Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

Objective It analyzes the equity of pharmacists'allocation in China's healthcare organizations from 2012 to 2021,in order to provide reference for improving the service accessibility of pharmacists.Methods Based on the degree of agglomeration,analyzing the current situation and changing trend of pharmacists'allocation in healthcare organizations among different areas and provinces.Results The current allocation of pharmacists in China's healthcare organizations has not met the requirements.The situation in the eastern economically developed areas is better than that in other areas of the country either by geography or by population.While the western areas are large and sparsely populated,so the accessibility of pharmacist service is poor based on geographical allocation,but the equity is good based on population allocation.In the central area,the accessibility of pharmacist service is better when the allocation is based on geographical,but the equity is worse when the allocation is based on population.Conclusion China should further enrich the team of pharmacists in healthcare organizations to promote the coordinated development of different provinces.Furthermore,it also helps to promote the equity of pharmacists'allocation in China's healthcare organizations.

Objective It analyzes the equity of pharmacists'allocation in China's healthcare organizations from 2012 to 2021,in order to provide reference for improving the service accessibility of pharmacists.Methods Based on the degree of agglomeration,analyzing the current situation and changing trend of pharmacists'allocation in healthcare organizations among different areas and provinces.Results The current allocation of pharmacists in China's healthcare organizations has not met the requirements.The situation in the eastern economically developed areas is better than that in other areas of the country either by geography or by population.While the western areas are large and sparsely populated,so the accessibility of pharmacist service is poor based on geographical allocation,but the equity is good based on population allocation.In the central area,the accessibility of pharmacist service is better when the allocation is based on geographical,but the equity is worse when the allocation is based on population.Conclusion China should further enrich the team of pharmacists in healthcare organizations to promote the coordinated development of different provinces.Furthermore,it also helps to promote the equity of pharmacists'allocation in China's healthcare organizations.

Objective It analyzes the equity of pharmacists'allocation in China's healthcare organizations from 2012 to 2021,in order to provide reference for improving the service accessibility of pharmacists.Methods Based on the degree of agglomeration,analyzing the current situation and changing trend of pharmacists'allocation in healthcare organizations among different areas and provinces.Results The current allocation of pharmacists in China's healthcare organizations has not met the requirements.The situation in the eastern economically developed areas is better than that in other areas of the country either by geography or by population.While the western areas are large and sparsely populated,so the accessibility of pharmacist service is poor based on geographical allocation,but the equity is good based on population allocation.In the central area,the accessibility of pharmacist service is better when the allocation is based on geographical,but the equity is worse when the allocation is based on population.Conclusion China should further enrich the team of pharmacists in healthcare organizations to promote the coordinated development of different provinces.Furthermore,it also helps to promote the equity of pharmacists'allocation in China's healthcare organizations.

Objective It analyzes the equity of pharmacists'allocation in China's healthcare organizations from 2012 to 2021,in order to provide reference for improving the service accessibility of pharmacists.Methods Based on the degree of agglomeration,analyzing the current situation and changing trend of pharmacists'allocation in healthcare organizations among different areas and provinces.Results The current allocation of pharmacists in China's healthcare organizations has not met the requirements.The situation in the eastern economically developed areas is better than that in other areas of the country either by geography or by population.While the western areas are large and sparsely populated,so the accessibility of pharmacist service is poor based on geographical allocation,but the equity is good based on population allocation.In the central area,the accessibility of pharmacist service is better when the allocation is based on geographical,but the equity is worse when the allocation is based on population.Conclusion China should further enrich the team of pharmacists in healthcare organizations to promote the coordinated development of different provinces.Furthermore,it also helps to promote the equity of pharmacists'allocation in China's healthcare organizations.

