Identifying signs and symptoms of urinary tract infection from emergency department clinical notes using large language models.

BACKGROUND: Natural language processing (NLP) tools including recently developed large language models (LLMs) have myriad potential applications in medical care and research, including the efficient labeling and classification of unstructured text such as electronic health record (EHR) notes. This opens the door to large-scale projects that rely on variables that are not typically recorded in a structured form, such as patient signs and symptoms. OBJECTIVES: This study is designed to acquaint the emergency medicine research community with the foundational elements of NLP, highlighting essential terminology, annotation methodologies, and the intricacies involved in training and evaluating NLP models. Symptom characterization is critical to urinary tract infection (UTI) diagnosis, but identification of symptoms from the EHR has historically been challenging, limiting large-scale research, public health surveillance, and EHR-based clinical decision support. We therefore developed and compared two NLP models to identify UTI symptoms from unstructured emergency department (ED) notes. METHODS: The study population consisted of patients aged ≥ 18 who presented to an ED in a northeastern U.S. health system between June 2013 and August 2021 and had a urinalysis performed. We annotated a random subset of 1250 ED clinician notes from these visits for a list of 17 UTI symptoms. We then developed two task-specific LLMs to perform the task of named entity recognition: a convolutional neural network-based model (SpaCy) and a transformer-based model designed to process longer documents (Clinical Longformer). Models were trained on 1000 notes and tested on a holdout set of 250 notes. We compared model performance (precision, recall, F1 measure) at identifying the presence or absence of UTI symptoms at the note level. RESULTS: A total of 8135 entities were identified in 1250 notes; 83.6% of notes included at least one entity. Overall F1 measure for note-level symptom identification weighted by entity frequency was 0.84 for the SpaCy model and 0.88 for the Longformer model. F1 measure for identifying presence or absence of any UTI symptom in a clinical note was 0.96 (232/250 correctly classified) for the SpaCy model and 0.98 (240/250 correctly classified) for the Longformer model. CONCLUSIONS: The study demonstrated the utility of LLMs and transformer-based models in particular for extracting UTI symptoms from unstructured ED clinical notes; models were highly accurate for detecting the presence or absence of any UTI symptom on the note level, with variable performance for individual symptoms.

Quantifying H&E staining results, grading and predicting IDH mutation status of gliomas using hybrid multi-dimensional MRI.

OBJECTIVE: To assess the performance of hybrid multi-dimensional magnetic resonance imaging (HM-MRI) in quantifying hematoxylin and eosin (H&E) staining results, grading and predicting isocitrate dehydrogenase (IDH) mutation status of gliomas. MATERIALS AND METHODS: Included were 71 glioma patients (mean age, 50.17 ± 13.38 years; 35 men). HM-MRI images were collected at five different echo times (80-200 ms) with seven b-values (0-3000 s/mm2). A modified three-compartment model with very-slow, slow and fast diffusion components was applied to calculate HM-MRI metrics, including fractions, diffusion coefficients and T2 values of each component. Pearson correlation analysis was performed between HM-MRI derived fractions and H&E staining derived percentages. HM-MRI metrics were compared between high-grade and low-grade gliomas, and between IDH-wild and IDH-mutant gliomas. Using receiver operational characteristic (ROC) analysis, the diagnostic performance of HM-MRI in grading and genotyping was compared with mono-exponential models. RESULTS: HM-MRI metrics FDvery-slow and FDslow demonstrated a significant correlation with the H&E staining results (p < .05). Besides, FDvery-slow showed the highest area under ROC curve (AUC = 0.854) for grading, while Dslow showed the highest AUC (0.845) for genotyping. Furthermore, a combination of HM-MRI metrics FDvery-slow and T2Dslow improved the diagnostic performance for grading (AUC = 0.876). DISCUSSION: HM-MRI can aid in non-invasive diagnosis of gliomas.

Study on mechanism underlying the acceleration of pitting corrosion of B30 copper-nickel alloy by sulfate-reducing bacteria in seawater.

