Abstract Bone remodeling requires precise coordination between osteoblast-mediated bone formation and osteoclast-driven resorption. However, directly targetable and therapeutically actionable mediators that can coordinately modulate both processes during regeneration remain relatively limited. Here, we identify immunoglobulin superfamily member 10 (IGSF10) as a dual-function modulator of bone remodeling. Igsf10- deficient mice exhibit reduced bone mass, elevated osteoclast activity, and impaired osteogenesis. Recombinant IGSF10 protein restores osteogenic capacity and suppresses osteoclastogenesis in knockout cells, while exerting pro-osteogenic and anti-resorptive effects in wild-type mesenchymal and monocyte-derived cultures. Mechanistically, IGSF10 activates a noncanonical EGFR–STAT1 signaling pathway, distinct from BMP2–Smad signaling. Co-immunoprecipitation and molecular docking confirm IGSF10–EGFR interaction, and blockade of EGFR abrogates IGSF10-induced osteogenesis and its inhibitory effects on osteoclastogenesis. In vivo, IGSF10 promotes bone regeneration in both calvarial and periodontal defect models and exhibits synergy with subtherapeutic BMP2. These findings position IGSF10 as a previously unrecognized dual-acting regulator that coordinates bone formation and resorption in a context-dependent manner, with potential therapeutic value for craniofacial and skeletal regeneration.

Rare-earth oxide (REO) nanomaterials are promising photonic platforms, yet their practical emission efficiency is limited by the intrinsically weak absorption of parity-forbidden 4f-4f transitions. Here, we report a coumarin-based molecular sensitization strategy that markedly enhances the photoluminescence of Eu-doped Y2O3 nanoplatelets by addressing ligand-oxide interfacial chemistry. Using four coumarin derivatives with identical chromophore backbones but varied anchoring-group acidities, we reveal that interfacial chemical compatibility, rather than energy-level alignment alone, governs sensitization efficiency. Strongly acidic carboxylic acid groups induce surface reconstruction and defect formation, leading to pronounced nonradiative quenching, whereas ester and phenolic hydroxyl functionalities enable stable surface anchoring while preserving oxide lattice integrity. The optimal ligand, ethyl 7-hydroxycoumarin-3-carboxylate (EHC), delivers a 149-fold increase in Eu3+ emission by suppressing defect-mediated nonradiative pathways without compromising the structural integrity of the oxide lattice. Furthermore, the coexistence of fast, broadband ligand S1 emission and slow, narrowband Eu3+ emission within a single hybrid nanomaterial enables a proof-of-concept demonstration of dual-channel optical signal routing and information encryption. Our work establishes that beyond conventional energy-level matching, interfacial chemical compatibility serves as a crucial design principle for molecularly sensitized REO nanomaterials, providing guidance for the development of robust, efficient, and multifunctional rare-earth nanophotonic emitters.

Precise mapping of leukemic cells onto the known hematopoietic hierarchy is important for understanding the cell-of-origin and mechanisms underlying disease initiation and development. However, this task remains challenging because of the high interpatient and intrapatient heterogeneity of leukemia cell clones as well as the differences that exist between leukemic and normal hematopoietic cells. Using single-cell RNA sequencing (scRNA-seq) data with a curated clustering approach, we constructed a comprehensive reference hierarchy of normal hematopoiesis. This reference hierarchy was accomplished through multistep clustering and annotating over 100,000 bone marrow mononuclear cells derived from 25 healthy donors. We further employed the cosine distance algorithm to develop a likelihood score to determine the similarities of leukemic cells to their putative normal counterparts. Using our scoring strategies, we mapped the cells of acute myeloid leukemia (AML) and B cell precursor acute lymphoblastic leukemia (BCP-ALL) samples to their corresponding counterparts. The reference hierarchy also facilitated bulk RNA sequencing (RNA-seq) analysis, enabling the development of a least absolute shrinkage and selection operator (LASSO) score model to reveal subtle differences in lineage aberrancy within AML or BCP-ALL patients. To facilitate interpretation and application, we established an R-based package (HematoMap) that offers a fast, convenient, and user-friendly tool for identifying and visualizing lineage aberrations in leukemia from scRNA-seq and bulk RNA-seq data. Our tool provides curated resources and data analytics for understanding leukemogenesis, with the potential to enhance leukemia risk stratification and personalized treatments. The HematoMap is available at https://github.com/NRCTM-bioinfo/HematoMap.

