Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Objective To explore the effects and mechanisms of bone marrow mesenchymal stem cell(BMMSC)-derived exosomes(BMMSC-Exo)on hypoxia/reoxygenation(H/R)-induced injury in rat cardiomyocyte cell line(H9c2).Methods BMMSC-Exosomes were isolated by ultracentrifugation.The cells were divided into three groups:control,H/R,and H/R+BMMSC-Exo(H/R+Exo).A hypoxia/reoxygenation(H/R)injury model was es-tablished by exposing cells to 12 hours of hypoxia followed by 6 hours of reoxygenation.Flow cytometry was used to detect cell apoptosis,DHE staining was used to assess cellular ROS levels,JC-1 immunofluorescence staining was used to evaluate mitochondrial membrane potential,and Western blot was used to detect mitochondrial autophagy-re-lated proteins.Results BMMSC-Exo treatment significantly alleviated oxidative stress,restored mitochondrial mem-brane potential,reduced mitochondrial autophagy levels,and effectively decreased cardiomyocyte apoptosis.Conclu-sions Bone marrow mesenchymal stem cell-derived exosomes alleviate H/R-induced cardiomyocyte injury.

Background Improper settings of outdoor smoking points in public places may increase the risk of secondhand smoke exposure among the population. Conducting research on air pollution in and around smoking spots and related influencing factors can provide valuable insights for optimizing the setting of outdoor smoking points. Objective To investigate the influence of the number of smokers at outdoor smoking points and the distance on the diffusion characteristics of surrounding air pollutants, in order to optimize the setting of outdoor smoking points. Methods Surrounding the exhibition halls in the China International Import Expo (CIIE), two outdoor smoking points were randomly selected, one on the first floor (ground level) and the other on the second floor (16 m above ground), respectively. At 0, 3, 6, and 9 m from the smoking points in the same direction, validated portable air pollutant monitors were used to measure the real-time fine particulate matter (PM_2.5) and carbon dioxide (CO₂) concentrations for consecutive 5 d during the exhibition, as well as the environmental meteorological factors at 0 m with weather meters including wind speed, wind direction, and air pressure. An open outdoor atmospheric background sampling point was selected on each of the two floors to carry out parallel sampling. Simultaneously, the number of smokers at each smoking point were double recorded per minute. The relationships between the number of smokers, distance from the smoking points, and ambient PM_2.5 and CO₂ concentrations were evaluated by generalized additive regression models for time-series data after adjustment of confounders such as temperature, relative humidity, and wind speed. Results The median numbers of smokers at smoking points on the first and second floors were 6 [interquartile range (IQR): 3, 9] and 9 (IQR: 6, 13), respectively. Windless (wind speed <0.6 m·s⁻¹) occupied most of the time (85.9%) at both locations. The average concentration of ambient PM_2.5 at the smoking points (0 m) [mean ± standard deviation, (106±114) μg·m⁻³] was 4.2 times higher than that of the atmospheric background [(25±7) μg·m⁻³], the PM_2.5 concentration showed a gradient decline with the increase of distance from the smoking points, and the average PM_2.5 concentration at 9 m points [(35±22) μg·m⁻³] was close to the background level (1.4 times higher). The maximum concentration of CO₂ [(628±23) μmol·mol⁻¹] was observed at 0 m, and its average value was 1.3 times higher than that of the atmospheric background [(481±40) μmol·mol⁻¹], and there was no gradient decrease in CO₂ concentration with increasing distance at 0, 3, 6, and 9 m points. The regression analyses showed that, taking smoking point as the reference, every 3 m increase in distance was associated with a decrease of ambient PM_2.5 by 24.6 [95% confidence interval (95%CI): 23.5, 25.8] μg·m⁻³ (23.2%) and CO₂ by 54.1 (95%CI: 53.1, 55.1) μmol·mol⁻¹ (8.6%). Every one extra smoker at the smoking point was associated with an average increase of PM_2.5 and CO₂ by 2.0 (95%CI: 1.7, 2.8) μg·m⁻³ and 1.0 (95%CI: 0.7，1.2) μmol·mol⁻¹, respectively. The sensitivity analysis indicated that, under windless conditions, the concentrations of PM_2.5 and CO₂ at the smoking points were even higher but the decreasing and dispersion characteristics remained consistent. Conclusion Outdoor smoking points could significantly increase the PM_2.5 concentrations in the surrounding air and the risks of secondhand smoke exposure, despite of the noticeable decreasing trend with increasing distance. Considering the inevitable poor dispersion conditions such as windless and light wind, outdoor smoking points are recommended to be set at least 9 m or farther away from non-smoking areas.

Objective:To discuss how to construct the medical insurance access for medical service items based on Health Tech-nology Assessment(HTA)applicable to China.Methods:This study consolidated the current medical insurance access in some prov-inces and cities from China and identified deficiencies through the expert interview.We summarized the experience and indicators contained in the HTA report in UK and Singapore by using literature analysis.Results:In most regions of China,the management of medical services price is gradually moving from exclusion items based on certain conditions to access approach,lacking of tools for assessment.In UK and Singapore,the medical insurance access mechanism mainly consists of subject selection,scoping,HTA imple-mentation and decision-making,in the HTA report,with the data including clinical evidence,cost evidence and budget impact on health system,etc.Conclusion:Building an evidence-based health policy decision-making framework through multi-criteria deci-sion analysis and the construction of medical insurance access mechanism based on HTA can be achieved by developing national guidelines,multi-scenario HTA systems,and enhancing the supervision on the process of HTA.

