Objective To establish a human luminal breast cancer stem cell(BCSC)model and investigate the inhibitory effects of astragaloside Ⅳ(AS-Ⅳ)on BCSC growth.Methods MCF-7 breast cancer cells were cultured in stem cell-specific medium to induce BCSC formation.The BCSCs were then divided into a blank control group and an AS-Ⅳ treatment group,both groups were given PBS or AS-Ⅳ treatment.Morphological changes were observed after intervention.The therapeutic efficacy of AS-Ⅳ was evaluated using 3D spheroid formation and cell viability assays.Transcriptomic profiling and gene expression analysis were performed to elucidate the underlying mechanisms.Results Compared with the MCF7 breast cancer cells,MCF7 breast cancer stem cell mammospheres exhibited accelerated growth(P＜0.01)and significantly increased expression of the stemness marker ALDH1A1(P＜0.01).Further comparison with the blank control group revealed that astragaloside Ⅳ(AS-Ⅳ)treatment significantly inhibited MCF7 breast cancer stem cell proliferation(P＜0.001)and slowed mammosphere growth(P＜0.01).Transcriptomic analysis demonstrated that differentially expressed genes(DEGs)induced by stem cell modeling and AS-Ⅳ intervention were enriched in the cellular senescence signaling pathway.AS-Ⅳ intervention substantially increased the number of SA-β-gal-positive cells(P＜0.01).RT-PCR analysis confirmed that AS-Ⅳsignificantly upregulated mRNA expression of IL-1α(P＜0.01),P21(P＜0.001),and P53(P＜0.05)in MCF7 breast cancer stem cells.Conclusion Astragaloside Ⅳ suppresses the growth of human luminal breast cancer stem cells by inducing cellular senescence.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Objective:It aims to deepen the understanding of the coupled and coordinated development of health investment and economic growth,and to provide a scientific basis for the development of health policies for China's ten largest urban ag-glomerations.Methods:Based on the provincial panel data of ten major urban agglomerations from 2013 to 2022,entropy weight method,coupled coordination degree model,spatial autocorrelation model and quantile regression model are used for analysis.Results:In observation period,the level of two-system coupling and coordination grows from 0.397 in 2013 to 0.645 in 2022;the global Moran's I decreases from-0.020 to-0.357.In the dynamic leapfrog analysis,22.2%of provinces and munici-palities experience positive leapfrogging,while 16.7%of provinces and municipalities show negative leapfrogging.Baesd on lo-calised Moran Index,the quantile regression results show that the proportion of the people in higher education,the level of ur-banization and the level of labor force have a positive influence on the level of coupling and coordination between these two sys-tems,with the β coefficient showing a tendency of increasing and then decreasing;medical research institutes have a negative influence on the level of coupling and coordination between these two systems on the 0.1-0.3 quantile;the level of foreign invest-ment has a positive influence on the 0.1 quantile,and the 0.6-0.8 quartile has a negative effect.GDP per capita has a weak ef-fect on the level of coordination between these two systems.Conclusion:The two-system coupling and coordination level of the ten major urban agglomerations shows an overall increase,but there are regional differences,and it is affected by the integra-tion of science and education,economic level and human resources.

Objective To compare the in vitro degradation rate,cytotoxicity,in vivo osteogenic ability,and in vivo biotoxicity of a new type of biodegradable implant material Zn-2Cu-xSr(x=0,0.5,and 1 wt.％)alloy and evaluate its application prospects in the orthopedic field.Methods The in vitro degradation ability of Zn,Zn-2Cu,Zn-2Cu-0.5Sr,Zn-2Cu-1Sr,and Ti materials was evaluated by pH moni-toring and material degradation rate.Cell proliferation experiment and cytoskeleton fluorescence staining were used to compare the in vitro cell compatibility of Zn,Zn-2Cu,Zn-2Cu-0.5Sr,Zn-2Cu-1Sr,and blank control.Micro-computed tomography(CT)scanning and bone min-eral density detection were used to evaluate the in vivo osteogenic ability of Zn,Zn-2Cu,Zn-2Cu-0.5Sr,and Zn-2Cu-1Sr.HE staining was used to compare the in vivo biotoxicity of Zn-2Cu-1Sr and blank control.Results There were no statistical differences in the pH values between the Zn,Zn-2Cu,Zn-2Cu-0.5Sr,Zn-2Cu-1Sr,and Ti groups(P＞0.05).The degradation rate in the Zn-2Cu-0.5Sr group was signifi-cantly lower than that in the Zn-2Cu-1Sr and Zn-2Cu groups(P＜0.05).The cell proliferation rate in the blank control group was signifi-cantly lower than that in the Zn-2Cu-0.5Sr and Zn-2Cu-1Sr groups(P＜0.05).The bone mineral density in the Zn-2Cu-1Sr group was significantly higher than that in the Zn-2Cu and Zn-2Cu-0.5Sr groups(P＜0.05).HE staining showed no abnormal or pathological mor-phology in the rats'heart,liver,lung,and kidney tissues in the Zn-2Cu-1Sr group.Conclusion Adding trace amounts of Cu and Sr to Zn can reduce the degradation rate and improve the biocompatibility and osteogenic ability of the material.