Aims: The aim of this study was to systematically analyze the role of Brucea javanica in the treatment of cervical cancer (CC) and its underlying mechanisms by means of network pharmacology and molecular docking. Background: Brucea javanica is a traditional Chinese herbal medicine used for the treatment of malaria and cancers, but its mechanism of action in CC is unknown. Objective: The objective of the study is screening of active chemical constituents of Brucea javanica by Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and investigating their potential targets involved in CC therapy. Methods: The GeneCards database was used for the disease targets of CC, the drug-compound-disease target network was constructed by using the Cytoscape 3.8.0 software. Then, the key targets in the protein-protein interaction (PPI) network were identified, and the "clusterProfiler" was used for the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The qRT-PCR, CCK-8, and flow cytometry were used to assess the expression levels of specific target genes in CC cells, as well as their effects on cell proliferation, apoptosis, and reactive oxygen species (ROS) levels, respectively. Protein-compound complex analysis was performed using molecular dynamics simulation. Results: A total of 15 active compounds and their 86 treatment targets were obtained from the Brucea javanica analysis, in which 51 target genes were associated with the CC-related disease targets. Then, a PPI analysis identified 12 key genes (including EGFR, TP53, BCL2, AKT1, JUN, TNF, CASP3, IL6, MMP9, ERBB2, CCND1, and PTGS2) that were related to oxidative stress, PI3K-Akt, IL-17, p53, and JAK-STAT pathways, inflammatory response, and apoptosis pathways. In addition, AKT1 showed upregulation at the mRNA level in SiHa cells, and the knockdown of AKT1 significantly reduced the proliferation of CC cells and increased apoptosis and ROS levels. Molecular docking and dynamics simulations revealed a close binding between the active compounds and targets. Conclusions: The present research comprehensively examined the active compounds, potential targets, and pathways of Brucea javanica in CC treatment, providing a novel insight for CC treatment.

Choriocarcinoma (CC) is a highly malignant tumor that occurs in women. Methyltransferase-like 3 (METTL3) is a key protein of m6A methyltransferase complex and its role in CC has been studied, but the study of exosomal METTL3 in CC has not been reported. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to assess the expressions of related genes. Cell counting kit-8 (CCK-8) assay, wound healing assay, transwell assay, and relevant kit assays were employed to detect the behaviors of tumor cells after different treatments. Moreover, exosome-related researches were performed using kits and transmission electron microscope. Online software was applied to predict the relationship between METTL3 and F-box and WD repeat domain containing 8 (Fbxw8), verified by methylated RNA immunoprecipitation (MeRIP)-qPCR. Furthermore, xenograft mouse models were constructed for validation experiments in vivo. METTL3 was overexpressed in CC cell lines, and was a promoter of CC progression and glycolysis. In addition, METTL3 was highly expressed in tumor cell-derived exosomes and decreased with the addition of GW4869, an exosome inhibitor. Similarly, the knockdown of tumor cell-derived METTL3 also inhibited CC progression and glycolysis. Mechanically, tumor cell-derived exosomal METTL3 motivated the malignant progression of CC by mediating m6A methylation and expression of Fbxw8. In vivo, tumor cell-derived exosomal METTL3 also expedited tumor growth through Fbxw8. Tumor cell-derived exosomal METTL3 promotes glycolysis in CC via regulating m6A methylation modification on Fbxw8 mRNA to further amplify tumor malignant progression, and this will provide a new target for the treatment of CC in the future.

