Tumor microenvironment plays a key role in oncogenesis, development and therapeutic response. In recent years, scholars at home and abroad have paid more and more attention to the regulation of tumor microenvironment. Radiation therapy, as an important means of tumor treatment, not only kills tumor cells directly, but also affects the efficacy of radiation therapy by influencing natural killer (NK) cells to regulate the tumor microenvironment. In this article, the research progress in the regulation of tumor microenvironment by radiation therapy through NK cells was reviewed, including the mechanism of NK cell regulation by radiation therapy, the functional changes of NK cells in the tumor microenvironment, as well as the therapeutic strategies based on the above mechanism and the potential application prospects, aiming to provide novel ideas for future basic research and clinical applications.

The role of radiotherapy in activating antitumor immune responses has attracted growing attention. Proton beam therapy (PBT), owing to its unique physical and biological properties, holds great potential in cancer immunotherapy. PBT not only directly kills tumor cells but also induces immunogenic cell death, remodels the tumor microenvironment, and modulates immune cell functions. Moreover, PBT shows distinct advantages in inducing systemic immune responses and establishing immune memory. Recent studies have demonstrated that PBT offers unique benefits over conventional photon radiotherapy in activating antitumor immunity and exhibits marked synergistic effects when combined with immune checkpoint inhibitors (ICIs). This review systematically summarizes recent advances in understanding the role and mechanisms of PBT in tumor immune modulation, discusses the prospects of its combination with immunotherapy, and provides new insights and theoretical evidence for comprehensive cancer treatment.

Objective To investigate the functional changes of dendritic cells(DCs)in patients at different stages of hepatitis B virus(HBV)infection and analyze the mechanisms underlying DC dysfunction.Methods Single-cell RNA sequencing dataset GSE182159 was downloaded from the GEO database and classified into healthy control(HC),immune active(IA),and immune tolerant(IT)groups based on infection stage.Peripheral blood samples were collected from 7 IA patients,7 IT patients,and 12 healthy controls.Flow cytometry was used to isolate classical dendritic cells(cDC)and plasmacytoid dendritic cells(pDC).The expression levels of transcription factors in cDC and pDC were measured by quantitative real-time PCR(qRT-PCR).Bioinformatics analyses were per-formed using R and Python package.Results The proportions of DCs in IA and IT groups were higher than that in HC group.Func-tional enrichment analysis revealed that the differentially expressed genes(DEGs)of cDCs in the IA group were primarily enriched for the processes,such as inflammatory response,MHC classⅡantigen processing and presentation,cell migration,signal transduction,metabolism,and immune response.In contrast the IT group exhibited lower enrichment intensity and a significant reduction in interfer-on responses.The DEGs of pDC in the IA group were enriched in the processes of MHC-Ⅱantigen presentation,Fc receptor signal transduction,and metabolism,whereas those in the IT group were showed enrichment only in Fc receptor signal transduction and me-tabolism with a lower intensity.Both groups exhibited reduced synthesis of typesⅠandⅡinterferons in pDC,with the IT group showing a more pronounced downregulation.Cell-cell communication analysis demonstrated enhanced interactions between myeloid cells(except pDC)and T cells in the IA group,whereas the interactions between cDC/pDC and T cells in the IT group were reduced.Transcription factor analysis revealed that STAT2,STAT3,IRF1,and IRF5 were highly expressed in the IA group but their expression exhibited low-er expression levels in the IT group.In contrast,BHLHE40 was broadly upregulated in both cDC and pDC subsets within the IT group.The qRT-PCR results were consistent with the findings from the single-cell transcription factor analysis.Conclusion The IT phase of hepatitis B infection represents a critical period for cDC dysfunction,characterized by significant suppression of MHCⅡantigen presen-tation,metabolism,and interferon responsiveness.The functional impairment of pDC precedes that of cDC,as evidenced by a marked downregulation of interferon synthesis capacity observed during the IA phase.

Objective To investigate the functional changes of dendritic cells(DCs)in patients at different stages of hepatitis B virus(HBV)infection and analyze the mechanisms underlying DC dysfunction.Methods Single-cell RNA sequencing dataset GSE182159 was downloaded from the GEO database and classified into healthy control(HC),immune active(IA),and immune tolerant(IT)groups based on infection stage.Peripheral blood samples were collected from 7 IA patients,7 IT patients,and 12 healthy controls.Flow cytometry was used to isolate classical dendritic cells(cDC)and plasmacytoid dendritic cells(pDC).The expression levels of transcription factors in cDC and pDC were measured by quantitative real-time PCR(qRT-PCR).Bioinformatics analyses were per-formed using R and Python package.Results The proportions of DCs in IA and IT groups were higher than that in HC group.Func-tional enrichment analysis revealed that the differentially expressed genes(DEGs)of cDCs in the IA group were primarily enriched for the processes,such as inflammatory response,MHC classⅡantigen processing and presentation,cell migration,signal transduction,metabolism,and immune response.In contrast the IT group exhibited lower enrichment intensity and a significant reduction in interfer-on responses.The DEGs of pDC in the IA group were enriched in the processes of MHC-Ⅱantigen presentation,Fc receptor signal transduction,and metabolism,whereas those in the IT group were showed enrichment only in Fc receptor signal transduction and me-tabolism with a lower intensity.Both groups exhibited reduced synthesis of typesⅠandⅡinterferons in pDC,with the IT group showing a more pronounced downregulation.Cell-cell communication analysis demonstrated enhanced interactions between myeloid cells(except pDC)and T cells in the IA group,whereas the interactions between cDC/pDC and T cells in the IT group were reduced.Transcription factor analysis revealed that STAT2,STAT3,IRF1,and IRF5 were highly expressed in the IA group but their expression exhibited low-er expression levels in the IT group.In contrast,BHLHE40 was broadly upregulated in both cDC and pDC subsets within the IT group.The qRT-PCR results were consistent with the findings from the single-cell transcription factor analysis.Conclusion The IT phase of hepatitis B infection represents a critical period for cDC dysfunction,characterized by significant suppression of MHCⅡantigen presen-tation,metabolism,and interferon responsiveness.The functional impairment of pDC precedes that of cDC,as evidenced by a marked downregulation of interferon synthesis capacity observed during the IA phase.

