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.

This study employed bioinformatics to screen the feature genes related to efferocytosis in diabetic kidney disease(DKD) and explores traditional Chinese medicine(TCM) regulating these feature genes. The GSE96804 and GSE30528 datasets were integrated as the training set, and the intersection of differentially expressed genes and efferocytosis-related genes(ERGs) was identified as DKD-ERGs. Subsequently, correlation analysis, protein-protein interaction(PPI) network construction, enrichment analysis, and immune infiltration analysis were performed. Consensus clustering was conducted on DKD patients based on the expression levels of DKD-ERGs, and the expression levels, immune infiltration characteristics, and gene set variations between different subtypes were explored. Eight machine learning models were constructed and their prediction performance was evaluated. The best-performing model was evaluated by nomograms, calibration curves, and external datasets, followed by the identification of efferocytosis-related feature genes associated with DKD. Finally, potential TCMs that can regulate these feature genes were predicted. The results showed that the training set contained 640 differentially expressed genes, and after intersecting with ERGs, 12 DKD-ERGs were obtained, which demonstrated mutual regulation and immune modulation effects. Consensus clustering divided DKD into two subtypes, C1 and C2. The support vector machine(SVM) model had the best performance, predicting that growth arrest-specific protein 6(GAS6), S100 calcium-binding protein A9(S100A9), C-X3-C motif chemokine ligand 1(CX3CL1), 5'-nucleotidase(NT5E), and interleukin 33(IL33) were the feature genes of DKD. Potential TCMs with therapeutic effects included Astragali Radix, Trionycis Carapax, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma, which mainly function to clear heat, replenish deficiency, activate blood, resolve stasis, and promote urination and drain dampness. Molecular docking revealed that the key components of these TCMs, including β-sitosterol, quercetin, and sitosterol, exhibited good binding activity with the five target genes. These results indicated that efferocytosis played a crucial role in the development and progression of DKD. The feature genes closely related to both DKD and efferocytosis, such as GAS6, S100A9, CX3CL1, NT5E, and IL33, were identified. TCMs such as Astragali Radix, Trionycis Carapa, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma may provide a new therapeutic strategy for DKD by regulating efferocytosis.
Humans ; Computational Biology ; Diabetic Nephropathies/physiopathology* ; Protein Interaction Maps ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; Phagocytosis/genetics* ; Efferocytosis

Wastewater-based epidemiology has emerged as a transformative surveillance tool for estimating substance consumption and monitoring disease prevalence, particularly during the COVID-19 pandemic. It enables the population-level monitoring of illicit drug use, pathogen prevalence, and environmental pollutant exposure. In this perspective, we summarize the key challenges specific to the Chinese context: (1) Sampling inconsistencies, necessitating standardized 24-hour composite protocols with high-frequency autosamplers (≤ 15 min/event) to improve the representativeness of samples; (2) Biomarker validation, requiring rigorous assessment of excretion profiles and in-sewer stability; (3) Analytical method disparities, demanding inter-laboratory proficiency testing and the development of automated pretreatment instruments; (4) Catchment population dynamics, reducing estimation uncertainties through mobile phone data, flow-based models, or hydrochemical parameters; and (5) Ethical and data management concerns, including privacy risks for small communities, mitigated through data de-identification and tiered reporting platforms. To address these challenges, we propose an integrated framework that features adaptive sampling networks, multi-scale wastewater sample banks, biomarker databases with multidimensional metadata, and intelligent data dashboards. In summary, wastewater-based epidemiology offers unparalleled scalability for equitable health surveillance and can improve the health of the entire population by providing timely and objective information to guide the development of targeted policies.
China/epidemiology* ; Humans ; Wastewater/analysis* ; COVID-19/epidemiology* ; Public Health ; Wastewater-Based Epidemiological Monitoring ; SARS-CoV-2

