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.

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 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.

Objective    To study the safety of right vertical infra-axillary thoracotomy (RVIAT) in the repair of ventricular septal defect (VSD) and the optimal age for RVIAT. Methods    Between June 2014 and June 2018, 441 children underwent VSD repair via RVIAT in our hospital. According to the age, they were divided into four groups: a 4 months to 1 year old group (R1 group, n=123), a 1-2 years old group (R2 group, n=106), a 2-5 years old group (R3 group, n=166), a >5 years old group (R4 group, n=46). The clinical effects of the patients were compared. Results    All the operations were successfully performed and no serious complication was found in all groups. No statistical difference was observed in the operation time, blood loss during operation, thoracic drainage 24 h after operation among groups (P>0.05). The cardiopulmonary bypass time, aortic cross-blocking time and ICU stay time in the R1 and R2 groups were longer than those in the R3 and R4 groups (P<0.05). In the R1 group, the postoperative ventilating time and postoperative hospital stay time were longer, and the blood transfusion volume was more than those in the R3 and R4 groups (P<0.05). The incidence of postoperative complications was higher in the R4 group than that in the R1 and R3 groups (P<0.05). Conclusion    VSD repair via RVIAT may be more effective in children >2 years old, and 2-5 years old may be the optimal age.

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.

Objective: To investigate the association between genetic variation of kinase insert domain receptor (KDR) and the prognosis in colorectal cancer (CRC) patients received 5-FU based adjuvant chemotherapy. Methods: The clinical data of 176 CRC patients, who underwent surgical treatment at the Department of Anus and Intestine Surgery, People’s Hospital of Zhengzhou during January 2012 and December 2017, were retrospectively analyzed, and 93 cases of tumor tissues were collected for this study. The genotype of KDR polymorphism locus was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). qPCR was used to detect the expression of KDR mRNAin colorectal cancer tissues. The correlation between the polymorphism genotypes and other variables was analyzed by logistic regression model. The expression of different genotypes of KDR was analyzed by nonparametric test. The relationship between KDR genotype and prognosis of patients was analyzed by Kaplan-Meier survival analysis, and the other variables were adjusted by Cox risk scale model. Results: Of the polymorphisms analyzed, only rs2071559 was of clinical significance. The distribution frequency of KDR rs2071559 in 176 CRC patients was as follows: TT genotype in 95 cases (53.98%), TC genotype in 70 cases (39.77%) and CC genotype in 11 cases (6.25%); the minor allele frequency was 0.26; and the distribution of three genotypes was in accordance with Hardy-Weinberg's Equilibrium (P=0.690). The median disease free survival (mDFS) of patients carrying C allele and wild type TT genotype was 4.4 and 3.2 years, respectively (P<0.05); The median overall survival (mOS) of patients with TC/CC genotype and TT genotype was 5.2 and 4.0 years, respectively (P<0.05). After COX model modification, the effect of TC/CC genotype on mOS was still statistically significant (OR=0.55, P<0.05). The mRNA expression of KDR in cancer tissues of the patients with TC/CC genotypes were significantly lower than those of the wild type TT genotype (P<0.01). Conclusion: The polymorphism of KDR rs2071559 is associated with clinical outcomes in patients with colorectal cancer. KDR rs2071559 may affect the prognosis of colorectal cancer patients by affecting the mRNAexpression of KDR.

OBJECTIVE: Improve the integrity of the digestive electron microscope equipment and reduce the cost of equipment failure maintenance. METHODS: By studying the composition and function of the digestive electron microscope system and analyzing the causes of common faults, a targeted preventive maintenance plan is developed, equipment users are graded, and a training system is established. RESULTS: The user of the device can skillfully analyze the cause of the malfunction and timely deal with the sudden failure of the diagnosis and treatment, thereby reduce the risk of diagnosis and treatment and the investment in hospital maintenance. CONCLUSIONS Through the analysis and processing of the digestive electron microscope system, point detection leakage, grading training, preventive maintenance can significantly improve the equipment integrity rate, reduce the risk of clinical diagnosis and treatment, effectively reduce the number of equipment failures, and reduce maintenance costs.
Equipment Failure ; Maintenance and Engineering, Hospital ; Microscopy, Electron ; instrumentation

OBJECTIVETo investigate the expression of miR-29b in cholangiocarcinoma and explore its effects on cell proliferation and apoptosis of cholangiocarcinoma cells.

METHODSReal-time PCR was used to detect the expression of miR-29b in cholangiocarcinoma cells line QBC939 and cholangiocarcinoma tissues. The lentiviral vector LV-hsa-miR-29b and blank vector were constructed to infect QBC939 cells. MTT assay and cell clone formation assay were performed to assess the changes in the cell proliferation and clone formation, respectively; flow cytometry was employed to evaluate the effect of miR-29b overexpression on cell cycle and apoptosis.

RESULTSThe expression of miR-29b was significantly down-regulated in QBC939 cells and cholangiocarcinoma tissues as compared with H-69 cells and normal tissues ( < 0.01). Compared with the blank vector, the lentiviral vector LV-hsa-miR-29b caused significantly increased expression of miR-29b in QBC939 cells ( < 0.01), which exhibited suppressed cell proliferation and clone formation ( < 0.01 or 0.05), cell cycle arrest at the S phase ( < 0.05), and significantly increased cell apoptosis ( < 0.01).

CONCLUSIONSAs a tumor-suppressing miRNA, miR-29b is down-regulated in cholangiocarcinoma, and its overexpression can suppress the proliferation and induce apoptosis of cholangiocarcinoma cells.

China ; Depressive Disorder, Major ; genetics ; Humans ; Polymorphism, Single Nucleotide ; Sirtuin 1 ; genetics