Remineralization is a common strategy for the repair of early demineralized tooth enamels, but the harsh dynamic oral environment often hampers its efficacy. Rapid remineralization is expected to address this challenge, however, the stabilizers of remineralization materials often resist their transformation required for repair. Here, by dissolving the ions of calcium and phosphate in glycerol-dominant solvents, we obtain the calcium phosphate clusters (1–2 nm), which are stabilized by glycerol (with high viscosity and affinity to clusters), but can perform a fast enamel repair via the water-triggered transformation in both static and dynamic environments. Upon the in vitro and in vivo (female Sprague-Dawley rats) studies, the clusters swiftly enter the nano-/micro-sized enamel defect sites, then form a compact hydroxyapatite repair layer within a short time (30 min, much faster than the conventional materials), and significantly recovers mechanical properties. This material is promising for large-scale preparation and applications in dental remineralization. Using remineralization materials to grow hydroxyapatite crystals on the surfaces is a common strategy for the repair of early demineralized tooth enamels but often stabilizers used for reparation and storage slow down the mineralization process. Here the authors use glycerol stabilized calcium phosphate cluster, which can perform a fast enamel repair via water-triggered transformation.

Graphene-based nanomaterials, including graphene oxide (GO) and graphene quantum dots (GQDs), exhibit exceptional properties, which might facilitate the functional modification of TiO2 nanotubes (NTs) for enhanced rapid osseointegration. This study investigated the effects of GO/GQD-deposited TiO2-NTs on cell proliferation, osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs), and early osseointegration in male 6-week-old Sprague Dawley (SD) rats. TiO2-NTs (control group) were fabricated on titanium substrates via anodic oxidation. GO and GQDs were electrochemically deposited onto the TiO2-NTs using cyclic voltammetry with 0.5 mg/mL GO and 0.1 mg/mL GQD dispersions to form NT-GO and NT-GQDs. In vitro assays evaluated cell adhesion, proliferation, and osteogenic differentiation. Implants were randomly inserted into one femoral epiphysis of nine rats (n = 3), and osseointegration was evaluated using micro-computed tomography and sequential fluorescence labeling at 2, 4, and 6 weeks post-implantation. Statistical analysis was conducted using ANOVA. Cyclic voltammetry successfully synthesized NT-GO and NT-GQDs, with Raman spectra confirming D and G bands. Both NT-GO and NT-GQDs exhibited superior cell adhesion, proliferation, and enhanced osteogenic differentiation compared with TiO2-NTs. Notably, the NT-GQDs significantly promoted new bone formation in vivo. The integration of graphene nanomaterials onto TiO2-NTs improves biocompatibility and accelerates osteogenesis, suggesting a promising strategy for enhancing osseointegration in orthopedic and dental implants.

Venetoclax-azacitidine (VEN/AZA) has transformed acute myeloid leukemia (AML) therapy, yet reliable predictors of response remain lacking. We employ a multidisciplinary strategy combining ex vivo drug sensitivity testing, transcriptomic profiling, functional assays, and clinical data to identify determinants of VEN/AZA response. Core genes consistently associated with responsiveness are validated through CRISPR-Cas9 screening, with silencing of BCL2L1 and PINK1 preferentially enhancing drug sensitivity. Building on these insights, we develop and validate an eight-gene random forest model (RF8) that achieves high accuracy across four independent cohorts (n = 498). RF8 distills the downstream effects of genetic alterations to assist in predicting treatment response and outperforms existing genetic mutation-based signatures. Moreover, RF8 scores show a nearly monotonic relationship with clinical response probabilities and survival outcomes, enabling precise patient stratification. These findings demonstrate the feasibility of integrating transcriptomic and drug-response data to guide VEN/AZA therapy, representing an advance toward personalized therapeutic strategies.

