Objective To analyze the dosimetric differences between Monaco Monte Carlo(MC)algorithm and Pinnacle collapse cone convolution(CCC)algorithm for the same machine model using the 6 MV flatten-filter free(FFF)mode,thus providing a reference for the clinical application of these two treatment planning systems.Methods According to the MPPG5 and TRS430 reports,the acceptance and commissioning of Monaco MC algorithm model and Pinnacle CCC algorithm model in Department of Radiation Oncology,Shenzhen Hospital,Cancer Hospital of Chinese Academy of Medical Sciences were performed.A retrospectively analysis was conducted on 30 cases,including 10 cases of nasopharyngeal cancer,6 cases of lung cancer,4 cases of esophageal cancer,and 10 cases of cervical cancer.For each case,a 6 MV FFF plan was designed in Pinnacle using CCC algorithm.A 2.5 mm dose grid was selected for plan optimization and dose calculation.The plan was then exported to Monaco,where dose to medium was calculated using MC algorithm and a 2.5 mm dose grid with a 1%uncertainty for each control point.Both calculations in Pinnacle and Monaco took into account the impact of the treatment couch and immobilization devices on dose attenuation.The dose differences to the target volumes and major organs at risk between Pinnacle and Monaco for 3 different body parts including the head,chest and abdomen were compared.Results(1)For nasopharyngeal cancer,compared with Pinnacle CCC algorithm,Monaco MC algorithm lowered the Vpd of PTVp,PTVn,PTVrpn,PTV1 and PTV2 by 9.98%,2.64%,15.0%,1.93%and 8.01%,elevated the Dmax of PTVp,PTVn and PTVrpn by 2.98%,5.62%and 2.39%,increased the Dmean of PTVn and PTV1 by 1.87%and 0.72%,respectively;and the Dmax of the brainstem,the Dmax of the optic chiasm,and the Dmean of the right parotid gland were 3.83%lower,7.03%higher and 1.32%higher in Monaco MC algorithm as compared with Pinnacle CCC algorithm,respectively.(2)For lung cancer and esophageal cancer,Monaco MC algorithm showed increases of 2.37%,4.18%,15.30%,6.36%and 1.04%in the Dmax of PGTV,the V20,V5 and Dmean of lungs,and the V30 of heart as compared with Pinnacle CCC algorithm,respectively.(3)For cervical cancer,the Vpd of PTV_LR,Dmax of PTV_LR,the V40 of the rectum,the Dmax of the small intestine,and the Dmean of humeral head were 7.70%lower,3.70%higher,4.31%lower,3.05%higher and 2.07%higher in Monaco MC algorithm than in Pinnacle CCC algorithm,respectively.These differences were statistically significant(P<0.05).Conclusion For the above 3 treatment sites,significant differences are found in dose calculations for target areas and organs at risk between Monaco MC algorithm and Pinnacle CCC algorithm for the same treatment plan.Attention should be paid to the differences in dose algorithms for different treatment planning systems in clinical applications,which may have impacts on patient survival rates and organ toxicity.

Exosome play a crucial role in human immunodeficiency virus（HIV）infection. They share high similarities with HIV virions in physicochemical properties and secretion mechanisms：both the formation and secretion of exosome and the budding of HIV depend on the endosomal sorting complex required for transport（ESCRT）complex and VPS4 protein，with their membrane structures being phospholipid bilayers and comparable ranges of diameter and density. These similarities pose challenges to related research. Exosome participate in HIV infection through multiple mechanisms，including promoting HIV entry，inhibiting HIV replication，activating HIV latent reservoirs，and engaging in host antiviral immune responses. In terms of clinical applications，the potential of exosome as biomarkers or vaccine carriers has attracted attention，showing translational prospects. In summary，exosome influence the progression of HIV infection through complex mechanisms，and their application prospects in diagnostic markers，vaccine development，and therapeutic targets merit in-depth exploration.

Exosome play a crucial role in human immunodeficiency virus（HIV）infection. They share high similarities with HIV virions in physicochemical properties and secretion mechanisms：both the formation and secretion of exosome and the budding of HIV depend on the endosomal sorting complex required for transport（ESCRT）complex and VPS4 protein，with their membrane structures being phospholipid bilayers and comparable ranges of diameter and density. These similarities pose challenges to related research. Exosome participate in HIV infection through multiple mechanisms，including promoting HIV entry，inhibiting HIV replication，activating HIV latent reservoirs，and engaging in host antiviral immune responses. In terms of clinical applications，the potential of exosome as biomarkers or vaccine carriers has attracted attention，showing translational prospects. In summary，exosome influence the progression of HIV infection through complex mechanisms，and their application prospects in diagnostic markers，vaccine development，and therapeutic targets merit in-depth exploration.

