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.

Objective:To evaluate the detection capability of the contrast-enhanced three-dimensional turbo spin-echo (CE-SPACE) sequence for brain metastases (BM), aiming to provide evidence for precise target delineation in stereotactic radiotherapy (SRT).Methods:A total of 123 BM patients who received radiotherapy at the Affiliated Cancer Hospital of Zhengzhou University from May to November 2024 were enrolled. All patients underwent contrast-enhanced (CE) MRI and CT scans in the same treatment position, with images rigidly registered in the Eclipse planning system. Two experienced radiation oncologists independently delineated BM lesions on CE-MPRAGE and CE-SPACE sequences in a blinded manner. Patients were divided into the delayed group (10 min, n=61) and a priority group (5 min, n=62) based on the time interval between gadolinium injection and CE-SPACE acquisition. The non-parametric Wilcoxon rank-sum test was used to compare the lesion counts and volume differences between the two imaging sequences. Point-biserial correlation analysis was performed to assess the correlation between the additional lesions identified by CE-SPACE and lesion volume. Results:The overall analysis demonstrated that CE-SPACE detected 421 BM lesions, achieving an 8.2% higher detection rate than CE-MPRAGE ( Z=3.78, P<0.001). In terms of lesion volume, the median BM lesions volume identified by CE-SPACE [0.30(0.07,1.53)cm 3] was 8.7% larger than that by CE-MPRAGE [0.23 (0.04, 1.34) cm 3] ( Z=12.88, P<0.001). CE-SPACE demonstrated superior sensitivity for lesions ≤ 0.06 cm3, with negative correlation between the number of additional lesions detected and lesion volume ( r=-0.104, P=0.034). Subgroup analysis revealed that in the delayed group, CE-SPACE detected significantly more lesions [median 2 (1, 3.5) vs. 2 (1, 3), P=0.002] and larger volumes [0.39 (0.08, 2.24) cm3 vs. 0.29 (0.05, 1.99) cm3, P<0.001] than CE-MPRAGE. In the priority group, CE-SPACE detected significantly larger lesion volumes [0.55 (0.09, 2.06) cm3 vs. 0.45 (0.08, 1.88) cm3, P<0.001], but no significant difference was observed in lesion counts between two sequences ( P=0.059). Conclusions:Three-dimensional CE-SPACE sequence offers superior detection sensitivity for small BM (≤ 0.06 cm3), providing crucial guidance for accurate target delineation in SRT.

