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.

Objective To compare the clinical outcomes of subxiphoid robot-assisted thoracoscopic surgery (SRATS) and intercostal robot-assisted thoracoscopic surgery (IRATS) in the treatment of anterior mediastinal tumors. Methods A retrospective analysis was conducted on patients with anterior mediastinal tumors who underwent robot-assisted surgery in the Department of Thoracic Surgery, Gansu Provincial Hospital, from May 2020 to July 2022. According to the surgical approach, patients were divided into an SRATS group and an IRATS group. Perioperative data were compared between the two groups. Results A total of 87 patients were included. There were 41 patients in the SRATS group [23 males, 18 females; mean age, (44.51±11.28) years] and 46 patients in the IRATS group [21 males, 25 females; mean age, (46.67±8.76) years]. Compared with the IRATS group, the SRATS group had significantly less intraoperative blood loss [(24.41±6.67) mL vs. (37.93±9.23) mL, P<0.001], shorter postoperative drainage duration [(1.73±0.59) days vs. (2.54±0.50) days, P<0.001], lower postoperative drainage volume [(94.46±34.08) mLvs. (116.72±24.90) mL, P=0.001], lower visual analogue scale (VAS) pain scores on postoperative day 1 [(3.66±0.76) points vs. (4.15±0.84) points, P=0.005] and day 3 [(2.41±0.59) points vs. (2.89±0.82) points, P=0.003], shorter postoperative hospital stay [(4.12±0.81) days vs. (4.98±1.02) days, P<0.001], and lower hospitalization costs [(4.51±0.65) ten thousand yuan vs. (4.86±0.68) ten thousand yuan, P=0.020]. There were no statistical differences between the two groups in operative time or incidence of postoperative complications (P>0.05). Conclusion Both SRATS and IRATS are safe and effective for the treatment of anterior mediastinal tumors. However, SRATS is less invasive and more conducive to enhanced postoperative recovery.

OBJECTIVE To systematically evaluate the efficacy and safety of 6 kinds of GLP-1RAs in the treatment of type 2 diabetes mellitus （T2DM） patients with overweight or obesity， and to provide evidence-based reference for clinical practice. METHODS A comprehensive search was conducted in PubMed， Embase， Web of Science， the Cochrane Library， CNKI， VIP， Wanfang Data， and CBM from the inception to December 1， 2025. Randomized controlled trials （RCTs） were screened according to inclusion and exclusion criteria. Data extraction and risk of bias assessment were performed on the included studies. Network meta-analysis was conducted using Stata 17.0 software. RESULTS A total of 29 eligible RCTs were included， involving 7 404 patients. Six GLP-1RAs were evaluated： semaglutide， liraglutide， exenatide， dulaglutide， polyethylene glycol loxenatide， and beinaglutide. In terms of glycemic control， semaglutide had the highest probability of ranking first in reducing glycated hemoglobin （HbA1c） and fasting plasma glucose levels， followed by polyethylene glycol loxenatide. In terms of weight management， semaglutide showed the highest probability of ranking first， followed by liraglutide and exenatide. Regarding safety， dulaglutide had the highest probability of ranking first in reducing the incidence of gastrointestinal adverse events； none of the GLP-1RAs significantly increased the risk of severe hypoglycemia. Subgroup analysis revealed that liraglutide 1.8 mg， qd and exenatide extend-release 2.0 mg， qw demonstrated superior efficacy in reducing HbA1c and body weight compared with other doses/dosage forms of the same agents. CONCLUSIONS For T2DM patients with overweight or obesity， semaglutide offers the greatest benefits in glycemic control and weight reduction， while dulaglutide demonstrates superior gastrointestinal tolerability. Liraglutide 1.8 mg， qd and exenatide extend-release 2.0 mg， qw show relatively better overall efficacy in glycemic control and weight reduction among the same agents.

Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

Background High-speed train engineers' lower extremities are constrained by compulsive vigilance pedal tasks and limited space beneath the control console during driving. Shifts in alertness triggered by running route observation may share the same mental resource required by moderate-to-low physical exertion. Current research on improving cab design and maintaining optimal on-duty attention allocation remains limited. Objective To examine variations in lower extremity muscle load, gaze-tracking behavior, and driving performance under various combinations of vigilance pedal positions and route scenarios during simulated high-speed train tasks. To identify optimal working condition combinations that promote level and variety of physical activity and facilitate rational attention allocation. Methods A 4×2 within-subjects design were employed (4 vigilance pedal position profiles: knee front, side, and any; 2 route scenarios: monotonous and complex). Nine male college volunteers were recruited as simulated drivers to perform designated interval driving tasks. Surface electromyography and eye tracking were used to assess leg muscle load and gaze behavior respectively. Task performance and subjective fatigue were recorded. Results In all simulation driving tasks, skeletal muscle loads were low with the percentage of maximum voluntary contraction (%MVC) at approximately 4%. No fatigue tendencies were observed within single trial blocks (7 min), and the subjective fatigue ratings remained relatively low. While the activation of the dominant-side tibialis anterior was higher for the knee pedal than for the front (%MVC: 3.7% ± 3.13% vs. 1.08% ± 0.72%) or the side pedals (%MVC: 3.7% ± 3.13% vs. 1.4% ± 0.77%). The activation level of the dominant-side gastrocnemius was higher for the knee pedal than for the other three pedal profiles. For the any pedal condition, the intercept of the instantaneous median frequency curve for the dominant-side rectus femoris was lower in the monotonous route than in the complex route [(111.18 ± 35.78) Hz vs. (153.33 ± 39.12) Hz]. Among eye-tracking metrics, total fixations were higher during knee-level pedaling than side pedaling, while more saccades were recorded in monotonous routes than in complex ones. Regarding task performance, the any pedal yielded fewer missed signals than the front pedal, with 2/3 and 1/3 of participants preferring the front and knee pedals, respectively. The activation levels of the dominant tibialis anterior and dominant gastrocnemius muscles during the knee pedal × complex route combination were higher than any combination involving the front pedal. No statistically significant effect of pedal position or route scenario was found on other indicators. Conclusion The combination of knee pedal and complex route provides an optimal working setting for maximizing leg muscle mobility without compromising attention allocation or driving performance. It is recommended that train engineers modulate attention during monotonous routes to avoid emotional tension and increased muscle strain caused by over-monitoring. Given the ergonomic characteristics of high cognitive load, low physical exertion levels, and highly restricted lower limb mobility among high-speed train engineers, future cab designs should consider incorporating knee-level vigilance pedal and adjust safety alertness rules to allow reset via either front or knee pedal.

