Objective: To analyze the demographic characteristics of patients with red blood cell transfusion reactions, the usage of red blood cell preparations, and the differences in the composition ratio of adverse reactions based on multi-center data from the Haemovigilance Network, in order to reveal the clinical characteristics of red blood cell transfusion and its underlying issues. Methods: Clinical data of patients who experienced transfusion reactions after red blood cell transfusion in the Haemovigilance Network from 2018 to 2023 were collected. The demographic characteristics of patients who experienced transfusion reactions with different types of red blood cell preparations, the utilization of these preparations, and the differences of the composition ratios of transfusion reactions were analyzed. Count data were expressed as numbers (n) or percentages (%), and comparisons between groups were performed using the Chi-square test. Results: Red blood cell transfusion reactions were more common in females (53.56%), with the majority of patients aged 50-69 years (35.54%). The Han polulation accounted for the vast majority of patients (92.77%), and patients in the hematology and obstetrics/gynecology departments had a relatively high proportion of transfusion reactions (13.26% and 14.26%, respectively). Leukocyte-reduced red blood cells and suspended red blood cells were the most common types of transfusion reactions reported among red blood cell preparations. Allergic reactions and non-hemolytic febrile reactions were the most common transfusion reactions, and there were significant differences in the composition ratios of allergic reactions (χ =869.89, P<0.05) and non-hemolytic febrile reactions (χ =812.75, P<0.05) across various types of red blood cell preparations. Conclusion: There are differences in the demographic characteristics and composition ratio of transfusion reactions among different red blood cell preparations. The management of red blood cell transfusion reactions should be tailored to patient characteristics and conditions, and the selection and use of blood products should be optimized to reduce or avoid the occurrence of transfusion reactions, such as considering the use of washed red blood cells for patients with a history of transfusion allergies or those prone to allergies.

Background Job burnout and depressive symptoms are prevalent among occupational populations, with a close relationship between them. Sleep quality, as a potential mediating factor, significantly affects the mental health of workers. Objective To explore the relationship between job burnout, sleep quality, and depressive symptoms, and determine whether sleep quality mediates the relationship between job burnout and depressive symptoms. Methods From April 25 to May 1, 2024, this study employed cluster sampling to conduct a questionnaire survey among individuals engaged in various occupations across five cities in the Ningxia Hui Autonomous Region. The questionnaires included socio-demographic information, as well as the Chinese Maslach Burnout Inventory (CMBI), the Pittsburgh Sleep Quality Index (PSQI), and the Patient Health Questionnaire-9 (PHQ-9) for assessing burnout, sleep quality, and depressive symptoms, respectively. Out of the 4106 questionnaires distributed, a total of 3837 questionnaires were valid, and the valid recovery rate was 93.45%. The distribution among demographic variables in burnout, sleep quality and depressive symptoms were statistically analyzed. A binary logistic regression model was used for multifactor correlation analysis; Pearson correlation was used to test the correlation between burnout, sleep quality, and depressed mood. Modelling and mediated effect path mapping were performed using Amos 24.0 software. Results The postive rate of occupational burnout in the workers was 97.49% (3741/3837), the positive rate of poor sleep quality was 66.77% (2526/3837), and the positive rate of depressive symptoms was 75.68% (2904/3837). There were statistically significant differences in depressive symptoms by ages, shift types, working years, marital status, smoking habits, drinking habits, and exercising frequency (P < 0.05). The logistic model indicated that working years, drinking habits, job burnout, and overall sleep quality were significant factors influencing the occurrence of depressive symptoms (P < 0.05). The correlation analysis revealed positive correlations between depressive symptom scores and job burnout scores (r=0.045, P < 0.01), between depressive symptom scores and sleep quality scores (r=0.480, P < 0.01), and between job burnout scores and sleep quality scores (r=0.054, P < 0.01). Furthermore, the indirect effect of job burnout on depressive symptoms through sleep quality was 0.100 (95%CI: 0.204, 0.252; P < 0.01). Conclusion Job burnout and sleep quality are significant factors associated with the occurrence of depressive symptoms among occupational populations, and sleep quality plays a partial mediating role in depressive symptoms associated with job burnout. This finding may provide a scientific basis for developing intervention strategies to control depressive symptoms among workers.