The choice of biopsy method is critical in diagnosing prostate cancer (PCa). This retrospective cohort study compared systematic biopsy (SB) or cognitive fusion-targeted biopsy combined with SB (CB) in detecting PCa and clinically significant prostate cancer (csPCa). Data from 2572 men who underwent either SB or CB in Fudan University Shanghai Cancer Center (Shanghai, China) between January 2019 and December 2023 were analyzed. Propensity score matching (PSM) was used to balance baseline characteristics, and detection rates were compared before and after PSM. Subgroup analyses based on prostate-specific antigen (PSA) levels and Prostate Imaging-Reporting and Data System (PI-RADS) scores were performed. Primary and secondary outcomes were the detection rates of PCa and csPCa, respectively. Of 2572 men, 1778 were included in the PSM analysis. Before PSM, CB had higher detection rates for both PCa (62.9% vs 52.4%, odds ratio [OR]: 1.54, P < 0.001) and csPCa (54.9% vs 43.3%, OR: 1.60, P < 0.001) compared to SB. After PSM, CB remained superior in detecting PCa (63.1% vs 47.9%, OR: 1.86, P < 0.001) and csPCa (55.0% vs 38.2%, OR: 1.98, P < 0.001). In patients with PSA 4-12 ng ml -1 (>4 ng ml -1 and ≤12 ng ml -1 , which is also applicable to the following text), CB detected more PCa (59.8% vs 40.7%, OR: 2.17, P < 0.001) and csPCa (48.1% vs 27.7%, OR: 2.42, P < 0.001). CB also showed superior csPCa detection in those with PI-RADS 3 lesions (32.1% vs 18.0%, OR: 2.15, P = 0.038). Overall, CB significantly improves PCa and csPCa detection, especially in patients with PSA 4-12 ng ml -1 or PI-RADS 3 lesions.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Propensity Score ; Retrospective Studies ; Middle Aged ; Aged ; Image-Guided Biopsy/methods* ; Prostate-Specific Antigen/blood* ; Prostate/diagnostic imaging*

Objective:To establish a preliminary performance validation protocol for the bioinformatics procedure of metagenomic next-generation sequencing (mNGS) in clinical laboratories.Methods:Three types of simulated datasets were designed and the CatⅠ dataset mainly consisted of pathogen reference genomes and human sequences. CatⅠA was a dataset composed of common pathogens mixed with human sequences and was used to evaluate the inclusiveness, accuracy, recall rates, precision, F1-Score, and other indicators of the mNGS bioinformatics procedure. CatⅠB was a dataset composed of closely related species of common pathogens mixed with human sequences, which was used to evaluate the discriminating ability of closely related species of bioinformatics procedure by calculating the detection rates and the relative abundance ratio of closely related species. The real data of 200 clinical samples was selected to construct CatⅡ and the simulated dataset consisted of colonized bacteria, experimental environment bacteria, reagent engineering bacteria, pathogen reference genomes, and human sequences, which was used to evaluate the sensitivity, specificity, and accuracy of bioinformatics pipeline for pathogens detection. The CatⅢ dataset was obtained from the negative bronchoalveolar lavage fluid BALF sequencing data mixed with 20 rare pathogens sequences in order to evaluate the positive detection rates and recall rates of rare pathogens in the bioinformatics analysis.Results:The analysis of the CatⅠA dataset showed that the positive consistency rate, inclusiveness, precision and accuracy of the bioinformatics peocedure under three sequence gradients were all greater than 99%, with a recall rate of 72.31% (95% CI 69.61%-75.01%) and a F1 Score of 82.00% (95% CI 79.77%-84.22%). In the CatⅠB dataset, the closely related species could be effectively detected at all sequence and proportion gradients, and the relative abundance ratio of closely related species was within 2 times of the design ratio except for the coronavirus, haemophilus, primate bocaparvovirus, human respiratory syncytial virus, and eimeria, indicating good ability to identify the closely related species. All the 24 species of pathogens included in CatⅡ dataset were effectively detected, with the sensitivity, specificity, and accuracy all greater than 90%. All rare pathogens were detected in the CatⅢ dataset, with a detection rate of 100%. Conclusions:With the simulated datasets, the performance validation scheme for the mNGS bioinformatics analysis was preliminary established and could evaluate the accuracy of sequence classification, the ability to identify the closely related species, and detection ability of common and rare pathogens, which may provide some references for the construction of mNGS process.

