First detection and biological characterization of an avian metaavulavirus 8 isolated from a migratory swan goose in Qinghai Lake, Northwest China.

Avian metaavulavirus 8 (AMAV-8), formerly known as avian paramyxovirus 8 (APMV-8), has been detected sporadically in wild birds worldwide since it was first identified in a Canadian goose in 1976. However, the presence of AMAV-8 in birds has never been reported in China. To understand the epidemiological situation of AMAV-8 and its ability to infect chickens, we conducted a surveillance study and in vivo analysis of the AMAV-8 isolate identified in total of 14,909 clinical samples collected from wild and domestic birds from 2014 to 2022 in China. However, in 2017, only one AMAV-8 virus (Y7) was successful isolated from the fresh droppings of a migratory swan goose in Qinghai Lake in Northwest China. Thereafter, we report the complete genome sequence of the Y7 strain with a genome length of 15,342 nucleotides and the Y7 isolate was genetically closely-related to wild bird-origin AMAV-8 viruses previously circulated in the United States, Japan, and Kazakhstan. Furthermore, AMAV-8 infections of one-day-old specific pathogen-free (SPF) chicks did not induce any clinical signs over the entire observation period but was associated with viral shedding for up to 8 days. Interestingly, although all birds infected with the Y7 strain seroconverted within the first week of infection, virus replication was only detected in the trachea but not in other tissues such as the brain, lung, or heart. Here, we report the complete genome, genetic and biological characterization, replication and pathogenicity analysis in vivo and first detection of AMAV-8 in China.

Holistic shape variation of the rib cage in an adult population.

Traumatic injuries to the thorax are a common occurrence, and given the disparity in outcomes, injury risk is non-uniformly distributed within the population. Rib cage geometry, in conjunction with well-established biomechanical characteristics, is thought to influence injury tolerance, but quantifiable descriptions of adult rib cage shape as a whole are lacking. Here, we develop an automated pipeline to extract whole rib cage measurements from a large population and produce distributions of these measurements to assess variability in rib cage shape. Ten measurements of whole rib cage shape were collected from 1,719 individuals aged 25-45 years old including angular, linear, areal, and volumetric measures. The resulting pipeline produced measurements with a mean percent difference to manually collected measurements of 1.7% ± 1.6%, and the whole process takes 30 s per scan. Each measurement followed a normal distribution with a maximum absolute skew value of 0.43 and a maximum absolute excess kurtosis value of 0.6. Significant differences were found between the sexes (p < 0.001) in all except angular measures. Multivariate regression revealed that demographic predictors explain 29%-68% of the variance in the data. The angular measurements had the three lowest R2 values and were also the only three to have little correlation with subject stature. Unlike other measures, rib cage height had a negative correlation with BMI. Stature was the dominant demographic factor in predicting rib cage height, coronal area, sagittal area, and volume. Subject weight was the dominant demographic factor for rib cage width, depth, axial area, and angular measurements. Age was minimally important in this cohort of adults from a narrow age range. Individuals of similar height and weight had average rib cage measurements near the regression predictions, but the range of values across all subjects encompassed a large portion of their respective distributions. Our findings characterize the variability in adult rib cage geometry, including the variation within narrow demographic criteria. In future work, these can be integrated into computer aided engineering workflows to assess the influence of whole rib cage shape on the biomechanics of the adult human thorax.

MixUNETR: A U-shaped network based on W-MSA and depth-wise convolution with channel and spatial interactions for zonal prostate segmentation in MRI.

Magnetic resonance imaging (MRI) plays a pivotal role in diagnosing and staging prostate cancer. Precise delineation of the peripheral zone (PZ) and transition zone (TZ) within prostate MRI is essential for accurate diagnosis and subsequent artificial intelligence-driven analysis. However, existing segmentation methods are limited by ambiguous boundaries, shape variations and texture complexities between PZ and TZ. Moreover, they suffer from inadequate modeling capabilities and limited receptive fields. To address these challenges, we propose a Enhanced MixFormer, which integrates window-based multi-head self-attention (W-MSA) and depth-wise convolution with parallel design and cross-branch bidirectional interaction. We further introduce MixUNETR, which use multiple Enhanced MixFormers as encoder to extract features from both PZ and TZ in prostate MRI. This augmentation effectively enlarges the receptive field and enhances the modeling capability of W-MSA, ultimately improving the extraction of both global and local feature information from PZ and TZ, thereby addressing mis-segmentation and challenges in delineating boundaries between them. Extensive experiments were conducted, comparing MixUNETR with several state-of-the-art methods on the Prostate158, ProstateX public datasets and private dataset. The results consistently demonstrate the accuracy and robustness of MixUNETR in MRI prostate segmentation. Our code of methods is available at https://github.com/skyous779/MixUNETR.git.

