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 explore the relationship between hyperopia reserve and ocular biometric parameters in 4-14 year-old Uyghur students from Hotan County, Xinjiang, and to provide scientific evidence for myopia prevention.METHODS: From September 1 to October 31, 2023, a stratified random cluster sampling method was used to select 3 264 students(3 264 eyes)from 6 schools in Hotan County. Participants underwent uncorrected distance visual acuity testing, cycloplegic refraction, and ocular biometric measurements. The correlation between spherical equivalent(SE)and ocular biometric parameters was analyzed by multiple linear regression.RESULTS: A total of 1 998 non-myopic students(1 998 eyes)were included in the study, with 1 354 students(67.77%)showing insufficient hyperopia reserve. The detection rate of insufficient hyperopia reserve decreased with age, from 94.12% at age 4 to 18.13% at age 14(P<0.001). Multiple linear regression analysis showed that in the group with sufficient hyperopia reserve, age, gender, uncorrected distance visual acuity, axial length(AL), and keratometry(K)explained 66.5% of the variance in SE; while in the group with insufficient hyperopia reserve, these factors explained only 28.0% of the SE variance.CONCLUSION: In non-myopic Uyghur students aged 4-14 in Hotan County, Xinjiang, the detection rate of insufficient hyperopia reserve was 67.77%. In the group with insufficient hyperopia reserve, age, gender, AL, and K explained only a small portion of the SE variance, suggesting that the refractive status of this population may be influenced by more complex factors.

BACKGROUND: Changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels may not fully translate into patient-reported health status in patients with heart failure (HF). We aimed to evaluate the correlation between NT-proBNP levels and patient-reported health status changes at one month after discharge of patients, and their associations with risk of death and rehospitalization in patients with acute HF. METHODS: We used data from the China Patient-centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study (PEACE 5p-HF Study). Patient-reported health status was measured by the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Patients who were hospitalized for HF and completed the KCCQ-12 and NT-proBNP tests before and one month after discharge were eligible in our study. We stratified patients into different groups based on NT-proBNP levels (i.e., improved, stable, and deteriorated) and KCCQ-12 scores (i.e., not deteriorated and deteriorated). We also examined the associations of the joint NT-proBNP and KCCQ-12 change with the risk of one-year and four-year clinical outcomes. RESULTS: A total of 2461 patients were included in the analysis. The mean age was 64.06 ± 13.51 years, and 36.37% (895/2461) of the study population were female. Among patients with improved NT-proBNP levels, 115 (10.95%) patients had deteriorated KCCQ-12 scores. The correlation between the change in the KCCQ-12 score and NT-proBNP level was weak ( r2 = 0.002, P = 0.013). Stratification by changes in the KCCQ-12 score revealed subgroups with distinctive risks, such that patients with deteriorated KCCQ-12 scores in any of the NT-proBNP change groups exhibited an increased risk of one-year all-cause death than participants with not deteriorated KCCQ-12 scores in any of the NT-proBNP change groups. Patients with improved NT-proBNP levels and deteriorated KCCQ-12 scores presented greater risks of one-year all-cause death (hazard ratio [HR]: 2.45, 95% confidence interval [CI]: 1.34-4.48) than patients with stable NT-proBNP levels and not deteriorated KCCQ-12 scores (HR [95% CI], 1.77 [1.25-2.53]). CONCLUSIONS: A discrepancy between changes in NT-proBNP levels and KCCQ-12 scores was common. The change in NT-proBNP levels was not sufficient to characterize critical aspects related to HF during one month after discharge of patients. Changes in the KCCQ-12 score exhibit complementary information to NT-proBNP levels for the prediction of clinical outcomes in patients with acute HF. REGISTRATION www.clinicaltrials.gov (No. NCT02878811).
Aged ; Female ; Humans ; Male ; Middle Aged ; Health Status ; Heart Failure/metabolism* ; Natriuretic Peptide, Brain/metabolism* ; Peptide Fragments/metabolism* ; Prospective Studies