The study aims to elucidate the mechanism through which 17β-estradiol facilitates osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). In our study, lentiviral transfection was employed to establish apoptosis repressor with caspase recruitment domain (ARC) knockdown or overexpression in BMSCs. The impact of 17β-estradiol on ARC expression was assessed using western blot, RT-PCR and immunofluorescence. Techniques such as ALP staining, ALP activity assay, western blot, RT-PCR and immunofluorescence staining were utilized to examine the influence of ARC expression levels on the osteogenic differentiation of BMSCs and the osteoclastic differentiation of Raw264.7 cell lines. Mitophagy flux levels in BMSCs were detected using the mitophagy detection kit. RNA sequencing and bioinformatics analyses were conducted to explore potential mechanisms of ARC regulation in BMSCs osteogenic differentiation. To sum up, 17β-estradiol can modulate bone homeostasis by adjusting ARC expression. ARC stimulates mitophagy in BMSCs via MAPK/Akt pathway, identifying ARC as a promising therapeutic target for postmenopausal osteoporosis (PMOP) treatment.

Aim or purpose: To investigate the role of IGSF10 in mitigating inflammation-driven alveolar bone loss and its underlying regulatory mechanisms. Materials and methods: In vivo: IGSF10-knockout (KO) and wild-type (WT) C57BL/6 mice (male, 8 weeks old) were subjected to LPS-induced experimental periodontitis under ethics committee approval. Alveolar bone morphology was assessed by micro-CT, while histopathological analysis (H&E staining), osteoclast activity (TRAP staining), and inflammatory markers (IL-1B immunohistochemistry) were evaluated. Recombinant IGSF10 was locally administered to both KO and WT mice with periodontitis. In vitro: Human periodontal ligament fibroblasts (PDLCs) were stimulated with LPS and treated with recombinant IGSF10. RNA sequencing and pathway enrichment analysis identified key signaling networks. Cytokine levels, STAT1 activation, and macrophage polarization were analyzed via ELISA, Western blot, and flow cytometry. Statistical analysis was performed using one-way ANOVA. Results: IGSF10 expression was significantly upregulated in inflamed periodontal tissues and LPS-stimulated PDLCs. Genetic ablation of IGSF10 exacerbated alveolar bone resorption and osteoclast activity in mice, while local administration of recombinant IGSF10 not only rescued bone loss in KO mice but also demonstrated therapeutic efficacy in WT periodontitis models by reducing bone resorption and inflammatory infiltration. Mechanistically, IGSF10 suppressed pro-inflammatory cytokine production and enhanced anti-inflammatory factor expression in PDLCs through STAT1 pathway activation, while promoting a shift toward M2 macrophage polarization. Conclusions: IGSF10 protects against periodontitis-induced alveolar bone loss by modulating STAT1-dependent anti-inflammatory signaling and immune cell reprogramming, highlighting its therapeutic potential in inflammatory bone disorders.

Acute myeloid leukemia (AML) has lagged in benefiting from immunotherapies, primarily due to the scarcity of actionable AML-specific antigens. Driver mutations represent promising immunogenic targets, but a comprehensive characterization of the AML neoantigen landscape and their impact on patient outcomes and the AML immune microenvironment remain unclear. Herein, we conducted matched DNA and RNA sequencing on 304 AML patients and extensively integrated data from additional ∼2,500 AML cases, identifying 49 driver genes, notably characterized by a significant proportion of insertions and deletions (indels). Neoantigen analysis showed that indels triggered a higher abundance of neoantigens both in quantity and quality compared to single nucleotide variants (SNVs) and gene fusions. By integrating peptide features pertinent to neoantigen presentation and T cell recognition, we developed two robust models of epitope immunogenicity that significantly enriched immunogenic neoepitopes. We validated 30 neoantigens through in vitro direct binding assays of predicted peptides to MHC proteins and confirmed the immunogenicity of 20 neoantigens using interferon-γ ELISpot and tetramer assays. Moreover, we demonstrated that patients with higher neoantigen loads, derived from driver mutations, exhibited poor clinical outcomes and an IFN-driven adaptive immune response, which was associated with immune suppression and tumor evasion. Through deconvolution of large-scale bulk transcriptomes, integration of single-cell RNA sequencing and multiparametric flow cytometry, we confirmed a strong association between neoantigen load and CD8+ T cell exhaustion. This study provides a comprehensive landscape of AML neoantigens derived from driver mutations, offering putative immunogenic targets and emphasizing the need for strategies to revitalize the immunosuppressive milieu.