Objective:To investigate the expression and clinical significance of angiomotin-like protein 1 (AMOTL1) and downstream related molecules of Hippo signaling pathway yes-associated protein (YAP) and TAZ in different cervical tissues.Methods:From January 2017 and July 2018 ,102 cervical cancer tissues, 50 cervical squamous epithelial high-grade lesions (HSIL) tissues, 45 low-grade lesions (LSIL) tissues and 50 chronic cervicitis tissues, all of which underwent surgical treatment and pathological diagnosis at Xuzhou Medical University Affiliated Hospital from January 2017 to July 2018, were selected. The expression of AMOTL1 and Hippo pathway downstream related proteins YAP and TAZ were evaluated by immunohistochemistry and their relationship with the clinicopathological parameters of cervical cancer were examined in the cervical tissues of each group. The comparison of inter group rates in count data was conducted using the chi square test. Adopting Spearman correlation analysis method to analyze the relationship between AMOTL1, YAP, and TAZ. Single factor survival analysis was performed using Kaplan Meier curves. Kaplan Meier method and multivariate Cox regression analysis were used to investigate the factors affecting the prognosis of cervical cancer patients.Results:The immunohistochemical results showed that the positive rates of AMOTL1 in chronic cervicitis, LSIL, HSIL, and cervical cancer were 12.00% (6/50), 17.78% (8/45), 28.00% (14/50), and 76.47% (78/102), respectively. The positive expression status of AMOTL1 in chronic cervicitis, LSIL, HSIL and cervical cancer were 12.00%(6/50), 17.78%(8/45), 28.00%(14/50), 76.47%(78/102). The positive rates of YAP in chronic cervicitis, LSIL, HSIL, and cervical cancer were 10.00% (5/50), 15.56% (7/45), 30.00% (15/50), and 63.73% (65/102), respectively. The positive expression of YAP in cervical cancer tissues was higher than that in other groups ( χ2=56.66, P<0.001). The positive rates of TAZ in chronic cervicitis, LSIL, HSIL, and cervical cancer were 8.00% (4/50), 17.78% (8/45), 30.00% (15/50), and 71.57% (73/102), respectively. The positive expression of TAZ in cervical cancer tissues was higher than that in other groups ( χ2=74.71, P<0.001), AMOTL1 positive expression is associated with the International Federation of Gynecology and Obstetrics (FIGO) staging ( χ2=16.28, P=0.001), tissue differentiation degree ( χ2=30.16, P<0.001), and lymph node metastasis ( χ2=5.81, P=0.016), YAP positive expression is associated with FIGO staging ( χ2=15.99, P<0.001), differentiation degree ( χ2=25.06, P<0.001), tumor diameter ( χ2=13.63, P=0.003), and lymph node metastasis ( χ2=5.78, P=0.016), and TAZ positive expression is associated with FIGO staging ( χ2=14.49, P<0.001). tissue differentiation degree ( χ2=25.32, P<0.001), and the presence or absence of lymph node metastasis ( χ2=4.95, P=0.026) are related. Spearman correlation analysis showed a positive correlation between AMOTL1 and YAP expression ( r=0.65, P<0.001), and a positive correlation between AMOTL1 and TAZ expression ( r=0.72, P<0.001), There was a positive correlation between YAP and TAZ expression ( r=0.68, P<0.001). Kaplan Meier survival analysis showed that individuals with positive expression of AMOTL1, YAP, and TAZ proteins had shorter survival times than those with negative expression ( χ2 values were 9.84, 8.64, and 18.57, respectively; P values were 0.002, 0.003, and <0.001, respectively). Multivariate Cox regression analysis showed that FIGO staging ( HR=3.18, 95% CI 1.09-9.29, P=0.034), lymph node metastasis ( HR=16.74, 95% CI 3.20-87.45, P=0.010), AMOTL1 positive expression ( HR=13.06, 95% CI 1.41-121.08, P=0.024), and YAP positive expression ( HR=9.75, 95% CI 1.59-59.52, P=0.014) were risk factors for poor prognosis in cervical cancer patients. Conclusion:AMOTL1, YAP, and TAZ may jointly participate in the malignant transformation process of cervical cancer. AMOTL1 and YAP are closely related to prognosis and may become potential prognostic indicators for cervical cancer.

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 value of chest contrast-enhanced CT(C-CECT)combined with artificial intelligence iterative reconstruction(AIIR)for bronchial artery(BA)imaging.Methods Seventy patients who underwent C-CECT were prospectively enrolled.The images were reconstructed with AIIR(AIIR group)and hybrid iterative reconstruction(HIR,HIR group),respectively.The overall image quality,the traceability of BA,the sharpness of BA and the diagnostic confidence of abnormalities of BA were subjectively graded using a 5-point scale by two radiologists,respectively.The subjective scores and inter-observer agreement were compared between groups.The noise(SD)in reconstructed images of thoracic aorta,pulmonary trunk,BA and spinal erectors,the contrast-to-noise ratio(CNR)of the above 3 arteries relative to spinal erectors,and the diameters of BA at the origin,bifurcation and pulmonary hilum were compared between groups.Results The scores of the overall image quality,the traceability of BA,the sharpness of BA and the diagnostic confidence of abnormalities of BA were all significantly higher in AIIR group than those in HIR group(all P＜0.001),all with good inter-observer agreement(Kappa=0.46-0.73).SD of the aorta,pulmonary artery trunk,BA and erector spinal muscle in AIIR group were lower than those in HIR group,while CNR of above 3 arteries were higher than those in HIR group(all P＜0.05).No significant difference of the diameter of BA at each position was found between groups(all P＞0.05),while the consistency of measurement of AIIR group was higher than that of HIR group(intra-class correlation coefficient:0.89-0.94 vs.0.63-0.78).Conclusion C-CECT combined with AIIR could significantly improve imaging quality and diagnostic confidence of BA.