Objective To investigate the underlying mechanisms contributing to the limited therapeutic efficacy of endocrine therapy combined with CDK4/6 inhibitors in HR+/HER2-low breast cancer,and to develop a breast cancer organoid model as a tool for the precise identification of HR+/HER2-low patients who are responsive to pan-TKI treatment.Methods Transcriptomics was employed to identify differentially expressed genes in HR+/HER2-0 and HR+/HER2-low breast cancer samples and to perform functional enrichment analysis.Tumor organoid models were established using breast cancer tissues obtained from clinical sources,and the differential sensitivity of these samples to therapeutic agents was assessed using Calcein-AM/PI cell viability staining and EdU-based cell proliferation assays.Results The results of transcriptomic enrichment analysis indicated that EGFR was signifi-cantly activated in HR+/HER2-low breast cancer and exhibited characteristics of resistance to TKIs.Breast cancer organoids were successfully established.Drug sensitivity testing revealed that the therapeutic efficacy of ET combined with CDK4/6 inhibitors was suboptimal in certain cases of HR+/HER2-low breast cancer,while the addition of TKIs effectively restored sensitivity to the ET+CDK4/6 inhibitor regimen(P<0.05).Conclusions TKI can restore the reduced sensitivity of HR+/HER2-low breast cancer to endocrine therapy combined with CDK4/6 inhibitors.Breast cancer organoids hold promise as screening tools for assessing drug sensitivity in clinical settings for patients with HR+/HER2-low breast cancer.

Objective:It aims to deepen the understanding of the coupled and coordinated development of health investment and economic growth,and to provide a scientific basis for the development of health policies for China's ten largest urban ag-glomerations.Methods:Based on the provincial panel data of ten major urban agglomerations from 2013 to 2022,entropy weight method,coupled coordination degree model,spatial autocorrelation model and quantile regression model are used for analysis.Results:In observation period,the level of two-system coupling and coordination grows from 0.397 in 2013 to 0.645 in 2022;the global Moran's I decreases from-0.020 to-0.357.In the dynamic leapfrog analysis,22.2%of provinces and munici-palities experience positive leapfrogging,while 16.7%of provinces and municipalities show negative leapfrogging.Baesd on lo-calised Moran Index,the quantile regression results show that the proportion of the people in higher education,the level of ur-banization and the level of labor force have a positive influence on the level of coupling and coordination between these two sys-tems,with the β coefficient showing a tendency of increasing and then decreasing;medical research institutes have a negative influence on the level of coupling and coordination between these two systems on the 0.1-0.3 quantile;the level of foreign invest-ment has a positive influence on the 0.1 quantile,and the 0.6-0.8 quartile has a negative effect.GDP per capita has a weak ef-fect on the level of coordination between these two systems.Conclusion:The two-system coupling and coordination level of the ten major urban agglomerations shows an overall increase,but there are regional differences,and it is affected by the integra-tion of science and education,economic level and human resources.

Objective To investigate the underlying mechanisms contributing to the limited therapeutic efficacy of endocrine therapy combined with CDK4/6 inhibitors in HR+/HER2-low breast cancer,and to develop a breast cancer organoid model as a tool for the precise identification of HR+/HER2-low patients who are responsive to pan-TKI treatment.Methods Transcriptomics was employed to identify differentially expressed genes in HR+/HER2-0 and HR+/HER2-low breast cancer samples and to perform functional enrichment analysis.Tumor organoid models were established using breast cancer tissues obtained from clinical sources,and the differential sensitivity of these samples to therapeutic agents was assessed using Calcein-AM/PI cell viability staining and EdU-based cell proliferation assays.Results The results of transcriptomic enrichment analysis indicated that EGFR was signifi-cantly activated in HR+/HER2-low breast cancer and exhibited characteristics of resistance to TKIs.Breast cancer organoids were successfully established.Drug sensitivity testing revealed that the therapeutic efficacy of ET combined with CDK4/6 inhibitors was suboptimal in certain cases of HR+/HER2-low breast cancer,while the addition of TKIs effectively restored sensitivity to the ET+CDK4/6 inhibitor regimen(P<0.05).Conclusions TKI can restore the reduced sensitivity of HR+/HER2-low breast cancer to endocrine therapy combined with CDK4/6 inhibitors.Breast cancer organoids hold promise as screening tools for assessing drug sensitivity in clinical settings for patients with HR+/HER2-low breast cancer.

