Bone metastasis,as a common terminal event in patients with advanced malignant tumors,significantly impacts patients'quality of life and survival prognosis,posing a major clinical challenge in the field of oncology.With the deepening understanding of tumor biology,the treatment paradigm for bone metastasis has progressively shifted from traditional palliative care to precise targeted interventions.Currently,clinical treatment strategies have demonstrated diversified development,with various therapeutic approaches-including radiotherapy,immunotherapy,bone-modifying agents,and small-molecule targeted drugs—achieving notable clinical progress.However,existing treatment regimens still face challenges such as significant interindividual variability in efficacy,frequent drug resistance,and prominent adverse effects.This article systematically reviews the latest advances in precision therapy for bone metastasis,provides an in-depth analysis of the strengths and limitations of different treatment strategies,and offers perspectives on future research directions and therapeutic prospects,aiming to provide reference for optimizing clinical practice and promoting translational research.

Objective To analyze the association between plasma circulating tumor DNA(ctDNA)TP53 mutation status and survival outcomes in breast cancer patients.Methods PubMed,Embase,and the Cochrane Library were searched for relevant literature published between 2000 and 2025,examining the impact of plasma ctDNA TP53 mutations on survival outcomes in breast cancer patients,including overall survival(OS),progression-free survival(PFS),or disease-free survival(DFS).Two researchers independently screened the literature according to predefined inclusion and exclusion criteria and extracted relevant data.The Newcastle-Ottawa scale and Cochrane Risk of Bias Assessment Tool were used to evaluate study quality.Meta-analysis,publication bias assessment,and sensitivity analysis were performed using Review Manager 5.3 and STATA 18.0 software.Results A total of 14 studies(13 cohort studies and 1 randomized controlled trial)in-volving 3521 breast cancer patients were included,among whom 921 had TP53 mutations.All studies were as-sessed as high-quality or low-risk.The random-effects model demonstrated that TP53 mutations were significantly associated with poorer OS(I2=77%,HR=1.82,95%CI:1.15-2.88,P=0.010),PFS(I2=63%,HR=1.68,95%CI:1.30-2.17,P＜0.001),and DFS(I2=85%,HR=1.98,95%CI:1.05-3.75,P=0.040).Funnel plots indicated no significant publication bias,and sensitivity analysis confirmed the stabil-ity and reliability of the results.Subgroup analyses based on study design,breast cancer stage and molecular subtype revealed that TP53 mutations were associated with worse prognosis in prospective studies(OS:HR=2.32,95%CI:1.84-2.92,P＜0.001;PFS:HR=1.83,95%CI:1.47-2.27,P＜0.001),metastatic/ad-vanced breast cancer(OS:HR=2.03,95%CI:1.44-2.87,P＜0.001;PFS:HR=1.90,95%CI:1.57-2.31,P＜0.001),and hormone receptor-positive and human epidermal growth factor receptor 2-negative(HR+HER2-)patients(OS:HR=2.11,95%CI:1.56-2.85,P＜0.001;PFS:HR=1.94,95%CI:1.62-2.33,P＜0.001).Among different treatment regimens,patients with TP53 mutations receiving trastuzumab combined with paclitaxel exhibited relatively better prognosis(PFS:HR=0.08,95%CI:0.02-0.30,P＜0.001).Conclusion Plasma ctDNA TP53 mutations are closely associated with survival outcomes in breast cancer patients and may serve as a potential predictor of poor prognosis,providing support for clinical manage-ment and prognostic assessment.

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections.Herein,we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering(SERS)and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease(MNase)in serum samples.The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine(TMB)molecules to SERS-enhanced oxidized TMB(oxTMB),accompanied by the color change from colorless to blue.In the presence of S.aureus,the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads(MBs)to release alkaline phosphatase(ALP),which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away.Using this"on-to-off"triggering strategy,the target S.aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode.Meanwhile,the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis(n=7)and healthy participants(n=3),as well as monitored the prog-nostic progression of the disease(n=2).Overall,benefiting from highly active and dense"hot spot"substrate,MNase-mediated cascade response strategy,and colorimetric/SERS dual-signal output,this methodology will offer a promising avenue for the early diagnosis of S.aureus infection.

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

Bone metastasis,as a common terminal event in patients with advanced malignant tumors,significantly impacts patients'quality of life and survival prognosis,posing a major clinical challenge in the field of oncology.With the deepening understanding of tumor biology,the treatment paradigm for bone metastasis has progressively shifted from traditional palliative care to precise targeted interventions.Currently,clinical treatment strategies have demonstrated diversified development,with various therapeutic approaches-including radiotherapy,immunotherapy,bone-modifying agents,and small-molecule targeted drugs—achieving notable clinical progress.However,existing treatment regimens still face challenges such as significant interindividual variability in efficacy,frequent drug resistance,and prominent adverse effects.This article systematically reviews the latest advances in precision therapy for bone metastasis,provides an in-depth analysis of the strengths and limitations of different treatment strategies,and offers perspectives on future research directions and therapeutic prospects,aiming to provide reference for optimizing clinical practice and promoting translational research.

Objective To analyze the association between plasma circulating tumor DNA(ctDNA)TP53 mutation status and survival outcomes in breast cancer patients.Methods PubMed,Embase,and the Cochrane Library were searched for relevant literature published between 2000 and 2025,examining the impact of plasma ctDNA TP53 mutations on survival outcomes in breast cancer patients,including overall survival(OS),progression-free survival(PFS),or disease-free survival(DFS).Two researchers independently screened the literature according to predefined inclusion and exclusion criteria and extracted relevant data.The Newcastle-Ottawa scale and Cochrane Risk of Bias Assessment Tool were used to evaluate study quality.Meta-analysis,publication bias assessment,and sensitivity analysis were performed using Review Manager 5.3 and STATA 18.0 software.Results A total of 14 studies(13 cohort studies and 1 randomized controlled trial)in-volving 3521 breast cancer patients were included,among whom 921 had TP53 mutations.All studies were as-sessed as high-quality or low-risk.The random-effects model demonstrated that TP53 mutations were significantly associated with poorer OS(I2=77%,HR=1.82,95%CI:1.15-2.88,P=0.010),PFS(I2=63%,HR=1.68,95%CI:1.30-2.17,P＜0.001),and DFS(I2=85%,HR=1.98,95%CI:1.05-3.75,P=0.040).Funnel plots indicated no significant publication bias,and sensitivity analysis confirmed the stabil-ity and reliability of the results.Subgroup analyses based on study design,breast cancer stage and molecular subtype revealed that TP53 mutations were associated with worse prognosis in prospective studies(OS:HR=2.32,95%CI:1.84-2.92,P＜0.001;PFS:HR=1.83,95%CI:1.47-2.27,P＜0.001),metastatic/ad-vanced breast cancer(OS:HR=2.03,95%CI:1.44-2.87,P＜0.001;PFS:HR=1.90,95%CI:1.57-2.31,P＜0.001),and hormone receptor-positive and human epidermal growth factor receptor 2-negative(HR+HER2-)patients(OS:HR=2.11,95%CI:1.56-2.85,P＜0.001;PFS:HR=1.94,95%CI:1.62-2.33,P＜0.001).Among different treatment regimens,patients with TP53 mutations receiving trastuzumab combined with paclitaxel exhibited relatively better prognosis(PFS:HR=0.08,95%CI:0.02-0.30,P＜0.001).Conclusion Plasma ctDNA TP53 mutations are closely associated with survival outcomes in breast cancer patients and may serve as a potential predictor of poor prognosis,providing support for clinical manage-ment and prognostic assessment.