Objective:To investigate the expression and clinical significance of angiomotin-like protein 1 (AMOTL1) and downstream related molecules of Hippo signaling pathway yes-associated protein (YAP) and TAZ in different cervical tissues.Methods:From January 2017 and July 2018 ,102 cervical cancer tissues, 50 cervical squamous epithelial high-grade lesions (HSIL) tissues, 45 low-grade lesions (LSIL) tissues and 50 chronic cervicitis tissues, all of which underwent surgical treatment and pathological diagnosis at Xuzhou Medical University Affiliated Hospital from January 2017 to July 2018, were selected. The expression of AMOTL1 and Hippo pathway downstream related proteins YAP and TAZ were evaluated by immunohistochemistry and their relationship with the clinicopathological parameters of cervical cancer were examined in the cervical tissues of each group. The comparison of inter group rates in count data was conducted using the chi square test. Adopting Spearman correlation analysis method to analyze the relationship between AMOTL1, YAP, and TAZ. Single factor survival analysis was performed using Kaplan Meier curves. Kaplan Meier method and multivariate Cox regression analysis were used to investigate the factors affecting the prognosis of cervical cancer patients.Results:The immunohistochemical results showed that the positive rates of AMOTL1 in chronic cervicitis, LSIL, HSIL, and cervical cancer were 12.00% (6/50), 17.78% (8/45), 28.00% (14/50), and 76.47% (78/102), respectively. The positive expression status of AMOTL1 in chronic cervicitis, LSIL, HSIL and cervical cancer were 12.00%(6/50), 17.78%(8/45), 28.00%(14/50), 76.47%(78/102). The positive rates of YAP in chronic cervicitis, LSIL, HSIL, and cervical cancer were 10.00% (5/50), 15.56% (7/45), 30.00% (15/50), and 63.73% (65/102), respectively. The positive expression of YAP in cervical cancer tissues was higher than that in other groups ( χ2=56.66, P<0.001). The positive rates of TAZ in chronic cervicitis, LSIL, HSIL, and cervical cancer were 8.00% (4/50), 17.78% (8/45), 30.00% (15/50), and 71.57% (73/102), respectively. The positive expression of TAZ in cervical cancer tissues was higher than that in other groups ( χ2=74.71, P<0.001), AMOTL1 positive expression is associated with the International Federation of Gynecology and Obstetrics (FIGO) staging ( χ2=16.28, P=0.001), tissue differentiation degree ( χ2=30.16, P<0.001), and lymph node metastasis ( χ2=5.81, P=0.016), YAP positive expression is associated with FIGO staging ( χ2=15.99, P<0.001), differentiation degree ( χ2=25.06, P<0.001), tumor diameter ( χ2=13.63, P=0.003), and lymph node metastasis ( χ2=5.78, P=0.016), and TAZ positive expression is associated with FIGO staging ( χ2=14.49, P<0.001). tissue differentiation degree ( χ2=25.32, P<0.001), and the presence or absence of lymph node metastasis ( χ2=4.95, P=0.026) are related. Spearman correlation analysis showed a positive correlation between AMOTL1 and YAP expression ( r=0.65, P<0.001), and a positive correlation between AMOTL1 and TAZ expression ( r=0.72, P<0.001), There was a positive correlation between YAP and TAZ expression ( r=0.68, P<0.001). Kaplan Meier survival analysis showed that individuals with positive expression of AMOTL1, YAP, and TAZ proteins had shorter survival times than those with negative expression ( χ2 values were 9.84, 8.64, and 18.57, respectively; P values were 0.002, 0.003, and <0.001, respectively). Multivariate Cox regression analysis showed that FIGO staging ( HR=3.18, 95% CI 1.09-9.29, P=0.034), lymph node metastasis ( HR=16.74, 95% CI 3.20-87.45, P=0.010), AMOTL1 positive expression ( HR=13.06, 95% CI 1.41-121.08, P=0.024), and YAP positive expression ( HR=9.75, 95% CI 1.59-59.52, P=0.014) were risk factors for poor prognosis in cervical cancer patients. Conclusion:AMOTL1, YAP, and TAZ may jointly participate in the malignant transformation process of cervical cancer. AMOTL1 and YAP are closely related to prognosis and may become potential prognostic indicators for cervical cancer.

To summarize the emergency nursing experience of 1 patient with neck suicide complicated with airway obstruction and hemorrhagic shock.Nursing points:to ensure airway safety and establish artificial airway;to optimize airway management and implement early sedation and wake-up;to control injury bleeding and limited fluid resuscitation;to establish a micro blood station in the emergency department and start a high-dose blood transfusion procedure;to carry out the refined target body temperature management to reduce complications;to optimize speech communication strategies and implement early psychological care.After 7 days of careful treatment and nursing,the patient's condition improved and recovered.After 2 months of follow-up,the patient recovered well.