Spatially resolved metabolomics visualizes heterogeneous distribution of metabolites in lung tissue and the anti-pulmonary fibrosis effect of Prismatomeris connate extract.

Pulmonary fibrosis (PF) is a chronic progressive end-stage lung disease. However, the mechanisms underlying the progression of this disease remain elusive. Presently, clinically employed drugs are scarce for the treatment of PF. Hence, there is an urgent need for developing novel drugs to address such diseases. Our study found for the first time that a natural source of Prismatomeris connata Y. Z. Ruan (Huang Gen, HG) ethyl acetate extract (HG-2) had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic (TGF-ß1/Smad) pathway. Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation, cellular response to reactive oxygen species, and extracellular matrix (ECM) disassembly. Moreover, mass spectrometry imaging (MSI) was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2, which was related to arginine biosynthesis and alanine, asparate and glutamate metabolism, the downregulation of arachidonic acid metabolism, and the upregulation of glycerophospholipid metabolism. In conclusion, we elaborated on the relationship between metabolite distribution and the progression of PF, constructed the regulatory metabolic network of HG-2, and discovered the multi-target therapeutic effect of HG-2, which might be conducive to the development of new drugs for PF.

Perianal Paget Disease.

This case report describes a woman in her 70s with an erythematous plaque with superficial erosion, focal white scale, and surrounding hyperpigmentation located circumferentially around the anus and extending anteriorly to involve the perineum.

Contrast-enhanced ultrasound appearance of adrenal hemorrhage after orthotopic liver transplantation: a retrospective study.

OBJECTIVES: This study aimed to identify the incidence of adrenal hemorrhage (AH) after OLT and to summarize the ultrasound (US) and contrast-enhanced ultrasound (CEUS) characteristics. METHODS: Patients with adrenal lesions after OLT at our hospital were retrospectively reviewed between January 2010 and November 2023. The reference diagnosis was defined on the basis of surgical data, computed tomography scans, and magnetic resonance imaging with at least 12 months of follow-up. The incidence of AH and the US and CEUS characteristics after OLT were analyzed and compared with those of adrenal metastases. RESULTS: A total of 23 patients (1.2%) with AH and 7 patients (0.35%) with suprarenal metastases were assessed. Compared with metastases, hematomas had more inhomogeneous echotextures (57% vs. 0.00%, P = 0.010), hypoechoic or mixed-echoic patterns (96% vs. 71%, P = 0.022), and anechoic areas (52% vs. 0.00%, P = 0.024), and their echotextures varied more over time (65% vs. 0.14%, P = 0.031). CEUS was performed on 12 patients with AH and 2 patients with metastases. A "jet-like" contrast superflux was observed in one actively bleeding hematoma, whereas no enhancement was observed in any static hematoma (100%). However, adrenal metastases had a contrast-enhanced appearance in the early arterial phase, followed by fast washout in the late phase (100%), and the difference was statistically significant (P < 0.001). CONCLUSION: The sonographic characteristics of AH after OLT vary over time. CEUS is recommended when adrenal lesions are detected, as CEUS can differentiate AH from metastases.

Five Undescribed Sesquiterpenes with Anti-inflammasome Activity Isolated from Saussurea laniceps.

Five previously undescribed guaialactone-type sesquiterpenes (1-5), called Lanicepsmines A-E, along with eleven know compounds (6-16), were isolated from the whole plant of Saussurea laniceps. NMR spectroscopic data analysis and MASS permitted the definition of their structures. The stereochemistry of the compounds was confirmed by ECD calculations. It is worth noting that compound 1 and 2 contain amino groups. Part of compounds were tested the anti-inflammasome activity, and compound 14 exhibited potent activity and decreased LDH level in a dose-dependent manner, with IC50 values of 0.698 µM.

Clinicopathologic and prognostic characteristics of tumor budding-like in giant cell tumor of bone.

