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Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, and is characterized by high heterogeneity, high malignancy, easy metastasis, and poor prognosis. Recurrence, metastasis, and multidrug resistance are the main problems that limit the therapeutic effect and prognosis of OS. PI3K/AKT/mTOR signaling pathway is often abnormally activated in OS tissues and cells, which promotes the rapid development, metastasis, and drug sensitivity of OS. Emerging evidence has revealed new insights into tumorigenesis through the interaction between the PI3K/AKT/mTOR pathway and non-coding RNAs (ncRNAs). Therefore, we reviewed the interactions between the PI3K/AKT/mTOR pathway and ncRNAs and their implication in OS. These interactions have the potential to serve as cancer biomarkers and therapeutic targets in clinical applications.
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BACKGROUNDS: Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen causing respiratory diseases in children. This study aimed to characterize epidemiological and disease severity shifts of M. pneumoniae: infections in Guangzhou, China during and after the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Throat swab samples were obtained from 5405 hospitalized patients with symptoms of acute respiratory infections to detect M. pneumoniae. Differences in epidemiological and clinical characteristics of M. pneumoniae: infections were investigated during 2020-2022 and after COVID-19 pandemic (2023). RESULTS: M. pneumoniae were detected in 849 (15.6%, 849/5405) patients. The highest annual positive rate was 29.4% (754/2570) in 2023, followed by 5.3% (72/1367) in 2022, 1.2% (12/1015) in 2021, and 2.0% (11/553) in 2020, with significantly increasing annual prevalence from 2020 to 2023. M. pneumoniae incidence peaked between July and December post-COVID-19 pandemic in 2023, with the highest monthly positive rate (56.4%, 165/293). Clinical characteristics and outcomes of patients with M. pneumoniae did not vary between periods during and after COVID-19 pandemic except that patients with M. pneumoniae post-COVID-19 pandemic were more likely to develop fever. Patients with severe M. pneumoniae pneumonia (SMPP) were more likely to develop respiratory complications, myocardial damage, and gastrointestinal dysfunction than those with non-SMPP. Patients with SMPP had lower lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and higher IL-4, IL-6, IL-10 levels than those with non-SMPP. Bronchoalveolar lavage fluid specimens from infected patients were obtained to identify macrolide resistance mutations. Macrolide-resistant M. pneumoniae (MRMP) proportion in 2023 was 91.1% (215/236). CONCLUSION: Outbreaks of M. pneumoniae: occurred in Guangzhou, China in 2023 upon Non-pharmaceutical interventions easing. Despite the increasing incidence of M. pneumoniae, the disease severity remained similar during and after the COVID-19 pandemic.
Subject(s)
COVID-19 , Mycoplasma pneumoniae , Pneumonia, Mycoplasma , Humans , China/epidemiology , Pneumonia, Mycoplasma/epidemiology , Pneumonia, Mycoplasma/microbiology , COVID-19/epidemiology , Mycoplasma pneumoniae/genetics , Mycoplasma pneumoniae/isolation & purification , Male , Female , Child , Adult , Adolescent , Middle Aged , Child, Preschool , Young Adult , Disease Outbreaks , SARS-CoV-2/genetics , Infant , Aged , Incidence , Prevalence , PandemicsABSTRACT
Billions of cells are eliminated daily from our bodies1-4. Although macrophages and dendritic cells are dedicated to migrating and engulfing dying cells and debris, many epithelial and mesenchymal tissue cells can digest nearby apoptotic corpses1-4. How these non-motile, non-professional phagocytes sense and eliminate dying cells while maintaining their normal tissue functions is unclear. Here we explore the mechanisms that underlie their multifunctionality by exploiting the cyclical bouts of tissue regeneration and degeneration during hair cycling. We show that hair follicle stem cells transiently unleash phagocytosis at the correct time and place through local molecular triggers that depend on both lipids released by neighbouring apoptotic corpses and retinoids released by healthy counterparts. We trace the heart of this dual ligand requirement to RARγ-RXRα, whose activation enables tight regulation of apoptotic cell clearance genes and provides an effective, tunable mechanism to offset phagocytic duties against the primary stem cell function of preserving tissue integrity during homeostasis. Finally, we provide functional evidence that hair follicle stem cell-mediated phagocytosis is not simply redundant with professional phagocytes but rather has clear benefits to tissue fitness. Our findings have broad implications for other non-motile tissue stem or progenitor cells that encounter cell death in an immune-privileged niche.
