ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

OBJECTIVE To predict biomarkers of type 2 inflammation in chronic rhinosinusitis with nasal polyps(CRSwNP)by employing peripheral blood indicators.METHODS CRSwNP patients admitted to the Rhinology Department of Beijing Tongren Hospital from June 2020 to May 2022 were enrolled and their basic clinical data were collected.The blood percentage of eosinophils(Eos%),Eos count,periostin and total IgE,as well as mucosal interleukin-5(IL-5)and Staphylococcus aureus enterotoxin-immunoglobulin E(SE-IgE)were tested.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of each blood indicator for positive mucosal expression of IL-5/SE-IgE.The logistic regression was employed to screen multiple blood indicators with predictive value for positive mucosal expression of IL-5/SE-IgE in order to construct a nomogram model.RESULTS The proportion of asthma,blood Eos%,periostin and total IgE in CRSwNP patients showed statistical differences between IL-5/SE-IgE positive and negative subgroups.ROC univariate analysis demonstrated that blood Eos%,Eos count,periostin and total IgE could predict mucosal IL-5 positivity with AUC ranging from 0.655 to 0.784,and mucosal SE-IgE positivity with AUC ranging from 0.721-0.802.The logistic regression confirmed that blood Eos%and total IgE,as well as blood periostin and total IgE were independent predictors for mucosal IL-5 and SE-IgE positivity,respectively.The nomogram models were constructed for predicting IL-5/SE-IgE positivity in CRSwNP mucosa,with consistency incides(C-index)of 0.804 and 0.81,indicating good predictive accuracy.CONCLUSION The nomograms constructed based on blood Eos%and total IgE,as well as blood periostin and total IgE,could have good predictive value for the positive mucosal expression of IL-5 and SE-IgE in the CRSwNP,which help to predict the severity of endotype and phenotype of CRSwNP.

Child ; Humans ; Adenoids/surgery* ; Hypertrophy/surgery*

Objective    To analyze the influencing factors for re-positive nucleic acid test in discharged corona-virus disease 2019 (COVID-19) patients in Chengdu, Sichuan Province, and to provide data support for the epidemics prevention and control. Methods    The clinical data of 660 discharged COVID-19 patients from January 23, 2020 to February 28, 2021 in our center were retrospectively analyzed. The patients were divided into two groups according to the reexamination of virus nucleic acid, including a negative group [549 patients, including 428 males and 121 females with a median age of 33.0 (28.0, 48.0) years] and a positive group [111 patients, including 76 males and 35 females with a median age of 39.0 (28.0, 51.0) years]. The clinical data of the two groups were compared. Results     The re-positive rate of the discharged patients was 16.82%. Univariate analysis showed that the re-positive rate of females was higher than that of males (χ2=4.608, P=0.032). The re-positive rate of confirmed patients was higher than that of asymptomatic infected patients (χ2=8.140, P=0.004). The re-positive rate of domestic patients was higher than that of imported patients (χ2=9.178, P=0.002). The counts of CD3+ (P=0.038), CD4+ (P=0.048) and CD8+ (P=0.040) T lymphocytes in the negative group were higher than those in the positive group. The binary logistic regression analysis showed that the clinical classification and CD8+ T lymphocyte count were independent risk factors affecting the recurrence of virility. Conclusion    The gender, origin, T lymphocyte subsets count and clinical type are the influencing factors for re-positive result, and clinical type and CD8+ T lymphocyte count are the independent influencing factors for re-positive result. Therefore, improving the immunity of infected patients, as well as early detection and timely treatment are effective means to reduce the re-positive occurrence.

