Objective:Based on HyperArc stereotactic radiotherapy(SRT)technique,six-dimensional free bed combined with double mask fixation was used to treat intracranial tumors,and the positioning errors of within batch and between batches were analyzed,so as to provide basis for the accuracy of clinical treatment of this technique.Methods:A total of 13 patients with intracranial tumors who admitted to Peking Union Medical College Hospital from March to July 2023 were retrospectively selected,and they were treated by using HyperArc SRT technique.The validation images of cone-beam computed tomography(CBCT)of within batch and between batches during treatment were analyzed.The positioning errors of three translational direction[left and right(x),head and foot(y)and abdominal and dorsal(z)]and rotational direction were analyzed.The each positioning error was set as group A,and the remaining error after the positioning error was corrected through six-dimensional free bed was set as group B,and the error post treatment was set as group C.The difference between group B and group C was defined as the change of within batch.According to the margin formula,the positioning error of within batch was used to calculate the required range of margin.Results:Under the mode of six-dimensional free bed correction combined with double mask fixation,a total of 59 times of HyperArc SRT on head were performed.In the comparison of the average errors on the six-dimensional direction among groups A,B and C,the errors of group A on x direction and y direction were respectively(0.119±0.039)and(-0.133±0.047)cm,and the differences of them between group A and group B[(0.004±0.002)and(0.018±0.005)cm]were significant(t=2.890,-3.224,P<0.05).There were no significant differences on other directions between the two groups(P>0.05).The error of RX direction of group B was(0.033±0.021)°,and the difference of that between group B and group C[(0.122±0.045)°]was significant(t=-2.306,P<0.05),while there were no significant differences on other directions(P>0.05).In the margin of the design of the plan of intracranial tumors,the x,y and z directions were respectively 0.6,0.9 and 0.4 mm.Conclusion:In the radiotherapy of using HyperArc SRT technique for intracranial tumors,the use of six-dimensional free bed combined with double mask treatment can significantly shorten the margin,and ensure accurate irradiation for gross tumor volume(GTV)and simultaneously reduce the irradiation volume and dose of surrounding normal tissue.

The incomplete degradation of tumour cells by macrophages(Mφ)is a contributing factor to tumour progression and metastasis,and the degradation function of Mφ is mediated through phagosomes and lysosomes.In our preliminary experiments,we found that overactivation of NADPH oxidase 2(NOX2)reduced the ability of Mφ to degrade engulfed tumour cells.Above this,we screened out liquiritin from Glycyrrhiza uralensis Fisch,which can significantly inhibit NOX2 activity and inhibit tumours,to elucidate that suppressing NOX2 can enhance the ability of Mφ to degrade tumour cells.We found that the tumour environment could activate the NOX2 activity in Mφ phagosomes,causing Mφ to produce excessive reactive oxygen species(ROS),thus prohibiting the formation of phagolysosomes before degradation.Conversely,inhibiting NOX2 in Mφ by liquiritin can reduce ROS and promote phagosome-lysosome fusion,therefore improving the enzymatic degradation of tumour cells after phagocytosis,and subse-quently promote T cell activity by presenting antigens.We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox,blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox,thereby inhibiting the activity of NOX2.This study elucidates the specific mechanism by which Mφ cannot degrade tumour cells after phagocytosis,and indicates that liquiritin can promote the ability of Mφ to degrade tumour cells by suppressing NOX2.