With the rise of data-intensive research, data literacy has become a critical capability for improving scientific data quality and achieving artificial intelligence (AI) readiness. In the biomedical domain, data are characterized by high complexity and privacy sensitivity, calling for robust and systematic data management skills. This paper reviews current trends in scientific data governance and the evolving policy landscape, highlighting persistent challenges such as inconsistent standards, semantic misalignment, and limited awareness of compliance. These issues are largely rooted in the lack of structured training and practical support for researchers. In response, this study builds on existing data literacy frameworks and integrates the specific demands of biomedical research to propose a comprehensive, lifecycle-oriented data literacy competency model with an emphasis on ethics and regulatory awareness. Furthermore, it outlines a tiered training strategy tailored to different research stages-undergraduate, graduate, and professional, offering theoretical foundations and practical pathways for universities and research institutions to advance data literacy education.
Artificial Intelligence ; Humans ; Biomedical Research

OBJECTIVE: To explore the feasibility and effectiveness of repairing surgical defect in pharyngo-laryngeal malignant tumor with free rectus femoris flap. METHODS: The clinical data of 34 patients with surgical defects in pharyngo-laryngeal malignant tumor who met the selection criteria between July 2014 and August 2024 were retrospectively analyzed. There were 25 males and 9 females, aged 25-82 years, with a median age of 54 years. The disease duration ranged from 2 months to 2 years, with a median of 7 months. The tumor locations included the oropharynx, hypopharynx, cervical esophagus, and larynx. Pathological types included squamous cell carcinoma (29 cases), myoepithelial carcinoma (2 cases), adenoid cystic carcinoma (1 case), and diffuse large B-cell lymphoma (2 cases). TNM staging: 16 cases of T ₄N ₁M ₀, 3 cases of T ₄N ₂M ₀, 3 cases of T ₄N ₀M ₀, 10 cases of T ₃N ₁M ₀, and 2 cases of T ₃N ₀M ₀. The 2017 American Joint Committee on Cancer (AJCC) staging was stage Ⅲ in 2 cases and stage Ⅳ in 32 cases. The blood supply of the proximal rectus femoris muscle was observed by enhanced CT of the lower limb vessels before operation, and the surgical defects ranged from 3.0 cm×2.0 cm to 12.0 cm×8.5 cm. The blood supply and perforators of rectus femoris muscle were explored during operation, and the free rectus femoris flap pedicled with the direct vascular stem of rectus femoris muscle was used to repair the defect. For the patients with pharyngeal fistula or obvious neck swelling after operation, the blood supply of the flap was analyzed by vascular enhanced CT to determine the corresponding strategies of nutritional support, anti-infection, dressing change and drainage. Radiotherapy and chemotherapy were supplemented in 27 patients with lymph node metastasis after operation. RESULTS: All the 34 patients were followed up 1-10 years, with an average of 3 years. The flap was found to be necrotic by fibrolaryngoscopy at 1 week after operation in 2 cases, and the incision healed after dressing change and nutritional support, and no reoperation was performed. The flap was in good condition at 1 week after operation in 4 cases, and the signs of gradual necrosis of the flap were found within 1 month after operation, of which 2 cases were healed after dressing change, 1 case was removed the necrotic tissue by reoperation, and 1 case was healed after pectoralis major myocutaneous flap was used to repair the pharyngeal tissue defect. The flaps survived in 28 cases, including 4 cases of pharyngeal fistula, which healed by dressing change. Twenty-two cases achieved satisfactory results in swallowing or phonation. Two patients with total laryngectomy and voice reconstruction underwent reoperation to seal the voice tube because of postoperative aspiration. During the follow-up, 1 case had tracheal stomal recurrence, 2 cases had bone metastasis, and 1 case had bone and lung metastasis. CONCLUSION The free rectus femoris flap has good flexibility, the volume of the flap is easy to adjust, and the incision of the donor site is concealed, which is expected to become a new choice for the repair of the surgical defect in pharyngo-laryngeal malignant tumor.
Humans ; Male ; Middle Aged ; Female ; Aged ; Adult ; Plastic Surgery Procedures/methods* ; Retrospective Studies ; Laryngeal Neoplasms/pathology* ; Aged, 80 and over ; Pharyngeal Neoplasms/pathology* ; Free Tissue Flaps/blood supply* ; Quadriceps Muscle/transplantation* ; Surgical Wound/surgery* ; Treatment Outcome