Objective To investigate the expression of dihydrolipoamide S-acetyltransferase(DLAT)in hepatocellular carcinoma(HCC)tissues and its impact on immunotherapy efficacy,aiming to identify a new biomarker for prognosis assessment and immunotherapy response prediction.Methods Bioinformatics methods were used to analyze the transcriptomic data,clinical pathological characteristics and survival information of HCC patients from TCGA database.The expression of DLAT in HCC and its correlation with clinical features were evaluated,along with its relationship with immune infiltration,immune checkpoint-related genes,and immunotherapy response.Results DLAT was highly expressed in HCC tissues and associated with poor prognosis(HR=1.63,P=0.006).The proportion of R1&R2 residual tumors were significantly higher in the DLAT high-expression group(4.1％vs 1.2％,P=0.011).Immune infiltration analysis revealed that high DLAT expression was negatively correlated with Th 17,DC cells,B cells and T cells,while positively correlated with T helper cells,Tcm and Tem cells.Furthermore,DLAT expression showed significant positive correlations with key immune checkpoint genes(PDCD1LG2,HAVCR2,TIGIT,and PVR),and TIDE algorithm predicted poor response to immune checkpoint inhibitor therapy in the DLAT high-expression group.Conclusion High expression of DLAT in HCC tissues is a risk factor for poor prognosis and may serve as a potential biomarker for prognostic assessment and immunotherapy response prediction in HCC patients.

Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab sequences and sequence segments, missing the individual residue sites. This study introduces Site-specific Immunogenicity for Therapeutic Antibody (SITA), a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody, but also individual residues, based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures. A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Ab-Ab structural complexes. On an independent testing dataset derived from 13 Ab-Ab structural complexes, SITA successfully predicted the epitope sites for Ab-Ab structures with a receiver operating characteristic (ROC)-area unver the ROC curve (AUC) of 0.85 and a precision-recall (PR)-AUC of 0.305 at the residue level. Furthermore, the SITA score can significantly distinguish immunogenicity levels of whole human Abs, therapeutic Abs and non-human-derived Abs. More importantly, analysis of an additional 25 therapeutic Abs revealed that over 70% of them were detected with decreased immunogenicity after modification compared to their parent variants. Among these, nearly 66% Abs successfully identified actual modification sites from the top five sites with the highest SITA scores, suggesting the ability of SITA scores for guide the humanization of antibody. Overall, these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Antibody humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic antibodies originated from animal models.Computational suggestions have long been desired,but available tools focused on immunogenicity calculation of whole antibody sequences and sequence segments,missing the individual residue sites.This study introduces Site-specific Immunogenicity for Therapeutic Antibody(SITA),a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody,but also individual residues,based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures.A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Antibody-Antibody structural complexes.On an independent testing dataset derived from 13 Antibody-Antibody structural complexes,SITA successfully predicted the epitope sites for Antibody-Antibody structures with a receiver operating characteristic(ROC)-area unver the ROC curve(AUC)of 0.85 and a precision-recall(PR)-AUC of 0.305 at the residue level.Furthermore,the SITA score can significantly distinguish immunogenicity levels of whole human antibodies,therapeutic antibodies and non-human-derived antibodies.More importantly,analysis of an additional 25 thera-peutic antibodies revealed that over 70％of them were detected with decreased immunogenicity after modification compared to their parent variants.Among these,nearly 66％antibodies successfully iden-tified actual modification sites from the top five sites with the highest SITA scores,suggesting the ability of SITA scores for guide the humanization of antibody.Overall,these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Objective To investigate the expression of dihydrolipoamide S-acetyltransferase(DLAT)in hepatocellular carcinoma(HCC)tissues and its impact on immunotherapy efficacy,aiming to identify a new biomarker for prognosis assessment and immunotherapy response prediction.Methods Bioinformatics methods were used to analyze the transcriptomic data,clinical pathological characteristics and survival information of HCC patients from TCGA database.The expression of DLAT in HCC and its correlation with clinical features were evaluated,along with its relationship with immune infiltration,immune checkpoint-related genes,and immunotherapy response.Results DLAT was highly expressed in HCC tissues and associated with poor prognosis(HR=1.63,P=0.006).The proportion of R1&R2 residual tumors were significantly higher in the DLAT high-expression group(4.1％vs 1.2％,P=0.011).Immune infiltration analysis revealed that high DLAT expression was negatively correlated with Th 17,DC cells,B cells and T cells,while positively correlated with T helper cells,Tcm and Tem cells.Furthermore,DLAT expression showed significant positive correlations with key immune checkpoint genes(PDCD1LG2,HAVCR2,TIGIT,and PVR),and TIDE algorithm predicted poor response to immune checkpoint inhibitor therapy in the DLAT high-expression group.Conclusion High expression of DLAT in HCC tissues is a risk factor for poor prognosis and may serve as a potential biomarker for prognostic assessment and immunotherapy response prediction in HCC patients.