In this paper, the relationship between the pitting corrosion formation of B30 copper-nickel (CuNi) alloy and the metabolism of sulfate-reducing bacteria (SRB) was investigated. Combined with the influence of temperature during the actual operation of the cooling systems, the evolution law of the alloy passivation film was analyzed, and the mechanism of SRB promoting the accelerated development of B30 CuNi alloy pitting corrosion was revealed. The results show that SRB significantly promoted the pitting formation and development of B30 CuNi alloy. The maximum pitting depth was 3.9 µm in the sterile system and 15.3 µm with SRB, which was 3.9 times higher than that of sterile system. The loose porous Cu2S film formed by SRB metabolites and copper matrix was easily penetrated by corrosive anions, which promoted copper dissolution and led to pit nucleation. The sulfide adsorbed on the surface prevented or delayed the passivation of B30 CuNi alloy by blocking the adsorption site of O atom, and the corrosion nuclei continued to grow. The non-uniformity caused by the film peeling accelerated the longitudinal development of pitting corrosion, and the expansion and coalescence of adjacent pits caused the transverse development of pitting corrosion. Temperature had a certain influence on the SRB and the formation of B30 CuNi alloy passivation film. The passivation film was formed rapidly at 50 °C with poor quality and the passivation property of Cu2O film was weakened. With the increase of temperature, the pitting potential of sterile system negative shifted from 0.447 to 0.360 V (vs. SCE), while SRB system from 0.340 to 0.198 V (vs. SCE), and the pitting resistance decreased. The passivation film with defects and the Cu2S reduced the barrier efficiency of the film and accelerated the pitting corrosion of B30 CuNi alloy.

Landscape of brain myeloid cell transcriptome along the spatiotemporal progression of Alzheimer's disease reveals distinct sequential responses to Aß and tau.

Human microglia are critically involved in Alzheimer's disease (AD) progression, as shown by genetic and molecular studies. However, their role in tau pathology progression in human brain has not been well described. Here, we characterized 32 human donors along progression of AD pathology, both in time-from early to late pathology-and in space-from entorhinal cortex (EC), inferior temporal gyrus (ITG), prefrontal cortex (PFC) to visual cortex (V2 and V1)-with biochemistry, immunohistochemistry, and single nuclei-RNA-sequencing, profiling a total of 337,512 brain myeloid cells, including microglia. While the majority of microglia are similar across brain regions, we identified a specific subset unique to EC which may contribute to the early tau pathology present in this region. We calculated conversion of microglia subtypes to diseased states and compared conversion patterns to those from AD animal models. Targeting genes implicated in this conversion, or their upstream/downstream pathways, could halt gene programs initiated by early tau progression. We used expression patterns of early tau progression to identify genes whose expression is reversed along spreading of spatial tau pathology (EC > ITG > PFC > V2 > V1) and identified their potential involvement in microglia subtype conversion to a diseased state. This study provides a data resource that builds on our knowledge of myeloid cell contribution to AD by defining the heterogeneity of microglia and brain macrophages during both temporal and regional pathology aspects of AD progression at an unprecedented resolution.

Luminescence properties of a green-emitting mechanoluminescent phosphor CaSrGa4O8:xTb3+ without pre-excitation.

In this study, both mechanoluminescence (ML) and long persistent luminescence (LPL) characteristics were first observed in CaSrGa4O8 doped with Tb3+ ions, which confirmed that CaSrGa4O8 is a high-quality host for luminescent material research. Notably, the samples show stronger mechanoluminescent intensity with increasing Tb3+ doping. Additionally, the introduction of Tb3+ led to a shift of the thermoluminescence peak towards higher temperatures and a substantial increase in its intensity, suggesting that Tb3+ doping enhances the overall trap concentration and introduces deeper trap energy levels. Presumably, the free carriers in the system recombine upon mechanical stimulation, releasing energy that is transferred to Tb3+ ions. Investigations into the intrinsic structure, matrix effects, and trap evolution of the material confirmed that deep and shallow traps are responsible for the observed ML and LPL phenomena, respectively. The elucidation of the unique luminescent properties of the material provides us with some guidance for the development of new multi-functional luminescent materials.

A case report: co-occurrence of probable Vogt-Koyanagi-Harada disease and diabetic retinopathy.