Tumor microenvironment plays a key role in oncogenesis, development and therapeutic response. In recent years, scholars at home and abroad have paid more and more attention to the regulation of tumor microenvironment. Radiation therapy, as an important means of tumor treatment, not only kills tumor cells directly, but also affects the efficacy of radiation therapy by influencing natural killer (NK) cells to regulate the tumor microenvironment. In this article, the research progress in the regulation of tumor microenvironment by radiation therapy through NK cells was reviewed, including the mechanism of NK cell regulation by radiation therapy, the functional changes of NK cells in the tumor microenvironment, as well as the therapeutic strategies based on the above mechanism and the potential application prospects, aiming to provide novel ideas for future basic research and clinical applications.

The role of radiotherapy in activating antitumor immune responses has attracted growing attention. Proton beam therapy (PBT), owing to its unique physical and biological properties, holds great potential in cancer immunotherapy. PBT not only directly kills tumor cells but also induces immunogenic cell death, remodels the tumor microenvironment, and modulates immune cell functions. Moreover, PBT shows distinct advantages in inducing systemic immune responses and establishing immune memory. Recent studies have demonstrated that PBT offers unique benefits over conventional photon radiotherapy in activating antitumor immunity and exhibits marked synergistic effects when combined with immune checkpoint inhibitors (ICIs). This review systematically summarizes recent advances in understanding the role and mechanisms of PBT in tumor immune modulation, discusses the prospects of its combination with immunotherapy, and provides new insights and theoretical evidence for comprehensive cancer treatment.

Objective:To conduct visualization analysis,induction and summary for the study status,focus and trend in the dose measurement field of flash radiotherapy(Flash-RT)through bibliometric methods on the basis of the Web of Science Collection(WOS),and analyze the technical bottleneck of Flash-RT dose measurement.Methods:In the WOS database,the("FLASH radiotherapy"or"ultra high dose rate"or"FLASH irradiation")and TS=("dosimetric system"or"dosimeters"or"dosimetry")were used as the theme terms,and all relevant literatures about the study of Flash-RT dose measurement that were included in the Core Collection of WOS database were retrieved.The citation analysis function of WOS and Citespace software(Version 6.2)were used to conduct visualization analysis for the publication trends,sources and research focus of the included literature of Flash-RT dose measurement,and to draw corresponding visualization knowledge maps.Results:The literatures were mainly published during January 2015 and November 2023,and a total of 86 papers were included in the analysis by screening,which included 78 articles and 8 reviews.The top three countries in terms of publication volume were respectively the United States(38 papers),France(19 papers)and Italy(19 papers).The research focuses were respectively Cherenkov,radiotherapy,passive dosimeter,conventional radiation,laser particle acceleration,ionization chamber and proton therapy as cluster analysis.Currently,the study of Flash-RT dose measurement mainly focused on the relevant fields included Flash-RT radiation source,dose rate,and the equipment and method of dose measurement.Conclusion:Flash-RT is a new technology with a key breakthrough in the basic field of radiotherapy,and this technique faces many difficulties and challenges in the clinical translation process of this technique.With the continuous development of science and technique,and deepeningaccumulation of related researchclinical big data,the method and procedure of accurate and efficient dose measurement dosimetry methods and procedures will promote and realize the update and iteration of Flash-RT experiment research and device technique,which will successfully realize the clinical the broader application prospects of this technology.

