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 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.

Root position plays an important role in healthy, stable, and aesthetic orthodontic treatment. In the past, two-dimensional radiographic images were used to assess the accuracy and precision of tooth root positions. In recent years, the use of cone beam CT (CBCT) and its reconstructed images to measure the three-dimensional spatial position and angle of root position has become mainstream. The root position is mainly described by measuring the relationship between the root and adjacent structures in the buccolingual, vertical, and mesiodistal directions as well as the root angle. The thickness of the alveolar bone on the buccolingual side of the root represents the buccolingual position, the vertical height in the alveolar bone and the relationship between apex and maxillary sinus represents the vertical position, the interroot alveolar bone thickness represents the mesiodistal position of the root, and the root angle is mostly based on incisal mandibular plane angle, angulation, torque, and other angles in the traditional two-dimensional measurement. Fitting CBCT and digital model data can be used to monitor the relationship between root and alveolar bone during orthodontic treatment, but a more comprehensive, standardized three-dimensional tooth root position measurement method is required to make full use of the root data provided by CBCT to study the relative optimal position of the tooth root at different anatomical levels, which combines with computer technology to optimize the digital design of orthodontic diagnosis and treatment.

【Objective】 To investigate the matrix effect on the determination of potency in Recombinant Human Coagulation Factor Ⅷ for Injection (rFⅧ). 【Methods】 Two different detection matrices were used to establish two methods for detecting the potency in Recombinant Human Coagulation Factor Ⅷ for Injection. And the matrix effect on the determination of potency was determined, including specificity, linearity, repeatability, accuracy and intermediate precision. 【Results】 As to the specificity, the recoveries of the two substrates at high vs low concentration level were 112% and 110% vs 104% and 109%, respectively. As to the linearity, in the range of (0.125-1.000) IU/mL, the correlation coefficient between concentration and coagulation time of standard/ sample was higher than 0.99. As to the accuracy/repeatability, the recoveries of two matrices was 104% and 102%, and RSD was 2.4% and 1.9%. As to the intermediate precision, personnel factor of two matrices was 0.72 and 0.23, date factor was 0.79 and 0.85, and RSD(for 12 times) was 4.2% and 3.0%. Comparison of two matrices was as follows: Deviation in test results of 6 batches of rFⅧ was all lower than 5%. There was no significant difference between two matrices. 【Conclusion】 The two matrices for potency detection show good performance including specificity, linearity, repeatability, accuracy, and intermediate precision. They are suitable for the determination of potency in rFⅧ products.

The incidence of inflammatory myofibroblastic sarcoma is low, and bladder origin is more rare. We reported a 58-year-old patient with painless gross hematuria for one week. Total abdominal CT examination showed soft tissue mass in the anterior wall of the bladder, which was considered as bladder cancer, and bladder tumor resection was performed. Postoperative pathology showed inflammatory myofibroblastic sarcoma. Therefore, radical cystectomy was performed because of the high degree of malignancy. There was no recurrence during 3 years follow-up.

Objective:To construct a training program for specialist nurse in Hybrid Operation Room based on the Context, Input, Process and Product (CIPP) model, and to explore its effect.Methods:Based on the CIPP model, a training program for specialist nurse in Hybrid Operation Room was constructed. From March 2020 to March 2021, 100 Operating Room nurses from Shanghai East Hospital affiliated to Tongji University were selected by convenience sampling and divided into the control group and the observation group, with 50 cased in each group. The control group adopted the conventional training for specialist nurses, while the observation group adopted the CIPP model training program for specialist nurses in Hybrid Operation Room. The training effect of the nurses in the Operating Room was compared between the two groups.Results:After the training, the scores of nurses in the observation group were higher than those in the control group in terms of specialist theory and operational skills, and the differences were statistically significant ( P<0.05) . After the training, the preoperative operation standard, intraoperative operation standard rate , operation standardization rate of surgical instruments and operation coordination of nurses in the observation group were better than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The training program for specialist nurses in hybrid surgery based on the CIPP model can improve the operational skills of nurses in the Hybrid Operation Room, and is conducive to improving the quality of Operating Room management.

Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses

Objective:To explore the effect of the operation process query system and the psychological impact on the surgical patient's family members.Methods:From April to October 2019, 198 family members of patients whose operation time> 1 hour were selected from the Shanghai East Hospital, Tongji University. The patients were divided into a control group and an observation group according to the order of operation, with 99 cases in each group. Both groups implemented preoperative visits, preoperative assessments, and preoperative education. The control group performed routine nursing of Operating Room and did not specifically inform family members of the information about the operation process during the operation. The family members of the observation group could view information about the operation process in the operation progress query system. The State-Trait Anxiety Inventory (S-AI) was used to assess the anxiety of the family members of the two groups of patients, and we compared the changes of pulse, respiration and blood pressure before and during the operation of the two groups of family members, and compared the satisfaction of the family members of the two groups after the operation.Results:The anxiety scores and vital signs of the family members of the two groups of patients during the operation were higher than those before the operation. The family members of the observation group had an intraoperative anxiety score of (49.01±7.91) , pulse (92.97±8.76) times/min, respiration (20.13±1.64) times/min, systolic blood pressure (122.06±11.69) mmHg, diastolic blood pressure (82.86±6.45) mmHg, all lower than those of the control group, the differences were statistically significant ( t=20.494, 6.749, 26.784, 4.387, 8.139; P<0.01) . The total satisfaction of the family members of the observation group after the operation was 95.96% (95/99) , and that of the control group was 63.64% (63/99) , and the difference was statistically significant (χ 2=34.932, P<0.01) . Conclusions:The application of the operation query system can effectively alleviate the psychological anxiety of the family members of the surgical patients and improve the satisfaction of the family members of the patients with the operation.