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: As an age-related neurodegenerative disease, the prevalence of mild cognitive impairment (MCI) increases with age. Within the framework of traditional Chinese medicine, spleen-kidney deficiency syndrome (SKDS) is recognized as the most frequent MCI subtype. Due to the covert and gradual onset of MCI, in community settings it poses a significant challenge for patients and their families to discern between typical aging and pathological changes. There exists an urgent need to devise a preliminary diagnostic tool designed for community-residing older adults with MCI attributed to SKDS (MCI-SKDS). METHODS: This investigation enrolled 312 elderly individuals diagnosed with MCI, who were randomly distributed into training and test datasets at a 3:1 ratio. Five machine learning methods, including logistic regression (LR), decision tree (DT), naive Bayes (NB), support vector machine (SVM), and gradient boosting (GB), were used to build a diagnostic prediction model for MCI-SKDS. Accuracy, sensitivity, specificity, precision, F1 score, and area under the curve were used to evaluate model performance. Furthermore, the clinical applicability of the model was evaluated through decision curve analysis (DCA). RESULTS: The accuracy, precision, specificity and F1 score of the DT model performed best in the training set (test set), with scores of 0.904 (0.845), 0.875 (0.795), 0.973 (0.875) and 0.973 (0.875). The sensitivity of the training set (test set) of the SVM model performed best among the five models with a score of 0.865 (0.821). The area under the curve of all five models was greater than 0.9 for the training dataset and greater than 0.8 for the test dataset. The DCA of all models showed good clinical application value. The study identified ten indicators that were significant predictors of MCI-SKDS. CONCLUSION The risk prediction index derived from machine learning for the MCI-SKDS prediction model is simple and practical; the model demonstrates good predictive value and clinical applicability, and the DT model had the best performance. Please cite this article as: Ai YT, Zhou S, Wang M, Zheng TY, Hu H, Wang YC, Li YC, Wang XT, Zhou PJ. Development of a machine learning-based risk prediction model for mild cognitive impairment with spleen-kidney deficiency syndrome in the elderly. J Integr Med. 2025; 23(4): 390-397.
Humans ; Cognitive Dysfunction/diagnosis* ; Aged ; Male ; Female ; Machine Learning ; Spleen ; Aged, 80 and over ; Kidney ; Medicine, Chinese Traditional

Objective To observe the effectiveness of fluorescence labeling-based assay bundle intervention in the prevention and control of multidrug-resistant organism(MDRO)infection.Methods Patients who were detected MDRO in a hospital from January to December 2022 were selected as the research subjects.MDRO monitoring data and implementation status of prevention and control measures were collected.Fluorescence labeling assay was adopted to monitor the cleaning and disinfection effectiveness of the surrounding object surface of the bed units.Based on the bundled prevention and control measures as well as management mode of the pre-intervention group,the post-intervention group implemented enhanced rectification measures for the problems found by the pre-interven-tion group.Changes in relevant indicators between January-June 2022(before intervention)and July-December 2022(after intervention)were compared.Results There were 136 MDRO-infected patients in the pre-intervention group,208 MDRO strains were detected and 10 healthcare-associated infection(HAI)occurred.There were 128 MDRO-infected patients in the post-intervention group,198 MDRO strains were detected and 9 HAI occurred.Af-ter intervention,the total detection rates of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-re-sistant Acinetobacter baumannii(CRAB),and total MDRO from patients decreased significantly compared to before intervention(all P＜0.05).After intervention,the detection rates of MRSA,carbapenem-resistant Pseudomonas aeruginosa(CRPA),CRAB,and total MDRO from the surrounding object surface were all lower than those before intervention(all P＜0.05).The detection rate of MDRO from surrounding object surface before intervention was 34.52％,which showed a decreased trend after intervention(P＜0.05).The clearance rate of fluorescent labeled markers before intervention was 41.84％,which showed an upward trend after implementing intervention measures(from July to December),and increased to 85.00％at the end of intervention(November-December).The comp-liance rates of issuing isolation medical orders,placing isolation labels,using medical supplies exclusively,and cor-rectly handling medical waste after intervention have all increased compared to before intervention(all P＜0.05).Conclusion Adopting fluorescence labeling-based assay bundle intervention can effectively improve the effectiveness of MDRO infection prevention and control.