Tumor metastasis is the leading cause of high mortality in most cancers, and numerous studies have demonstrated that the malignant crosstalk of multiple components in the tumor microenvironment (TME) together promotes tumor metastasis. Cancer-associated fibroblasts (CAFs) are the major stromal cells and crosstalk centers in the TME of various kinds of tumors, such as breast cancer, pancreatic cancer, and prostate cancer. Recently, the CAF-induced pro-tumor metastatic TME has gained wide attention, being considered as one of the effective targets for tumor therapy. With in-depth research, CAFs have been found to promote tumor metastasis through multiple mechanisms, such as inducing epithelial-mesenchymal transition in tumor cells, remodeling the extracellular matrix, protecting circulating tumor cells, and facilitating the formation of a pre-metastatic niche. To enhance the anti-tumor metastasis effect, therapeutic strategies designed by combining nano-drug delivery systems with CAF modulation are undoubtedly a desirable choice, as evidenced by the research over the past decades. Herein, we introduce the physiological properties of CAFs, detail the possible mechanisms whereby CAFs promote tumor metastasis, categorize CAFs-based nano-drug delivery strategies according to their anti-metastasis functions and discuss the current challenges, possible solutions, as well as the future directions in order to provide a theoretical basis and reference for the utilization of CAFs-based nano-drug delivery strategies to promote tumor metastasis therapy.

The persistent high prevalence and poor survival outcomes of lung cancer underscore the urgent need for innovative therapeutic modalities. Here, we present a novel multifunctional delivery platform for the synergistic treatment of lung malignancies, combining in situ-triggerable photodynamic therapy (PDT) with radiotherapy. The new platform CLL was developed by loading a new reactive oxygen species (ROS)-triggerable photosensitizer, luminol-conjugated chlorin e6 (Ce6), into liposomes. CLL can be activated through the bioluminescence resonance energy transfer effect under oxidative stress, thereby producing singlet oxygen for targeted tumor treatment without external irradiation. In vitro studies showed significant cytotoxic effects of CLL in both 4T1 and A549 tumor cells. Furthermore, a PDT-radiopharmaceutical combination nanotherapy CLL-¹⁷⁷Lu was engineered by incorporating the radionuclide ¹⁷⁷Lu into CLL. CLL-¹⁷⁷Lu demonstrated synergistic antitumor effects in 4T1 and A549 tumor cells, as well as in mouse models of 4T1 breast cancer lung metastasis or A549 tumor xenografts. Mechanistically, CLL-¹⁷⁷Lu can induce singlet oxygen/ROS generation, enhance tumor cell apoptosis, and promote M1 macrophage-mediated immunotherapy. Preliminary assessments showed a favorable profile for CLL-¹⁷⁷Lu, highlighting its potential as a promising nanotherapy for cancer treatment. Additionally, CLL can serve as a versatile platform for delivering a range of therapies to achieve synergistic antitumor effects.

ObjectiveTo investigate the clinical features of patients with hepatolenticular degeneration （HLD） aged above 35 years. MethodsA retrospective analysis was performed for the clinical data of the patients with HLD， aged above 35 years， who attended West China School of Public Health， Sichuan University， from April 2018 to April 2023， and according to their clinical symptoms， they were divided into mixed type group with 13 patients， liver type group with 12 patients， and brain type group with 5 patients. Related data were collected， including general information （sex， clinical manifestation， age at confirmed diagnosis， time from initial symptoms to confirmed diagnosis， and family history）， laboratory examination （routine blood test， liver and renal function， serum copper， serum ceruloplasmin， urinary copper， and coagulation function）， and radiological examination. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups； the Fisher’s exact test was used for comparison of categorical data between groups. ResultsFor the 30 patients with HLD， the male/female ratio was 3∶1， and the mean age was 46.13±5.88 years； the patients with positive Kayser-Fleischer ring of the cornea accounted for 43.33%， and the patients with liver cirrhosis accounted for 66.67%. There were significant differences between the three groups in globulin， albumin/globulin ratio， alanine aminotransferase， prothrombin time， international normalized ratio， and activated partial thromboplastin time （F=5.893， 4.513， 4.424， 5.029， 5.248， and 4.942， all P<0.05）. ConclusionMost patients are male among the patients diagnosed with HLD after 35 years of age， with the main clinical types of mixed type and liver type， and such patients tend to have poor liver and coagulation functions. For unexplained liver function abnormalities and liver cirrhosis in this age group， the indicators such as serum ceruloplasmin and urinary copper should be screened as early as possible， and liver and kidney function and coagulation function should be monitored.