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Perfluorooctanoic acid (PFOA) is a highly recalcitrant organic pollutant, and its bioaccumulation severely endangers human health. While various methods are developed for PFOA removal, the targeted design of adsorbents with high efficiency and reusability remains largely unexplored. Here the rational design and synthesis of two novel zirconium-based metalâorganic frameworks (MOFs) bearing free ortho-hydroxy sites, namely noninterpenetrated PCN-1001 and twofold interpenetrated PCN-1002, are presented. Single crystal analysis of the pure ligand reveals that intramolecular hydrogen bonding plays a pivotal role in directing the formation of MOFs with free hydroxy groups. Furthermore, the transformation from PCN-1001 to PCN-1002 is realized. Compared to PCN-1001, PCN-1002 displays higher chemical stability due to interpenetration, thereby demonstrating an exceptional PFOA adsorption capacity of up to 632 mg g-1 (1.53 mmol g-1), which is comparable to the reported record values. Moreover, PCN-1002 shows rapid kinetics, high selectivity, and long-life cycles in PFOA removal tests. Solid-state nuclear magnetic resonance results and density functional theory calculations reveal that multiple hydrogen bonds between the free ortho-hydroxy sites and PFOA, along with Lewis acid-base interaction, work collaboratively to enhance PFOA adsorption.
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The loss of midbrain dopaminergic (DA) neurons is the fundamental pathological feature of Parkinson's disease (PD). PD causes chronic pain in two-thirds of patients. Recent studies showed that the activation of the pedunculopontine tegmental nucleus (PPTg) can effectively relieve inflammatory pain and neuropathic pain. The PPTg is located in the pontomesencephalic tegmentum, a target of deep brain stimulation (DBS) treatment in PD, and is involved in motor control and sensory integration. To test whether the lesion of midbrain DA neurons induced pain hypersensitivity, and whether the chemogenetic activation of the PPTg could modulate the pain, the AAV-hM3Dq receptor was transfected and expressed into the PPTg neurons of 6-hydroxydopamine-lesioned mice. In this study, von Frey, open field, and adhesive tape removal tests were used to assess animals' pain sensitivity, locomotor activity, and sensorimotor function and somatosensory perception, respectively. Here, we found that the lesion of midbrain DA neurons induced a minor deficit in voluntary movement but did not affect sensorimotor function and somatosensory perception in the tape removal test. The results showed that lesion led to pain hypersensitivity, which could be alleviated both by levodopa and by the chemogenetic activation of the PPTg. Activating the PPTg may be a potential therapeutic strategy to relieve pain phenotypes in PD.
Subject(s)
Dopaminergic Neurons , Mesencephalon , Pedunculopontine Tegmental Nucleus , Animals , Pedunculopontine Tegmental Nucleus/metabolism , Dopaminergic Neurons/metabolism , Mice , Mesencephalon/metabolism , Male , Parkinson Disease/therapy , Parkinson Disease/physiopathology , Pain/etiology , Pain/metabolism , Mice, Inbred C57BL , Deep Brain Stimulation/methods , Disease Models, Animal , Levodopa/pharmacology , OxidopamineABSTRACT
Coal is one of the most important fossil energy sources and is ensuring global energy security. Annual maximum NDVI (Normalized Difference Vegetation Index) data is an important indicator for the research in balancing coal mining and vegetation conservation. However, the existing annual maximum NDVI data displayed lower values with temporally inconsistent and a noticeable mosaic line. Here we propose an algorithm for automatically generating the annual maximum NDVI of China's coal bases in Google Earth Engine called: Auto-NDVIcb. The accuracy of the Auto-NDVIcb algorithm has been verified with an average RMSE of 0.087 for the 14 coal bases from 2013 to 2022. Based on the proposed Auto-NDVIcb algorithm, an annual maximum NDVI dataset for all 14 coal bases in China from 2013 to 2022 was publicly released. This dataset can be fast and automatically updated online. Hence, the public dataset will continuously serve to monitor the vegetation change induced by coal mining, exploring the mechanism of vegetation degradation, and providing scientific data for developing vegetation protection policies in coal mines.