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

Objective To investigate the effect of G9a histone methyltransferase inhibitor BIX01294 on the proliferation of vascular smooth muscle cell(VSMC)and its underlying mechanism.Methods Twelve SD rats were divided into the control group and the treatment group,with 6 rats in each group.The rats were anesthetized by intraperitoneal injection with sodium pentobarbital,then exposed the common carotid artery and the internal and external carotid artery after disinfection and skin preparation,ligated the distal end of the internal and external jugular veins,clamped the proximal end of the common carotid artery,cut the external carotid artery,inserted the balloon catheter,blocked the blood flow by compression,and ligated the proximal end of the external carotid artery after withdrawing the balloon.The common carotid artery clamping state of rats in the treatment group was maintained after withdrawing the balloon,then restored the blood flow after perfusion with 100 μmol/L BIX01294 solution for 30 seconds;rats in the control group were restored the blood flow after perfusion with PBS for 30 seconds.VSMC were divided into the normal group and the BIX01294 groups.Cells in the normal group were cultured in low glucose medium containing 2%fetal bovine serum,and cells in the BIX01294 groups were co-treated with 2.5,5.0,7.5 and 10.0 μmol/L BIX01294 on the basis of the normal group,respectively.CCK-8 assay and EDU assay were used to detect the cell activity and proliferative ability respectively,to screen appropriate concentration of BIX01294.The cell apoptosis was detected by TUNEL assay between the normal group and the BIX01294 group,and the control group and the treatment group.Western blot was used to detect the expression levels of autophagy-and apoptosis-related proteins in the normal group and BIX01294 group.Results Compared with 0 μmol/L,the activity and proliferative ability of VSMC decreased in a concentration-dependent manner after treatment with BIX01294 at different concentrations(P<0.05).Compared with the normal group,the apoptosis level of VSMC in the BIX01294 group was increased(P<0.05),the expression of VSMC autophagy-and apoptosis-related proteins of LC3Ⅰ/Ⅱ and Bax were up-regulated(P<0.05),and the expression of Bcl-2 and p62 proteins were down-regulated(P<0.05).In vivo test results showed that BIX01294 local perfusion aggravated the apoptosis of carotid VSMC.Conclusion BIX01294 activates VSMC autophagy and apoptosis and inhibits its proliferation.

The aim of this experiment was to study the effects of different feeding modes on growth performance,blood biochemical indexes and intestinal flora of lactating Holstein male calves.Twenty-four newborn Holstein male calves with body mass of(40.00±1.01)kg and similar day old were selected and randomly divided into four groups of six calves each.The subgroups were low-milk group(LM),high-milk group(HM),high-milk milk replacer feeding group(HMR),and low-milk switching to high-milk milk replacer feeding group(CMR).The results showed that:At 45 d,the body mass of calves in the HM group was significantly higher than that of calves in the other groups(P＜0.05),and at 60 d,the body mass of calves in the HM group was significantly higher than that of calves in the LM &.CMR groups(P＜0.05).At 90 d,the body mass of calves in the LM group was significantly higher than that of calves in the HM group.Throughout the ex-perimental period,the average daily weight gain and average pellet feed intake of calves in the LM group were significantly higher than that of calves in the HM group(P＜0.05).The calf globulin level in the HMR group was significantly higher than that in the LM and HM groups(P＜0.05);the plasma immunoglobulin A level of calves in the HM group was significantly lower than that of calves in the LM and HMR groups(P＜0.05);and the plasma immunoglobulin M level of calves in the HM group was significantly higher than that of calves in the LM and CMR groups(P＜0.05),and HMR group was also significantly higher than that of LM group(P＜0.05);plasma glutathione peroxidase level of calves in HMR group was significantly higher than that of LM group(P＜0.05);plasma malondialdehyde level of calves in LM group was significantly higher than that of calves in HMR and HM groups(P＜0.05),and CMR group was also significantly higher than that of HM group(P＜0.05).Relative abundance of Thermodesulfovibrio was higher in the HM group(P＜0.05),relative abundance of Bacteroidetes in the LM group was significantly higher than that in the HMR and HM groups(P＜0.05),relative abundance of Blautia in the HM group(P＜0.05),and relative abundance of Corynebacterium in the CMR group was significantly higher than that in the LM and HM groups(P＜0.05).In summary,calves in the LM group had better weaning weights and pellet feed intake;calves in the CMR group could compensate for growth by supplemental feeding of milk replacer to obtain more optimal weaning weights and pel-let feed intake;the HMR group proved that milk-free feeding could ensure stable growth of calves;and calves in the HM group had a better pre-lactation growth performance,lower levels of oxida-tive stress,and a healthier fecal flora.