Objective:To construct a rat model of osteoporosis induced by lead exposure, simulate the effects of lead exposure on the skeletal system of rats, and provide reliable basic data support for subsequent research.Methods:In July 2021, 40 eight-week-old SPF-grade SD rats were selected and randomly divided into 5 experimental groups according to body weight stratification randomization: blank control group, positive control group, low-dose, medium-dose and high-dose groups, with 8 rats in each group. Continuous intragastric administration (1 ml/100 g) for 60 days was performed respectively with ultrapure water, 0.4 g/L prednisone acetate, 2.0 g/L, 4.0 g/L, and 8.0 g/L lead acetate (PbAc). During the experiment, the general condition and weight changes of the rats were recorded in detail. After model establishment, biological samples of rats were collected. The levels of blood lead, serum calcium, phosphorus, tartrate-resistant acid phosphatase (TRAP) and bone alkaline phosphatase (BALP) in rats were determined. Additionally, micro-computed tomography (Micro-CT) was used to perform 3D reconstruction of the rat femurs and examine ultrastructural changes. One-way analysis of variance was used to compare multiple groups of data, and LSD or SNK methods were used for pairwise comparisons between groups.Results:During the experiment, there were no obvious abnormalities in feeding and drinking, behavioral activities, and fur color of rats in each group, and the body weight maintained normal and gentle growth. Compared with the blank control group, the levels of blood lead, serum calcium, phosphorus, TRAP and BALP in each dose group of PbAc were significantly increased ( P<0.05), while the femoral bone mineral density, bone volume/total volume and trabecular thickness were significantly decreased ( P<0.05). Compared with the blank control group, the trabecular separation of the femur in the high-dose group was significantly increased, and the trabecular number was significantly decreased ( P<0.05). Compared with the blank control group, the bone mass loss of the femur in each dose group of PbAc was severe in rats. Conclusion:PbAc can cause osteoporosis in rats, and osteoporosis assessment indicators such as bone resorption and bone formation markers in rats, femoral bone mineral density and its ultrastructure can all evaluate the success of model construction.

Objective:To construct a rat model of osteoporosis induced by lead exposure, simulate the effects of lead exposure on the skeletal system of rats, and provide reliable basic data support for subsequent research.Methods:In July 2021, 40 eight-week-old SPF-grade SD rats were selected and randomly divided into 5 experimental groups according to body weight stratification randomization: blank control group, positive control group, low-dose, medium-dose and high-dose groups, with 8 rats in each group. Continuous intragastric administration (1 ml/100 g) for 60 days was performed respectively with ultrapure water, 0.4 g/L prednisone acetate, 2.0 g/L, 4.0 g/L, and 8.0 g/L lead acetate (PbAc). During the experiment, the general condition and weight changes of the rats were recorded in detail. After model establishment, biological samples of rats were collected. The levels of blood lead, serum calcium, phosphorus, tartrate-resistant acid phosphatase (TRAP) and bone alkaline phosphatase (BALP) in rats were determined. Additionally, micro-computed tomography (Micro-CT) was used to perform 3D reconstruction of the rat femurs and examine ultrastructural changes. One-way analysis of variance was used to compare multiple groups of data, and LSD or SNK methods were used for pairwise comparisons between groups.Results:During the experiment, there were no obvious abnormalities in feeding and drinking, behavioral activities, and fur color of rats in each group, and the body weight maintained normal and gentle growth. Compared with the blank control group, the levels of blood lead, serum calcium, phosphorus, TRAP and BALP in each dose group of PbAc were significantly increased ( P<0.05), while the femoral bone mineral density, bone volume/total volume and trabecular thickness were significantly decreased ( P<0.05). Compared with the blank control group, the trabecular separation of the femur in the high-dose group was significantly increased, and the trabecular number was significantly decreased ( P<0.05). Compared with the blank control group, the bone mass loss of the femur in each dose group of PbAc was severe in rats. Conclusion:PbAc can cause osteoporosis in rats, and osteoporosis assessment indicators such as bone resorption and bone formation markers in rats, femoral bone mineral density and its ultrastructure can all evaluate the success of model construction.

Objective To propose a novel mechanical method and index to in-vivo characterize the health status of cancellous bone during the percutaneous kyphoplasty(PKP),and validate its feasibility and consistency.Methods According to the theory of elasticity,the expression and physical significance of the mechanical index K were given.Then using clinical images of the lumbar spine L4,three-dimensional finite element simulations were conducted to verify the validity of the theoretical results,as well as the consistency of the methodology and the indexes were verified for studies of different balloon shapes and puncture routes.Results The internal pressure of the balloon linearly varied with the injected fluid volume.The mechanical index K was closely related to the bone shear modulus and could well reflect the health status of cancellous bones.The balloon shape had a trivial influence on the Kresults,and the relative difference between the cylindrical and ellipsoidal shapes was less than 2％.The influence of surgical access route on the K results was also very small,and the relative difference between the routes by vertebral pedicle and by lateral margin of vertebral pedicle was less than 0.5％.Conclusions The in-vivo mechanical method and the mechanical index K can characterize the bone health of patients with good consistency.This study has a great significance for providing guidelines of the optimization of PKP operation plan and postoperative rehabilitation,collecting in vivo data of bone mechanical properties,and improving the diagnosis and treatment of osteoporosis in clinic.