Objective To investigate the differences of characteristic of bone marrow plasma cells in patients of different plasma cell dyscrasias according to International Myeloma Working Group(IMWG)criteria.Methods We analyzed the serological and bone marrow flow cytometry results of patients with plasma cell dyscrasias diagnosed and treated in Department of Hematology,Zhongshan Hospital(Xiamen Branch),Fudan University from Jun 12,2019 to Sep 5,2023 retrospectively.Results A total of 102 patients,63 males and 39 females,aged 22 to 85 years,were included,including 46 patients with monoclonal gammaglobulinemia of unknown significance,39 patients with multiple myeloma,5 patients with smoldering multiple myeloma and 12 patients with light-chain amyloidosis.All patients had M proteinemia,including 58 patients with IgG type and 44 patients with non-IgG type.Plasma cells were detected in the bone marrow of all patients.Clonal plasma cells were detected in the bone marrow of 79 patients.Normal plasma cells were detected in the bone marrow of 63 patients.Both clonal and normal plasma cells were detected in the bone marrow of 40 patients.Clonal plasma cells from bone marrow of 52 patients expressed CD56 and 12 patients expressed CD117.There were no significant differences in gender,age among different disease groups.There were statistical differences in M protein type,the concentration of M protein,serum involved/uninvolved free light chain ratio,the proportion of plasma cells in bone marrow nucleated cells,the proportion of clonal plasma cells in bone marrow nucleated cells,the proportion of clonal plasma cells in all bone marrow plasma cells,and the proportion of normal plasma cells in all bone marrow plasma cells among different disease groups(P<0.05).There was statistical difference in the expression of CD56 in clonal plasma cells among different disease groups(P=0.009),but no statistical difference in the expression of CD117.Conclusion The proportion of clonal plasma cells to all nucleated cells,the proportion of clonal plasma cells to all plasma cells,and the proportion of CD56 expression in abnormal plasma cells in the bone marrow of patients with light amyloidosis were similar to those of monoclonal gammopathy of undetermined significance,but significantly different from those of patients with multiple myeloma.

Objective To compare the clinical characteristics of diabetes mellitus(DM)patients complicated with pyogenic liver abscess(PLA)and non-DM(NDM)patients complicated with PLA,and provide evidence for clinical diagnosis and treatment.Methods PLA patients who admitted to an affiliated hospital of Anhui Medical University from July 2002 to February 2022 were selected and divided into DM+PLA group and NDM+PLA group according to whether they had DM.General condition,clinical manifestations and signs.complications,biochemical and patho-genic examination results,imaging findings,as well as clinical efficacy and influencing factors of the two groups of patients were analyzed retrospectively.Results 695 PLA patients were included in the analysis,191(27.5％)in the DM+PLA group and 504(72.5％)in the NDM+PLA group.The proportions of males and complication of hypertension in the DM+PLA group were higher than those in the NDM+PLA group,while the proportion of bi-liary diseases and malignant tumors was lower(all P＜0.05).The proportions of patients developing fever,fa-tigue,as well as concurrent anemia and hypoalbuminemia in the DM+PLA group were higher than those in the NDM+PLA group(all P＜0.05).Compared with the NDM+PLA group,the neutrophil count and percentage in the DM+PLA group increased,while total protein,albumin content,and albumin/globulin ratio all decreased(all P＜0.05).The proportions of the detection of Klebsiella pneumoniae and the occurrence of liver right lobe abscess in DM+PLA patients were higher than those of the NDM+PLA group(both P＜0.05).Multivariate logistic re-gression analysis revealed that malignant tumor was a risk factor for affecting the clinical efficacy of PLA patients,invasive treatment was a protect factor for affecting the clinical efficacy of PLA patients,while blood sugar was a risk factor for affecting the clinical efficacy of NDM+PLA patients.Conclusion DM+PLA patients have more se-vere infection symptoms than NDM+PLA patients,and are accompanied by higher proportions of Klebsiella pneu-moniae infection and liver right lobe abscess.It is necessary to strengthen attention to patients with malignant tumor and control blood sugar level,and timely supplement with invasive treatment if necessary.

