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 aimed to establish an analytical method capable of simultaneously quantifying the prototype components of Si-Ni-San and screening their metabolites to elucidate its tissue distribution and metabolic characteristics in an ulcerative colitis (UC) mouse model. To this end, an integrated analysis strategy based on UPLC-QqQ-MS was developed and validated, combining the targeted quantification of 12 prototype components with a pseudo-targeted metabolite screening technique based on ion pair list-triggered data-dependent acquisition. Samples were extracted with 80% methanol (100 mg/mL) and processed with internal standards. Separation was achieved on a Waters Acquity UPLC HSS PFP column using a gradient elution with a mobile phase consisting of acetonitrile and 5 mmol/L ammonium acetate containing 0.1% formic acid. Analysis was performed using an electrospray ionization (ESI) source in multiple reaction monitoring mode. Methodological validation confirmed that all parameters met the requirements for bio-sample analysis. Application of this method revealed that the content of Si-Ni-San prototype components in the colon, liver, and kidneys of UC mice was significantly higher than that in healthy mice. Furthermore, the number of phase II metabolites was markedly greater than that of phase I metabolites in all tested samples. The results demonstrate the reliability of the established method and preliminarily reveal the tissue distribution characteristics of Si-Ni-San under UC conditions and its metabolism pattern dominated by phase II conjugation, which provides a methodological basis and experimental data for further in-depth research into its effective target tissues and pharmacodynamic material basis.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Objective:To evaluate the role of cannabinoid receptor 1 (CB1) in the spinal membrane in electroacupuncture (EA)-induced alleviation of morphine-triggered opioid-induced hyperalgesia (OIH) and the relationship with phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) in rats.Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 240-260 g, in which intrathecal catheters were successfully implanted, were divided into 4 groups ( n=12 each) using a random number table method: normal saline group (NS group), morphine group (M group), morphine+ EA group (ME group), and morphine+ EA+ CB1 antagonist group (MEA group). The OIH model was established by intrathecal injection of morphine 15 μg (10 μl) twice a day for 7 consecutive days. The equal volume of normal saline 10 μl was given instead in NS group. EA of the " Yanglingquan" (GB34) and " Zusanli" (ST36) acupoints lasting 30 min was performed after the first administration of medication each day, with a current intensity of 2 mA and frequency of 2 Hz in ME group. In MEA group, morphine (15 μg) and CB1 antagonist AM251 30 μg (10 μl) were intrathecally injected twice a day for 7 consecutive days, with other treatments similar to those previously described in ME group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before administration (T 0) and on days 1, 3, 5 and 7 after administration (T 1-4). Rats were deeply anesthetized and sacrificed at T 3, 4 after administration, and the L 4-6 spinal cord tissues were collected for determination of the expression of membrane CB1, ERK1/2 and p-ERK1/2 by Western blot. Results:Compared with NS group, the MWT was significantly decreased and the TWL was shortened at T 3, 4 in M, ME and MEA groups, the expression of spinal membrane CB1 and p-ERK1/2 was significantly up-regulated at T 4 after administration in M group, and the expression of spinal membrane CB1 was significantly up-regulated at T 3, 4 after administration in ME and MEA groups ( P<0.05). Compared with M group, the MWT was significantly increased and the TWL was prolonged at T 3, 4, and the expression of p-ERK1/2 was down-regulated at T 4 after administration in ME group ( P<0.05), no significant change was found in MWT or TWL at T 3, 4 in MEA group ( P>0.05), and the expression of spinal membrane CB1 was significantly up-regulated at T 3, 4 after administration in ME and MEA groups ( P<0.05). Compared with ME group, the MWT was significantly decreased and the TWL was shortened at T 3, 4, and the expression of spinal membrane CB1 and p-ERK1/2 was up-regulated at T 4 after administration in MEA group ( P<0.05). Conclusions:Up-regulation of spinal membrane CB1 expression is involved in EA-mediated alleviation of morphine-induced OIH, which is associated with the inhibition of ERK1/2 phosphorylation in rats.