Cancer is one of the major diseases of high morbidity and mortality worldwide,and its therapeutic approaches are facing great challenges.Immunotherapy,especially the activation of innate immunity represented by the cGAS-STING signaling pathway,is the current research hotspot in tumor immunotherapy.Activation of innate immune response by gas therapy is the latest development in tumor therapeutic approaches,especially the use of gas signaling molecules(NOx CO,H2S and SO2)to activate the cGAS-STING signaling pathway to induce intrinsic immunity of the organism,which leads to anti-tumor immunotherapy.Although intrinsic immunity activated by gas signaling molecules plays an important role in tumor immunotherapy,few reviews have been reported on its association with the cGAS-STING signaling mechanism.In this paper,we will comprehensively describe how gas signaling molecules damage the mitochondrial matrix and DNA damage through oxidative/nitrosative stress,thereby activating the cGAS-STING signaling pathway and triggering the innate immune cascade,aiming to summarize the process of activation of anti-tumor immune effects by gas signaling molecules,and to provide more references for the gas therapies in the future anti-tumor immunity research.

Cholesterol(CH)plays a crucial role in enhancing the membrane stability of drug delivery systems(DDS).However,its association with conditions such as hyperlipidemia often leads to criticism,overshadowing its influence on the biological effects of formulations.In this study,we reevaluated the delivery effect of CH using widely applied lipid microspheres(LM)as a model DDS.We conducted comprehensive in-vestigations into the impact of CH on the distribution,cell uptake,and protein corona(PC)of LM at sites of cardiovascular inflammatory injury.The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage.Then,the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy.Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma(PPAR-γ)expression in vascular endothelial cells and estrogen receptor alpha(ERα)protein levels in myocardial cells,thereby enhancing LM uptake at cardiovascular inflam-mation sites.Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V(Apoa5);this may be a major contributing factor to their prolonged circu-lation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites.It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations.The findings enhance the conceptualization of CH and LM delivery,providing novel strategies for investigating prescription factors' bioactivity.

Objective To observe the value of T1 mapping combining diffusion weighted imaging(DWI)for noninvasive preoperative predicting tumor-infiltrating lymphocyte(TIL)level in invasive breast cancer.Methods Totally 143 patients with invasive breast cancer were retrospectively collected and divided into high group(TIL≥10％,n=73)and low group(TIL＜10％,n=70)according to TIL level by postoperation pathology.Clinicopathological information were collected,MRI features of breast cancer lesions were documented,mean T1 values(T1mean)and mean ADC values(ADCmean)were measured,and then were compared between groups.Multivariate logistic regression analysis was used to identify independent predictive factors of TIL levels,and a nomogram was constructed based on regression model.The receiver operating characteristic(ROC)curve and the area under the curve(AUC)were used to evaluate the predictive value for TIL levels.Results Compared with low group,high group had higher proportion of human epidermal growth factor receptor 2(HER2)positivity(P＜0.05),and showed more circular/oval shapes and more smooth margins but less peritumoral edema(all P＜0.05).Significant differences of lesions enhancement pattern was found between groups(P＜0.05).T1mean and ADCmean were both higher in high group than those in low group(both P＜0.05).Lesions enhancement pattern,T1mean and ADCmean were all independent predictors of TIL levels in breast cancer.The AUC of nomogram combining the above 3 factors for predicting TIL level was 0.848,significantly higher than that of lesions enhancement pattern(AUC=0.569,Z=5.384,P＜0.05)and T1mean(AUC=0.662,Z=3.876,P＜0.05),but not statistically different with that of ADCmean(AUC=0.814,Z=1.578,P=0.115).Decision curve analysis showed that this nomogram had good clinical application value.Conclusion Combining T1 mapping and DWI could effectively predict level of TIL level in breast cancer before surgery.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.

Objective:To investigate the temporal dynamics of strategy monitoring during prospective memory testin individuals with varying degrees of media multitasking.Methods:Twenty heavy media multitaskers and twen-ty light media multitaskers were identified through the media use questionnaire.Using a dual-task paradigm and e-vent-related potential technique,the two groups' accuracy,response time,and the amplitudes of frontal positive components reflecting strategy monitoring were compared across the early,middle,and late stages of the prospective memory test.Results:Heavy media multitaskers exhibited significantly faster response times compared to light media multitaskers(P＜0.001),with no statistical difference in accuracy(P＞0.05).Moreover,the amplitude of frontal positive components in heavy media multitaskers was greater than that in light media multitaskers(P＜0.05)across all three stages,and the amplitude increased gradually with the passing of time in heavy media multi-taskers(P＜0.05).Conclusion:Heavy media multitaskers tend to allocate more cognitive resources to strategic mo-nitoring over time,while light media multitaskers maintain a relatively consistent level of strategic monitoring.

Although tumor immunotherapy has transformed cancer treatment，its efficacy against solid tumors remains limited by the immunosuppressive tumor microenvironment，inefficient drug delivery，and off-target toxicity. Engineered bacterial therapy has recently attracted considerable interest as a promising therapeutic strategy owing to its capacity for selective tumor colonization and immunomodulation. Meanwhile，ultrasound technology provides a non-invasive，spatially precise，and real-time controllable means to improve the performance and applicability of bacterial-mediated therapies. This review summarizes recent advances in ultrasound-regulated bacterial therapy for cancer immunotherapy. Beginning with an examination of the mechanisms through which engineered bacteria modulate antitumor immunity，it is followed by an elucidation of how ultrasound technology exploits its biological effects and spatiotemporal control capabilities to simultaneously enhance bacterial therapy's safety/efficacy and enable tumor treatment visualization，thereby activating systemic immune responses. Finally，current challenges and future directions for clinical translation are critically discussed. In conclusion，ultrasound-regulated bacterial therapy represents an emerging interdisciplinary approach with the potential to overcome key limitations in solid tumor immunotherapy.