BACKGROUND: Bilateral retinal detachment and choroidal detachment in a patient are rare occurrences. The presence of bilateral diabetic retinopathy (DR) in such a case is even rarer and complicates the condition. CASE PRESENTATION: In this study, we document a case of unconventional VKH. Manifestations in this patient included intense peripheral retinal detachment and choroidal detachment, along with vitreous opacities akin to cotton wool spots, concurrent with DR. The diagnosis was considered as probable VKH with DR. Treatment according to VKH protocols, including high-dose corticosteroids, yielded positive results. CONCLUSIONS: VKH can co-occurrence with DR. VKH manifestations vary, and early, aggressive, and long-term treatment is essential. The complexity of treatment increases with concurrent DR, necessitating the use of immunosuppressants.

Identification of IGF2 promotes skin wound healing by co-expression analysis.

Oral mucosa is an ideal model for studying scarless wound healing. Researchers have shown that the key factors which promote scarless wound healing already exist in basal state of oral mucosa. Thus, to identify the other potential factors in basal state of oral mucosa will benefit to skin wound healing. In this study, we identified eight gene modules enriched in wound healing stages of human skin and oral mucosa through co-expression analysis, among which the module M8 was only module enriched in basal state of oral mucosa, indicating that the genes in module M8 may have key factors mediating scarless wound healing. Through bioinformatic analysis of genes in module M8, we found IGF2 may be the key factor mediating scarless wound healing of oral mucosa. Then, we purified IGF2 protein by prokaryotic expression, and we found that IGF2 could promote the proliferation and migration of HaCaT cells. Moreover, IGF2 promoted wound re-epithelialization and accelerated wound healing in a full-thickness skin wound model. Our findings identified IGF2 as a factor to promote skin wound healing which provide a potential target for wound healing therapy in clinic.

Elucidating the changes in the heterogeneity and function of radiation-induced cardiac macrophages using single-cell RNA sequencing.

Purpose: A mouse model of irradiation (IR)-induced heart injury was established to investigate the early changes in cardiac function after radiation and the role of cardiac macrophages in this process. Methods: Cardiac function was evaluated by heart-to-tibia ratio, lung-to-heart ratio and echocardiography. Immunofluorescence staining and flow cytometry analysis were used to evaluate the changes of macrophages in the heart. Immune cells from heart tissues were sorted by magnetic beads for single-cell RNA sequencing, and the subsets of macrophages were identified and analyzed. Trajectory analysis was used to explore the differentiation relationship of each macrophage subset. The differentially expressed genes (DEGs) were compared, and the related enriched pathways were identified. Single-cell regulatory network inference and clustering (SCENIC) analysis was performed to identify the potential transcription factors (TFs) which participated in this process. Results: Cardiac function temporarily decreased on Day 7 and returned to normal level on Day 35, accompanied by macrophages decreased and increased respectively. Then, we identified 7 clusters of macrophages by single-cell RNA sequencing and found two kinds of stage specific macrophages: senescence-associated macrophage (Cdkn1ahighC5ar1high) on Day 7 and interferon-associated macrophage (Ccr2highIsg15high) on Day 35. Moreover, we observed cardiac macrophages polarized over these two-time points based on M1/M2 and CCR2/major histocompatibility complex II (MHCII) expression. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses suggested that macrophages on Day 7 were characterized by an inflammatory senescent phenotype with enhanced chemotaxis and inflammatory factors, while macrophages on Day 35 showed enhanced phagocytosis with reduced inflammation, which was associated with interferon-related pathways. SCENIC analysis showed AP-1 family members were associated with IR-induced macrophages changes. Conclusion: We are the first study to characterize the diversity, features, and evolution of macrophages during the early stages in an IR-induced cardiac injury animal model.

Discovery of Small Molecule Interleukin 17A Inhibitors with Novel Binding Mode and Stoichiometry: Optimization of DNA-Encoded Chemical Library Hits to In Vivo Active Compounds.

Dysregulation of IL17A drives numerous inflammatory and autoimmune disorders with inhibition of IL17A using antibodies proven as an effective treatment. Oral anti-IL17 therapies are an attractive alternative option, and several preclinical small molecule IL17 inhibitors have previously been described. Herein, we report the discovery of a novel class of small molecule IL17A inhibitors, identified via a DNA-encoded chemical library screen, and their subsequent optimization to provide in vivo efficacious inhibitors. These new protein-protein interaction (PPI) inhibitors bind in a previously undescribed mode in the IL17A protein with two copies binding symmetrically to the central cavities of the IL17A homodimer.