Objective:Based on HyperArc stereotactic radiotherapy(SRT)technique,six-dimensional free bed combined with double mask fixation was used to treat intracranial tumors,and the positioning errors of within batch and between batches were analyzed,so as to provide basis for the accuracy of clinical treatment of this technique.Methods:A total of 13 patients with intracranial tumors who admitted to Peking Union Medical College Hospital from March to July 2023 were retrospectively selected,and they were treated by using HyperArc SRT technique.The validation images of cone-beam computed tomography(CBCT)of within batch and between batches during treatment were analyzed.The positioning errors of three translational direction[left and right(x),head and foot(y)and abdominal and dorsal(z)]and rotational direction were analyzed.The each positioning error was set as group A,and the remaining error after the positioning error was corrected through six-dimensional free bed was set as group B,and the error post treatment was set as group C.The difference between group B and group C was defined as the change of within batch.According to the margin formula,the positioning error of within batch was used to calculate the required range of margin.Results:Under the mode of six-dimensional free bed correction combined with double mask fixation,a total of 59 times of HyperArc SRT on head were performed.In the comparison of the average errors on the six-dimensional direction among groups A,B and C,the errors of group A on x direction and y direction were respectively(0.119±0.039)and(-0.133±0.047)cm,and the differences of them between group A and group B[(0.004±0.002)and(0.018±0.005)cm]were significant(t=2.890,-3.224,P<0.05).There were no significant differences on other directions between the two groups(P>0.05).The error of RX direction of group B was(0.033±0.021)°,and the difference of that between group B and group C[(0.122±0.045)°]was significant(t=-2.306,P<0.05),while there were no significant differences on other directions(P>0.05).In the margin of the design of the plan of intracranial tumors,the x,y and z directions were respectively 0.6,0.9 and 0.4 mm.Conclusion:In the radiotherapy of using HyperArc SRT technique for intracranial tumors,the use of six-dimensional free bed combined with double mask treatment can significantly shorten the margin,and ensure accurate irradiation for gross tumor volume(GTV)and simultaneously reduce the irradiation volume and dose of surrounding normal tissue.

In recent years,more and more researches has focused on the correlation between cognitive activity and physiological variables.The change of pupil is regarded as an important target in the cognitive process,and has become a hot research field.This review focuses on the three key brain regions that regulate pupil change,and reflects the neurophysiological mechanism behind pupil change by elaborating the neural pathways related to pupil change and cognitive performance.Based on recent studies on pupil change in cognitive diseases,it aims to promote the application of pupil change in the field of cognitive science in the future.

Objective:To present a set of clinically representative quality assurance (QA) test cases for stereotactic radiosurgery (SRT) plans of multiple intracranial metastases, in order to assess the plan quality and machine execution capabilities.Methods:Based on the clinical characteristics of multiple brain metastases, four groups of test cases with three target volumes (TVs), six TVs, nine TVs, and TVs near organs at risk (OARs) were designed. For these cases, SRT plans were developed, and plan quality was assessed using metrics including the Radiation Therapy Oncology Group conformality index (RTOG CI), gradient index (GI), homogeneity index (HI), and the volume of normal brain tissue receiving a dose of 24 Gy ( V24 Gy), which was defined as the volume enclosed by the 24 Gy isodose line around the Brain-PTV ( V24 Gy of Brain-PTV). Verification plans were generated for each test case, including the verification of point doses, planar doses (PD), and SRS MapCHECK (SMC) semiconductor matrix planar doses. Compared with the calculated result of the treatment planning system (TPS), the criteria for the γ analysis of planar doses were set at 1 mm/2% and 2 mm/2%. Results:For the four groups of test cases, the mean CI, GI, HI, and V24 Gy of Brain-PTV were 1.04±0.03, 3.79±0.40, 0.73±0.01 and (7.46±3.80) cm 3, respectively. The mean deviations of the point doses were 0.88%±0.98%, 1.47%±0.79%, 1.52%± 0.76%, and 1.17% ± 0.38%, respectively. The mean γ passing rates of the single fields for PDs were greater than 98% at 2 mm/2% and exceeding 96% at 1 mm/2%, and the mean γ pass rates of the SMC semiconductor matrix for PDs were 97.75% ± 2.31% and 99.33% ± 0.62%, at 1 mm/2% and 2 mm/2% respectively. Conclusions:The proposed QA test cases for SRT of multiple intracranial metastases allow for the effective assessments of the plan quality and machine execution capabilities and, thus, can assist various centers in clinical applications.

