansand rehabilitation programs.
10.Compact Fundus Imaging System Using Shack-Hartmann Wavefront Sensing for High-speed Auto-focus
Zhe-Kai LIN ; Long CHEN ; Geng-Yong ZHENG ; Jin-Tian HUANG ; Jia-Xin DONG ; Shang-Pan YANG ; Wen-Zheng DING ; Ding-An HAN ; Xue-Hua WANG ; Ya-Guang ZENG
Progress in Biochemistry and Biophysics 2026;53(4):1076-1086
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.

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