Anisotropic growth of gold anchors on CdSe semiconductor quantum platelets for self-assembled architectures with well-connected electronic circuits for the electrochemical detection of enrofloxacin.

Anisotropic growth of nanomaterials enables advances in building diverse and complex architectures, which exhibit unique properties and enrich the choice of nano-building modules for electrochemical sensor devices. Herein, an anisotropic growth method was proposed to anchor gold nanoparticles (AuNPs) onto both ends of quasi-two-dimensional CdSe semiconductor quantum nanoplatelets (NPLs), appearing with a monodisperse and uniform nano-dumbbell shape. Then, these AuNPs were exploited as natural anchor points and further initiated self-assembly to create complex architectures via dithiol bridges. Detailed studies illustrated that the covalent Se-Au bonds facilitate effective charge transfer in the internal metal-semiconductor (M-S) electric field. The narrowed energy gap and up-shifted highest occupied molecular orbital were favored for electron removal during the electro-oxidation process. The ultrathin CdSe NPLs supplied a large specific surface area, carrying remaining holes and abundant active sites for target electro-catalysis. As a result, using the assembled complex as the electrode matrix with well-connected electronic circuits, a reliable electrochemical sensor was achieved for enrofloxacin detection. Under the optimal conditions, the current response exhibits two linear dynamic ranges, 0.01-10.0 µM and 10.0-250 µM, and the detection limit was calculated as 0.0026 µM. This work not only opens up broad application prospects for heterogeneous M-S combinations as effective electrochemical matrixes but also develops reliable antibiotic assays for food and environmental safety.

Neuroprotective and anti-inflammatory effects of eicosane on glutamate and NMDA-induced retinal ganglion cell injury.

AIM: To investigate the protective effects, antioxidant potential, and anti-inflammatory mechanisms of eicosane on glutamate-induced cell damage and on N-methyl-D-aspartate (NMDA)-induced retinal ganglion cell (RGC) injury in a mouse model of glaucoma. METHODS: The protective effects of eicosane on the rat R28 retinal precursor cell line were assessed using cell counting kit-8 assays and Hoechst-propidium iodide staining. Intracellular reactive oxygen species (ROS) production was measured using the fluorescent probe 2'-7'-dichlorofluorescin diacetate and flow cytometry. The protective role of eicosane on NMDA-induced RGC injury in a mouse glaucoma model was determined by immunostaining of frozen sections of retina. The effects of eicosane on the metabolome of the retina in mice with NMDA-induced RGC damage were evaluated by liquid chromatography-mass spectroscopy (LC-MS) and untargeted metabolomics analyses. RESULTS: Eicosane treatment significantly attenuated glutamate-induced damage to R28 cells in vitro. Eicosane also protected RGCs against NMDA-induced injury in a mouse glaucoma model. Untargeted metabolomics analyses showed that eicosane increased multiple metabolites, including L-arginine and L-carnitine, in the retina. CONCLUSION: Eicosane has protective effects, antioxidant potential, and anti-inflammatory properties in an in vitro model of glutamate-induced cell damage and in an in vivo model of NMDA-induced RGC injury in mouse glaucoma through modulation of L-arginine and/or L-carnitine metabolism.

Regime shift in microalgal dynamics: Impact of water level changes on planktonic and benthic algal biomass.

Whole-lake microalgal biomass surveys were carried out in Lake Balaton to investigate the seasonal, spatial, and temporal changes of benthic algae, as well as to identify the drivers of the phytobenthos. Phytobenthos was controlled mainly by light: the highest benthic algal biomass was in the shallow littoral region characterized by large grain size (sand) with good light availability but lower nutrient content in the sediment. During the investigated period, phytoplankton biomass showed a significant decrease in almost the entire lake. At the same time, the biomass of benthic algae increased significantly in the eastern areas, increasing the contribution of total lake microalgae biomass (from 20 % to 27 %). Benthic algal biomass increase can be explained by the better light supply, owing to the artificially maintained high water level which greatly mitigates water mixing. The decrease in planktonic algal biomass could be attributed to increased zooplankton grazing, which is otherwise negatively affected by mixing. As a result of the high water level, the trophic structure of the lake has been rearranged in recent decades with a shift from the planktonic life form to the benthic one while the nutrient supply has largely remained unchanged.