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The Bloch band theory and Brillouin zone (BZ) that characterize wave-like behaviors in periodic mediums are two cornerstones of contemporary physics, ranging from condensed matter to topological physics. Recent theoretical breakthrough revealed that, under the projective symmetry algebra enforced by artificial gauge fields, the usual two-dimensional (2D) BZ (orientable Brillouin two-torus) can be fundamentally modified to a non-orientable Brillouin Klein bottle with radically distinct manifold topology. However, the physical consequence of artificial gauge fields on the more general three-dimensional (3D) BZ (orientable Brillouin three-torus) was so far missing. Here, we theoretically discovered and experimentally observed that the fundamental domain and topology of the usual 3D BZ can be reduced to a non-orientable Brillouin Klein space or an orientable Brillouin half-turn space in a 3D acoustic crystal with artificial gauge fields. We experimentally identify peculiar 3D momentum-space non-symmorphic screw rotation and glide reflection symmetries in the measured band structures. Moreover, we experimentally demonstrate a novel stacked weak Klein bottle insulator featuring a nonzero Z2 topological invariant and self-collimated topological surface states at two opposite surfaces related by a nonlocal twist, radically distinct from all previous 3D topological insulators. Our discovery not only fundamentally modifies the fundamental domain and topology of 3D BZ, but also opens the door towards a wealth of previously overlooked momentum-space multidimensional manifold topologies and novel gauge-symmetry-enriched topological physics and robust acoustic wave manipulations beyond the existing paradigms.
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Metasurface holograms represent a common category of metasurface devices that utilize in-plane phase gradients to shape wavefronts, forming holographic images through the application of the generalized Snell's law (GSL). While conventional metasurfaces focus solely on phase gradients, metagratings, which incorporate higher-order wave diffraction, further expand the GSL's generality. Recent advances in certain acoustic metagratings demonstrate an updated GSL extension capable of reversing anomalous transmission and reflection, whose reversal is characterized by the parity of the number of wave propagation trips through the metagrating. However, the current extension of GSL remains limited to 1D metagratings, unable to access 2D holographic images in 3D spaces. Here, the GSL extension to 2D metagratings for manipulating waves within 3D spaces is investigated. Through this analysis, a series of acoustic metagrating holograms is experimentally demonstrated. These holographic images exhibit the unique ability to switch between transmission and reflection types independently. This study introduces an additional dimension to modern holography design and metasurface wavefront manipulation.
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Linker installation is a potent strategy for integrating specific properties and functionalities into metal-organic frameworks (MOFs). This method enhances the structural diversity of frameworks and enables the precise construction of robust structures, complementing the conventional postsynthetic modification approaches, by fully leveraging open metal sites and active organic linkers at targeting locations. Herein, we demonstrated an insertion of a d-camphorate linker into a flexible Zr-based MOF, PCN-700, through linker installation. The resultant homochiral MOF not only exhibits remarkable stability but also functions as a highly efficient luminescent material for enantioselective sensing. Competitive absorption and energy/electron transfer processes contribute to the sensing performance, while the difference in binding affinities dominates the enantioselectivity. This work presents a straightforward route to crafting stable homochiral MOFs for enantioselective sensing.