Background High-speed train engineers' lower extremities are constrained by compulsive vigilance pedal tasks and limited space beneath the control console during driving. Shifts in alertness triggered by running route observation may share the same mental resource required by moderate-to-low physical exertion. Current research on improving cab design and maintaining optimal on-duty attention allocation remains limited. Objective To examine variations in lower extremity muscle load, gaze-tracking behavior, and driving performance under various combinations of vigilance pedal positions and route scenarios during simulated high-speed train tasks. To identify optimal working condition combinations that promote level and variety of physical activity and facilitate rational attention allocation. Methods A 4×2 within-subjects design were employed (4 vigilance pedal position profiles: knee front, side, and any; 2 route scenarios: monotonous and complex). Nine male college volunteers were recruited as simulated drivers to perform designated interval driving tasks. Surface electromyography and eye tracking were used to assess leg muscle load and gaze behavior respectively. Task performance and subjective fatigue were recorded. Results In all simulation driving tasks, skeletal muscle loads were low with the percentage of maximum voluntary contraction (%MVC) at approximately 4%. No fatigue tendencies were observed within single trial blocks (7 min), and the subjective fatigue ratings remained relatively low. While the activation of the dominant-side tibialis anterior was higher for the knee pedal than for the front (%MVC: 3.7% ± 3.13% vs. 1.08% ± 0.72%) or the side pedals (%MVC: 3.7% ± 3.13% vs. 1.4% ± 0.77%). The activation level of the dominant-side gastrocnemius was higher for the knee pedal than for the other three pedal profiles. For the any pedal condition, the intercept of the instantaneous median frequency curve for the dominant-side rectus femoris was lower in the monotonous route than in the complex route [(111.18 ± 35.78) Hz vs. (153.33 ± 39.12) Hz]. Among eye-tracking metrics, total fixations were higher during knee-level pedaling than side pedaling, while more saccades were recorded in monotonous routes than in complex ones. Regarding task performance, the any pedal yielded fewer missed signals than the front pedal, with 2/3 and 1/3 of participants preferring the front and knee pedals, respectively. The activation levels of the dominant tibialis anterior and dominant gastrocnemius muscles during the knee pedal × complex route combination were higher than any combination involving the front pedal. No statistically significant effect of pedal position or route scenario was found on other indicators. Conclusion The combination of knee pedal and complex route provides an optimal working setting for maximizing leg muscle mobility without compromising attention allocation or driving performance. It is recommended that train engineers modulate attention during monotonous routes to avoid emotional tension and increased muscle strain caused by over-monitoring. Given the ergonomic characteristics of high cognitive load, low physical exertion levels, and highly restricted lower limb mobility among high-speed train engineers, future cab designs should consider incorporating knee-level vigilance pedal and adjust safety alertness rules to allow reset via either front or knee pedal.

The surgical management of empyema (excluding those caused by mycobacterium tuberculosis and non-tuberculous mycobacteria) is rapidly evolving towards minimally invasive, precise, and stepwise approaches. The traditional three-stage classification (exudative, fibrinopurulent, and organizing) has limitations in guiding dynamic clinical decision-making. For the first time, this consensus explicitly identifies two critical junctures in the pathological progression of empyema: "early transformation" (stage Ⅰ to Ⅱ) and "late transformation" (stage Ⅱ to Ⅲ), and thereby constructs a corresponding "identification-early warning-intervention" stepwise therapeutic framework. The consensus emphasizes that proactive debridement via video-assisted thoracoscopic surgery should be performed during the early transformation phase to halt disease progression. Conversely, during the late transformation phase, therapeutic goals should be rationally adjusted to prioritize adequate drainage, avoiding futile pleural decortication. Moreover, the consensus underscores the pivotal role of precise perioperative etiological diagnosis (e.g. metagenomic nest-generation sequencing) and standardized anti-infective therapy. Integrating practical experiences from multiple thoracic surgery centers in China and relevant evidence-based literature, this consensus formulates recommendations on the precise definitions of staging, surgical indications for each phase, key technical points, perioperative management, and training systems. It aims to promote the standardized and individualized surgical management of empyema, ultimately optimizing patient prognosis.

Objective To investigate the clinical prognostic value of the prognostic nutritional index (PNI) in patients with renal cell carcinoma (RCC) undergoing partial nephrectomy.Methods A retrospective analysis was conducted on the clinical data of RCC patients who underwent partial nephrectomy at our hospital during 2020 and 2024.The optimal cutoff value of PNI was determined based on the maximum Youden index from the receiver operating characteristic (ROC) curve.The clinicopathological characteristics, overall survival (OS), and progression-free survival (PFS) between patients with different PNI levels were compared.Cox regression analysis was used to explore the independent prognostic factors for RCC patients. Results Based on the ROC curve, the optimal cutoff value corresponding to the maximum Youden index was calculated to be 46.675, at which point the sensitivity was 65.3% and the specificity was 62.2%.Of the 815 patients included in the study, 293 (36.0%) patients had a PNI＜46.675.Cox regression analysis confirmed that preoperative PNI, tumor diameter, ISUP classification, and ECOG score were independent risk factors for postoperative OS in patients with RCC who underwent PN (P＜0.05).In addition, preoperative PNI, tumor diameter, ISUP classification and ECOG score were independent risk factors for postoperative PFS (P＜0.05).After covariates in the multivariable Cox regression model were adjusted, patients in the low PNI group demonstrated significantly shorter overall survival (HR=2.392, P＜0.001) and significantly poorer progression-free survival (HR=2.076, P＜0.001) compared to those in the high PNI group.Conclusion Preoperative PNI has significant clinical value in evaluating the prognosis of RCC patients undergoing partial nephrectomy.An elevated preoperative PNI is associated with a better prognosis.