Background: Acute myeloid leukemia (AML), a malignant blood disease, is caused by the excessive growth of undifferentiated myeloid cells, which disrupt normal hematopoiesis and may invade several organs. Given the high heterogeneity in prognosis, identifying stable prognostic biomarkers is crucial for improved risk stratification and personalized treatment strategies. Although glycolysis has been extensively studied in cancer, its prognostic significance in AML remains unclear. Methods: Glycolysis-related prognostic genes were identified by differential expression profiles. We modeled prognostic risk by least absolute shrinkage and selection operator (LASSO) regression and validated it by Kaplan–Meier (KM) survival analysis, receiver operating characteristic (ROC) curves, and independent datasets (BeatAML2.0, GSE37642, GSE71014). Mechanisms were further explored through immune microenvironment analysis and drug sensitivity scores. Results: Differential expression and survival correlation analysis across the genes associated with glycolysis revealed multiple glycolytic genes associated with the outcomes of AML. We constructed a seven-gene prognostic model (G6PD, TFF3, GALM, SOD1, NT5E, CTH, FUT8). Kaplan–Meier analysis demonstrated significantly reduced survival in high-risk patients (hazard ratio (HR) = 3.4, p < 0.01). The model predicted the 1-, 3-, and 5-year survival outcomes, achieving area under the curve (AUC) values greater than 0.8. Immune profiling indicated distinct cellular compositions between risk groups: high-risk patients exhibited elevated monocytes and neutrophils but reduced Th1 cell infiltration. Drug sensitivity analysis showed that high-risk patients exhibited resistance to crizotinib and lapatinib but were more sensitive to motesanib. Conclusions: We established a novel glycolysis-related gene signature for AML prognosis, enabling effective risk classification. Combined with immune microenvironment analysis and drug sensitivity analysis, we screened metabolic characteristics and identified an immune signature to provide deeper insight into AML. Our findings may assist in identifying new therapeutic targets and more effective personalized treatment regimes.

Aim or purpose: To investigate the systemic role of IGSF10 in regulating bone homeostasis and remodeling, focusing on its molecular interplay with osteogenic networks. Materials and methods: Osteoblast-specific IGSF10-knockout mice (Oc-Cre;Igsf10flox/flox, 8-week-old females) and Igsf10flox controls were analyzed. Bone microarchitecture was assessed by micro-CT. Osteoclast activity was evaluated via TRAP staining. Bone marrow stromal cells (BMSCs) from knockout and control mice were subjected to osteogenic induction in vitro, with or without IGSF10 treatment. Primary human PDLCs were cultured in basal medium or osteogenic induction medium (OIM) ± recombinant IGSF10. Osteogenic markers (Runx2, ALP, Bsp) were analyzed by qPCR and Western blot. Mineralization was assessed via ALP staining (day 7) and Alizarin Red S quantification (day 14). RNA-seq and pathway enrichment analysis were performed on IGSF10-treated PDLCs to identify regulatory networks. Statistical analysis was performed using unpaired t-test and one-way ANOVA. Results: Osteoblast-specific IGSF10 knockout mice demonstrated reduced trabecular bone density and thickness in femurs and mandibles under basal conditions, independent of osteoclast activity. BMSCs from knockout mice exhibited impaired osteogenic differentiation (reduced Runx2, ALP, and mineralization), which was partially restored by exogenous IGSF10, while IGSF10 synergized with osteogenic signals to enhance mineralization in human periodontal fibroblasts. RNA-seq revealed that IGSF10 activated interferon-associated transcriptional networks during osteogenic programming, suggesting a novel regulatory axis in bone formation. Conclusions: IGSF10 regulates bone formation by enhancing differentiation and mineralization through activation of interferon-associated transcriptional networks, providing a potential therapeutic target for bone regeneration.