Mn-Based Mullites for Environmental and Energy Applications.

Mn-based mullite oxides AMn2O5 (A = lanthanide, Y, Bi) is a novel type of ternary catalyst in terms of their electronic and geometric structures. The coexistence of pyramid Mn3+-O and octahedral Mn4+-O makes the d-orbital selectively active toward various catalytic reactions. The alternative edge- and corner-sharing stacking configuration constructs the confined active sites and abundant active oxygen species. As a result, they tend to show superior catalytic behaviors and thus gain great attention in environmental treatment and energy conversion and storage. In environmental applications, Mn-based mullites have been demonstrated to be highly active toward low-temperature oxidization of CO, NO, volatile organic compounds (VOCs), etc. Recent research further shows that mullites decompose O3 and ozonize VOCs from -20 °C to room temperature. Moreover, mullites enhance oxygen reduction reactions (ORR) and sulfur reduction reactions (SRR), critical kinetic steps in air-battery and Li-S batteries, respectively. Their distinctive structures also facilitate applications in gas-sensitive sensing, ionic conduction, high mobility dielectrics, oxygen storage, piezoelectricity, dehydration, H2O2 decomposition, and beyond. A comprehensive review from basic physicochemical properties to application certainly not only gains a full picture of mullite oxides but also provides new insights into designing heterogeneous catalysts.

A Systematic Review and Meta-Analysis of the Predictive Power of China-PAR Against Cardiovascular Disease.

Background and Purpose: To evaluate the predictive power of the China-PAR model for cardiovascular disease (CVD).Methods: Dominate databases, including PubMed, Web of Science, CNKI, Wanfang Data Knowledge Service Platform, Chinese Biomedical Literature Service System, and VIP self-built database, were searched from January 1, 2016 to February 22, 2022. The primary outcome included observed events and predicted events by China-PAR. Meta-analysis was performed using RevMan 5.3 software. Stroke, arteriosclerotic cardiovascular disease (ASCVD), male, and female were divided into subgroup analyses. Funnel plots were used to assess publication bias.Results: A total of nine studies, which included 221,918 participants, were analyzed. Meta-analysis showed the combined observed incidence of CVD was 3.97%, and the combined predicted incidence was 9.59% by China-PAR. There was no significant difference between the observed and the predicted events. Subgroup analysis showed there was no statistical significance between the observed and the predicted events for stroke or for ASCVD. The difference between the observed and the predicted events by China-PAR was not statistically significant in either males or females.Conclusions: China-PAR model has important public health significance to further improve the primary prevention strategy of CVD.

Xinyang tablet alleviated cardiac dysfunction in a cardiac pressure overload model by regulating the receptor-interacting serum/three-protein kinase 3/FUN14 domain containing 1-mediated mitochondrial unfolded protein response and mitophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Xinyang tablet (XYT) has been used for heart failure (HF) for over twenty years in clinical practice, but the underlying molecular mechanism remains poorly understood. AIMS OF THE STUDY: In the present study, we aimed to explore the protective effects of XYT in HF in vivo and in vitro. MATERIALS AND METHODS: Transverse aortic constriction was performed in vivo to establish a mouse model of cardiac pressure overload. Echocardiography, tissue staining, and real-time quantitative PCR (qPCR) were examined to evaluate the protective effects of XYT on cardiac function and structure. Adenosine 5'-triphosphate production, reactive oxygen species staining, and measurement of malondialdehyde and superoxide dismutase was used to detect mitochondrial damage. Mitochondrial ultrastructure was observed by transmission electron microscope. Immunofluorescence staining, qPCR, and Western blotting were performed to evaluate the effect of XYT on the mitochondrial unfolded protein response and mitophagy, and to identify its potential pharmacological mechanism. In vitro, HL-1 cells and neonatal mouse cardiomyocytes were stimulated with Angiotensin II to establish the cell model. Western blotting, qPCR, immunofluorescence staining, and flow cytometry were utilized to determine the effects of XYT on cardiomyocytes. HL-1 cells overexpressing receptor-interacting serum/three-protein kinase 3 (RIPK3) were generated by transfection of RIPK3-overexpressing lentiviral vectors. Cells were then co-treated with XYT to determine the molecular mechanisms. RESULTS: In the present study, XYT was found to exerta protective effect on cardiac function and structure in the pressure overload mice. And it was also found XYT reduced mitochondrial damage by enhancing mitochondrial unfolded protein response and restoring mitophagy. Further studies showed that XYT achieved its cardioprotective role through regulating the RIPK3/FUN14 domain containing 1 (FUNDC1) signaling. Moreover, the overexpression of RIPK3 successfully reversed the XYT-induced protective effects and significantly attenuated the positive effects on the mitochondrial unfolded protein response and mitophagy. CONCLUSIONS: Our findings indicated that XYT prevented pressure overload-induced HF through regulating the RIPK3/FUNDC1-mediated mitochondrial unfolded protein response and mitophagy. The information gained from this study provides a potential strategy for attenuating mitochondrial damage in the context of pressure overload-induced heart failure using XYT.