Objective:To provide suggestions for exploring the ICER threshold's calculation method and reasonable estimation in China.Methods:It summarizes the consensus and analyze the disputes on thresholds in China based on theoretical and empirical research by literature review,compares the thresholds derived from willingness to pay versus opportunity cost methods.Results:Theoretical researches on threshold of China mainly focus on method for calculation,health output index,and health equity,etc.The controversy persists over the threshold's characteristics.The health care demand-side perspective willingness-to-pay method was the most widely used in the empirical studies,but the results of the thresholds measured by this method varied widely;the thresholds measured by the health care supply-side perspective opportunity cost method were lower than the thresholds obtained from the demand-side perspective.Conclusion:It is still essential to discuss the threshold's characteristics and establish the methods framework complementing both demand and supply side for Chinese health insurance,and to standardize and normalize the measurement methods,as well as to set up multi-level thresholds according to the preferences of the population,the severity of the disease,and so on,in order to take into account both economy and equity.

Objective:To discuss how to construct the medical insurance access for medical service items based on Health Tech-nology Assessment(HTA)applicable to China.Methods:This study consolidated the current medical insurance access in some prov-inces and cities from China and identified deficiencies through the expert interview.We summarized the experience and indicators contained in the HTA report in UK and Singapore by using literature analysis.Results:In most regions of China,the management of medical services price is gradually moving from exclusion items based on certain conditions to access approach,lacking of tools for assessment.In UK and Singapore,the medical insurance access mechanism mainly consists of subject selection,scoping,HTA imple-mentation and decision-making,in the HTA report,with the data including clinical evidence,cost evidence and budget impact on health system,etc.Conclusion:Building an evidence-based health policy decision-making framework through multi-criteria deci-sion analysis and the construction of medical insurance access mechanism based on HTA can be achieved by developing national guidelines,multi-scenario HTA systems,and enhancing the supervision on the process of HTA.

Objective:To provide suggestions for exploring the ICER threshold's calculation method and reasonable estimation in China.Methods:It summarizes the consensus and analyze the disputes on thresholds in China based on theoretical and empirical research by literature review,compares the thresholds derived from willingness to pay versus opportunity cost methods.Results:Theoretical researches on threshold of China mainly focus on method for calculation,health output index,and health equity,etc.The controversy persists over the threshold's characteristics.The health care demand-side perspective willingness-to-pay method was the most widely used in the empirical studies,but the results of the thresholds measured by this method varied widely;the thresholds measured by the health care supply-side perspective opportunity cost method were lower than the thresholds obtained from the demand-side perspective.Conclusion:It is still essential to discuss the threshold's characteristics and establish the methods framework complementing both demand and supply side for Chinese health insurance,and to standardize and normalize the measurement methods,as well as to set up multi-level thresholds according to the preferences of the population,the severity of the disease,and so on,in order to take into account both economy and equity.

Objective:To discuss how to construct the medical insurance access for medical service items based on Health Tech-nology Assessment(HTA)applicable to China.Methods:This study consolidated the current medical insurance access in some prov-inces and cities from China and identified deficiencies through the expert interview.We summarized the experience and indicators contained in the HTA report in UK and Singapore by using literature analysis.Results:In most regions of China,the management of medical services price is gradually moving from exclusion items based on certain conditions to access approach,lacking of tools for assessment.In UK and Singapore,the medical insurance access mechanism mainly consists of subject selection,scoping,HTA imple-mentation and decision-making,in the HTA report,with the data including clinical evidence,cost evidence and budget impact on health system,etc.Conclusion:Building an evidence-based health policy decision-making framework through multi-criteria deci-sion analysis and the construction of medical insurance access mechanism based on HTA can be achieved by developing national guidelines,multi-scenario HTA systems,and enhancing the supervision on the process of HTA.

Objective:To provide suggestions for exploring the ICER threshold's calculation method and reasonable estimation in China.Methods:It summarizes the consensus and analyze the disputes on thresholds in China based on theoretical and empirical research by literature review,compares the thresholds derived from willingness to pay versus opportunity cost methods.Results:Theoretical researches on threshold of China mainly focus on method for calculation,health output index,and health equity,etc.The controversy persists over the threshold's characteristics.The health care demand-side perspective willingness-to-pay method was the most widely used in the empirical studies,but the results of the thresholds measured by this method varied widely;the thresholds measured by the health care supply-side perspective opportunity cost method were lower than the thresholds obtained from the demand-side perspective.Conclusion:It is still essential to discuss the threshold's characteristics and establish the methods framework complementing both demand and supply side for Chinese health insurance,and to standardize and normalize the measurement methods,as well as to set up multi-level thresholds according to the preferences of the population,the severity of the disease,and so on,in order to take into account both economy and equity.