Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

Therapeutic cancer vaccines have experienced a resurgence over the past ten years. Cancer vaccines are typically designed to enhance specific stages of the cancer-immunity cycle, primarily by activating the immune system to promote tumor regression and overcome immune resistance. In this review, we summarize the significant recent advancements in cancer immunotherapy based on the cancer-immunity cycle, including the effector cell function, infiltration, initiation, and exhaustion. We summarize the identification of tumor antigens and their delivery through cancer vaccines. We discuss how specific stages of the cancer-immunity cycle have been leveraged to augment anti-tumor immune responses and improve vaccine efficacy. Additionally, the impact of aging and myelosuppression, two prevalent forms of immunological stress, on the effectiveness of therapeutic cancer vaccines is deliberated. Finally, we summarize the current status of various therapeutic cancer vaccines at different clinical trial phases.
Humans ; Cancer Vaccines/therapeutic use* ; Neoplasms/therapy* ; Immunotherapy/methods* ; Antigens, Neoplasm/immunology* ; Animals

Objective It aims to analyze the resource distribution of Chinese gradeA teritary hospitals across six regions from 2012 to 2021,so as to further understand the changes in inter-regional health resource allocation.Methods Based on the"Thirteenth Five-Year Plan"for the Establishment of National Medical Centers and Regional Medical Centers,it utilizes indicators such as the annual growth rate,coefficient of variation,agglomeration degree,and Theil index to explore the resource allocation in Chinese gradeA teritary hospitals from 2012 to 2021.Comparative and trend analyses are also conducted.Results The regional difference of high-quality medical resources in the country has continued to narrow,especially with an increased rate of reduction since 2017.The Theil index of resource allocation in grade A teritary hospitals in various regions of the country has decreased from 0.035 0 to 0.020 5,indicating a positive trend towards fairness and a gradual increase in regional development coordination.An imbalance in the geographical distribution of resources among third-class medical institutions persists across various regions of China.Conclusion The resource allocation of grade A teritary hospitals in the western region should fully consider geographical factors and change the traditional single"human-oriented"resource allocation mode.Grade A teritary hospitals in economically developed areas still need to increase resource investment,conduct proactive population monitoring,early warning,and macro resource planning.The resource allocation of third-class medical institutions should focus on both intra-regional development and inter-regional collaboration to enhance the quality and efficiency of resource distribution.

Objective It aims to analyze the resource distribution of Chinese gradeA teritary hospitals across six regions from 2012 to 2021,so as to further understand the changes in inter-regional health resource allocation.Methods Based on the"Thirteenth Five-Year Plan"for the Establishment of National Medical Centers and Regional Medical Centers,it utilizes indicators such as the annual growth rate,coefficient of variation,agglomeration degree,and Theil index to explore the resource allocation in Chinese gradeA teritary hospitals from 2012 to 2021.Comparative and trend analyses are also conducted.Results The regional difference of high-quality medical resources in the country has continued to narrow,especially with an increased rate of reduction since 2017.The Theil index of resource allocation in grade A teritary hospitals in various regions of the country has decreased from 0.035 0 to 0.020 5,indicating a positive trend towards fairness and a gradual increase in regional development coordination.An imbalance in the geographical distribution of resources among third-class medical institutions persists across various regions of China.Conclusion The resource allocation of grade A teritary hospitals in the western region should fully consider geographical factors and change the traditional single"human-oriented"resource allocation mode.Grade A teritary hospitals in economically developed areas still need to increase resource investment,conduct proactive population monitoring,early warning,and macro resource planning.The resource allocation of third-class medical institutions should focus on both intra-regional development and inter-regional collaboration to enhance the quality and efficiency of resource distribution.

Objective It aims to analyze the resource distribution of Chinese gradeA teritary hospitals across six regions from 2012 to 2021,so as to further understand the changes in inter-regional health resource allocation.Methods Based on the"Thirteenth Five-Year Plan"for the Establishment of National Medical Centers and Regional Medical Centers,it utilizes indicators such as the annual growth rate,coefficient of variation,agglomeration degree,and Theil index to explore the resource allocation in Chinese gradeA teritary hospitals from 2012 to 2021.Comparative and trend analyses are also conducted.Results The regional difference of high-quality medical resources in the country has continued to narrow,especially with an increased rate of reduction since 2017.The Theil index of resource allocation in grade A teritary hospitals in various regions of the country has decreased from 0.035 0 to 0.020 5,indicating a positive trend towards fairness and a gradual increase in regional development coordination.An imbalance in the geographical distribution of resources among third-class medical institutions persists across various regions of China.Conclusion The resource allocation of grade A teritary hospitals in the western region should fully consider geographical factors and change the traditional single"human-oriented"resource allocation mode.Grade A teritary hospitals in economically developed areas still need to increase resource investment,conduct proactive population monitoring,early warning,and macro resource planning.The resource allocation of third-class medical institutions should focus on both intra-regional development and inter-regional collaboration to enhance the quality and efficiency of resource distribution.