Asparagine endopeptidase deficiency mitigates radiation-induced brain injury by suppressing microglia-mediated neuronal senescence.

Mounting evidence supports the role of neuroinflammation in radiation-induced brain injury (RIBI), a chronic disease characterized by delayed and progressive neurological impairment. Asparagine endopeptidase (AEP), also known as legumain (LGMN), participates in multiple malignancies and neurodegenerative diseases and may potentially be involved in RIBI. Here, we found AEP expression was substantially elevated in the cortex and hippocampus of wild-type (Lgmn+/+) mice following whole-brain irradiation. Lgmn knockout (Lgmn-/-) alleviated neurological impairment caused by whole-brain irradiation by suppressing neuronal senescence. Bulk RNA and metabolomic sequencing revealed AEP's involvement in the antigen processing and presentation pathway and neuroinflammation. This was further confirmed by co-culturing Lgmn+/+ primary neurons with the conditioned media derived from irradiated Lgmn+/+ or Lgmn-/- primary microglia. Furthermore, esomeprazole inhibited the enzymatic activity of AEP and RIBI. These findings identified AEP as a critical factor of neuroinflammation in RIBI, highlighting the prospect of targeting AEP as a therapeutic approach.

Identification of Age-Related Characteristic Genes Involved in Severe COVID-19 Infection Among Elderly Patients Using Machine Learning and Immune Cell Infiltration Analysis.

Elderly patients infected with severe acute respiratory syndrome coronavirus 2 are at higher risk of severe clinical manifestation, extended hospitalization, and increased mortality. Those patients are more likely to experience persistent symptoms and exacerbate the condition of basic diseases with long COVID-19 syndrome. However, the molecular mechanisms underlying severe COVID-19 in the elderly patients remain unclear. Our study aims to investigate the function of the interaction between disease-characteristic genes and immune cell infiltration in patients with severe COVID-19 infection. COVID-19 datasets (GSE164805 and GSE180594) and aging dataset (GSE69832) were obtained from the Gene Expression Omnibus database. The combined different expression genes (DEGs) were subjected to Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Diseases Ontology functional enrichment analysis, Gene Set Enrichment Analysis, machine learning, and immune cell infiltration analysis. GO and KEGG enrichment analyses revealed that the eight DEGs (IL23A, PTGER4, PLCB1, IL1B, CXCR1, C1QB, MX2, ALOX12) were mainly involved in inflammatory mediator regulation of TRP channels, coronavirus disease-COVID-19, and cytokine activity signaling pathways. Three-degree algorithm (LASSO, SVM-RFE, KNN) and correlation analysis showed that the five DEGs up-regulated the immune cells of macrophages M0/M1, memory B cells, gamma delta T cell, dendritic cell resting, and master cell resisting. Our study identified five hallmark genes that can serve as disease-characteristic genes and target immune cells infiltrated in severe COVID-19 patients among the elderly population, which may contribute to the study of pathogenesis and the evaluation of diagnosis and prognosis in aging patients infected with severe COVID-19.

[Elesclomol-Cu Induces Cuproptosis in Human Acute Myeloid Leukemia Cells].