[Objective] To understand the resistance mechanisms, virulence characteristics, and pathogenicity of hypervirulent Klebsiella pneumoniae (hvKp), which causes pyogenic liver abscess (PLA), and to provide related data for clinical treatment of infection caused by this type of bacteria. [Methods] We collected three strains of Klebsiella pneumoniae isolated from the liver abscess fluid of patients with liver abscesses in various departments of The First Affiliated Hospital of Xi’an Jiaotong University. The hypervirulent phenotypes were determined by the wire test, and drug sensitivity was assessed using the VITEK 2 compact automatic microbiological analyzer. Molecular characteristics such as podocarp serotypes, multi-locus sequence typing (MLST), virulence genes, and drug resistance genes were identified through whole-genome sequencing. Additionally, a mouse infection model was established to evaluate pathogenicity. [Results] The isolates were sticky, with mucous thread pulling length >5 mm, all of which exhibited high viscosity phenotypes. Except 146007, which is a multidrug-resistant bacterium, the other two strains had higher antibiotic sensitivity. Whole genome sequencing revealed that the isolates were of high-virulence type, carrying the toxin plasmid rmpADC/rmpA2, iron uptake system, bacterial hairs, secretion system, and other virulence factors. All the three isolates tested positive for rmpA/rmpA2 combined with iucA/iutA, indicating they could be classified as hvKp. Multiple resistance genes were detected, such as β-lactamase like blaTEM, blaSHV, and blaCTX-M. The isolates were highly pathogenic to mice, as evidenced by the diseased organs of the deceased mice observed on autopsy. [Conclusion] The three strains of hvKp isolated in this study carried multiple drug-resistant genes and were highly pathogenic, which suggests that in laboratories and clinical practices it is imperative to promptly identify and adopt necessary disposal strategies to prevent further spread of hvKp.

Platelet transfusion is one of the critical clinical therapies of neonatal thrombocytopenia and significant preventive measures of bleeding diseases in preterm infants.The platelet transfusion rate is high in clinical practice，whereas some controversies emerge in its clinical application.Platelet transfusion decision-making should take into account the platelet count and the causes of thrombocytopenia.In addition，the presence of bleeding tendency and platelet effects on other systemic disorders should be considered.Clinicians often need to make rapid decisions about whether to transfuse platelets in a critically situation.On the basis of the comprehensive overview of issues that are closely pertinent to the field of clinical practice，this article is dedicated to elucidate the advancements in clinical research pertaining to neonatal platelet transfusions，aiming to serve as a reference for clinicians when making transfusion decisions and to chart a course for future clinical investigations.

Objective:To explore the characteristics of latent profiles of health literacy in elderly patients with multiple chronic conditions (MCCs), and to analyze the impacts of the profiles on patients′ health promoting lifestyle, and to provide reference for developing intervention strategies.Methods:From July 2022 to May 2023, elderly patients with multiple chronic conditions in Nanfang Hospital, Southern Medical University were selected as the survey subjects by cross-sectional survey method. The General Information Questionnaire, All Aspects of Health Literacy Scale and Health Promoting Lifestyle Profile-Ⅱ were used for investigation. The latent profile analysis was conducted with the 11 entries of health literacy in elderly patients with MCCs as the explicit indicators. The difference of clinical data in potential profiles of health literacy were compared, and regression mixture model was implemented to analyze the impacts of different profiles on health promoting lifestyle of patients.Results:Totally 198 valid questionnaires [127 males and 71 females with 60-80(64.57 ± 4.60) years old] were collected, with the effective recovery rate of 94.3%. The latent profiles of health literacy in elderly patients with MCCs was divided into 3 profiles, high literacy and high efficiency in health information application group 51 cases (25.8%), moderate literacy and moderate efficiency in health information application group 87 cases (43.9%), low literacy and low efficiency in health information application group 60 cases (30.3%). Education level [high school or technical secondary school: OR(95% CI)=0.134(0.034-0.531), college degree or above: OR(95% CI)=0.056(0.005-0.670)], per capita monthly income of families [3 000-5 000yuan: OR(95% CI)=0.176(0.052-0.593), >5 000 yuan: OR(95% CI)=0.095(0.024-0.370)], years of illness [>5years: OR(95% CI)=0.204(0.053-0.787)], and number of co-occurring diseases [4-5kinds: OR(95% CI)=3.500(1.324-4.252)] were the influencing factors of high literacy and high efficiency in health information application group (all P<0.05). Per capita monthly income of families [3 000-5 000yuan: OR(95% CI)=0.336(0.150-0.752)] and years of illness[1-5years: OR(95% CI)=0.266(0.098-0.721)] were the influencing factors of moderate literacy and moderate efficiency in health information application group (all P<0.05). There were statistically significant difference in the total score of Health Promoting Lifestyle Profile-Ⅱ and the scores of each dimension among elderly patients with MCCs between 3 latent profiles ( F=32.12-81.04, all P<0.05). Conclusions:The health literacy of elderly patients with MCCs is significantly heterogeneous, and there are significant differences in health promoting lifestyle among the profiles. Medical staff should formulate personalized intervention strategies based on the classification characteristics of health literacy of MCCs elderly patients to improve their health promoting lifestyle.