Objective:To investigate the application and clinical efficacy of customized, 3D-printed femoral bone marrow stems in the revision of tumor prostheses.Methods:A retrospective analysis was performed for the data of 11 patients (7 males and 4 females) aged 53.1±11.7 years (range, 38-75 years), who underwent 3D-printed customized revision of femoral intramedullary stems due to loosening of femoral tumor prostheses at the 960th Hospital of the Joint Support Force of the PLA from June 2021 to June 2023. The pathological types of tumors associated with the initial surgeries included 4 cases of giant cell tumor of bone, 5 cases of osteosarcoma, 1 case of chondrosarcoma, and 1 case of plasma cell tumor. The tumor was located at the distal femur in 8 cases and the proximal femur in 3 cases. The procedures included 3 initial revisions, 7 secondary revisions, and 1 tertiary revision. The average limb shortening measured 4.6±2.2 cm (range, 2.5-9.0 cm). Prior to revision, all prostheses were fixed with bone cement, revealing enlargement of the femoral medullary cavity and cortical bone thinning. Among them, 5 cases had intramedullary stems permeabilizing the femoral cortex, and 1 case had femoral cleavage fractures. All 11 patients received personalized data for the design and 3D printing of femoral bone marrow stems.Results:The lengths and diameters of the 3D-printed porous femoral bone marrow stems ranged from 80 to 160 mm and 20 to 22 mm, respectively. Ten patients were fitted with cylindrical intramedullary handles, while one received a conical intramedullary handle. A successful revision with the 3D-printed stems was achieved in 10 patients; however, 1 case failed to accommodate the conical handle and was instead revised with a bone cement prosthesis. During the implantation of the intramedullary stems, three patients experienced minor cortical splitting, which was managed with bundling and fixation during the procedure. Immediate stability was attained for all prostheses during surgery, yet postoperative limb shortening did not undergo significant correction. All patients exhibited normal healing of their postoperative incisions. The visual analog scale for limb pain decreased significantly from 8.0±0.8 points before surgery to 1.0±0.4 points three months postoperatively ( t=25.957, P<0.001). By six months after the surgery, none of the patients reported any limb pain. Follow-up data for all 11 patients indicated an average follow-up duration of 25.2±7.5 months (range, 16-36 months), during which limb function improved satisfactorily. The Musculoskeletal Tumor Society (MSTS) score increased from 7.9±1.4 points preoperatively to 20.9±2.7 points at the last follow-up, with this change also being statistically significant ( t=14.229, P<0.001). Imaging evaluations revealed normal lower limb force lines, no rotation or longitudinal displacement of the prosthetic stem, and successful integration with the femur. Conclusion:Personalized intramedullary stems produced through 3D printing demonstrate significant clinical effectiveness in femoral tumor prosthesis revision surgery, making them a viable option for such procedures.

Objective:To develop an artificial intelligence (AI)-based platelet review strategy to identify abnormal platelet histograms with no significant difference between initial impedance platelet count (PLT-I) and PLT-F results.Methods:This study included 5 119 routine blood analysis in Nanfang Hospital of Southern Medical University and its Ganzhou branch from July 2023 and March 2024. Specimens exhibiting abnormal platelet histograms and an initial platelet count >40×10?/L underwent review using the fluorescent platelet count (PLT-F) channel. Consistency of the results was defined as a difference between impedance platelet count (PLT-I) and PLT-F less than ±20% of the PLT-F results. A deep learning model was developed using platelet and red blood cell histogram data from a training set of 3 807 specimens. The model′s diagnostic performance was evaluated on an independent external validation set ( n=805) using receiver operating characteristic (ROC) curve analysis. Changes in the number of reviewed samples and sample turnaround time were analyzed to assess its clinical utility. Results:The deep learning model based on platelet and red blood cell histograms achieved an area under the ROC curve (AUC) of 0.854 in the training set. At a cutoff value of 0.1, the sensitivity was 0.954 and specificity was 0.358. The model could reduce review by 16.80% (190/1 131). In the validation set, the AUC was 0.805, with a sensitivity of 0.955 and specificity of 0.307, corresponding to a reduction of 17.41% (47/270) in reviewed specimens.Conclusion:The platelet review prediction model developed based on deep learning technology can efficiently identify samples with consistent results before and after review, reducing unnecessary reviews and shortening specimen testing time, thereby improving the efficiency of platelet test.

BACKGROUND: The objective of this study was to investigate the potential link between myopia in adolescents and exposure to per- and polyfluoroalkyl substances (PFASs). METHODS: This investigation included 1971 subjects with accessible PFAS level data, myopia status, and associated variables from four cycles of the National Health and Nutritional Examination Survey (NHANES). The investigation focused on specific PFAS compounds found in the serum, including perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), chosen for their frequent detection. Owing to the skewed nature of the PFAS level data, the PFAS levels were log-transformed (Ln-PFAS) prior to analysis. Logistic regression, restricted cubic spline modeling, subgroup analysis, and sensitivity analysis were used to examine the associations between exposure to PFASs and the onset of myopia. RESULTS: PFOA levels were significantly associated with myopia risk (OR: 1.33; 95% CI: 1.05-1.69; P = 0.019). More specifically, with respect to the first quartile, the second quartile (OR_Q2: 1.69; 95% CI: 1.16-2.46; P = 0.007), third quartile (OR_Q3: 1.45; 95% CI: 1.03-2.03; P = 0.035), and highest quartile (OR_Q4: 1.58; 95% CI: 1.12-2.21; P = 0.010) of participants presented with increased myopia risk. Mediation analysis revealed that PFOA and myopia risk were partially mediated by serum albumin (ALB), with a mediation percentage of 22.48% (P = 0.008). A nonlinear inverted U-shaped relationship was identified between the level of PFOA and myopia risk (P for nonlinearity = 0.005). CONCLUSION Our findings suggest a potential link between exposure to PFOA and the likelihood of myopia development in young individuals and a mediating effect of serum ALB on this relationship. Notably, PFOA was identified as a key PFAS significantly contributing to the observed link between PFAS exposure and myopia risk. The potential threat of PFOA to myopia should be examined further.
Humans ; Fluorocarbons/adverse effects* ; Myopia/blood* ; Adolescent ; Male ; Female ; Prevalence ; Environmental Exposure/adverse effects* ; Nutrition Surveys ; Environmental Pollutants/adverse effects* ; United States/epidemiology* ; Alkanesulfonic Acids/blood* ; Caprylates/blood* ; Serum Albumin/metabolism* ; Child ; Sulfonic Acids