Tripterifordin and neotripterifordin are important ent-kaurane diterpenoids in the Chinese medicinal herb Tripterygium wilfordii, possessing significant anti-HIV(human immunodeficiency virus) activity. On the basis of elucidating the natural biosynthetic pathways of these compounds, heterologous production with microbial cell factories can help to alleviate the reliance on plant resources and provide abundant raw materials for sustainable production. TwKO is the first CYP450 enzyme involved in the biosynthesis of tripterifordin and neotripterifordin. This study aimed to enhance the catalytic activity of TwKO by site-directed mutagenesis to benefit the production of tripterifordin and neotripterifordin in yeast. The AlphaFold DB established based on the AlphaFold 2 was employed to obtain the protein model of TwKO. According to multiple sequence alignments and principles of natural evolution, the key residues influencing the binding of TwKO to the substrate were identified. Subsequently, functional characterization of the mutants were conducted in Saccharomyces cerevisiae. A total of 71 mutants were obtained, among which 11 and 11 mutants had the abilities of enhancing the production of 16α-hydroxy-ent-kaurenol and 16α-hydroxy-ent-kaurenoic acid, respectively. In addition, 10 mutants could increase the proportion of the oxidation product of 16α-hydroxy-ent-kaurenol. In particular, R304 was identified as a key residue affecting the catalytic specificity of TwKO, the mutation of which led to the specific prodiction of 16α-hydroxy-ent-kaurenol. This study was the first to reveal the key residue affecting the catalytic activity of TwKO and obtained the mutants with increased TwKO activity, lay a foundation for the biosynthesis of tripterifordin and neotripterifordin.
Tripterygium/chemistry* ; Mutagenesis, Site-Directed ; Diterpenes, Kaurane/chemistry* ; Plant Proteins/chemistry* ; Cytochrome P-450 Enzyme System/chemistry* ; Saccharomyces cerevisiae/metabolism*

AIM: To evaluate retinal vascularization caused by the intravitreal injection of Conbercept in the treatment of a series of retinopathy of prematurity(ROP)cases in Type Ⅰ(threshold and pre-threshold period)and aggressive ROP(A-ROP).METHODS: The data of 34 ROP cases(67 eyes)treated by intravitreal injection of Conbercept(IVC)in the ophthalmology department of the Xiamen Children's Hospital from July 2017 to March 2020 were retrospectively analyzed. Reactivation, which refers to recurrence of acute phase features, occurred at any stage of the disease in the presence or absence of other diseases. RESULT: The average gestational age of the 34 children was 28.82±2.32wk. The average birth weight was 1155.18±398.22g. The lesion zone of 19 cases(37 eyes)was Zone Ⅰ. In 10 cases(20 eyes), the lesion was in Zone Ⅱ, and in 5 cases(10 eyes), the lesion was in the posterior Zone Ⅱ. The total effective rate of disease control in ROP children treated with once IVC was 73.1%(49/67), and the vascularization of Zone Ⅱ was completed. The patients showed variable changes in the vascularization in Zone Ⅲ. For the patients who received one treatment and did not reactivate, the average rate of Type Ⅰ vascularization of ROP was 9.11±2.49wk, and the A-ROP was 13.40±4.04wk. The rate of A-ROP vascularization in Zone Ⅱ was significantly longer compared to Type Ⅰ.CONCLUSION: IVC effectively completes vascularization in Zone Ⅱ.

Mice ; Animals ; Tandem Mass Spectrometry ; Alpha-Amanitin ; Chromatography, Liquid ; Metabolomics ; Chromatography, High Pressure Liquid/methods*

Most drugs need to interact with cell membrane to reach the biological target, so that membrane affinity assay is an important early screening step in drug discovery. However, at present, the traditional oil-water distribution method is still used, a new, simple and accurate method for membrane affinity assay is urgently needed. In this study, according to the colorimetric principle, a new assay model based on polydiacetylene vesicles was optimized through a series of experiments including different concentrations of vesicle solution, temperature, or pH reaction environment. On this basis, tetracaine hydrochloride, 2-methylimidazole and histamine were used as model drugs to measure the membrane affinity constants and verify the between-batch precision of the optimized assay model (relative standard deviation less than 5%). In addition, polydiacetylene vesicles were stable for up to 180 days, demonstrating the potential application of the assay model. This strategy is simple, stable, reliable, with high reproducibility, low cost and easy to promote, which provided a new tool and a new direction for the high-throughput assay of membrane affinity.

Relevant research in recent years has demonstrated that the atrial fibrillation occurrence rate is significantly higher in patients with cirrhosis. The most common indication for long-term anticoagulant therapy is chronic atrial fibrillation. The use of anticoagulant therapy greatly reduces the incidence rate of ischemic stroke. Patients with cirrhosis combined with atrial fibrillation have an elevated risk of bleeding and embolism during anticoagulant therapy due to cirrhotic coagulopathy. At the same time, the liver of such patients will go through varying levels of metabolism and elimination while consuming currently approved anticoagulant drugs, thereby increasing the complexity of anticoagulant therapy. This article summarizes the clinical studies on the risks and benefits of anticoagulant therapy in order to provide a reference for patients with cirrhosis combined with atrial fibrillation.
Humans ; Atrial Fibrillation/epidemiology* ; Stroke/epidemiology* ; Anticoagulants/therapeutic use* ; Hemorrhage ; Liver Cirrhosis/drug therapy* ; Risk Factors