Objective To analyze the dosimetric differences between Monaco Monte Carlo(MC)algorithm and Pinnacle collapse cone convolution(CCC)algorithm for the same machine model using the 6 MV flatten-filter free(FFF)mode,thus providing a reference for the clinical application of these two treatment planning systems.Methods According to the MPPG5 and TRS430 reports,the acceptance and commissioning of Monaco MC algorithm model and Pinnacle CCC algorithm model in Department of Radiation Oncology,Shenzhen Hospital,Cancer Hospital of Chinese Academy of Medical Sciences were performed.A retrospectively analysis was conducted on 30 cases,including 10 cases of nasopharyngeal cancer,6 cases of lung cancer,4 cases of esophageal cancer,and 10 cases of cervical cancer.For each case,a 6 MV FFF plan was designed in Pinnacle using CCC algorithm.A 2.5 mm dose grid was selected for plan optimization and dose calculation.The plan was then exported to Monaco,where dose to medium was calculated using MC algorithm and a 2.5 mm dose grid with a 1%uncertainty for each control point.Both calculations in Pinnacle and Monaco took into account the impact of the treatment couch and immobilization devices on dose attenuation.The dose differences to the target volumes and major organs at risk between Pinnacle and Monaco for 3 different body parts including the head,chest and abdomen were compared.Results(1)For nasopharyngeal cancer,compared with Pinnacle CCC algorithm,Monaco MC algorithm lowered the Vpd of PTVp,PTVn,PTVrpn,PTV1 and PTV2 by 9.98%,2.64%,15.0%,1.93%and 8.01%,elevated the Dmax of PTVp,PTVn and PTVrpn by 2.98%,5.62%and 2.39%,increased the Dmean of PTVn and PTV1 by 1.87%and 0.72%,respectively;and the Dmax of the brainstem,the Dmax of the optic chiasm,and the Dmean of the right parotid gland were 3.83%lower,7.03%higher and 1.32%higher in Monaco MC algorithm as compared with Pinnacle CCC algorithm,respectively.(2)For lung cancer and esophageal cancer,Monaco MC algorithm showed increases of 2.37%,4.18%,15.30%,6.36%and 1.04%in the Dmax of PGTV,the V20,V5 and Dmean of lungs,and the V30 of heart as compared with Pinnacle CCC algorithm,respectively.(3)For cervical cancer,the Vpd of PTV_LR,Dmax of PTV_LR,the V40 of the rectum,the Dmax of the small intestine,and the Dmean of humeral head were 7.70%lower,3.70%higher,4.31%lower,3.05%higher and 2.07%higher in Monaco MC algorithm than in Pinnacle CCC algorithm,respectively.These differences were statistically significant(P<0.05).Conclusion For the above 3 treatment sites,significant differences are found in dose calculations for target areas and organs at risk between Monaco MC algorithm and Pinnacle CCC algorithm for the same treatment plan.Attention should be paid to the differences in dose algorithms for different treatment planning systems in clinical applications,which may have impacts on patient survival rates and organ toxicity.