Objective It aims to analyze the resource distribution of Chinese gradeA teritary hospitals across six regions from 2012 to 2021,so as to further understand the changes in inter-regional health resource allocation.Methods Based on the"Thirteenth Five-Year Plan"for the Establishment of National Medical Centers and Regional Medical Centers,it utilizes indicators such as the annual growth rate,coefficient of variation,agglomeration degree,and Theil index to explore the resource allocation in Chinese gradeA teritary hospitals from 2012 to 2021.Comparative and trend analyses are also conducted.Results The regional difference of high-quality medical resources in the country has continued to narrow,especially with an increased rate of reduction since 2017.The Theil index of resource allocation in grade A teritary hospitals in various regions of the country has decreased from 0.035 0 to 0.020 5,indicating a positive trend towards fairness and a gradual increase in regional development coordination.An imbalance in the geographical distribution of resources among third-class medical institutions persists across various regions of China.Conclusion The resource allocation of grade A teritary hospitals in the western region should fully consider geographical factors and change the traditional single"human-oriented"resource allocation mode.Grade A teritary hospitals in economically developed areas still need to increase resource investment,conduct proactive population monitoring,early warning,and macro resource planning.The resource allocation of third-class medical institutions should focus on both intra-regional development and inter-regional collaboration to enhance the quality and efficiency of resource distribution.

Objective It aims to analyze the resource distribution of Chinese gradeA teritary hospitals across six regions from 2012 to 2021,so as to further understand the changes in inter-regional health resource allocation.Methods Based on the"Thirteenth Five-Year Plan"for the Establishment of National Medical Centers and Regional Medical Centers,it utilizes indicators such as the annual growth rate,coefficient of variation,agglomeration degree,and Theil index to explore the resource allocation in Chinese gradeA teritary hospitals from 2012 to 2021.Comparative and trend analyses are also conducted.Results The regional difference of high-quality medical resources in the country has continued to narrow,especially with an increased rate of reduction since 2017.The Theil index of resource allocation in grade A teritary hospitals in various regions of the country has decreased from 0.035 0 to 0.020 5,indicating a positive trend towards fairness and a gradual increase in regional development coordination.An imbalance in the geographical distribution of resources among third-class medical institutions persists across various regions of China.Conclusion The resource allocation of grade A teritary hospitals in the western region should fully consider geographical factors and change the traditional single"human-oriented"resource allocation mode.Grade A teritary hospitals in economically developed areas still need to increase resource investment,conduct proactive population monitoring,early warning,and macro resource planning.The resource allocation of third-class medical institutions should focus on both intra-regional development and inter-regional collaboration to enhance the quality and efficiency of resource distribution.

Objective It aims to analyze the resource distribution of Chinese gradeA teritary hospitals across six regions from 2012 to 2021,so as to further understand the changes in inter-regional health resource allocation.Methods Based on the"Thirteenth Five-Year Plan"for the Establishment of National Medical Centers and Regional Medical Centers,it utilizes indicators such as the annual growth rate,coefficient of variation,agglomeration degree,and Theil index to explore the resource allocation in Chinese gradeA teritary hospitals from 2012 to 2021.Comparative and trend analyses are also conducted.Results The regional difference of high-quality medical resources in the country has continued to narrow,especially with an increased rate of reduction since 2017.The Theil index of resource allocation in grade A teritary hospitals in various regions of the country has decreased from 0.035 0 to 0.020 5,indicating a positive trend towards fairness and a gradual increase in regional development coordination.An imbalance in the geographical distribution of resources among third-class medical institutions persists across various regions of China.Conclusion The resource allocation of grade A teritary hospitals in the western region should fully consider geographical factors and change the traditional single"human-oriented"resource allocation mode.Grade A teritary hospitals in economically developed areas still need to increase resource investment,conduct proactive population monitoring,early warning,and macro resource planning.The resource allocation of third-class medical institutions should focus on both intra-regional development and inter-regional collaboration to enhance the quality and efficiency of resource distribution.

Objective It aims to analyze the resource distribution of Chinese gradeA teritary hospitals across six regions from 2012 to 2021,so as to further understand the changes in inter-regional health resource allocation.Methods Based on the"Thirteenth Five-Year Plan"for the Establishment of National Medical Centers and Regional Medical Centers,it utilizes indicators such as the annual growth rate,coefficient of variation,agglomeration degree,and Theil index to explore the resource allocation in Chinese gradeA teritary hospitals from 2012 to 2021.Comparative and trend analyses are also conducted.Results The regional difference of high-quality medical resources in the country has continued to narrow,especially with an increased rate of reduction since 2017.The Theil index of resource allocation in grade A teritary hospitals in various regions of the country has decreased from 0.035 0 to 0.020 5,indicating a positive trend towards fairness and a gradual increase in regional development coordination.An imbalance in the geographical distribution of resources among third-class medical institutions persists across various regions of China.Conclusion The resource allocation of grade A teritary hospitals in the western region should fully consider geographical factors and change the traditional single"human-oriented"resource allocation mode.Grade A teritary hospitals in economically developed areas still need to increase resource investment,conduct proactive population monitoring,early warning,and macro resource planning.The resource allocation of third-class medical institutions should focus on both intra-regional development and inter-regional collaboration to enhance the quality and efficiency of resource distribution.