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 analyze the monitoring data of cardio-cerebrovascular diseases prevention and control system in Yichang in 2022, and to provide data support and experience for the precise prevention and treatment of cardio-cerebrovascular diseases. Methods Acute cardiovascular and cerebrovascular event data were collected from the Yichang Cardio-cerebrovascular Events Monitoring System from January 1, 2022 to December 31, 2022. Descriptive analysis was conducted for the data collected. Statistical analysis was performed using SPSS 20.0 software, and a chi-square test was used to analyze the count data. Results A total of 37,217 cases of cardio-cerebrovascular events were monitored in Yichang in 2022. The crude incidence and the standardized incidence were 983.84/100,000 and 541.55/100,000, respectively. The incidence in males was higher than females (554.93/100,000 vs 428.91/100,000，χ² =464.52，P＜0.05). The top three diseases were cerebral infarction, acute myocardial infarction, and cerebral hemorrhage. The incidence of events increased with age, and 79.80% of the cases were over 60 years old. The main onset time was from May to August. Conclusion The use of the cardio-cerebrovascular events monitoring system in Yichang and the implementation of ^“mandatory reporting card^” monitoring can timely obtain the epidemic characteristics of the diseases, provide support for the precise formulation of prevention and control strategies and measures, reduce underreporting rates, and improve the monitoring system, which is worthy of reference and promotion.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective To investigate the characteristics of TCM constitution distribution in hepatitis B cirrhosis patients with dysplastic nodules(DN),and to provide a basis for the prevention and treatment of precancerous lesions of liver cancer.Methods This study was conducted among 113 hepatitis B cirrhosis patients with DN,105 hepatitis B cirrhosis patients with regenerative nodules(RN),and 70 hepatitis B cirrhosis patients with small hepatocellular carcinoma(sHCC)who were hospitalized in Guangdong Provincial Hospital of Traditional Chinese Medicine from May 2015 to March 2023.Related data were collected,including age,sex,liver function Child-Pugh class,TCM constitution type,and laboratory markers.A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups;the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups;the chi-square test was used for comparison of categorical data between groups,and the Bonferroni correction method was used for further comparison between two groups.Results The main TCM constitution types of hepatitis B cirrhosis patients with DN were Qi-deficiency constitution(27 patients,23.89%),blood-stasis constitution(26 patients,23.01%),and phlegm-dampness constitution(23 patients,20.35%).There were significant differences between the three groups in the proportion of patients with phlegm-dampness constitution or damp-heat constitution(&chi;2=6.822 and 6.383,both P<0.05);the hepatitis B cirrhosis patients with RN had the highest proportion of patients with phlegm-dampness constitution(30.48%),followed by those with DN(20.35%)and those with sHCC(14.29%),while the hepatitis B cirrhosis patients with sHCC had the highest proportion of patients with damp-heat constitution(27.14%),followed by those with DN(16.81%)and those with RN(12.38%).There were significant differences between the hepatitis B cirrhosis DN patients with different TCM constitution types in sex,age,Child-Pugh class,prealbumin,albumin(Alb),aspartate aminotransferase,total bilirubin(TBil),total bile acid,and alpha-fetoprotein(all P<0.05).Compared with the male hepatitis B cirrhosis DN patients,female patients showed a significantly higher proportion of patients with Qi-deficiency constitution(&chi;2=4.895,P=0.027).Among the patients with Qi-deficiency constitution,the patients with Child-Pugh class A liver function accounted for a significantly lower proportion than those with Child-Pugh class B liver function(&chi;2=6.380,P=0.012),while among the patients with phlegm-dampness constitution,the patients with Child-Pugh class A liver function accounted for a significantly higher proportion than those with Child-Pugh class B liver function(&chi;2=8.515,P=0.004).The patients with phlegm-dampness constitution had significantly higher levels of prealbumin and Alb than those with the other four constitutions(all P<0.05),as well as significantly lower levels of TBil and total bile acid than those with damp-heat constitution(P<0.05);the patients with Yin-deficiency constitution had a significantly lower level of Alb than those with qi-deficiency constitution,blood-stasis constitution,or phlegm-dampness constitution(all P<0.05);the patients with Yin-deficiency constitution had a significantly lower proportion of patients with abnormal alpha-fetoprotein than those with non-Yin-deficiency constitutions(&chi;2=4.448,P=0.035).Conclusion Hepatitis B cirrhosis patients with DN mainly have the TCM constitution types of Qi deficiency,blood stasis,and phlegm dampness.The patients with phlegm-dampness constitution seem to have a low probability of carcinogenesis,while those with damp-heat constitution and Yin-deficiency constitution have a relatively high risk of carcinogenesis.