Objective: To analyze the phenotypic-genotypic characteristics of hereditary deafness caused by OTOA gene variations. Methods: Family histories, clinical phenotypes and gene variations of six pedigrees were analyzed, which were diagnosed with hearing loss caused by OTOA gene variations at the PLA General Hospital from September 2015 to January 2022. The sequence variations were verified by Sanger sequencing and the copy number variations were validated by multiplex ligation-dependent probe amplification (MLPA) in the family members. Results: The hearing loss phenotype caused by OTOA variations ranged from mild to moderate in the low frequencies, and from moderate to severe in the high frequencies in the probands, which came from six sporadic pedigrees, among which a proband was diagnosed as congenital deafness and five were diagnosed as postlingual deafness. One proband carried homozygous variations and five probands carried compound heterozygous variations in OTOA gene. Nine pathogenic variations (six copy number variations, two deletion variations and one missense variation) and two variations with uncertain significance in OTOA were identified in total, including six copy number variations and five single nucleotide variants, and three of the five single nucleotide variants were firstly reported [c.1265G>T(p.Gly422Val),c.1534delG(p.Ala513Leufs*11) and c.3292C>T(p.Gln1098fs*)]. Conclusions: OTOA gene variations can lead to autosomal recessive nonsyndromic hearing loss. In this study, the hearing loss caused by OTOA defects mostly presents as bilateral, symmetrical, and postlingual, and that of a few presents as congenital. The pathogenic variations of OTOA gene are mainly copy number variations followed by deletion variations and missense variations.
Humans ; DNA Copy Number Variations ; Hearing Loss, Sensorineural/genetics* ; Deafness/genetics* ; Hearing Loss/genetics* ; Phenotype ; Genotype ; Nucleotides ; Pedigree ; Mutation ; GPI-Linked Proteins/genetics*

Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.
Humans ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; Facial Paralysis/etiology* ; Diagnosis, Differential ; Jugular Foramina ; Retrospective Studies ; Cough ; Hoarseness ; Neoplasm Recurrence, Local ; Chondrosarcoma/surgery*