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Construction of robust heterogeneous catalysts with atomic precision is a long-sought pursuit in the catalysis field due to its fundamental significance in taming chemical transformations. Herein, we present the synthesis of a single-crystalline pyrazolate metal-organic framework (MOF) named PCN-300, bearing a lamellar structure with two distinct Cu centers and one-dimensional (1D) open channels when stacked. PCN-300 exhibits exceptional stability in aqueous solutions across a broad pH range from 1 to 14. In contrast, its monomeric counterpart assembled through hydrogen bonding displays limited stability, emphasizing the role of Cu-pyrazolate coordination bonds in framework robustness. Remarkably, the synergy of the 1D open channels, excellent stability, and the active Cu-porphyrin sites endows PCN-300 with outstanding catalytic activity in the cross dehydrogenative coupling reaction to form the C-O bond without the "compulsory" ortho-position directing groups (yields up to 96%), outperforming homogeneous Cu-porphyrin catalysts. Moreover, PCN-300 exhibits superior recyclability and compatibility with various phenol substrates. Control experiments reveal the synergy between the Cu-porphyrin center and framework in PCN-300 and computations unveil the free radical pathway of the reaction. This study highlights the power of robust pyrazolate MOFs in directly activating C-H bonds and catalyzing challenging chemical transformations in an environmentally friendly manner.
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Quantum Hall systems host chiral edge states extending along the one-dimensional boundary of any two-dimensional sample. In solid state materials, the edge states serve as perfectly robust transport channels that produce a quantized Hall conductance; due to their chirality, and the topological protection by the Chern number of the bulk band structure, they cannot be spatially localized by defects or disorder. Here, we show experimentally that the chiral edge states of a lossy quantum Hall system can be localized. In a gyromagnetic photonic crystal exhibiting the quantum Hall topological phase, an appropriately structured loss configuration imparts the edge states' complex energy spectrum with a feature known as point-gap winding. This intrinsically non-Hermitian topological invariant is distinct from the Chern number invariant of the bulk (which remains intact) and induces mode localization via the "non-Hermitian skin effect." The interplay of the two topological phenomena-the Chern number and point-gap winding-gives rise to a non-Hermitian generalization of the paradigmatic Chern-type bulk-boundary correspondence principle. Compared to previous realizations of the non-Hermitian skin effect, the skin modes in this system have superior robustness against local defects and disorders.
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Further development in the area of medicinal chemistry requires facile and atom-economical C-N bond formation from readily accessible precursors using recyclable and reusable catalysts with low process toxicity. In this work, direct N-alkylation of amines with alcohols is performed with a series of Ir-phosphine-functionalized metal-organic framework (MOF) heterogeneous catalysts. The grafted monophosphine-Ir complexes were studied comprehensively to illustrate the ligand-dependent reactivity. The afforded MOF catalysts exhibited high reactivity and selectivity toward N-alkylamine product formation, especially UiO-66-PPh2-Ir, which showed 90% conversion after recycling with no catalyst residue remaining in the product after the reaction. Furthermore, analyses of the active catalyst, mechanistic studies, control experiments, and H2 adsorption tests are consistent with the conclusion that immobilization of the iridium complex on the MOF support enables the formation of the iridium-monophosphine complex and enhances its stability during the reaction. To illustrate the potential of the catalyst for application in medicinal chemistry, two pharmaceutical precursors were synthesized with up to 99% conversion and selectivity.
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Photonic Chern insulators are known for their topological chiral edge states (CESs), whose absolute existence is determined by the bulk band topology, but concrete dispersion can be engineered to exhibit various properties. For example, the previous theory suggested that the edge dispersion can wind many times around the Brillouin zone to slow down light, which can potentially overcome fundamental limitations in conventional slow-light devices: narrow bandwidth and keen sensitivity to fabrication imperfection. Here, we report the first experimental demonstration of this idea, achieved by coupling CESs with resonance-induced nearly flat bands. We show that the backscattering-immune hybridized CESs are significantly slowed down over a relatively broad bandwidth. Our work thus paves an avenue to broadband topological slow-light devices.
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Hyperbolic lattices are a new type of synthetic materials based on regular tessellations in non-Euclidean spaces with constant negative curvature. While so far, there has been several theoretical investigations of hyperbolic topological media, experimental work has been limited to time-reversal invariant systems made of coupled discrete resonances, leaving the more interesting case of robust, unidirectional edge wave transport completely unobserved. Here, we report a non-reciprocal hyperbolic network that exhibits both Chern and anomalous chiral edge modes, and implement it on a planar microwave platform. We experimentally evidence the unidirectional character of the topological edge modes by direct field mapping. We demonstrate the topological origin of these hyperbolic chiral edge modes by an explicit topological invariant measurement, performed from external probes. Our work extends the reach of topological wave physics by allowing for backscattering-immune transport in materials with synthetic non-Euclidean behavior.
