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: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Humans ; Genome-Wide Association Study ; Sleep Apnea, Obstructive/genetics*

OBJECTIVE: To investigate the cytotoxic effect and its mechanism of the micromolecule compound on the leukemia cells. METHODS: The cytotoxic effects of 28 Nilotinib derivatives on K562, KA, KG, HA and 32D cell lines were detected by MTT assays, and the compound Nilo 22 was screen out. Cell apoptosis and cell cycle on leukemia cells were detected by flow cytometry. The effect of compound screened out on leukemogenesis potential of MLL-AF9 leukemia mice GFP RESULTS: Nilo 22 serves as the most outstanding candidate out of 28 Nilotinib derivatives, which impairs leukemia cell lines, but spares normal hematopoietic cell line. Comparing with Nilotinib, Nilo 22 could induce the apoptosis of GFP CONCLUSION Nilo 22 shows a significant cytotoxic effect on mice and human leukemia cells, especially for drug resistance cells. Nilo 22 is a promising anti-leukemia agent to solve the common clinical problems of drug resistance and relapse of leukemia.
Animals ; Apoptosis/drug effects* ; Cell Cycle/drug effects* ; Cell Line, Tumor ; Humans ; Leukemia ; Mice ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Telomerase/metabolism* ; Telomere/metabolism*

Objective:To explore the effects of Shenwei Ningyu pills （SNP）， a new Chinese medicine for depression， on the immunoinflammatory response mediated by Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88） signaling pathway in the hippocampus of rats exposed to chronic restraint stress （CRS）. Method:Forty-four male Sprague Dawley rats were randomly enrolled into a normal group， a model group， an escitalopram group， and an SNP group. Except for the rats in the normal group， all rats were exposed to CRS and isolated rearing for 21 days continuously. Rats in the escitalopram group and the SNP group were administered with escitalopram （30 mg·kg^-1） and SNP （18 mg·kg^-1） one hour prior to CRS， respectively. The changes in body weight， sucrose preference index， horizontal movement scores， and vertical movement scores were observed by body weight assessment， sucrose preference test， and open field test. The expression of hippocampal TLR4 and MyD88 was detected by Western blot. The content of serum interleukin-1β （IL-1β）， IL-10， and tumor necrosis factor-α （TNF-α） was detected by enzyme-linked immunosorbent assay （ELISA）. Result:The results of the behavioral assessment showed that there was no significant difference in the changes of behavioral baselines among the groups before intervention. However， significant differences were found among the groups following different interventions. The body weight， sugar preference index， horizontal movement score， and vertical movement score of rats in the model group decreased after CRS for 21 days as compared with those in the normal group （P<0.01）. The above indicators in the SNP group and the escitalopram group were higher than those in the model group （P<0.01）， which indicated that SNP exerted an obvious antidepressant effect. The results of Western blot and ELISA showed that compared with the normal group， the model group showed elevated levels of hippocampal TLR4 and MyD88 and serum IL-1β and TNF-α （P˂0.01） and dwindled serum IL-10 （P˂0.01）， while SNP and escitalopram reversed the conditions in the model group （P˂0.01） except for TNF-α. Conclusion:The present study indicated that the antidepressant effect of SNP was presumedly achieved by inhibiting the immunoinflammatory response mediated by the TLR4/Myd88 signaling pathway in CRS rats.

Objective::To compare the protective effect of different bile (porcine bile, oxgall and sheep bile) and their Arisaema cum Bile on rats with acute lung injury, so as to provide reference for the selection of bile and the classification of decoction pieces of Arisaema cum Bile. Method::Wistar male rats were randomly divided into 8 groups (n=12), including blank group, model group, porcine bile group, oxgall group, sheep bile group, Arisaema cum Bile with porcine bile group, Arisaema cum Bile with oxgall group and Arisaema cum Bile with sheep bile group. Rats in each treatment group were given corresponding drug solution by gavage at 2.52 g·kg^-1 every day, and rats in the model group and the blank group were given the same volume of normal saline by gavage every day for a total of 8 days. On the 8^th day, after 1 h of administration, rats in the model group and each treatment group were intraperitoneally injected lipopolysaccharide (LPS, 2 mg·kg^-1) to prepare rat lung injury model. Blood and lung tissues were collected from every four rats at 3, 6, 24 h after LPS injection, respectively. Lung coefficient, lung water content and wet weight/dry weight ratio of lung tissue (W/D) were measured, and the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and thromboxane B₂ (TXB₂) in serum and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the contents of malondialdehyde (MDA) and matrix metalloproteinase-9 (MMP-9) in lung tissue were determined by enzyme linked immunosorbent assay (ELISA). The pathological morphology of rat lung tissue was observed and the score of lung tissue injury was calculated. Result::Compared with the model group at the same time point, the lung coefficient, W/D, lung water content, contents of TNF-α, IL-6 and TXB₂ in serum, contents of MDA and MMP-9 in lung tissue of rats in each treatment group were all decreased, and most of them had significant differences (P<0.05, P<0.01), but the activities of GSH-Px and SOD were all increased, and most of them had significant differences (P<0.05, P<0.01). The oxgall group and the sheep bile group were superior to the porcine bile group in most of the indexes, the Arisaema cum Bile with oxgall group and the Arisaema cum Bile with sheep bile group were superior to the Arisaema cum Bile with porcine bile group, and some of them had significant differences(P<0.05, P<0.01). Conclusion::Each bile group and each Arisaema cum Bile group all have protective effects on rats with acute lung injury induced by LPS, and the therapeutic effect of oxgall and sheep bile is better than that of porcine bile, the therapeutic effect of Arisaema cum Bile prepared by oxgall and sheep bile is better than that of Arisaema cum Bile prepared by porcine bile.