Objective:To analyze the effects of different dose calculation grid size of Monaco system on the physical and biological dosimetry of target area and organ at risk (OAR) in T 4 nasopharyngeal carcinoma. Methods:A total of 18 patients with stage T 4 nasopharyngeal carcinoma who received radiotherapy in the Department of Radiotherapy of Yunnan Cancer Hospital from October 2020 to April 2022 were selected to complete the delineation of target areas and OAR in the Monaco 5.11.03 system, and the volumetric intensity modulated arc therapy (VMAT) plan was developed on the 3 mm grid with the optimization mode of target area priority. The 3 mm grid group plan was replicated without changing any other parameters, and the physical plan was re-established on the 1, 2, 4 and 5 mm grids, and then the five plans were normalized to the prescription dose to cover 95% of the target volume. The planning time, D 2%, D 50%, D 98%, conformity index (CI), homogeneity index (HI), gradient index (GI), tumor control probability (TCP), D 2% and D mean of important OAR around the target area were calculated and statistically analyzed. Results:Planning primary tumor gross target volume (PGTVp) : The D 2% of 1, 2, 3, 4 and 5 mm groups were (76.94±0.66), (75.98±0.76), (75.56±0.67), (75.67±0.73) and (75.94±0.85) Gy, respectively, with a statistically significant difference ( F=9.86, P<0.001). The CI of 1, 2, 3, 4 and 5 mm groups were 0.75±0.05, 0.78±0.04, 0.78±0.05, 0.79±0.04 and 0.78±0.04, respectively, with a statistically significant difference ( F=2.61, P=0.041). There were statistically significant differences in D 50%, D 98%, HI, equivalent uniform dose (EUD) and tumor control probability (TCP) among the groups ( H=17.14, P=0.002; F=9.35, P<0.001; H=25.43, P<0.001; F=5.85, P<0.001; H=17.65, P=0.001). There was no statistically significant difference in GI among the groups ( P>0.05). Pairwise comparison showed that D 2% in 2, 3, 4, 5 mm groups compared with 1 mm group, D 50% in 5 mm group compared with 2, 3 mm groups, D 98% in 4 mm group compared with 1, 2 mm groups, D 98% in 5 mm group compared with 1, 2, 3 mm groups, CI in 5 mm group compared with 1 mm group, HI in 2, 3, 4, 5 mm groups compared with 1 mm group, EUD in 3 mm group was compared with 1 mm group, EUD in 5 mm group compared with 2, 3 mm groups, TCP in 3 mm group compared with 1 mm group, and TCP in 5 mm group compared with 3 mm group, there were statistically significant differences (all P<0.05). Planning nodal gross target volume (PGTVn) : The D 2% of 1, 2, 3, 4 and 5 mm groups were (76.36±0.59), (75.36±0.62), (75.04±0.68), (75.25±0.72) and (75.39±0.77) Gy, respectively, with a statistically significant difference ( F=10.32, P<0.001). The HI of 1, 2, 3, 4 and 5 mm groups were 1.08 (1.08, 1.08), 1.07 (1.06, 1.07), 1.06 (1.06, 1.07), 1.06 (1.06, 1.07), 1.06 (1.06, 1.07), 1.06 (1.06, 1.08), respectively, with a statistically significant difference ( H=22.00, P<0.001) ; There were statistically significant differences in D 50%, D 98% and EUD among the groups ( H=11.79, P=0.019; H=20.49, P<0.001; F=12.14, P=0.016). Pairwise comparison showed that there were statistically significant differences in D 2% between 2, 3, 4, 5 mm groups and 1 mm group, D 98% between 4 mm group and 1 mm group, D 98% between 5 mm group and 1, 2 mm groups, HI between 2, 3, 4 mm groups and 1 mm group, and EUD between 3 mm group and 1 mm group (all P<0.05). Planning primary tumor clinical target volume 1 (PCTVp1) : The D 2% of 1, 2, 3, 4 and 5 mm groups were (76.59±0.63), (75.64±0.65), (75.64±0.98), (75.41±0.70) and (75.71±0.84) Gy, respectively, with a statistically significant difference ( F=9.53, P<0.001). The D 50% of 1, 2, 3, 4, 5 mm groups were (72.09±0.34), (71.85±0.39), (71.82±0.45), (72.04±0.56), (72.43±0.66) Gy, respectively, with a statistically significant difference ( F=4.20, P=0.019). There was no statistically significant difference in the other indexes among the groups (all P>0.05). Pairwise comparison showed that there were statistically significant differences in D 2% between 2, 3, 4, 5 mm groups and 1 mm group, and in D 50% between 2, 3 mm groups and 1 mm group (all P<0.05). Planning nodal clinical target volume 1 (PCTVn1) : There were no statistically significant differences in all indexes among the groups (all P>0.05). Planning clinical target volume 2 (PCTV2) : The D 2% of 1, 2, 3, 4 and 5 mm groups were (75.57±0.50), (74.87±0.67), (74.51±0.51), (74.61±0.63) and (75.00±0.74) Gy, respectively, with a statistically significant difference ( F=8.27, P<0.001). Pairwise comparison showed that the D 2% of the 2, 3, 4 mm groups were significantly different from that of the 1 mm group (all P<0.05). The calculation time of physical plan in 1, 2, 4 and 5 mm groups was 987.00 (848.00, 1 091.00), 120.50 (99.75, 134.00), 26.00 (24.00, 34.25) and 21.50 (18.75, 34.75) s, respectively, with a statistically significant difference ( H=61.62, P<0.001). Pairwise comparison showed that there were statistically significant differences in the calculation time between 4 mm group and 1, 2 mm groups, 5 mm group and 1, 2 mm groups (all P<0.05). There was no statistically significant difference in the dosimetric parameters of OAR around the target area among the groups (all P>0.05) . Conclusion:The physical dose and biological dose of the important OAR around the target area and the target area change with the change of dose calculation grid size when formulating the physical plan of radiotherapy for T 4 nasopharyngeal carcinoma. Considering the quality of the physical plan and the calculation time, when the Monaco system formulates the VMAT plan for T 4 nasopharyngeal carcinoma patients, the plan can be optimized on the 3 mm computing grid and copied to the 1 mm computing grid for recalculation.