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Lineage plasticity-a state of dual fate expression-is required to release stem cells from their niche constraints and redirect them to tissue compartments where they are most needed. In this work, we found that without resolving lineage plasticity, skin stem cells cannot effectively generate each lineage in vitro nor regrow hair and repair wounded epidermis in vivo. A small-molecule screen unearthed retinoic acid as a critical regulator. Combining high-throughput approaches, cell culture, and in vivo mouse genetics, we dissected its roles in tissue regeneration. We found that retinoic acid is made locally in hair follicle stem cell niches, where its levels determine identity and usage. Our findings have therapeutic implications for hair growth as well as chronic wounds and cancers, where lineage plasticity is unresolved.
Subject(s)
Adult Stem Cells , Cell Plasticity , Epidermis , Hair Follicle , Tretinoin , Wound Healing , Animals , Mice , Adult Stem Cells/cytology , Adult Stem Cells/physiology , Cell Lineage/drug effects , Cell Lineage/physiology , Cell Plasticity/drug effects , Cell Plasticity/physiology , Epidermis/drug effects , Epidermis/physiology , Hair Follicle/cytology , Hair Follicle/drug effects , Hair Follicle/physiology , Tretinoin/metabolism , Tretinoin/pharmacology , Wound Healing/drug effects , Wound Healing/physiology , Rejuvenation/physiology , Cell Culture Techniques , Neoplasms/pathology , Mice, Inbred C57BLABSTRACT
As hypothetical topological defects in the geometry of spacetime, vortex strings could have played many roles in cosmology, and their distinct features can provide observable clues about the early universe's evolution. A key feature of vortex strings is that they can interact with Weyl fermionic modes and support massless chiral-anomaly states along strings. To date, despite many attempts to detect vortex strings in astrophysics or to emulate them in artificially created systems, observation of these vortex-string chiral modes remains experimentally elusive. Here we report experimental observations of vortex-string chiral modes using a metamaterial system. This is implemented by inhomogeneous perturbation of Yang-monopole phononic metamaterials. The measured linear dispersion and modal profiles confirm the existence of topological modes bound to and propagating along the string with the chiral anomaly. Our work provides a platform for studying diverse cosmic topological defects in astrophysics and offers applications as topological fibres in communication techniques.
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Perfluorooctanoic acid (PFOA) is an environmental contaminant ubiquitous in water resources, which as a xenobiotic and carcinogenic agent, severely endangers human health. The development of techniques for its efficient removal is therefore highly sought after. Herein, we demonstrate an unprecedented zirconium-based MOF (PCN-999) possessing Zr6 and biformate-bridged (Zr6)2 clusters simultaneously, which exhibits an exceptional PFOA uptake of 1089 mg/g (2.63 mmol/g), representing a ca. 50% increase over the previous record for MOFs. Single-crystal X-ray diffraction studies and computational analysis revealed that the (Zr6)2 clusters offer additional open coordination sites for hosting PFOA. The coordinated PFOAs further enhance the interaction between coordinated and free PFOAs for physical adsorption, boosting the adsorption capacity to an unparalleled high standard. Our findings represent a major step forward in the fundamental understanding of the MOF-based PFOA removal mechanism, paving the way toward the rational design of next-generation adsorbents for per- and polyfluoroalkyl substance (PFAS) removal.
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3D metal-organic frameworks (MOFs) have gained attention as heterogeneous photocatalysts due to their porosity and unique host-guest interactions. Despite their potential, MOFs face challenges, such as inefficient mass transport and limited light penetration in photoinduced energy transfer processes. Recent advancements in organic photocatalysis have uncovered a variety of photoactive cores, while their heterogenization remains an underexplored area with great potential to build MOFs. This gap is bridged by incorporating photoactive cores into 2D MOF nanosheets, a process that merges the realms of small-molecule photochemistry and MOF chemistry. This approach results in recyclable heterogeneous photocatalysts that exhibit an improved mass transfer efficiency. This research demonstrates a bottom-up synthetic method for embedding photoactive cores into 2D MOF nanosheets, successfully producing variants such as PCN-641-NS, PCN-643-NS, and PCN-644-NS. The synthetic conditions were systematically studied to optimize the crystallinity and morphology of these 2D MOF nanosheets. Enhanced host-guest interactions in these 2D structures were confirmed through various techniques, particularly solid-state NMR studies. Additionally, the efficiency of photoinduced energy transfer in these nanosheets was evidenced through photoborylation reactions and the generation of reactive oxygen species (ROS).