The mitochondrial unfolded protein response(UPRmt)represents a crucial intracellular stress response mechanism that plays a fundamental role in maintaining mitochondrial and cellular homeostasis. Growing evidence suggests that dysregulation of UPRmt contributes significantly to the pathogenesis of various systemic disorders, including neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, as well as age-related pathologies. Emerging research has particularly highlighted the involvement of UPRmt in ocular diseases, including cataracts, glaucoma, and diabetic retinopathy. This comprehensive review examines the physiological functions of UPRmt and its regulatory mechanisms in age-related eye diseases. The roles of key UPRmt downstream effector molecules in ocular cell populations such as lens epithelial cells, retinal pigment epithelial cells, and retinal ganglion cells are systematically analyzed. Importantly, the dual regulatory nature of UPRmt in ocular pathophysiology is discussed, that is, its moderate activation promotes mitochondrial homeostasis, mitigates oxidative stress, and suppresses inflammatory responses, its chronic or excessive activation triggers apoptotic pathways, induces metabolic dysfunction, and ultimately accelerates disease progression. By elucidating these mechanisms, our review provides novel insights into ocular disease pathogenesis and proposes potential therapeutic strategies targeting UPRmt modulation for the prevention and treatment of age-related eye disorders.

AIM: To investigate the correlation of degree of myopia in adolescents with axial length, corneal curvature and axial ratio.METHODS: Cross-sectional study. A total of 246 adolescents(492 eyes)aged 8-18 years consecutively enrolled for orthokeratology lens fitting at the Fifth Affiliated Hospital of Zhengzhou University between 2021 and 2023 were included based on random sampling method, with 447 eyes finally included due to the elimination of 45 eyes that did not meet the inclusion criteria. Biometric measurements under scotopic conditions assessed axial length(AL), corneal radius of curvature(CR), and AL/CR ratio. Cycloplegic refraction determined spherical equivalent(SE), classifying eyes into mild(216 eyes)or moderate(231 eyes)myopia groups. Furthermore, the correlation of degree of myopia with AL, CR and AL/CR was analyzed by multiple linear regression analysis.RESULTS: A statistically significant difference in myopia severity was observed between the 8-12-year-old and 13-18-year-old age groups(all P<0.001). There were statistically significant differences between mild and moderate groups in SE, AL and AL/CR(all P<0.001). Linear regression analysis revealed significant negative correlations of SE with AL and AL/CR(r=-0.531, -0.598, all P<0.001). The areas under the ROC curve(AUC)for predicting moderate myopia were 0.812(95% CI: 0.773-0.852)for AL/CR combined with gender and age, 0.800(95% CI: 0.759-0.841)for AL/CR alone, 0.726(95% CI: 0.680-0.773)for AL alone, and 0.548(95% CI: 0.494-0.601)for CR alone. The optimal AL/CR cut-off value for predicting moderate myopia was 3.189(sensitivity: 0.632, specificity: 0.852), suggesting its potential as a clinical threshold.CONCLUSION: In adolescents with mild-to-moderate myopia, AL/CR, AL, and SE showed significant negative correlations. The combination of AL/CR with gender and age demonstrated the highest diagnostic accuracy for SE. AL/CR shows independent predictive value for myopia degree in adolescents, irrespective of refractive status.

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

OBJECTIVE To analyze the cost-effectiveness of abemaciclib， palbociclib and ribociclib combined with aromatase inhibitors （AI） in first-line treatment of hormone receptor-positive （HR+） advanced breast cancer from the perspective of Chinese medical system. METHODS The 20-year disease course of the patients was simulated by the partitioned survival model， and the simulation period was determined to be 4 weeks， the model output was the total cost and quality-adjusted life year （QALY）， the cost and effect were discounted at a discount rate of 5%. A network meta-analysis was constructed by systematically searching relevant clinical trials to obtain the efficacy parameters of abemaciclib， palbociclib and ribociclib combined with AI. Survival fitting and extrapolation were performed based on the survival curve of the placebo group in MONALEESA-2 trial. Cost-effectiveness was assessed by incremental cost-effectiveness ratio （ICER） and incremental net monetary benefit （INMB）， with a willingness-to-pay threshold of 3 times China’s per capita gross domestic product （GDP） in 2023； one-way sensitivity analysis and probability sensitivity analysis were used to detect the influence of parameters on the results and the robustness of the incremental analysis results. RESULTS In the 20-year simulation， compared with palbociclib+AI scheme， the ICER of ribociclib+AI scheme was 58 558.38 yuan/QALY and the INMB was 62 988.20 yuan. Compared with ribociclib+AI scheme， the ICER of abemaciclib+AI scheme was 264 928.34 yuan/QALY and the INMB was 344.84 yuan. One-way sensitivity analysis showed that the incremental analysis results of abemaciclib+AI scheme compared to ribociclib+AI scheme were not robust. Probabilistic sensitivity analysis confirmed that the probability of ribociclib+AI scheme becoming the most economical was the highest when the threshold was 1-3 times China’s per capita GDP in 2023. CONCLUSIONS Ribociclib+AI scheme is more likely to be the most economical first-line treatment than abemaciclib+AI scheme and palbociclib+AI scheme in Chinese patients with HR+ advanced breast cancer when threshold is 1-3 times China’s per capita GDP in 2023.

