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.

AIM:To investigate the effects of electroacupuncture at the Taiyang on refractive parameters and the expression of β-catenin and integrin β1 in the ciliary body of mice with form-deprivation myopia(FDM).METHODS:A total of 48 3-week-old healthy C57BL/6J mice were randomly divided into 4 groups: normal control(NC), FDM group, sham acupuncture(sham), and electroacupuncture at Taiyang acupoint(Taiyang), with 12 mice in each group. Mice in the FDM, sham, and Taiyang groups, wore translucent custom-made eye masks on the right eye to induce myopia. The Taiyang group received electroacupuncture stimulation at the Taiyang acupoint, while the sham group underwent non-penetrating stimulation with a blunt wooden stick. No intervention was performed on the NC group. Refraction and axial length were measured by infrared autorefractor and optical coherence tomography(OCT)before modeling and at 4 wk after modeling. The expression levels of β-catenin and integrin β1 in the ciliary body of mice at 4 wk after modeling were detected using quantitative real-time PCR(qPCR)and Western blotting(WB).RESULTS:After modeling for 4 wk, compared with the NC group, the FDM and sham groups showed significantly decreased refractive power(both P<0.05), elongated axial length(both P<0.05), and increased β-catenin and integrin β1 expression. Compared with the FDM and sham groups, the Taiyang group showed significantly increased refractive power(both P<0.05), shortened axial length(both P<0.05), and decreased β-catenin and integrin β1 expression.CONCLUSION:Electroacupuncture stimulation at the Taiyang acupoint effectively delayed the progression of myopia in FDM mice, and this effect may be partially mediated through modulating the expression of β-catenin and integrin β1 in the ciliary body.

Insulin-like growth factor-1(IGF-1)is a multifunctional growth factor which plays an important role in various physiological and pathological processes of the body by regulating biological behaviors such as cell proliferation, differentiation, and migration. Studies have found that abnormal expression of IGF-1 in the retina, sclera and other eye tissues can participate in the occurrence, development and prognosis of various ophthalmic diseases by regulating retinal autophagy flux and angiogenesis, adipogenic differentiation of orbital soft tissues and degradation of scleral extracellular matrix. This paper systematically integrates the expression level changes and mechanism of action of IGF-1 in ophthalmic diseases such as diabetic retinopathy(DR), age-related macular degeneration(ARMD), retinopathy of prematurity(ROP), Graves' ophthalmopathy, myopia, corneal injury and uveal melanoma(UM), and combines the latest clinical and animal experimental evidence to evaluate the bright prospects and potential risks of IGF-1 targeted therapy, in order to provide new ideas and theoretical basis for the prevention and treatment of ophthalmic diseases.

Objective To investigate the effects of different culture conditions(RPMI-1640,DMEM and DMEM/F12 medium)on the passage of MPM cells isolated from the tissues of Malignant pleural mesothelioma(MPM),and to study the effects of CDKN2B on the proliferation,invasion and apoptosis of MPM cells.Methods MPM cells were isolated from MPM tissues and cultured in RPMI-1640,DMEM and DMEM/F12 medium,respectively.Cell proliferation was examined by CCK-8,and the nuclei and chromosomes were observed by Wright-Giemsa staining.Fluorescence intensities of Calretinin,CD141,CK5,EMA and WT-1 were conducted by immunofluorescence assay.The mRNA and protein expression of CDKN2B were detected by RT-qPCR and Western blot,respectively.Transwell was used to detect cell invasion and flow cytometry was used to detect cell apoptosis.Results The established MPM cells showed good viability when passaged to the 10th generation in RPMI-1640,DMEM and DMEM/F12 cultures,and the MPM markers Calretinin,CD141,CK5,EMA and WT-1 were all expressed in the cells.The viability of MPM cells in RPMI-1640 culture medium was relatively stable.CDKN2B was downregulated in MPM cells(P<0.05),and overexpression of CDKN2B significantly suppressed the proliferation(P<0.05),invasion(P<0.05)and epithelial interstitial transformation of MPM cells(P<0.01),and promoted the apoptosis(P<0.01).Conclusion The established MPM cells were stably passaged in RPMI-1640 culture medium,and CDKN2B may be a potential target for the diagnosis and treatment of MPM.

The aim of this study was to investigate the virulence determinants and genetic diversity of foodborne Yersinia enterocolitica from Wenzhou.A total of 71 strains of Yersinia enterocolitica were isolated from food and foodborne diarrhea ca-ses in Wenzhou,and their biotypes,serotypes,and drug resistance were analyzed.On the basis of whole genome sequencing,we assessed virulence gene profiles,and performed multilocus sequence typing(MLST)and core gene multilocus sequence typ-ing(cgMLST).A total of 94.4％(67/71)of isolates belonged to biotype 1A,and the highest proportion had serotype lA/O∶5(29.6％,21/71).The sensitivity rates of the isolates to 14 antibiotics exceeded 95.8％.A total of 16 categories and 126 viru-lence genes were identified,with two strains carrying the pYV plasmid and chromosome-related virulence genes.ST3(31.6％,12/38)was the most widespread MLST type,and cgMLST analysis revealed no dense clusters of genotypes except for strains sharing the same ST.In conclusion,pathogenic strains were identified from foodborne Yersinia enterocolitica in Wenzhou and were found to exhibit high genetic polymorphism.Enhanced regulatory supervision is essential to prevent the outbreak of food-borne diseases caused by Yersinia enterocolitica.