Objective:To explore the choice willingness and related factors of peritoneal dialysis patients regarding automated peritoneal dialysis (APD), in order to provide a basis for future technological improvements and enhancing the application rate of APD.Methods:This was a single-center cross-sectional study. Patients newly initiated on peritoneal dialysis due to end-stage renal disease in the Renal Division, Peking University First Hospital between January 1, 2021 and May 30, 2023 were enrolled. Demographic characteristics, clinical information, and laboratory data were collected. After completing initial training on APD and providing hands-on experience, a self- designed semi-quantitative questionnaire survey was administered to assess patients' willingness to adopt APD and to evaluate potential barriers to its implementation. Factors associated with patients' choice of APD were further analyzed.Results:A total of 203 newly enrolled peritoneal dialysis patients were included in the study, with an age of (53.40±15.86) years, and 57.1% (116 patients) of the participants were male. Among them, 71 patients (35.0%) chose APD, while 132 (65.0%) did not. There were no significant differences in the clinical characteristics between the APD group and the non-APD group (all P>0.05). Compared with the non-APD group, the APD group had a higher proportion of individuals who frequently traveled for business ( χ2=11.442, P<0.001) and a higher proportion with smaller peritoneal cavity volumes ( χ2=5.639, P=0.018). Among patients in the two group, significant differences were observed in self-rated difficulty of APD operation ( χ2=22.291, P<0.001), availability of space for APD setup ( χ2=21.773, P<0.001), 8-hour nocturnal APD treatment ( χ2=17.540, P<0.001), learning difficulty of machine operation ( P<0.001), learning difficulty of machine setting ( P<0.001), impact of APD on sleep ( χ2=6.826, P=0.033), impact of APD on nocturnal urination ( χ2=19.428, P<0.001), and annual cost of APD equipment ( χ2=39.066, P<0.001). Multivariate logistic regression analysis indicated that reimbursement for APD supplies ( OR=3.736, 95% CI 1.655-8.435, P=0.002), with smaller abdominal cavity volume ( OR=58.610, 95% CI 5.000-687.007, P=0.001), the acceptability of 8-hour nocturnal APD treatment ( OR=5.312, 95% CI 1.256-22.461, P=0.023), the low degree of difficulty in learning machine setting ( OR=29.299, 95% CI 2.025-423.812, P=0.013) and the annual cost of accessible APD equipment ( OR=3.643, 95% CI 1.348-9.842, P=0.011) were independent factors associated with patients' choice of APD treatment. Conclusion:Reimbursement for APD supplies, smaller abdominal cavity volume, the acceptability of 8-hour nocturnal APD treatment, the low degree of difficulty in learning machine setting, and the annual cost of accessible APD equipment are the main factors related patients' decision to choose APD treatment.

Objective To investigate the value of chest contrast-enhanced CT(C-CECT)combined with artificial intelligence iterative reconstruction(AIIR)for bronchial artery(BA)imaging.Methods Seventy patients who underwent C-CECT were prospectively enrolled.The images were reconstructed with AIIR(AIIR group)and hybrid iterative reconstruction(HIR,HIR group),respectively.The overall image quality,the traceability of BA,the sharpness of BA and the diagnostic confidence of abnormalities of BA were subjectively graded using a 5-point scale by two radiologists,respectively.The subjective scores and inter-observer agreement were compared between groups.The noise(SD)in reconstructed images of thoracic aorta,pulmonary trunk,BA and spinal erectors,the contrast-to-noise ratio(CNR)of the above 3 arteries relative to spinal erectors,and the diameters of BA at the origin,bifurcation and pulmonary hilum were compared between groups.Results The scores of the overall image quality,the traceability of BA,the sharpness of BA and the diagnostic confidence of abnormalities of BA were all significantly higher in AIIR group than those in HIR group(all P＜0.001),all with good inter-observer agreement(Kappa=0.46-0.73).SD of the aorta,pulmonary artery trunk,BA and erector spinal muscle in AIIR group were lower than those in HIR group,while CNR of above 3 arteries were higher than those in HIR group(all P＜0.05).No significant difference of the diameter of BA at each position was found between groups(all P＞0.05),while the consistency of measurement of AIIR group was higher than that of HIR group(intra-class correlation coefficient:0.89-0.94 vs.0.63-0.78).Conclusion C-CECT combined with AIIR could significantly improve imaging quality and diagnostic confidence of BA.