BACKGROUND: Currently, tumor budding (TB) is defined as an important factor for a poor prognosis in various types of cancers. The authors identified a significant presence of TB-like structures at the tumor invasive front in giant cell tumor of bone (GCTB), which may have the same biologic function as TB. The objective of this report was to describe the distribution of TB in GCTB and investigate its correlation with clinicopathologic characteristics, the immune microenvironment, survival prognosis, and response to denosumab treatment. METHODS: This multicenter cohort study included 426 patients with GCTB who received treatment between 2012 and 2021 at four centers. Two independent pathologists performed visual assessments of TBL structures in hematoxylin-and-eosin-stained tumor sections. Immunohistochemistry was used to evaluate tumor-infiltrating lymphocyte subtypes (CD3-positive, CD4-positive, CD8-positive, CD20-positive, programmed cell death protein-1-positive, programmed cell death-ligand 1positive, and FoxP3-positive) as well as Ki-67 expression levels in 426 tissue samples. These parameters were then analyzed for associations with patient outcomes (local recurrence-free survival [LRFS] and overall survival [OS]), clinicopathologic characteristics, and response to denosumab treatment. RESULTS: High-grade TB was associated with poorer LRFS and OS in both patient groups. In addition, TB was correlated with various clinicopathologic features, tumor-infiltrating lymphocyte expression, and response to denosumab treatment. TB outperformed the traditional Enneking and Campanacci staging systems in predicting patient LRFS and OS. CONCLUSIONS: The current data support the assessment of TBL structures as a reliable prognostic tool in GCTB, potentially aiding in the development of personalized treatment strategies for patients.

Piezo1 regulates TGF-ß1 induced epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is involved in local tissue remodeling in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the function of Piezo1 in EMT process remains unclear. This study aimed to characterize potential roles of Piezo1 in EMT process in CRSwNP. METHODS: Overall, 22 nasal polyp (NP) tissues from patients with CRSwNP and 20 middle turbinate from healthy individuals were obtained during surgery. The expression of Piezo1, E-cadherin, vimentin, and α-smooth muscle actin (α-SMA) was measured by using western blot (Wb) in NP tissues and primary human nasal epithelial cells (pHNECs) and the location and level were assessed by immunofluorescence staining. BEAS-2B cells were stimulated with transforming growth factor (TGF)-ß1 to induce EMT in vitro model and examined using qRT-PCR. BEAS-2B cells were treated with Yoda1 and RuR to calculate protein level by Wb analysis. Yoda1 and RuR treated NP murine model was evaluated by H&E (hematoxylin-eosin) staining and immunohistochemistry. RESULTS: Compared with the control group, E-cadherin was decreased while the level of Piezo1, vimentin, and α-SMA was increased in NP group. Piezo1, vimentin, and α-SMA were upregulated in TGF-ß1-induced BEAS-2B cells. Yoda1 inhibited E-cadherin expression and promoted Piezo1 and the aforementioned mesenchymal markers, whereas RuR showed contrary results. The results from the murine model treated with Yoda1 and RuR were consistent with those results in the EMT model in vitro. CONCLUSION: Piezo1 is linked with EMT process in CRSwNP and the activation of Piezo1 exacerbates EMT process of nasal polyps.

[Review and prospects of pesticide use and residues in cultivation of medicinal and food homologous substances].

As people's living standards and awareness of health care are increasing in recent years, the demand for the medicinal and food homologous substances is rising. Promoting the healthy development of this industry to meet people's growing demand and popularizing the TCM concept of preventive treatment of diseases are essential for building a healthy China. The abuse of pesticides by some growers in the one-sided pursuit of economic benefits causes serious pesticide residue, which affects the safety and effectiveness of the medicinal and food homologous substances. Since pesticide residues has received increasing attention, the reasonable control of pesticide residues becomes an important part of the research on these herbs, which, however, is rarely studied. This paper reviewed the publications involving pesticide residues in the cultivation of medicinal and food homologous substances that were published in the last two decades, and put forward the problems faced by the cultivation. According to the current situation of this industry, this paper proposed the management suggestions for the control of pesticide residues in the cultivation. This review will provide the government with data and references for formulating relevant policies and standards to promote the high-quality development of the industry of medicinal and food homologous substances and guarantee the development of TCM and the building of a healthy China.

Structural analysis, anti-inflammatory activity of the main water-soluble acidic polysaccharides (AGBP-A3) from Panax quinquefolius L berry.