OBJECTIVE: To investigate the effects of elesclomol-Cu (ES-Cu) on the proliferation and cuproptosis of human acute myeloid leukemia (AML) cells. METHODS: The effects of ES-Cu on the proliferation of AML cells and the AML cells pre-treated with ammonium tetrathiomolybdate (TTM) were examined by CCK-8 assay. The Calcein/PI kit was used to detected the changes in activity and cytotoxicity of AML cells induced by ES-Cu. Flow cytometry and Cytation3 fully automated cell imaging multifunctional detection system were used to analyze DCFH-DA fluorescence intensity, so as to determine the level of reactive oxygen species (ROS). The GSH and GSSG detection kits were used to measure the intracellular GSH content. Western blot was used to detected the expression of cuproptosis-related proteins ATP7B, FDX1, DLAT and DPYD. RESULTS: ES-Cu inhibited the proliferation of Kasumi-1 and HL-60 cells in a concentration-dependent manner (r Kasumi-1=-0.99， r HL-60=-0.98). As the concentration of ES-Cu increased, the level of intracellular ROS also increased (P <0.01-0.001). TTM could significantly reverse the inhibitory effect of ES-Cu on cell proliferation and its promoting effect on ROS. With the increase of ES-Cu concentration, the content of GSH was decreased (r =-0.98), and Western blot showed that the protein expressions of ATP7B, FDX1, DLAT and DPYD were significantly reduced (P <0.05). CONCLUSION: ES-Cu can induce cuproptosis in AML cells, which provides a new idea for the treatment of AML.

Deliberate self-harm among pediatric psychiatric inpatients in China: A single-center retrospective study.

BACKGROUND: For children and adolescents, deliberate self-harm (DSH) is becoming a mental health problem of concern. Despite several studies on the prevalence and factors of DSH in the world, there is little information on DSH among children and adolescents in China. This study explores the prevalence, types, associated risk factors and tendency of DSH in pediatric psychiatric inpatients in China. AIM: To understand the situation of DSH among hospitalized children and adolescents and its related factors. METHODS: In this study, we retrospectively studied 1414 hospitalized children and adolescents with mental illness at Xiamen Mental Health Center from 2014 to 2019, extracted the demographic and clinical data of all patients, and analyzed clinical risk factors of DSH. RESULTS: A total of 239 (16.90%) patients engaged in at least one type of DSH in our study. Cutting (n = 115, 48.12%) was the most common type of DSH. Females (n = 171, 71.55%) were more likely to engage in DSH than males (n = 68, 28.45%). DSH was positively associated with depressive disorders [OR = 3.845 (2.196-6.732); P < 0.01], female [OR = 2.536 (1.815-3.542); P < 0.01], parental marital status [OR = 5.387 (2.254-12.875); P < 0.01] and negative family history of psychiatric illness [OR = 7.767 (2.952-20.433); P < 0.01], but not with occupation, substance use and history of physical abuse. CONCLUSION: Our findings suggest that for patients with depression, females, an abnormal marriage of parents, and no history of mental illness, attention should be paid to the occurrence of DSH.

Association between Glycosylated Hemoglobin and Serum Uric Acid: A US NHANES 2011-2020.

Background: Serum uric acid (SUA) and glycosylated hemoglobin (HbA1c) were closely related to the body's metabolism. This study aimed to investigate the relationship between HbA1c and SUA in adults. Methods: This study selected 7293 participants aged ≥20 from 2011 to 2020 in the National Health and Nutrition Examination Survey (NHANES). The multivariate linear regression model was used to test the association between HbA1c and SUA. Subgroup analysis was performed according to age, gender, race, and body mass index (BMI). This study solved the relationship between HbA1c and SUA by fitting a smooth curve. Finally, the inflection point in the nonlinear relationship was calculated by the recursive algorithm, and the relationship between HbA1c and SUA on both sides of the inflection point was analyzed by the two-segment piecewise linear regression model. Results: All 7293 participants found a negative correlation between HbA1c and SUA by completely adjusting the model (ß = -7.93 and 95% CI: -9.49--6.37). In addition, when this study was stratified by gender, age, race, and BMI status, this negative correlation was still statistically significant. In the subgroup analysis, we found that the relationship between the two had different results due to gender differences. In men, HbA1c had a significant negative correlation with SUA. However, in women, the HbA1c value was positively correlated with SUA before 6.8%, and the HbA1c value was negatively correlated with SUA after 6.8%, which indicates that the relationship between HbA1c and SUA in women has changed in prediabetes and diabetes. Conclusion: This study shows that HbA1c is positively correlated with SUA in American adults before 7%. There is a negative correlation after the HbA1c value of 7%.