OBJECTIVE: To investigate the anti-inflammatory effect of rutaecarpine (RUT) on monosodium urate crystal (MSU)-induced murine peritonitis in mice and further explored the underlying mechanism of RUT in lipopolysaccharide (LPS)/MSU-induced gout model in vitro. METHODS: In MSU-induced mice, 36 male C57BL/6 mice were randomly divided into 6 groups of 8 mice each group, including the control group, model group, RUT low-, medium-, and high-doses groups, and prednisone acetate group. The mice in each group were orally administered the corresponding drugs or vehicle once a day for 7 consecutive days. The gout inflammation model was established by intraperitoneal injection of MSU to evaluate the anti-gout inflammatory effects of RUT. Then the proinflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and the proportions of infiltrating neutrophils cytokines were detected by flow cytometry. In LPS/MSU-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and proinflammatory cytokines were measured by ELISA. The percentage of pyroptotic cells were detected by flow cytometry. Respectively, the mRNA and protein levels were measured by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, the nuclear translocation of nuclear factor κB (NF-κB) p65 was observed by laser confocal imaging. Additionally, surface plasmon resonance (SPR) and molecular docking were applied to validate the binding ability of RUT components to tumor necrosis factor α (TNF-α) targets. RESULTS: RUT reduced the levels of infiltrating neutrophils and monocytes and decreased the levels of the proinflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 (IL-6, all P<0.01). In vitro, RUT reduced the production of IL-1β, IL-6 and TNF-α. In addition, RT-PCR revealed the inhibitory effects of RUT on the mRNA levels of IL-1β, IL-6, cyclooxygenase-2 and TNF-α (P<0.05 or P<0.01). Mechanistically, RUT markedly reduced protein expressions of tumor necrosis factor receptor (TNFR), phospho-mitogen-activated protein kinase (p-MAPK), phospho-extracellular signal-regulated kinase, phospho-c-Jun N-terminal kinase, phospho-NF-κB, phospho-kinase α/β, NOD-like receptor thermal protein domain associated protein 3 (NLRPS), cleaved-cysteinyl aspartate specific proteinase-1 and cleaved-gasdermin D in macrophages (P<0.05 or P<0.01). Molecularly, SPR revealed that RUT bound to TNF-α with a calculated equilibrium dissociation constant of 31.7 µmol/L. Molecular docking further confirmed that RUT could interact directly with the TNF-α protein via hydrogen bonding, van der Waals interactions, and carbon-hydrogen bonding. CONCLUSION RUT alleviated MSU-induced peritonitis and inhibited the TNFR1-MAPK/NF-κB and NLRP3 inflammasome signaling pathway to attenuate gouty inflammation induced by LPS/MSU in THP-1 macrophages, suggesting that RUT could be a potential therapeutic candidate for gout.
Animals ; NF-kappa B/metabolism* ; Male ; Indole Alkaloids/therapeutic use* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Inflammation/complications* ; Uric Acid ; Quinazolines/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Gout/chemically induced* ; Inflammasomes/metabolism* ; Cytokines/metabolism* ; THP-1 Cells ; Mitogen-Activated Protein Kinases/metabolism* ; Mice ; Molecular Docking Simulation ; Lipopolysaccharides ; Quinazolinones

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.