Objective: To explore the effect of vaccination on viral negative conversion of children with COVID-19. Methods: A retrospective cohort study was conducted. A cohort of 189 children aged 3-14 years with COVID-19 admitted to Renji Hospital (South branch) of Shanghai Jiao Tong University School of Medicine from April 7^th to May 19^th 2022 was enrolled in the study. According to the vaccination status, the infected children were divided into an unvaccinated group and a vaccinated group. Age, gender, severity, clinical manifestations, and laboratory tests, etc. were compared between groups, by rank sum test or chi-square test. The effects of vaccination on viral negative conversion were analyzed by a Cox mixed-effects regression model. Additionally, a questionnaire survey was conducted among the parents of unvaccinated children to analyze the reasons for not being vaccinated. Results: A total of 189 children aged 3-14 years were enrolled, including 95 males (50.3%) and 94 females (49.7%), aged 5.7 (4.1,8.6) years. There were 117 cases (61.9%) in the unvaccinated group and 72 cases (38.1%) in the vaccinated group. The age of the vaccinated group was higher than that of the unvaccinated group (8.8 (6.8, 10.6) vs. 4.5 (3.6, 5.9) years, Z=9.45, P<0.001). No significant differences were found in clinical manifestations, disease severity, and laboratory results between groups (all P>0.05), except for the occurrence rate of cough symptoms, which was significantly higher in the vaccinated group than in the non-vaccinated group (68.1% (49/72) vs. 50.4% (59/117),χ²=5.67, P=0.017). The Kaplan-Meier survival curve and Cox mixed-effects regression model showed that the time to the viral negative conversion was significantly shorter in the vaccinated group compared with the unvaccinated group (8 (7, 10) vs. 11 (9, 12) d, Z=5.20, P<0.001; adjusted HR=2.19 (95%CI 1.62-2.97)). For questionnaire survey on the reasons for not receiving a vaccination, 115 questionnaires were distributed and 112 valid questionnaires (97.4%) were collected. The main reasons for not being vaccinated were that parents thought that their children were not in the range of appropriate age for vaccination (51 cases, 45.5%) and children were in special physical conditions (47 cases, 42.0%). Conclusion: Vaccination can effectively shorten the negative conversion time of children with COVID-19 and targeted programs should be developed to increase eligible children's vaccination rate for SARS-CoV-2 vaccination.
Child ; Female ; Male ; Humans ; COVID-19/prevention & control* ; COVID-19 Vaccines ; Retrospective Studies ; SARS-CoV-2 ; China/epidemiology* ; Vaccines

Objective: The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases. Methods: A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up. Results: Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases. Conclusions Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients.
COVID-19/complications* ; Follow-Up Studies ; Humans ; Olfaction Disorders/etiology* ; Pandemics ; Prospective Studies ; SARS-CoV-2

Fingerprints of 18 batches of substance benchmark of Shentong Zhuyu Decoction(SZD) were established by UPLC under the following conditions: Waters Sun Fire C_(18) column(3.0 mm×150 mm, 3.5 μm), column temperature of 35 ℃, gradient elution with mobile phase of acetonitrile(A)-0.1% phosphoric acid aqueous solution(B) at the flow rate of 0.4 mL·min~(-1), and detection by wavelength switching. A total of 16 common peaks were identified. The similarities among the fingerprints were calculated by Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 Edition) and the result showed they were in the range of 0.911-0.988. Based on the 16 common peaks, cluster analysis(CA), principal component analysis(PCA), and partial least square discriminant analysis(PLS-DA) all categorized the 18 batches of samples into two groups(S1, S2, S5-S8, S14, and S17 in one group, and S1, S2, S5-S8, S14, and S17 in another), and 11 most influential components were screened. Five known components with great difference among samples(hydroxysafflor yellow A, ferulic acid, benzoic acid, ecdysone, and ammonium glycyrrhizinate) were determined. The combination of multi-component content determination and fingerprints can reflect the overall cha-racteristics of the primary standards of SZD, which is simple, feasible, reproducible, and stable. This study can serve as a reference for the quality control of the primary standards of SZD.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/standards* ; Quality Control