Objective To compare the in vitro degradation rate,cytotoxicity,in vivo osteogenic ability,and in vivo biotoxicity of a new type of biodegradable implant material Zn-2Cu-xSr(x=0,0.5,and 1 wt.％)alloy and evaluate its application prospects in the orthopedic field.Methods The in vitro degradation ability of Zn,Zn-2Cu,Zn-2Cu-0.5Sr,Zn-2Cu-1Sr,and Ti materials was evaluated by pH moni-toring and material degradation rate.Cell proliferation experiment and cytoskeleton fluorescence staining were used to compare the in vitro cell compatibility of Zn,Zn-2Cu,Zn-2Cu-0.5Sr,Zn-2Cu-1Sr,and blank control.Micro-computed tomography(CT)scanning and bone min-eral density detection were used to evaluate the in vivo osteogenic ability of Zn,Zn-2Cu,Zn-2Cu-0.5Sr,and Zn-2Cu-1Sr.HE staining was used to compare the in vivo biotoxicity of Zn-2Cu-1Sr and blank control.Results There were no statistical differences in the pH values between the Zn,Zn-2Cu,Zn-2Cu-0.5Sr,Zn-2Cu-1Sr,and Ti groups(P＞0.05).The degradation rate in the Zn-2Cu-0.5Sr group was signifi-cantly lower than that in the Zn-2Cu-1Sr and Zn-2Cu groups(P＜0.05).The cell proliferation rate in the blank control group was signifi-cantly lower than that in the Zn-2Cu-0.5Sr and Zn-2Cu-1Sr groups(P＜0.05).The bone mineral density in the Zn-2Cu-1Sr group was significantly higher than that in the Zn-2Cu and Zn-2Cu-0.5Sr groups(P＜0.05).HE staining showed no abnormal or pathological mor-phology in the rats'heart,liver,lung,and kidney tissues in the Zn-2Cu-1Sr group.Conclusion Adding trace amounts of Cu and Sr to Zn can reduce the degradation rate and improve the biocompatibility and osteogenic ability of the material.

Objective:To observe and analyze the surface electromyography activity of quadriceps femoris of knee osteoar-thritis(KOA)patients. Method:The surface electromyography of vastus lateralis,rectus femoris,and vastus medialis were recorded and analyzed in 30 KOA patients and 30 normal people during isokinetic knee flexion or extension at veloci-ties of 60 °/s,90 °/s or 180 °/s.We also record clinical indicators(muscle thickness and degree of knee pain)of the KOA group and evaluate the correlation between electromyographic data and clinical indicators. Result:Compared with the healthy control group,the KOA group had significantly lower knee extensor mo-ment during isokinetic knee flexion or extension at velocities of 60°/s(P＜0.001),90°/s(P＜0.01),or 180°/s(P＜0.01).Statistics showed that there were significant differences in the median frequency difference rate of vastus lateralis(P＜0.05)and root mean square value of rectus femoris(P＜0.01)between the healthy control group and the KOA group under 60°/s angular velocities.There was a significant difference in the root mean square value of rectus femoris(P＜0.05)between the two groups at velocities of 90°/s.Statistics revealed that the median frequency difference rate(P＜0.05)and root mean square value(P＜0.05)of rectus femoris had changed significantly at the velocities of 180°/s.The results of both multiple regression and random forest algo-rithm showed that knee extensor moment was the strongest predictor between electromyographic characteristics and clinical indicators. Conclusion:The strength of quadriceps femoris in KOA patients was decreased.Thus,the patient may need more muscles to complete the same action,which was easy to cause muscle fatigue.The knee extensor moment was closely related to the quadriceps femoris thickness and the degree of knee pain.It offers important advantag-es for the diagnosis and assessing the severity,which may provide the way for the future study of KOA.