Objective:To evaluate the safety and efficacy of tumor-treating fields (TTFields) and chemoradiation in patients with high-grade glioblastoma.Methods:Clinical data of 38 patients admitted to the Jiangsu Cancer Hospital from September 2021 to May 2023 who were diagnosed with high-grade glioblastoma (36 cases of World Health Organization grade Ⅳ and 2 cases of grade Ⅲ) were retrospectively analyzed. All patients received TTFields combined with concurrent chemoradiation after surgery. Response assessment in neuro-oncology (RANO) criteria was used to evaluate the glioma responses as tumor remission, stable or progression. Common terminology criteria for adverse events v5.0 and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Treatment compliance was assessed by data on the NovoTTF-200A therapeutic device, calculated as a percentage of daily TTFields usage time. Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test.Results:The median duration of treatment with TTFields in 38 patients was 20 h (rang: 2.4-22.6 h), and the median treatment compliance was 83% (range: 10%-94%). After 42 days of TTFields combined with concurrent chemoradiation, 12 patients who underwent complete tumor resection were assessed as stable according to RANO criteria. Among the 26 patients who underwent partial tumor resection, 23 (88%) were evaluated as disease remission according to RANO criteria. The 7-, 10-, 13-month progression-free survival rate was 81.0%、64.0%、49.5%, repectively. The common adverse events included grade 1 (45%) and grade 2 (8%) dAE, without grade 3-4 dAE. Typical presentations included contact dermatitis, blisters, lesions or ulcers, and abscesses. The median follow-up time was 10.0 months (range: 1.6-21.3 months). At follow-up as of July 2023, 26 of the 38 patients were stable and 12 had disease progression (8 died).Conclusion:The preliminary results show that TTFields combined with chemoradiation is effective, safe and reliable treatment for high-grade glioblastoma.

Objective To investigate the effect and mechanism of kudinoside D(KD-D)on proliferation,apoptosis and autophagy of human HCC-1806 breast cancer cells.Methods Human HCC-1806 breast cancer cells were treated with different concentrations of KD-D,and the cell viability was detected by CCK-8 method.EdU method was used to detect cell proliferation ability;the ability of cell clone formation was detected by crystal violet staining.Apoptosis was detected by flow cytometry(Annexin V-FITC/PI).Mitochondrial membrane potential was detected by JC-1 staining.The protein expressions of Cleaved Caspase-3,LC3 and P62 were detected by immunofluorescence.The protein expressions of Cleaved Caspase-3,Pan-AKT,Phosp-AKT and LC3Ⅱ were detected by Western Blot.Autophagy double-labeled mRFP-EGFP-LC3 adenovirus infection assay was used to detect cell autophagy flow.Results Compared with the control group,HCC-1806 cells were treated with 12.5,25,50,100,200,400 μmol·L-1 KD-D for 24 and 48 hours.With the increase of drug concentration and treatment time,the cell activity was significantly decreased(P＜0.001),the intracellular absorbance value was significantly decreased(P＜0.001),and the cell proliferation was inhibited.The cell clone formation counts in 60 and 80 μmol·L-1 KD-D groups were significantly decreased(P＜0.001).The proportion of early and late apoptosis in 50,100,150 μmol·L-1 KD-D groups were significantly increased(P＜0.05,P＜0.001).The proportion of red fluorescence in 40,60 and 80 μmol·L-1 KD-D groups were significantly decreased(P＜0.001),the proportion of green fluorescence was significantly increased(P＜0.01,P＜0.001),and the mitochondrial membrane potential of HCC-1806 cells decreased.The protein expression of Cleaved Caspase-3 in 60,80,100 μmol·L-1 KD-D group were significantly up-regulated(P＜0.001),and the protein expressions of Pan-AKT and Phosp-AKT in 60 μmol·L-1 KD-D group were significantly up-regulated(P＜0.001).In the 60 μmol·L-1 KD-D group,the number of LC3 protein fluorescent dots was significantly increased(P＜0.001),the average fluorescence intensity of P62 protein was significantly decreased(P＜0.001),the expression of LC3Ⅱ protein was significantly up-regulated(P＜0.001),the number of autophagosomes and autolysosomes were significantly increased(P＜0.01,P＜0.001),and the autophagic flow was activated.Compared with 60 μmol·L-1 KD-D group,the expression of Cleaved Caspase-3 and Pan-AKT protein in KD-D+AKT inhibitor(Afuresertib)group was significantly down-regulated(P＜0.01,P＜0.001),and the expression of Phosp-AKT protein was significantly up-regulated(P＜0.001).Conclusion KD-D can inhibit the proliferation of human breast cancer HCC-1806 cells and induce apoptosis and autophagy.The apoptosis of HCC-1806 cells induced by KD-D may be related to the activation of AKT signal and the expression of Cleaved Caspase-3.