Objective:The potential mechanism of cortex phellodendri chinsis in the improvement of rheumatoid arthritis (RA) through ferroptosis was analyzed based on network pharmacology.Methods:The main active components and their corresponding target proteins were screened by TCMSP database and Herb database, and the UniProt database was used to convert the corresponding target protein names into gene IDs. The targets of RA disease were obtained from GenCards, OMIM, DrugBank and DisGeNET databases. The FerrDb database was used to collect genes for Driver, Suppressors and Markers of ferroptosis. Then, Venny platform was used to obtain the intersection genes of Cortex phellodendri chinsis, RA and ferroptosis, and Cytoscape 3.9.1 software was used to plot the "active component-target-RA-ferroptosis" network diagram. Protein-protein interaction (PPI), gene ontology (GO) function, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using String and DAVID databases. PyMOL, AutoDock Vina software and RCSB PDB database were used for molecular docking between active ingredients and key genes.Results:A total of 11 active components (Quercetin, Beta-sitosterol, Melianone, Candletoxin A, Phellochin, Palmidin A, Worenine, Hispidone, Kihadalactone A, Niloticin, Stigmasterol) and 34 intersection genes (PTGS2、AR、JUN、PRKCA、TGFB1、EGFR、CDKN1A、MAPK1、RB1、IL6、TP53、HIF1A、HSPA5、HMOX1、CAV1、IFNG、ALOX5、PTEN、NFE2L2、PARP1、PPARA、GSTM1、MTOR、PIK3CA、MDM2、MAPK8、GSK3B、SIRT1、DHODH、EZH2、AKR1C2、AKR1C1、STAT3、MAPK3) were screened. Ten possible targets of Cortex phellodendri chinsis regulating ferroptosis and anti-RA were predicted, including TP53、JUN、STAT3、HIF1A、PTEN、SIRT1、EGFR、MTOR、MAPK3、AR. Ferroptosis pathway is regulated by mediating positive regulation of gene expression, response to drugs, HIF-1, FoxO, ErbB and other signaling pathways, thus combating the occurrence and progression of RA. The docking results showed that there were molecular binding sites between the key genes and their corresponding active components.Conclusion:Cortex phellodendri chinsis may treat RA through ferroptosis effect with multiple components, multiple targets, multiple pathways and mechanisms.

Objective:To explore the potential impact of lipid metabolism-related single nucleotide polymorphisms(SNP)on semen quality in men.Methods:We selected 284 semen samples from Xingtai Infertility Hospital and Hebei Human Sperm Bank collected between February and October 2023,33 from oligozoospermia(OS),97 from asthenozoospermia(AS)and 54 from oligoas-thenozoospermia(OAS)patients and the other 100 from normal men.We performed computer-assisted semen analysis(CASA)of the samples,extracted blood DNA and,using the Mass ARRAY? System,genotyped the target genes,determined the genotypes of 13 SNPs and compared their distribution,their correlation with BMI and semen quality in different groups.Results:The mutant homozygous(TT)genotype of the FADS2 rs2727270 gene seemed to be a risk factor for AS(OR=4.420,P=0.047),while the APOA2 rs5082-A allele and MC4R rs17782313 heterozygous(TC)genotype important protective factors for OS(OR=0.422 and 0.389;P=0.045 and 0.043,respectively).A significantly higher sperm concentration was found associated with the MC4R rs17782313 heter-ozygous(TC)genotype than with the homozygous(CC)genotype.Stratification analysis showed that the protective effect of the TC genotype was decreased with increased BMI and remained with the interaction of the rs5082 and rs17782313 genotypes.Conclusion:FADS2 rs2727270,APOA2 rs5082 and MC4R rs17782313 were significantly correlated with the risk of abnormal semen parameters.

Glyceryl phenylbutyrate(GPB)serves as a long-term management medication for Ornithine transcarbamylase deficiency(OTCD),effectively controlling hyperammonemia,but there is a lack of experience in using this medicine in China.This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,including a review of related literature.After diagnosis,the patient was treated with GPB,followed by efficacy follow-up and pharmacological monitoring.The 6-year and 6-month-old male patient exhibited poor speech development,disobedience,temper tantrums,and aggressive behavior.Blood ammonia levels peaked at 327 μmol/L;urine organic acid analysis indicated elevated uracil levels;cranial MRI showed extensive abnormal signals in both cerebral hemispheres.Genetic testing revealed de novo mutation in the OTC gene(c.241T＞C,p.S81P).Blood ammonia levels were approximately 43,80,and 56 μmol/L at 1,2,and 3 months after starting GPB treatment,respectively.During treatment,blood ammonia was well-controlled without drug-related adverse effects.The patient showed improvement in developmental delays,obedience,temperament,and absence of aggressive behavior.

Objectives:To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC).Methods:A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared.Results:There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant ( P＜0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant ( P＜0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions:Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.

Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85％of all cancer cases in the country.Several guidelines have been used to diagnose and treat liver cancer.However,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual patients.Therefore,it is necessary to establish a comprehensive and practical expert consensus,specifically for China,to enhance the diagnosis and treatment of HCC using the Delphi method.The classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were developed.These recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment prognosis.The findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.