Objective:To investigate the predictive value of color Doppler ultrasound combined with electrocardio-gram for right heart dys function in patients with pulmonary heart disease(PHD).Methods:A total of 100 PHD patients admitted in Dongcheng Branch of First Affiliated Hospital of Anhui Medical University between January 2020 and December 2023 were retrospectively analyzed.According to results of 6min walking test(6MWT),pa-tients were divided into good right heart function group(n=64,≥350m)and right heart dysfunction group(n=36,＜350m).The indexes of cardiac color ultrasound[isovolumic relaxation time(IVRT),isovolumetric contraction time(IVCT)and right ventricular Tei index],ECG[24h mean R-R interval standard deviation(SDNN),normal R-R interval standard deviation per 5min(SDANN)and the ratio of low frequency components to high frequency components(LF/HF)]were compared between two groups.Receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of color Doppler ultrasound,ECG and their combination for right heart dys-function in PHD patients.Spearman correlation coefficient was used to analyze the association of color Doppler ul-trasound,ECG and their combination with right heart dysfunction in PHD patients.Results:Compared with those in good right heart function group,patients in right heart dysfunction group had significant higher IVRT[(120.64±14.08)ms vs.(97.87±10.93)ms],IVCT[(84.28±12.33)ms vs.(71.92±10.61)ms]and Tei index[(0.85±0.11)vs.(0.63±0.07)](P＜0.001 all),and significant lower SDNN[(75.52±12.58)ms vs.(85.58±11.75)ms],SDANN[(63.86±10.92)ms vs.(76.75±11.71)ms]and LF/HF[(1.33±0.19)vs.(1.84±0.27)](P＜0.001 all).ROC curve indicated that the AUC of color Doppler ultrasound combined ECG in diagnosing right heart dysfunction in PHD patients was 0.911(95％CI 0.838～0.959),which was significantly higher than those of color Doppler ultrasound[0.775(95％CI 0.681～0.853),Z=2.404,P=0.016]and ECG[0.688(95％CI 0.588～0.777),Z=3.968,P=0.001]alone.Spearman correlation analysis indicated that there was a significant positive correlation of color Doppler ultrasound(r=0.547),ECG(r=0.375)and their combination(r=0.810)with right heart dysfunction in PHD patients(P＜0.001 all),and the correlation between combined detection and right heart dysfunction in PHD patients was significantly higher.Conclusion:Color Doppler ultrasound combined with ECG possesses high diagnostic performance for right heart dysfunction in PHD patients.

Objective:To present a set of clinically representative quality assurance (QA) test cases for stereotactic radiosurgery (SRT) plans of multiple intracranial metastases, in order to assess the plan quality and machine execution capabilities.Methods:Based on the clinical characteristics of multiple brain metastases, four groups of test cases with three target volumes (TVs), six TVs, nine TVs, and TVs near organs at risk (OARs) were designed. For these cases, SRT plans were developed, and plan quality was assessed using metrics including the Radiation Therapy Oncology Group conformality index (RTOG CI), gradient index (GI), homogeneity index (HI), and the volume of normal brain tissue receiving a dose of 24 Gy ( V24 Gy), which was defined as the volume enclosed by the 24 Gy isodose line around the Brain-PTV ( V24 Gy of Brain-PTV). Verification plans were generated for each test case, including the verification of point doses, planar doses (PD), and SRS MapCHECK (SMC) semiconductor matrix planar doses. Compared with the calculated result of the treatment planning system (TPS), the criteria for the γ analysis of planar doses were set at 1 mm/2% and 2 mm/2%. Results:For the four groups of test cases, the mean CI, GI, HI, and V24 Gy of Brain-PTV were 1.04±0.03, 3.79±0.40, 0.73±0.01 and (7.46±3.80) cm 3, respectively. The mean deviations of the point doses were 0.88%±0.98%, 1.47%±0.79%, 1.52%± 0.76%, and 1.17% ± 0.38%, respectively. The mean γ passing rates of the single fields for PDs were greater than 98% at 2 mm/2% and exceeding 96% at 1 mm/2%, and the mean γ pass rates of the SMC semiconductor matrix for PDs were 97.75% ± 2.31% and 99.33% ± 0.62%, at 1 mm/2% and 2 mm/2% respectively. Conclusions:The proposed QA test cases for SRT of multiple intracranial metastases allow for the effective assessments of the plan quality and machine execution capabilities and, thus, can assist various centers in clinical applications.