Objective To construct secretory IgA(sIgA)based on the previously screened IgG neutralizing antibody ZW2G10 against SARS-CoV-2,evaluate its activity and find out about the biodistribution of sIgA in ICR mice after nasal administration.Methods After expression,purification,and identification,sIgA was evaluated for its binding and neutralizing activity through ELISA and pseudovirus-based neutralization assays.SIgA was coupled with Alexa Fluor 750 dye and administered to mice via nasal administration.In vivo imaging was used to observe the biodistribution of sIgA.After dissection of the mice,the biodistribution of sIgA in various tissues and organs was observed.Results Compared with IgG,sIgA retained the binding ability to SARS-CoV-2 S proteins,and its neutralizing ability was enhanced.After nasal administration of a single dose of 1 mg/kg,sIgA could be retained in the lungs of mice for more than 72 hours.SIgA could be detected only in the nasal cavity and gastrointestinal tract within 8 h of administration,but not in the heart,liver,kidney,spleen,brain,bladder or blood.Conclusion In this study,a universal and efficient sIgA expression system has been established.sIgA can effectively target the respiratory tract and lungs after nasal administration.SIgA is expected to become a potential drug that provides immediate passive immune protection.

Objective: We aimed to investigate whether 2-[ 18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[ 18F]FDG PET/CT) can aid in evaluating the risk of malignancy in ampullary tumors detected by endoscopy. Materials and Methods: This single-center retrospective cohort study analyzed 155 patients (79 male, 76 female; mean age, 65.7 ± 12.7 years) receiving 2-[ 18F]FDG PET/CT for endoscopy-detected ampullary tumors 5–87 days (median, 7 days) after the diagnostic endoscopy between June 2007 and December 2020. The final diagnosis was made based on histopathological findings. The PET imaging parameters were compared with clinical data and endoscopic features. A model to predict the risk of malignancy, based on PET, endoscopy, and clinical findings, was generated and validated using multivariable logistic regression analysis and an additional bootstrapping method. The final model was compared with standard endoscopy for the diagnosis of ampullary cancer using the DeLong test. Results: The mean tumor size was 17.1 ± 7.7 mm. Sixty-four (41.3%) tumors were benign, and 91 (58.7%) were malignant. Univariable analysis found that ampullary neoplasms with a blood-pool corrected peak standardized uptake value in earlyphase scan (SUVe) ≥ 1.7 were more likely to be malignant (odds ratio [OR], 16.06; 95% confidence interval [CI], 7.13–36.18;P < 0.001). Multivariable analysis identified the presence of jaundice (adjusted OR [aOR], 4.89; 95% CI, 1.80–13.33; P = 0.002), malignant traits in endoscopy (aOR, 6.80; 95% CI, 2.41–19.20; P < 0.001), SUVe ≥ 1.7 in PET (aOR, 5.43; 95% CI, 2.00–14.72; P < 0.001), and PET-detected nodal disease (aOR, 5.03; 95% CI, 1.16–21.86; P = 0.041) as independent predictors of malignancy. The model combining these four factors predicted ampullary cancers better than endoscopic diagnosis alone (area under the curve [AUC] and 95% CI: 0.925 [0.874–0.956] vs. 0.815 [0.732–0.873], P < 0.001). The model demonstrated an AUC of 0.921 (95% CI, 0.816–0.967) in candidates for endoscopic papillectomy. Conclusion Adding 2-[ 18F]FDG PET/CT to endoscopy can improve the diagnosis of ampullary cancer and may help refine therapeutic decision-making, particularly when contemplating endoscopic papillectomy.