Background: Panax quinquefolius L, widely recognized for its valuable contributions to medicine, has aroused considerable attention globally. Different from the extensive research has been dedicated to the root of P. quinquefolius, its berry has received relatively scant focus. Given its promising medicinal properties, this study was focused on the structural characterizations and anti-inflammatory potential of acidic polysaccharides from the P. quinquefolius berry. Materials and methods: P. quinquefolius berry was extracted with hot water, precipitated by alcohol, separated by DEAE-52-cellulose column to give a series of fractions. One of these fractions was further purified via Sephadex G-200 column to give three fractions. Then, the main fraction named as AGBP-A3 was characterized by methylation analysis, NMR spectroscopy, etc. Its anti-inflammatory activity was assessed by RAW 264.7 cell model, zebrafish model and molecular docking. Results: The main chain comprised of α-L-Rhap, α-D-GalAp and ß-D-Galp, while the branch consisted mainly of α-L-Araf, ß-D-Glcp, α-D-GalAp, ß-D-Galp. The RAW264.7 cell assay results showed that the inhibition rates against IL-6 and IL-1ß secretion at the concentration of 625 ng/mL were 24.83 %, 11.84 %, while the inhibition rate against IL-10 secretion was 70.17 % at the concentration of 312 ng/mL. In the zebrafish assay, the migrating neutrophils were significantly reduced in number, and their migration to inflammatory tissues was inhibited. Molecular docking predictions correlated well with the results of the anti-inflammatory assay. Conclusion: The present study demonstrated the structure of acidic polysaccharides of P. quinquefolius berry and their effect on inflammation, providing a reference for screening anti-inflammatory drugs.

Blade-Coated Porous 3D Carbon Composite Electrodes Coupled with Multiscale Interfaces for Highly Sensitive All-Paper Pressure Sensors.

Flexible and wearable pressure sensors hold immense promise for health monitoring, covering disease detection and postoperative rehabilitation. Developing pressure sensors with high sensitivity, wide detection range, and cost-effectiveness is paramount. By leveraging paper for its sustainability, biocompatibility, and inherent porous structure, herein, a solution-processed all-paper resistive pressure sensor is designed with outstanding performance. A ternary composite paste, comprising a compressible 3D carbon skeleton, conductive polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate), and cohesive carbon nanotubes, is blade-coated on paper and naturally dried to form the porous composite electrode with hierachical micro- and nano-structured surface. Combined with screen-printed Cu electrodes in submillimeter finger widths on rough paper, this creates a multiscale hierarchical contact interface between electrodes, significantly enhancing sensitivity (1014 kPa-1) and expanding the detection range (up to 300 kPa) of as-resulted all-paper pressure sensor with low detection limit and power consumption. Its versatility ranges from subtle wrist pulses, robust finger taps, to large-area spatial force detection, highlighting its intricate submillimeter-micrometer-nanometer hierarchical interface and nanometer porosity in the composite electrode. Ultimately, this all-paper resistive pressure sensor, with its superior sensing capabilities, large-scale fabrication potential, and cost-effectiveness, paves the way for next-generation wearable electronics, ushering in an era of advanced, sustainable technological solutions.

In vitro heat insulation efficacy of 5% dextrose versus 0.9% saline during radiofrequency ablation.

PURPOSE: This study compared the efficacy of heat insulation between 5% dextrose and 0.9% saline in radiofrequency ablation (RFA). Accordingly, temperature variations and maximum temperatures were assessed at identical distances and heat field distributions. METHODS: Cubes of porcine liver tissue, measuring 10 mm across, were selected to precisely align the ablation boundary with the tissue boundary. An 18-gauge electrode with a 7-mm tip was inserted into each cube (10 per group) in a stainless-steel cup containing 40 mL of 5% dextrose or 0.9% saline. Fixed ablation was performed for 3 minutes using continuous mode at 30 W, simulating the typical thermal environment during thyroid RFA. Real-time temperature measurements were recorded by sensors positioned 0, 1, 3, and 5 mm from the cube's edge. A comparative analysis was conducted to assess the maximum temperature, temperature variation, and duration of temperatures exceeding 42℃. RESULTS: In both groups, the temperature curve declined with increasing distance from the edge of the ablated tissue. However, 0.9% saline exhibited higher maximum temperatures at 1, 3, and 5 mm compared to 5% dextrose (1 mm: 44.55°C±5.25°C vs. 34.68°C±3.07°C; 3 mm: 39.64°C±2.53°C vs. 29.22°C±2.21°C; 5 mm: 38.86°C±2.14°C vs. 28.74°C±2.51°C; all P<0.001). Considering a nerve injury threshold of 42°C, the 0.9% saline also displayed a greater proportion of samples reaching this temperature and a longer duration of temperatures exceeding it (P<0.05). CONCLUSION: The heat insulation efficacy of 5% dextrose at 1-5 mm exceeds that of 0.9% saline at identical distances and in a common thermal environment during thyroid RFA.