Osteoporosis is a prevalent metabolic bone disease. While drug therapy is essential to prevent bone loss in osteoporotic patients, current treatments are limited by side effects and high costs, necessitating the development of more effective and safer targeted therapies. Utilizing a zebrafish ( Danio rerio) larval model of osteoporosis, we explored the influence of the metabolite spermine on bone homeostasis. Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption. Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity. Notably, spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae. At the molecular level, Rac1 was identified as playing a pivotal role in mediating the anti-osteoporotic effects of spermine, with P53 potentially acting downstream of Rac1. These findings were confirmed using mouse ( Mus musculus) models, in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions, suggesting strong potential as a bone-strengthening agent. This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development, highlighting pivotal molecular mediators. Given their efficacy and safety, human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

Abstract Patients with primary refractory acute myeloid leukemia (AML) have a dismal long-term prognosis. Elucidating the resistance mechanisms to induction chemotherapy could help identify strategies to improve AML patient outcomes. Herein, we retrospectively analyzed the multiomics data of more than 1,500 AML cases and found that patients with spliceosome mutations had a higher risk of developing refractory disease. RNA splicing analysis revealed that the mis-spliced genes in refractory patients converged on translation-associated pathways, promoted mainly by U2AF1 mutations. Integrative analyses of binding and splicing in AML cell lines substantiated that the splicing perturbations of mRNA translation genes originated from both the loss and gain of mutant U2AF1 binding. In particular, the U2AF1S34F and U2AF1Q157R mutants orchestrated the inclusion of exon 11 (encoding a premature termination codon) in the eukaryotic translation initiation factor 4A2 (EIF4A2). This aberrant inclusion led to reduced eIF4A2 protein expression via nonsense-mediated mRNA decay. Consequently, U2AF1 mutations caused a net decrease in global mRNA translation that induced the integrated stress response (ISR) in AML cells, which was confirmed by single-cell RNA sequencing. The induction of ISR enhanced the ability of AML cells to respond and adapt to stress, contributing to chemoresistance. A pharmacologic inhibitor of ISR, ISRIB, sensitized U2AF1 mutant cells to chemotherapy. These findings highlight a resistance mechanism by which U2AF1 mutations drive chemoresistance and provide a therapeutic approach for AML through targeting the ISR pathway. Significance: U2AF1 mutations induce the integrated stress response by disrupting splicing of mRNA translation genes that improves AML cell fitness to enable resistance to chemotherapy, which can be targeted to improve AML treatment.

New evidence for piezoelectric nanomaterials across energy harvesting, piezocatalysis, and biomedicine fields, guiding and supporting future drug delivery system development.

Pulp regeneration remains a crucial target in the preservation of natural dentition. Using decellularized extracellular matrix is an appropriate approach to mimic natural microenvironment and facilitate tissue regeneration. In this study, we attempted to obtain decellularized extracellular matrix from periapical lesion (PL-dECM) and evaluate its bioactive effects. The decellularization process yielded translucent and viscous PL-dECM, meeting the standard requirements for decellularization efficiency. Proteomic sequencing revealed that the PL-dECM retained essential extracellular matrix components and numerous bioactive factors. The PL-dECM conditioned medium could enhance the proliferation and migration ability of periapical lesion-derived stem cells (PLDSCs) in a dose-dependent manner. Culturing PLDSCs on PL-dECM slices improved odontogenic/angiogenic ability compared to the type I collagen group. In vivo, the PL-dECM demonstrated a sustained supportive effect on PLDSCs and promoted odontogenic/angiogenic differentiation. Both in vitro and in vivo studies illustrated that PL-dECM served as an effective scaffold for pulp tissue engineering, providing valuable insights into PLDSCs differentiation. These findings pave avenues for the clinical application of dECM's in situ transplantation for regenerative endodontics.