AIM: To study the degree of astigmatism, axial distribution and axial symmetry pattern of binocular astigmatism in primary and secondary school students aged 7-18 years with myopia.METHODS:A total of 239 cases(478 eyes)of primary and secondary school students aged 7-18 years who underwent keratoplasty for myopia correction at the Fifth Affiliated Hospital of Zhengzhou University from 2020 to 2022 were randomly selected, and optometry was performed under ciliary muscle paralysis and was statistically analyzed.RESULTS:Astigmatism degree: 0.25 to 1.00 D accounted for 78.5%, 1.25 to 2.00 D accounted for 17.1%, and >2.00 D accounted for 4.4%. The axial distribution of astigmatism: 86.6% was astigmatism with the rule, 5.9% was astigmatism against the rule, and 7.5% was oblique astigmatism; both genders and different astigmatism degrees were dominated by astigmatism with the rule, and there were differences with the other two axes(both P<0.05). Axial symmetry pattern of astigmatism: the median axial difference in astigmatism between the direct symmetry model and the mirror symmetry model was 7° and 10°, respectively, with no statistical significance in both models(P=0.158), and there was no difference between the two in gender, degree of astigmatism, and axial distribution of astigmatism, but in the age group of 7-12 years old, the difference between the axial astigmatism of the direct symmetry model and the mirror symmetry model was statistically significant(P=0.027).CONCLUSION:The axial distribution of binocular astigmatism in myopic primary and middle school students is mostly astigmatism with the rule; the degree of astigmatism is more common from 0.25 to 1.0 D; however, there is no tendency for axial symmetry pattern of astigmatism.

This study using maltodextrin as raw material, 1%-5% polyvinylpyrrolidone K30 as template agent, 1%-5% ammonium bicarbonate as pore-forming agent, curcumin and ibuprofen as model drugs. Porous maltodextrin was prepared by template and pore-forming agent methods, respectively. The structure and drug delivery behavior of porous maltodextrin prepared by different technologies were comprehensively characterized. The results showed that the porous maltodextrin prepared by pore-forming agent method had larger specific surface area (6.449 4 m²·g^-1) and pore size (32.804 2 nm), which was significantly better than that by template agent method (3.670 2 m²·g^-1, 15.278 5 nm). The adsorption kinetics between porous maltodextrin prepared by pore-forming agent method and curcumin were suitable for quasi-first order adsorption kinetic model, and that between porous maltodextrin and ibuprofen were suitable for quasi-second order adsorption kinetic model. While the adsorption kinetics between porous maltodextrin prepared by template agent method and two model drugs were both suitable for the quasi-first order adsorption kinetic model. In addition, the dissolution behavior analysis showed that the porous maltodextrin prepared by the two technologies can significantly improve the dissolution behavior of insoluble drugs, and the drug release was both carried out by diffusion mechanism, which suitable for the Peppas kinetic release model, but the porous maltodextrin prepared by template agent method had a faster release rate. The change of nozzle diameter had no significant effect on the adsorption process and drug release behavior of porous maltodextrin. In conclusion, the porous maltodextrins prepared by two different technologies were both beneficial to the delivery of insoluble drugs, and the template agent method was the best for delivery of insoluble drugs. This study can provide theoretical basis for the preparation of porous particles, promote the application of porous particles in insoluble drugs, and improve the bioavailability of insoluble drugs.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.