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:To investigate the association of exposure to PM 2.5 and its constituents during pregnancy and fetal growth and to further identify critical windows of exposure for fetal growth. Methods:We included 4 089 mother-child pairs from the Jiangsu Birth Cohort Study between January 2016 and October 2019. Data of general characteristics, clinical information, daily average PM 2.5 exposure, and its constituents during pregnancy were collected. Fetal growth parameters, including head circumference (HC), abdominal circumference (AC), and femur length (FL), were measured by ultrasound after 20 weeks of gestation, and then estimated fetal weight (EFW) was calculated. Generalized linear mixed models were adopted to examine the associations of prenatal exposure to PM 2.5 and its constituents with fetal growth. Distributed lag nonlinear models were used to identify critical exposure windows for each outcome. Results:A 10 μg/m 3 increase in PM 2.5 exposure during pregnancy was associated with a decrease of 0.025 ( β=-0.025, 95% CI: -0.048- -0.001) in HC Z-score, 0.026 ( β=-0.026, 95% CI: -0.049- -0.003) in AC Z-score, and 0.028 ( β=-0.028, 95% CI:-0.052--0.004) in EFW Z-score, along with an increased risk of 8.5% ( RR=1.085, 95% CI: 1.010-1.165) and 13.5% ( RR=1.135, 95% CI: 1.016-1.268) for undergrowth of HC and EFW, respectively. Regarding PM 2.5 constituents, prenatal exposure to black carbon, organic matter, nitrate, sulfate (SO 42-) and ammonium consistently correlated with decreased HC Z-score. SO 42- exposure was also associated with decreased FL Z-scores. In addition, we found that gestational weeks 2-5 were critical windows for HC, weeks 4-13 and 19-40 for AC, weeks 4-13 and 23-37 for FL, and weeks 4-12 and 20-40 for EFW. Conclusions:Our findings demonstrated that exposure to PM 2.5 and its constituents during pregnancy could adversely affect fetal growth and the critical windows for different fetal growth parameters are not completely consistent.

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.