Objective It analyzes the equity of pharmacists'allocation in China's healthcare organizations from 2012 to 2021,in order to provide reference for improving the service accessibility of pharmacists.Methods Based on the degree of agglomeration,analyzing the current situation and changing trend of pharmacists'allocation in healthcare organizations among different areas and provinces.Results The current allocation of pharmacists in China's healthcare organizations has not met the requirements.The situation in the eastern economically developed areas is better than that in other areas of the country either by geography or by population.While the western areas are large and sparsely populated,so the accessibility of pharmacist service is poor based on geographical allocation,but the equity is good based on population allocation.In the central area,the accessibility of pharmacist service is better when the allocation is based on geographical,but the equity is worse when the allocation is based on population.Conclusion China should further enrich the team of pharmacists in healthcare organizations to promote the coordinated development of different provinces.Furthermore,it also helps to promote the equity of pharmacists'allocation in China's healthcare organizations.

Objective It analyzes the equity of pharmacists'allocation in China's healthcare organizations from 2012 to 2021,in order to provide reference for improving the service accessibility of pharmacists.Methods Based on the degree of agglomeration,analyzing the current situation and changing trend of pharmacists'allocation in healthcare organizations among different areas and provinces.Results The current allocation of pharmacists in China's healthcare organizations has not met the requirements.The situation in the eastern economically developed areas is better than that in other areas of the country either by geography or by population.While the western areas are large and sparsely populated,so the accessibility of pharmacist service is poor based on geographical allocation,but the equity is good based on population allocation.In the central area,the accessibility of pharmacist service is better when the allocation is based on geographical,but the equity is worse when the allocation is based on population.Conclusion China should further enrich the team of pharmacists in healthcare organizations to promote the coordinated development of different provinces.Furthermore,it also helps to promote the equity of pharmacists'allocation in China's healthcare organizations.

Objective It analyzes the equity of pharmacists'allocation in China's healthcare organizations from 2012 to 2021,in order to provide reference for improving the service accessibility of pharmacists.Methods Based on the degree of agglomeration,analyzing the current situation and changing trend of pharmacists'allocation in healthcare organizations among different areas and provinces.Results The current allocation of pharmacists in China's healthcare organizations has not met the requirements.The situation in the eastern economically developed areas is better than that in other areas of the country either by geography or by population.While the western areas are large and sparsely populated,so the accessibility of pharmacist service is poor based on geographical allocation,but the equity is good based on population allocation.In the central area,the accessibility of pharmacist service is better when the allocation is based on geographical,but the equity is worse when the allocation is based on population.Conclusion China should further enrich the team of pharmacists in healthcare organizations to promote the coordinated development of different provinces.Furthermore,it also helps to promote the equity of pharmacists'allocation in China's healthcare organizations.

Objective It analyzes the equity of pharmacists'allocation in China's healthcare organizations from 2012 to 2021,in order to provide reference for improving the service accessibility of pharmacists.Methods Based on the degree of agglomeration,analyzing the current situation and changing trend of pharmacists'allocation in healthcare organizations among different areas and provinces.Results The current allocation of pharmacists in China's healthcare organizations has not met the requirements.The situation in the eastern economically developed areas is better than that in other areas of the country either by geography or by population.While the western areas are large and sparsely populated,so the accessibility of pharmacist service is poor based on geographical allocation,but the equity is good based on population allocation.In the central area,the accessibility of pharmacist service is better when the allocation is based on geographical,but the equity is worse when the allocation is based on population.Conclusion China should further enrich the team of pharmacists in healthcare organizations to promote the coordinated development of different provinces.Furthermore,it also helps to promote the equity of pharmacists'allocation in China's healthcare organizations.

Lung cancer is characterized by high incidence and mortality rates and invasiveness, and its occurrence and development are influenced by various factors. Mitochondria, as ubiquitous organelles in the human body, regulate cellular processes, such as metabolism, signal transduction, oxidative stress, and genomic instability, thereby affecting the initiation and progression of lung cancer. This article summarizes the recent research progress on mitochondrial-targeted drugs, mitochondrial transfer, and mitochondrial gene therapy for lung cancer treatment. This work also discusses the principles and prospects of mitochondrial therapy to provide new insights for lung cancer treatment.