Child ; Humans ; Manometry ; Esophagus/physiology*

Objective: To document the anatomical structure of the area anterior to the anorectum passing through the levator hiatus between the levator ani slings bilaterally. Methods: Three male hemipelvises were examined at the Laboratory of Clinical Applied Anatomy, Fujian Medical University. (1) The anatomical assessment was performed in three ways; namely, by abdominal followed by perineal dissection, by examining serial cross-sections, and by examining median sagittal sections. (2) The series was stained with hematoxylin and eosin to enable identification of nerves, vessels, and smooth and striated muscles. Results: (1) It was found that the rectourethralis muscle is closest to the deep transverse perineal muscle where the longitudinal muscle of the rectum extends into the posteroinferior area of the membranous urethra. The communicating branches of the neurovascular bundle (NVB) were identified at the posterior edge of the rectourethralis muscle on both sides. The rectum was found to be fixed to the membranous urethra through the rectourethral muscle, contributing to the anorectal angle of the anterior rectal wall. (2) Serial cross-sections from the anal to the oral side were examined. At the level of the external anal sphincter, the longitudinal muscle of the rectum was found to extend caudally and divide into two muscle bundles on the oral side of the external anal sphincter. One of these muscle bundles angled dorsally and caudally, forming the conjoined longitudinal muscle, which was found to insert into the intersphincteric space (between the internal and external anal sphincters). The other muscle bundle angled ventrally and caudally, filling the gap between the external anal sphincter and the bulbocavernosus muscle, forming the perineal body. At the level of the superficial transverse perineal muscle, this small muscle bundle headed laterally and intertwined with the longitudinal muscle in the region of the perineal body. At the level of the rectourethralis and deep transverse perineal muscle, the external urethral sphincter was found to occupy an almost completely circular space along the membranous part of the urethra. The dorsal part of the external urethral sphincter was found to be thin at the point of attachment of the rectourethralis muscle, the ventral part of the longitudinal muscle of the rectum. We identified a venous plexus from the NVB located close to the oral and ventral side of the deep transverse perineal muscle. Many vascular branches from the NVB were found to be penetrating the longitudinal muscle and the ventral part of rectourethralis muscle at the level of the apex of the prostate. The rectourethral muscle was wrapped ventrally around the membranous urethra and apex of the prostate. The boundary between the longitudinal muscle and prostate gradually became more distinct, being located at the anterior end of the transabdominal dissection plane. (3) Histological examination showed that the dorsal part of the external urethral sphincter (striated muscle) is thin adjacent to the striated muscle fibers from the deep transverse perineal muscle and the NVB dorsally and close by. The rectourethral muscle was found to fill the space created by the internal anal sphincter, deep transverse perineal muscle, and both levator ani muscles. Many tortuous vessels and tiny nerve fibers from the NVB were identified penetrating the muscle fibers of the deep transverse perineal and rectourethral muscles. The structure of the superficial transverse perineal muscle was typical of striated muscle. These findings were reconstructed three-dimensionally. Conclusions: In intersphincteric resection or abdominoperineal resection for very low rectal cancer, the anterior dissection plane behind Denonvilliers' fascia disappears at the level of the apex of the prostate. The prostate and both NVBs should be used as landmarks during transanal dissection of the non-surgical plane. The rectourethralis muscle should be divided near the rectum side unless tumor involvement is suspected. The superficial and deep transverse perineal muscles, as well as their supplied vessels and nerve fibers from the NVB. In addition, the cutting direction should be adjusted according to the anorectal angle to minimize urethral injury.
Humans ; Male ; Rectum/surgery* ; Anal Canal/anatomy & histology* ; Rectal Neoplasms/surgery* ; Proctectomy ; Urethra/surgery*