This study aims to explore whether Naoxintong Capsules improve multiple cerebral infarctions and myocardial injury via promoting angiogenesis, thereby exerting a simultaneous treatment effect on both the brain and heart. Male SD rats were randomly divided into six groups: sham-operated group, model group, high-dose, medium-dose, and low-dose groups of Naoxintong Capsules(440, 220, and 110 mg·kg~(-1)), and nimodipine group(10.8 mg·kg~(-1)). Rat models of multiple cerebral infarctions were established by injecting autologous thrombus, and samples were collected and tested seven days after modeling. Evaluations included multiple cerebral infarction model assessments, neurological function scores, grip strength tests, and rotarod tests, so as to evaluate neuromotor functions. Morphological structures of brain and heart tissue were observed using hematoxylin-eosin(HE) staining, Nissl staining, and Masson staining. Network pharmacology was employed to screen the mechanisms of Naoxintong Capsules in improving multiple cerebral infarctions and myocardial injury. Neuronal and myocardial cell ultrastructures were observed using transmission electron microscopy. Apoptosis rate in brain neuronal cells was detected by TdT-mediated dUTP nick end labeling(TUNEL) staining, and reactive oxygen species(ROS) levels in myocardial cells were measured. Immunofluorescence was used to detect the expression of platelet endothelial cell adhesion molecule-1(CD31), antigen identified by monoclonal antibody Ki67(Ki67), hematopoietic progenitor cell antigen CD34(CD34), and hypoxia inducible factor-1α(HIF-1α) in brain and myocardial tissue. Western blot, and real-time quantitative polymerase chain reaction(RT-qPCR) were used to detect the expression of HIF-1α, vascular endothelial growth factor(VEGF), vascular endothelial growth factor receptor 2(VEGFR2), sarcoma(Src), basic fibroblast growth factor(bFGF), angiopoietin-1(Ang-1), and TEK receptor tyrosine kinase(Tie-2). Compared with the model group, the medium-dose group of Naoxintong Capsules showed significantly lower neurological function scores, increased grip strength, and prolonged time on the rotarod. Pathological damage in brain and heart tissue was reduced, with increased and more orderly arranged mitochondria in neurons and cardiomyocytes. Apoptosis in brain neuronal cells was decreased, and ROS levels in cardiomyocytes were reduced. The microvascular density and endothelial cells of new blood vessels in brain and heart tissue increased, with increased overlapping regions of CD31 and Ki67 expression. The relative protein and mRNA expression levels of HIF-1α, VEGF, VEGFR2, Src, Ang-1, Tie-2, and bFGF were elevated in brain tissue and myocardial tissue. Naoxintong Capsules may improve multiple cerebral infarctions and myocardial injury by mediating HIF-1α/VEGF expression to promote angiogenesis.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Cerebral Infarction/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Vascular Endothelial Growth Factor A/genetics* ; Capsules ; Signal Transduction/drug effects* ; Humans ; Brain/metabolism* ; Myocardium/metabolism* ; Apoptosis/drug effects*

OBJECTIVE: To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells. METHODS: A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1_126-134 ( RMFPNAPYL) complex (hereafter referred to as HLA-A2:WT1) was synthesized to evaluate the function of antigen processing and presentation machinery (APM) in AML cells. AML cell line THP1 was incubated with increasing concentrations of IFN-γ, hypomethylating agents (HMA), immunomodulatory drugs (IMiD), proteasome inhibitors (PI) and γ-secretase inhibitors (GSI), followed by measuring of HLA-ABC, HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points. RESULTS: The TCR-like antibody we generated only binds to HLA-A*0201⁺WT1⁺ cells, indicating the specificity of the antibody. HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ, showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM. Among the anti-tumor agents screened in this study, GSI (LY-411575) and HMA (decitabine and azacitidine) could significantly increase the HLA-A2:WT1 level. The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time. As proteasome inhibitors, carfilzomib could significantly decreased the expression of HLA-A2:WT1, while bortezomib had no significant effect on HLA-A2:WT1 expression. CONCLUSION HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Antineoplastic Agents/pharmacology* ; Antigen Presentation/drug effects* ; HLA-A2 Antigen/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Cell Line, Tumor ; Interferon-gamma

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL