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.

Objectives:To investigate the impact of bone hyperplasia in the thoracolumbar spine caused by diffuse idiopathic skeletal hyperostosis(DISH)on the changes of spinopelvic sagittal parameters between stand-ing and sitting positions.Methods:A total of 61 DISH patients[DISH group,42 males and 19 females,50-76(65.1±6.3)years]who underwent surgical treatment for lumbar spinal stenosis in our hospital between Jan-uary 2019 and December 2023 were retrospectively analyzed.100 age-and sex-matched non-DISH patients undergone the same surgical procedure during the same period were included as control[N-DISH group,63 males and 37 females,54-77(67.5±7.2)years].According to the distribution of osteophytes,the patients in the DISH group with ectopic ossification limited to the thoracic spine were categorized into the T-DISH group,while those with involvement of both thoracic and lumbar spines were divided in the L-DISH group.Preoper-atively,full-spine anteroposterior and lateral X-rays were taken in both standing and sitting positions.All patients were measured for spinopelvic sagittal parameters in standing and sitting positions,including sagittal vertical axis(SVA),pelvic tilt(PT),sacral slope(SS),pelvic incidence(PI),thoracic kyphosis(TK),lumbar lordosis(LL),and proximal femoral angle(PFA).The differences in standing and sitting positions and changes between DISH and N-DISH groups,T-DISH and L-DISH groups were compared.Results:In the standing position,the SVA(P=0.008)and TK(P=0.028)in the DISH group were significantly higher than those in the N-DISH group,while no significant differences were observed in PI,PT,SS,LL,and PFA(P＞0.05).In the sitting position,the TK(P=0.003)and LL(P=0.007)in the DISH group were significantly higher than those in the N-DISH group,whereas no significant differences were noted inSVA,PT,PI,SS,and PFA(P＞0.05).When transitioning from standing to sitting,the changes in SVA(P=0.021),PT(P=0.008),SS(P=0.001),TK(P=0.002),and LL(P＜0.001)in DISH group of patients were significantly smaller than those in N-DISH group of patients.Among DISH patients,the L-DISH group had significantly lower PI(P=0.016),SS(P=0.011),and LL(P=0.006)in the standing position compared to the T-DISH group,while no significant differences were observed in SVA,PT,TK,and PFA(P＞0.05).In the sitting position,the PI(P=0.008)and SS(P=0.007)of the L-DISH group were significantly lower than those of the T-DISH group,while no significant differences were observed in SVA,PT,TK,LL,and PFA(P＞0.05).The changes in LL when transitioning from standing to sitting were significantly lower in the L-DISH group compared to the T-DISH group(P=0.033),while the changes of other sagittal parameters showed no significant difference(P＞0.05).Conclusions:Bone hyperplasia in DISH patients significantly limits spinal mobility,and the restriction is more pronounced in patients with osteophytes extending to the lumbar spine compared to those with isolated thoracic involvement.

Objective:To investigate the expression,function,and clinical significance of CD24 in testicular germ cell tumors(TGCT).Methods:This study included 204 testicular germ cell tumor(TGCT)patients from the TCGA database and the TGCT-Changhai testicular germ cell tumor cohort(Changhai Hospital cohort).Prognostic analysis and multivariate analysis were employed to evaluate the association between CD24 expression and clinical characteristics.Immunohistochemistry(IHC)staining of tumor tissues was used to elucidate the mechanism by which CD24 regulated the tumor immune microenvironment(TIME)in TGCT.Finally,by analyzing the diffrences in PD-L1 expression levels and tumor-associated macrophage(TAM)M2-type cell infiltration rates between CD24 high-expression and low-expression groups,and employing the TIDE algorithm,we investigated the correlation between CD24 expression levels and immune escape scores as well as immunotherapy response rates.Results:Analysis of the TCGA database revealed that CD24 expression was significantly upregulated in TGCT with high clinical staging and M-stage(P<0.05).Compared to adjacent normal tissues,CD24 expression was significantly elevated in both primary and metastatic TGCT tissues(P<0.05).Significant differences in CD24 expression levels were observed across TNM stages and tumor progression statuses(all P<0.05).Univariate logistic regression analysis identified CD24 as a predictive factor for clinical outcomes in TGCT patients(OR=0.135,95%CI[0.035,0.516],P=0.003),and multivariate analysis further confirmed its role as an independent predictor(OR=0.057,95%CI[0.005,0.624],P=0.019).In TGCT tissues,CD24 mRNA levels correlated with immune cell markers CD206 and CD70(all P<0.05).Additionally,CD24 expression levels demonstrated significant predictive value in immune escape scoring and immunotherapy response rate assessments.Conclusions:CD24 is highly expressed in TGCT tissues and its expression is significantly correlated with the prognosis of TGCT patients,which makes it a potential new target point of biotherapy for testicular germ cell tumor patients.

Objectives:To investigate the impact of bone hyperplasia in the thoracolumbar spine caused by diffuse idiopathic skeletal hyperostosis(DISH)on the changes of spinopelvic sagittal parameters between stand-ing and sitting positions.Methods:A total of 61 DISH patients[DISH group,42 males and 19 females,50-76(65.1±6.3)years]who underwent surgical treatment for lumbar spinal stenosis in our hospital between Jan-uary 2019 and December 2023 were retrospectively analyzed.100 age-and sex-matched non-DISH patients undergone the same surgical procedure during the same period were included as control[N-DISH group,63 males and 37 females,54-77(67.5±7.2)years].According to the distribution of osteophytes,the patients in the DISH group with ectopic ossification limited to the thoracic spine were categorized into the T-DISH group,while those with involvement of both thoracic and lumbar spines were divided in the L-DISH group.Preoper-atively,full-spine anteroposterior and lateral X-rays were taken in both standing and sitting positions.All patients were measured for spinopelvic sagittal parameters in standing and sitting positions,including sagittal vertical axis(SVA),pelvic tilt(PT),sacral slope(SS),pelvic incidence(PI),thoracic kyphosis(TK),lumbar lordosis(LL),and proximal femoral angle(PFA).The differences in standing and sitting positions and changes between DISH and N-DISH groups,T-DISH and L-DISH groups were compared.Results:In the standing position,the SVA(P=0.008)and TK(P=0.028)in the DISH group were significantly higher than those in the N-DISH group,while no significant differences were observed in PI,PT,SS,LL,and PFA(P＞0.05).In the sitting position,the TK(P=0.003)and LL(P=0.007)in the DISH group were significantly higher than those in the N-DISH group,whereas no significant differences were noted inSVA,PT,PI,SS,and PFA(P＞0.05).When transitioning from standing to sitting,the changes in SVA(P=0.021),PT(P=0.008),SS(P=0.001),TK(P=0.002),and LL(P＜0.001)in DISH group of patients were significantly smaller than those in N-DISH group of patients.Among DISH patients,the L-DISH group had significantly lower PI(P=0.016),SS(P=0.011),and LL(P=0.006)in the standing position compared to the T-DISH group,while no significant differences were observed in SVA,PT,TK,and PFA(P＞0.05).In the sitting position,the PI(P=0.008)and SS(P=0.007)of the L-DISH group were significantly lower than those of the T-DISH group,while no significant differences were observed in SVA,PT,TK,LL,and PFA(P＞0.05).The changes in LL when transitioning from standing to sitting were significantly lower in the L-DISH group compared to the T-DISH group(P=0.033),while the changes of other sagittal parameters showed no significant difference(P＞0.05).Conclusions:Bone hyperplasia in DISH patients significantly limits spinal mobility,and the restriction is more pronounced in patients with osteophytes extending to the lumbar spine compared to those with isolated thoracic involvement.

Hydration status refers to the balance between the intake and discharge of water in the body. When the ingested and discharged water are roughly equal and the body is in water balance, it is the normal hydration status, and when the water intake is too little or too much, it is the "dehydration" or "overhydration status". The hydration status of the body not only affects metabolism, but also affects the functions of the urinary system, cardiovascular system, nervous system, etc. In order to further clarify the relationship between body hydration status and decompression sickness (DCS), this paper reviewed relevant studies and analyzed the interaction between hydration and decompression safety during diving. The primary causes of dehydration in diving are "hyperbaric diuresis", "immersion diuresis", breathing dry gas, heat, and cold. Dehydration not only promotes the occurrence of DCS but also reduces the aerobic work efficiency and athletic performance of divers, as well as affects cognition and mood. A study found that appropriate rehydration before and during diving can reduce the risk of DCS, which possibly associates with the increase of blood volume, plasma surface tension, and vasoconstriction. Fluid therapy is also important for those who already have DCS. This paper analyzed the amount, nature, timing, and effect of rehydration involved in the above links, comprehensively sorted out the relationship between hydration and diving safety, summarized the existing problems, and provided reference for practical application and future research.