Objective:To evaluate the efficacy and safety of ustekinumab (UST) for Crohn′s disease (CD) .Methods:A retrospective cohort study was conducted to collect clinical data of CD patients with active lesions in colonoscopy before the treatment of UST in Renji Hospital of Shanghai Jiaotong University School of Medicine from May 2020 to September 2021. Primary endpoint was the endoscopic response and remission rates at the 24th/32th week after the treatment of UST.Results:A total of 36 CD patients who were endoscopically active at baseline [25 men, 11 women; mean age, 29.8±8.7 years; disease duration, 38.0 (15.5, 66.1) months] were included. According to Montreal classification, 4 patients (11.1%) were L1 type (terminal ileum) , 4 (11.1%) were L2 type (colon) , 28 (77.8%) belonged to L3 type (ileocolon) , and upper digestive tract involvement occurred in 4 (11.1%) . As for disease behavior, 28 patients (77.8%) had non-structuring and non-penetrating lesions; 5 (13.9%) had structuring lesions and 3 (8.3%) had penetrating lesions. (1) Endoscopic activity: At the 24th/32th week, the endoscopic remission rate and response rate were 33.3% (12/36) and 63.9% (23/36) , respectively. There was no statistically significant difference in endoscopic remission rate and response rate between first-line and second-line usages of UST (all P>0.05) . (2) Clinical activity: Among the 36 patients, 16 were in the clinical active phase, and 20 patients were in the clinical remission phase at baseline. The clinical remission rate and clinical response rate of 16 clinical active patients at the 24th/32th week were 81.2% and 93.8% respectively. (3) Radiological activity: Twenty-seven patients completed the radiological evaluation at the 24th/32th week. In 3 patients with L1 lesions, 2 achieved response or partial response and no response in 1. In 24 patients with L3 lesions, radiological response occurred in 5 patients (20.8%) , partial response in 19 (79.2%) , and no response in 5 (20.8%) . In 19 patients with active perianal fistula at baseline, 6 achieved healing fistule at the 24th/32th week, 2 had partial response, 6 remained stable, while progress were seen in the other 5. (4) Serological and nutritive index: Compared with baseline values, the body mass index, hemoglobin and serum albumin levels of patients were significantly improved at the 24th/32th week (all P<0.05) , but the level of C-reactive protein and erythrocyte sedimentation rate at the 24th/32th week showed no significant difference (all P>0.05) . (5) Safety: No serious adverse events and infusion reactions were observed, and adverse events occurred in 2 patients. Conclusion:UST can effectively improve the endoscopic manifestations, clinical symptoms, imaging and nutritive index of CD patients with good safety.

Boron neutron capture therapy (BNCT) is an advanced method of precision radiotherapy for tumors. In BNCT, 10B enriched boron carriers enter and gather within tumor cells, then a thermal neutron beam triggers the 10B (n, α) 7Li reaction to release alpha and 7Li particle with low energy, which can kill tumor cells. Compared with conventional radiotherapy, BNCT has the characteristics of higher biological effect, more precise targeting, less damage to normal tissues and less treatment times. In this article, recent progress and existing problems of BNCT-related clinical research were reviewed.

Objective:To evaluate the efficacy and safety of ustekinumab (UST) for Crohn′s disease (CD) .Methods:A retrospective cohort study was conducted to collect clinical data of CD patients with active lesions in colonoscopy before the treatment of UST in Renji Hospital of Shanghai Jiaotong University School of Medicine from May 2020 to September 2021. Primary endpoint was the endoscopic response and remission rates at the 24th/32th week after the treatment of UST.Results:A total of 36 CD patients who were endoscopically active at baseline [25 men, 11 women; mean age, 29.8±8.7 years; disease duration, 38.0 (15.5, 66.1) months] were included. According to Montreal classification, 4 patients (11.1%) were L1 type (terminal ileum) , 4 (11.1%) were L2 type (colon) , 28 (77.8%) belonged to L3 type (ileocolon) , and upper digestive tract involvement occurred in 4 (11.1%) . As for disease behavior, 28 patients (77.8%) had non-structuring and non-penetrating lesions; 5 (13.9%) had structuring lesions and 3 (8.3%) had penetrating lesions. (1) Endoscopic activity: At the 24th/32th week, the endoscopic remission rate and response rate were 33.3% (12/36) and 63.9% (23/36) , respectively. There was no statistically significant difference in endoscopic remission rate and response rate between first-line and second-line usages of UST (all P>0.05) . (2) Clinical activity: Among the 36 patients, 16 were in the clinical active phase, and 20 patients were in the clinical remission phase at baseline. The clinical remission rate and clinical response rate of 16 clinical active patients at the 24th/32th week were 81.2% and 93.8% respectively. (3) Radiological activity: Twenty-seven patients completed the radiological evaluation at the 24th/32th week. In 3 patients with L1 lesions, 2 achieved response or partial response and no response in 1. In 24 patients with L3 lesions, radiological response occurred in 5 patients (20.8%) , partial response in 19 (79.2%) , and no response in 5 (20.8%) . In 19 patients with active perianal fistula at baseline, 6 achieved healing fistule at the 24th/32th week, 2 had partial response, 6 remained stable, while progress were seen in the other 5. (4) Serological and nutritive index: Compared with baseline values, the body mass index, hemoglobin and serum albumin levels of patients were significantly improved at the 24th/32th week (all P<0.05) , but the level of C-reactive protein and erythrocyte sedimentation rate at the 24th/32th week showed no significant difference (all P>0.05) . (5) Safety: No serious adverse events and infusion reactions were observed, and adverse events occurred in 2 patients. Conclusion:UST can effectively improve the endoscopic manifestations, clinical symptoms, imaging and nutritive index of CD patients with good safety.