Hypoxic Upregulation of IER2 Increases Paracrine GMFG Signaling of Endoplasmic Reticulum Stress-CAF to Promote Chordoma Progression via Targeting ITGB1.

Currently, the oncogenic mechanism of endoplasmic reticulum stress-CAF (ERS-CAF) subpopulation in chordoma remains unknown. Here, single-cell RNA sequencing, spatial transcriptomics, GeoMx Digital Spatial Profiler, data-independent acquisition proteomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence are used to unveil the precise molecular mechanism of how ERS-CAF affected chordoma progression. Results show that hypoxic microenvironment reprograms CAFs into ERS-CAF subtype. Mechanistically, this occurrs via hypoxia-mediated transcriptional upregulation of IER2. Overexpression of IER2 in CAFs promotes chordoma progression, which can be impeded by IER2 knockdown or use of ERS inhibitors. IER2 also induces expression of ERS-CAF marker genes and results in production of a pro-tumorigenic paracrine GMFG signaling, which exert its biological function via directly binding to ITGB1 on tumor cells. ITGB1 inhibition attenuates tumor malignant progression, which can be partially reversed by exogenous GMFG intervention. Further analyses reveal a positive correlation between ITGB1high tumor cell counts and SPP1+ macrophage density, as well as the spatial proximity of these two cell types. Clinically, a significant correlation of high IER2/ITGB1 expression with tumor aggressive phenotype and poor patient survival is observed. Collectively, the findings suggest that ERS-CAF regulates SPP1+ macrophage to aggravate chordoma progression via the IER2/GMFG/ITGB1 axis, which may be targeted therapeutically in future.

LD-CSNet: A latent diffusion-based architecture for perceptual Compressed Sensing.

Compressed Sensing (CS) is a groundbreaking paradigm in image acquisition, challenging the constraints of the Nyquist-Shannon sampling theorem. This enables high-quality image reconstruction using a minimal number of measurements. Neural Networks' potent feature induction capabilities enable advanced data-driven CS methods to achieve high-fidelity image reconstruction. However, achieving satisfactory reconstruction performance, particularly in terms of perceptual quality, remains challenging at extremely low sampling rates. To tackle this challenge, we introduce a novel two-stage image CS framework based on latent diffusion, named LD-CSNet. In the first stage, we utilize an autoencoder pre-trained on a large dataset to represent natural images as low-dimensional latent vectors, establishing prior knowledge distinct from sparsity and effectively reducing the dimensionality of the solution space. In the second stage, we employ a conditional diffusion model for maximum likelihood estimates in the latent space. This is supported by a measurement embedding module designed to encode measurements, making them suitable for a denoising network. This guides the generation process in reconstructing low-dimensional latent vectors. Finally, the image is reconstructed using a pre-trained decoder. Experimental results across multiple public datasets demonstrate LD-CSNet's superior perceptual quality and robustness to noise. It maintains fidelity and visual quality at lower sampling rates. Research findings suggest the promising application of diffusion models in image CS. Future research can focus on developing more appropriate models for the first stage.

Win-win integration: A mitochondria targeted AIE photosensitizer for hypochlorite detection and type I & type II photodynamic therapy.