The gradient coils of MRI equipment can induce vibrations in implantable medical devices, causing periodic vibrations of implantable medical devices with respect to the surrounding tissue. This not only results in instrument failure but also causes discomfort to the patient. Therefore, studying the vibration characteristics of implantable devices under different scanning sequences and the orientation of the device relative to the magnetic field is crucial for comprehending vibration performance. This study observed the vibration spectra of a full cranial bone-implanted neurostimulator by using laser vibrometry under typical rapid imaging sequences and explored the impact of different magnetic field orientations on vibration. The results demonstrated that the rapid echo sequences induced diverse and rich vibration components, whereas the planar echo sequences caused relatively simple vibrations. Additionally, the strongest vibrations normally occurred in the maximum conductive surface parallel to the phase-coded direction. It revealed the factors influencing the vibrations of skull fixation active implantable devices and provided guidance for enhancing device safety and protecting patient well-being during MR examinations.
Vibration ; Magnetic Resonance Imaging ; Deep Brain Stimulation/instrumentation* ; Magnetic Fields ; Humans

OBJECTIVE: To elucidate how spinal manipulative therapy (SMT) exerts its analgesic effects through regulating brain function in lumbar disc herniation (LDH) patients by utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: From September 2021 to September 2023, we enrolled LDH patients (LDH group, n=31) and age- and sex-matched healthy controls (HCs, n=28). LDH group underwent rs-fMRI at 2 distinct time points (TPs): prior to the initiation of SMT (TP1) and subsequent to the completion of the SMT sessions (TP2). SMT was administered once every other day for 30 min per session, totally 14 treatment sessions over a span of 4 weeks. HCs did not receive SMT treatment and underwent only one fMRI scan. Additionally, participants in LDH group completed clinical questionnaires on pain using the Visual Analog Scale (VAS) and the Japanese Orthopedic Association (JOA) score, whereas HCs did not undergo clinical scale assessments. The effects on the brain were jointly characterized using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). Correlation analyses were conducted between specific brain regions and clinical scales. RESULTS: Following SMT treatment, pain symptoms in LDH patients were notably alleviated and accompanied by evident activation of effects in the brain. In comparison to TP1, TP2 exhibited the most significant increase in ALFF values for Temporal_Sup_R and the most notable decrease in ALFF values for Paracentral_Lobule_L (voxelwise P<0.005; clusters >30; FDR correction). Additionally, the most substantial enhancement in ReHo values was observed for the Cuneus_R, while the most prominent reduction was noted for the Olfactory_R (voxelwise P<0.005; clusters >30; FDR correction). Moreover, a comparative analysis revealed that, in contrast to HCs, LDH patients at TP1 exhibited the most significant increase in ALFF values for Temporal_Pole_Sup_L and the most notable decrease in ALFF values for Frontal_Mid_L (voxelwise P<0.005; clusters >30; FDR correction). Furthermore, the most significant enhancement in ReHo values was observed for Postcentral_L, while the most prominent reduction was identified for ParaHippocampal_L (voxelwise P<0.005; clusters >30; FDR correction). Notably, correlation analysis with clinical scales revealed a robust positive correlation between the Cuneus_R score and the rate of change in the VAS score (r=0.9333, P<0.0001). CONCLUSIONS Long-term chronic lower back pain in patients with LDH manifests significant activation of the "AUN-DMN-S1-SAN" neural circuitry. The visual network, represented by the Cuneus_R, is highly likely to be a key brain network in which the analgesic efficacy of SMT becomes effective in treating LDH patients. (Trial registration No. NCT06277739).
Humans ; Magnetic Resonance Imaging ; Intervertebral Disc Displacement/diagnostic imaging* ; Male ; Female ; Brain/diagnostic imaging* ; Adult ; Manipulation, Spinal/methods* ; Middle Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management ; Rest ; Case-Control Studies

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*