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.

Purpose: Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. Methods: Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection. Results: Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20. Conclusion Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.

Purpose: Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. Methods: Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection. Results: Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20. Conclusion Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.

Purpose: Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. Methods: Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection. Results: Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20. Conclusion Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.

Objectives: . A novel J-shaped anterolateral thigh (ALT) flap reconstruction technique was developed to simultaneously restore swallowing and speech functions in patients following total laryngopharyngectomy. This study aimed to assess the outcomes and surgical complications in patients who underwent J-flap reconstruction over time. Methods: . Patients who underwent J-shaped ALT flap phonatory tube reconstruction were enrolled. Surgical morbidities and outcomes were evaluated every 3 months post-surgery for a period of 12 months or until death. Results: . Of the 36 patients, 13 underwent circumferential pharyngeal wall resection (circumferential defect [CD] group), and 23 underwent partial resection (partial defect [PD] group). After 12 months, 97% of the patients were able to resume oral intake without the need for a nasogastric tube, and 50% achieved fluent speech using the reconstructed phonatory tube. The CD group experienced a higher rate of delayed healing than the PD group (30.8% vs. 0%, p=0.012). Additionally, the PD group showed significantly higher percentages of individuals consuming solid food at both the 3- and 12-month intervals than the CD group (81.0% vs. 23.1% and 78.9% vs. 40%, respectively). Conclusions . This study investigated the progression of speech and swallowing functions over time after reconstruction of the voice tube with a J-flap. Using a J-shaped ALT flap phonatory tube effectively restored both speech and swallowing functions, providing long-term benefits, regardless of whether the defect was circumferential or partial.

Objectives: . A novel J-shaped anterolateral thigh (ALT) flap reconstruction technique was developed to simultaneously restore swallowing and speech functions in patients following total laryngopharyngectomy. This study aimed to assess the outcomes and surgical complications in patients who underwent J-flap reconstruction over time. Methods: . Patients who underwent J-shaped ALT flap phonatory tube reconstruction were enrolled. Surgical morbidities and outcomes were evaluated every 3 months post-surgery for a period of 12 months or until death. Results: . Of the 36 patients, 13 underwent circumferential pharyngeal wall resection (circumferential defect [CD] group), and 23 underwent partial resection (partial defect [PD] group). After 12 months, 97% of the patients were able to resume oral intake without the need for a nasogastric tube, and 50% achieved fluent speech using the reconstructed phonatory tube. The CD group experienced a higher rate of delayed healing than the PD group (30.8% vs. 0%, p=0.012). Additionally, the PD group showed significantly higher percentages of individuals consuming solid food at both the 3- and 12-month intervals than the CD group (81.0% vs. 23.1% and 78.9% vs. 40%, respectively). Conclusions . This study investigated the progression of speech and swallowing functions over time after reconstruction of the voice tube with a J-flap. Using a J-shaped ALT flap phonatory tube effectively restored both speech and swallowing functions, providing long-term benefits, regardless of whether the defect was circumferential or partial.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

The pathogenesis of rheumatoid arthritis patients exerts the features of wind-damp and stasis obstruction,sinew injury and bone damage,therefore,the therapy of dispelling wind and removing dampness,dredging blood vessels,unblocking meridians and collaterals,invigorating spleen and kidney,and strengthening muscles and bones was proposed,hereinafter referred to as Qushi Tongmai method.Under the guidance of Qushi Tongmai method,rheumatoid arthritis can be treated with Chinese medicine based on the modification of empirical formulas such as Kunduan Yimu Formula,Nanxu Yimu Granules and Santeng Shujin Formula,and classical formulas such as Guizhi Shaoyao Zhimu Decoction,Huangqi Guizhi Wuwu Decoction and Banxia Xiexin Decoction according to the deficiency and excess of healthy qi and pathogenic qi as well as the specific symptoms.Moreover,the soft exact,external treatment and functional exercise can be also included.The Chinese medicine therapy combined with the soft exact,external treatment and functional exercise constitutes a unique Chinese medicine system for the prevention and treatment of rheumatoid arthritis.The results of a series of clinical and experimental studies indicated that Qushi Tongmai method exerts efficiency-enhancing and toxin-reducing effect in the treatment of rheumatoid arthritis,and the establishment of Qushi Tongmai method is a theoretical innovation in exerting the advantages of Chinese medicine in the prevention and treatment of rheumatoid arthritis.

Objectives: . A novel J-shaped anterolateral thigh (ALT) flap reconstruction technique was developed to simultaneously restore swallowing and speech functions in patients following total laryngopharyngectomy. This study aimed to assess the outcomes and surgical complications in patients who underwent J-flap reconstruction over time. Methods: . Patients who underwent J-shaped ALT flap phonatory tube reconstruction were enrolled. Surgical morbidities and outcomes were evaluated every 3 months post-surgery for a period of 12 months or until death. Results: . Of the 36 patients, 13 underwent circumferential pharyngeal wall resection (circumferential defect [CD] group), and 23 underwent partial resection (partial defect [PD] group). After 12 months, 97% of the patients were able to resume oral intake without the need for a nasogastric tube, and 50% achieved fluent speech using the reconstructed phonatory tube. The CD group experienced a higher rate of delayed healing than the PD group (30.8% vs. 0%, p=0.012). Additionally, the PD group showed significantly higher percentages of individuals consuming solid food at both the 3- and 12-month intervals than the CD group (81.0% vs. 23.1% and 78.9% vs. 40%, respectively). Conclusions . This study investigated the progression of speech and swallowing functions over time after reconstruction of the voice tube with a J-flap. Using a J-shaped ALT flap phonatory tube effectively restored both speech and swallowing functions, providing long-term benefits, regardless of whether the defect was circumferential or partial.

Background/Aims: Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR). Methods: This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR. Results: The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5–40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7–67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1–62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12–2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21–0.81). Conclusions Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.