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As water scarcity becomes a pending global issue, hygroscopic materials prove a significant solution. Thus, there is a good cause following the structure-performance relationship to review the recent development of hygroscopic materials and provide inspirational insight into creative materials. Herein, traditional hygroscopic materials, crystalline frameworks, polymers, and composite materials are reviewed. The similarity in working conditions of water harvesting and carbon capture makes simultaneously addressing water shortages and reduction of greenhouse effects possible. Concurrent water harvesting and carbon capture is likely to become a future challenge. Therefore, an emphasis is laid on metal-organic frameworks (MOFs) for their excellent performance in water and CO2 adsorption, and representative role of micro- and mesoporous materials. Herein, the water adsorption mechanisms of MOFs are summarized, followed by a review of MOF's water stability, with a highlight on the emerging machine learning (ML) technique to predict MOF water stability and water uptake. Recent advances in the mechanistic elaboration of moisture's effects on CO2 adsorption are reviewed. This review summarizes recent advances in water-harvesting porous materials with special attention on MOFs and expects to direct researchers' attention into the topic of concurrent water harvesting and carbon capture as a future challenge.
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OBJECTIVE: Lumbosacral vertebral osteoblastic metastasis is treated with percutaneous vertebroplasty (PVP) combined with 125I seed implantation and PVP alone. Compared to PVP alone, we evaluated the effects of combination therapy with PVP and 125I seed implantation on pain, physical condition, and survival and evaluated the clinical value of PVP combined with 125I particle implantation. METHODS: We retrospectively analyzed 62 patients with lumbosacral vertebral osseous metastases treated at our hospital between 2016 and 2019. All the patients met the inclusion criteria for 125I implantation, and they were randomly divided into a combined treatment group and a pure PVP surgery group. The visual analog pain scale (VAS), Karnofsky Performance Status (KPS), and survival time were recorded at different time points, including preoperative, postoperative 1 day, 1 month, 3 months, 6 months, 12 months, and 36 months in each group. The variation in clinical indicators and differences between the groups were analyzed using SPSS version 20.0. Correlations between different variables were analyzed using the nonparametric Spearman's rank test. The Kaplan-Meier method was used to estimate the relationship between survival time and KPS score, VAS score, or primary tumor progression, and survival differences were analyzed using the log-rank test. Multivariate analyses were performed using a stepwise Cox proportional hazards model to identify independent prognostic factors. RESULTS: Compared to the PVP treatment group, the pain level in the combined treatment group was significantly reduced (P = 0.000), and the patient's physical condition in the combination treatment group significantly improved. Kaplan-Meier analysis showed that the survival rate of the PVP group was significantly lower than that of the combination group (P = 0.038). We also found that the median survival of patients in both groups significantly increased with an increase in the KPS score (14 months vs. 33 months) (P = 0.020). Patients with more than three transfer sections had significantly lower survival rates than those with one or two segments of the section (P = 0.001). Further, Cox regression analysis showed that age (P = 0.002), the spinal segment for spinal metastasis (P = 0.000), and primary tumor growth rate (P = 0.005) were independent factors that affected the long-term survival of patients with lumbosacral vertebral osseous metastases. CONCLUSIONS: PVP combined 125I seeds implantation surgery demonstrated superior effectiveness compared to PVP surgery alone in treating lumbosacral vertebral osseous metastases, which had feasibility in the clinical operation. Preoperative KPS score, spine transfer section, and primary tumor growth rate were closely related to the survival of patients with lumbosacral vertebral osteoblastic metastasis. Age, spinal segment for spinal metastasis, and primary tumor growth can serve as prognostic indicators and guide clinical treatment.