Objective To explore the differences in quality of life among patients with hepatocellular carcinoma(HCC)in different age groups and the impact of cognitive intervention on them.Methods A total of 148 postoperative HCC patients(observation group)who underwent follow-up examinations at The Third Affiliated Hospital of Naval Medical University from May 2020 to May 2021 were enrolled.They were divided into a young group(n=20),a middle-aged group(n=47),and an elderly group(n=81)according to the age.The differences of postoperative quality of life among HCC patients in different age groups were investigated.Meanwhile,214 HCC patients scheduled for surgical treatment were selected and randomly divide into an experimental group and a control group,with 107 patients in each group.They were also divided into a young group,a middle-aged group,and an elderly group according to the age.Routine care and routine care+cognitive intervention were implemented in the experimental group and control group,respectively.The impact of cognitive intervention on the quality of life of HCC patients in different age groups was investigated.Results The role function,emotional function,cognitive function,social function,and overall quality of life of the young HCC patients in the observation group were worse than those of the middle-aged and elderly patients,while the physical function of the elderly patients was worse than that of the young and middle-aged patients(P<0.05).Compared with the control group,the young and middle-aged HCC patients in the experimental group had statistically significant improvements in role,emotion,cognitive function and overall quality of life(P<0.05),while the elderly HCC patients in the experimental group were significantly higher than those in the control group(P<0.05).Conclusion The postoperative quality of life varies among HCC patients in different age groups.Cognitive intervention can improve the postoperative quality of life of HCC patients,especially for young and middle-aged HCC patients.

Objective:To improve the accuracy of cone-beam CT (CBCT) image registration by using a dose-guided registration algorithm based on multi-objective optimization.Methods:A total of 28 sets of CBCT images of 6 patients with lung cancer and 5 patients with cervical cancer admitted to Harbin Medical University Cancer Hospital in 2022 were retrospectively analyzed. Using the results of bone-based registration as the starting points for dose registration algorithm, the dose fluence weighted mean square errors of each displacement point in surrounding three-dimensional space were calculated, and the candidate displacement points were selected by unsupervised k-means clustering method. The three-dimensional dose distribution of each candidate displacement point was calculated by using the limited size pencil beam algorithm, and the dose histogram indexes were extracted as the optimization variables of the multi-objective optimization algorithm. After the Pareto optimal solution set obtained using multi-objective genetic algorithm, the optimal unique solution was then determined based on the predetermined objective weight scheme.Results:After dose optimization registration, the values of D 90%, D 95%, D 98%, D mean and conformity index (CI) of planning target volume (PTV) of lung cancer patients were increased by 0.23 Gy, 0.49 Gy, 1.05 Gy, 0.15 Gy, 0.03 compared with conventional registration, respectively, and no significant difference was found for the organs at risk (OAR). For cervical cancer cases, the values of D 90%, D 95%, D 98%, D mean and CI of PTV were increased by 0.72 Gy, 1.15 Gy, 2.53 Gy, 0.24 Gy, 0.05 compared with conventional registration, respectively, whereas the evaluation indexes of partial OAR were decreased by 1.06-1.81 Gy. Conclusion:The proposed dose-guided registration algorithm can improve the dose coverage for the target area, decrease the dose for OAR and reduce residual error of rigid registration algorithm, which can be implemented as part of online adaptive radiotherapy.

The lifelong teaching and learning abilities based on training the core competency of ophthalmology residents is a new hot spot in the curriculum design of ophthalmological standardized residency training. In the standardized residency training base of Xiangya Hospital of Central South University Ophthalmic Center, a graded lecturer training curriculum with residents as core has been designed to train the critical thinking, active learning, summarizing and presenting skills of residents at all levels. According to the different tasks, the residents can present themselves through online and offline platforms so that they can gradually grow into different levels of lecturers. Through the graded training of lecturers from low level to high level, step by step, the residents are trained as active learners from the thinking mode, become student-instructors or lecturers from the teaching ability, and be more competent for future study and work.

Objective: To compare the effect of intranasal dexmedetomidine and oral chloral hydrate in deep sedation of children. Methods: The Pubmed, EMBase, CENTRAL (Issue 4, 2018), Web of science, CBM, Wanfang Data, CNKI and VIP databases from the inception to January 2019 were searched. Randomized controlled trials (RCTs) with dexmedetomidine and chloral hydrate as interventions were included and the data were analyzed by RevMam 5.3 and Stata 12.0 software. The success rate of deep sedation, the indicator of sedation onset time, the recovery time, the incidence of vomiting and bradycardia were compared. Results: A total of 7 RCTs involving 1 007 patients were included for analysis. The results showed that the success rate of deep sedation (OR=2.55, 95%CI:1.46-4.44, P<0.01) and the incidence of bradycardia (OR=4.42, 95%CI:1.82-10.74, P<0.01) in the dexmedetomidine nasal group were significantly higher than those in the chloral hydrate oral group. The recovery time was significantly shorter (MD=-16.41, 95%CI:-21.54-11.28, P<0.01) and the incidence rate of vomiting (OR=0.04, 95%CI:0.01-0.17, P<0.01) in dexmedetomidine nasal group was significantly lower than those in the chloral hydrate oral group. There was no significant difference in the indicator of sedation onset time (MD=-0.47, 95%CI:-2.71-1.22, P=0.46). Conclusion Compared with the traditional oral chloral hydrate, intranasal dexmedetomidine has a higher sedation success rate and shorter recovery time after sedation with a lower incidence of nausea and vomiting.