Background: Over the past decade, there have been significant changes in the treatment landscape for chronic lymphocytic leukemia/Small Lymphocytic Lymphoma (CLL/SLL). These advancements have not only improved patient outcomes but also significantly altered our therapeutic goals for this disease. Aims: Evaluation of real-world outcomes for CLL/SLL patients in China as treatment strategies evolve. Methods: Demographic data, clinical characteristics, treatment and survival were retrospectively collected for CLL/SLL patients hospitalized in our center from February 2014 to October 2023. Results： The study cohort included 370 CLL/SLL patients, with the earliest onset year tracing back to 2000. There were 265 males and 105 females. At the time of admission, the median age was 66 years (range 29-89), and 193 patients (52%) were older than 65 years. A total of 139 individuals (38%) were classified as high-risk based on the Rai (III, IV) or Binet (C) staging system. Since 2020, fluorescence in situ hybridization (FISH) has been implemented for CLL/SLL patients in our center, resulting in 182 patients undergoing the test. Genomic abnormalities were detected in 124 (68%) of these patients: 49 (27%) had Trisomy 12, 34 (19%) had an RB1 deletion, 18 (10%) had an ATM deletion, and 13 (7%) had a TP53 deletion. IGHV mutation was present in 71% (80 out of 113) of the patients. There were 298 patients (81%) who had indications for treatment and received therapy. The median time to first treatment (TTFT) was 14 months (range 0-192 months). Among these, 11 patients experienced Richter transformation (RT) at the time of first treatment. Of the remaining 287 patients, 74 (26%) were treated with alkylating or nucleoside agents (CT), 74 (26%) received chemoimmunotherapy (CIT), and 139 (48%) were administered Bruton's tyrosine kinase inhibitors (BTKi) either as monotherapy or in combination therapy. Before 2018, first-line treatments for CLL/SLL primarily included CT and CIT, accounting for 54% and 43% of the 84 treated patients, respectively. Only 3 patients received ibrutinib as part of a clinical trial. However, since 2018, with the sequential approval of BTKi such as ibrutinib, zanubrutinib, and orelabrutinib in China, the proportion of patients receiving CT (14%) and CIT (19%) among the 203 patients has significantly decreased. Instead, a growing number of patients (67%) have been treated primarily with BTKi. With a median follow-up of 46.8 months (range 0.2-254.6 months) from the diagnosis of the disease, the estimated 18-year overall survival (OS) rate for all patients was 66%. For patients receiving first-line treatment (excluding the 11 mentioned with RT), the median follow-up times were 33 months for the CT group, 37 months for the CIT group, and 17 months for the BTKi group. The estimated 7-year OS rates for these three groups were 77%, 80%, and 71% (p=0.473), respectively. The 7-year progression-free survival (PFS) rates were 42%, 63%, and 72% (p=0.111), respectively. Our data suggest that BTKi-based treatment strategies can achieve better PFS, but there was no statistically significant difference compared to the CT and CIT groups. This may be due to the fact that most CT and CIT patients started treatment earlier and were more likely to be lost to follow-up, thereby underestimating the occurrence of PFS events. Including the 11 RT patients mentioned earlier, a total of 19 patients developed RT. Among these, 13 cases were diffuse large B-cell lymphoma, 2 were mantle cell lymphoma, 2 were Hodgkin lymphoma, 1 was B-cell prolymphocytic leukemia, and 1 was angioimmunoblastic T-cell lymphoma. The median time from disease onset to transformation was 34 months (range 1-221 months). The 18-year OS rates for patients with and without RT were 25% and 70% (p=0.008), respectively. Conclusion： This real-world study demonstrates significant advancements in the treatment of CLL/SLL over the past decade. The introduction and inclusion of BTKi in China's healthcare insurance policy have notably shifted treatment practices from CT and CIT to BTKi-based therapies. This transition has improved patient outcomes and prognosis. Due to the convenience of oral administration, an increasing number of patients are opting for BTKi as their first-line treatment.