BACKGROUND: Photodynamic therapy (PDT) is a pioneering and effective anticancer modality with low adverse effects and high selectivity. Hypochlorous acid or hypochlorite (HClO/ClO-) is a type of inflammatory cytokine. The abnormal increase of ClO- in tumor cells is related to tumor pathogenesis and may be a "friend" for the design and synthesis of responsive phototherapy agents. However, preparing responsive phototherapy agents for all-in-one noninvasive diagnosis and simultaneous in situ therapy in a complex tumor environment is highly desirable but still remains an enormously demanding task. RESULTS: An acceptor-π bridge-donor-π bridge-acceptor (A-π-D-π-A) type photosensitizer TPTPy was designed and synthesized based on the phenothiazine structure which was used as the donor moiety as well as a ClO- responsive group. TPTPy was a multifunctional mitochondria targeted aggregation-induced emission (AIE) photosensitizer which could quickly and sensitively respond to ClO- with fluorescence "turn on" performance (19-fold fluorescence enhancement) and enhanced type I reactive oxygen species (ROS) generation to effectively ablate hypoxic tumor cells. The detection limit of TPTPy to ClO- was calculated to be 185.38 nM. The well-tailored TPTPy anchoring to mitochondria and producing ROS in situ could disrupt mitochondria and promote cell apoptosis. TPTPy was able to image inflammatory cells and tumor cells through ClO- response. In vivo results revealed that TPTPy was successfully utilized for PDT in tumor bearing nude mice and exhibited excellent biological safety for major organs. SIGNIFICANCE AND NOVELTY: A win-win integration strategy was proposed to design a tumor intracellular ClO- responsive photosensitizer TPTPy capable of both type I and type II ROS production to achieve photodynamic therapy of tumor. This work sheds light on the win-win integration design by taking full advantage of the characteristics of tumor microenvironment to build up responsive photosensitizer for in situ PDT of tumor.

Accurate de novo design of heterochiral protein-protein interactions.

Abiotic D-proteins that selectively bind to natural L-proteins have gained significant biotechnological interest. However, the underlying structural principles governing such heterochiral protein-protein interactions remain largely unknown. In this study, we present the de novo design of D-proteins consisting of 50-65 residues, aiming to target specific surface regions of L-proteins or L-peptides. Our designer D-protein binders exhibit nanomolar affinity toward an artificial L-peptide, as well as two naturally occurring proteins of therapeutic significance: the D5 domain of human tropomyosin receptor kinase A (TrkA) and human interleukin-6 (IL-6). Notably, these D-protein binders demonstrate high enantiomeric specificity and target specificity. In cell-based experiments, designer D-protein binders effectively inhibited the downstream signaling of TrkA and IL-6 with high potency. Moreover, these binders exhibited remarkable thermal stability and resistance to protease degradation. Crystal structure of the designed heterochiral D-protein-L-peptide complex, obtained at a resolution of 2.0 Å, closely resembled the design model, indicating that the computational method employed is highly accurate. Furthermore, the crystal structure provides valuable information regarding the interactions between helical L-peptides and D-proteins, particularly elucidating a novel mode of heterochiral helix-helix interactions. Leveraging the design of D-proteins specifically targeting L-peptides or L-proteins opens up avenues for systematic exploration of the mirror-image protein universe, paving the way for a diverse range of applications.

Lymphocyte Infiltration Score and Spatial Characteristics Refined the Prognosis and Denosumab Treatment Responsiveness Indicators for Giant Cell Tumor of Bone.

PURPOSE: The prognostic value of lymphocyte infiltration score (LIS) and its nearest neighbor distance to tumor cells (NNDTC) in giant cell tumor of bone (GCTB) is currently not well established. This study aims to characterize LIS and NNDTC and examine their correlation with denosumab treatment responsiveness, clinicopathologic features, and patient prognosis. METHODS: Using multiplexed quantitative immunofluorescence, LIS was evaluated in 253 tumor specimens, whereas NNDTC was computed using HALO software. Subsequently, we analyzed the association of these parameters with patient outcomes (progression-free survival [PFS] and overall survival [OS]), clinicopathologic features, and denosumab treatment responsiveness. RESULTS: Low LIS was indicative of both poor PFS and OS (both P < .001). In addition, LIS was significantly associated with sex (P = .046), Enneking staging (P < .001), Ki-67 expression (P = .007), and denosumab treatment responsiveness (P = .005). Lower CD8+ (tumor interior [TI]) NNDTC, and CD3+ (TI) NNDTC were associated with worse PFS (P = .003 and .038, respectively), whereas lower CD8+ (TI) NNDTC was associated with worse OS (P = .001), but CD8+ (tumor infiltrating margin) NNDTC had the opposite effect (P = .002). Moreover, NNDTC showed a correlation with several clinicopathologic features. Importantly, LIS outperformed Enneking and Campanacci staging systems in predicting the clinical outcomes of GCTB. CONCLUSION: These findings suggest that LIS is a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy in patients with GCTB. These parameters may prove to be useful in guiding prognostic risk stratification and therapeutic optimization for patients.