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Background: B lymphocytes play a key role in immunosuppression. This study investigated the prognostic value of B cell subsets in sepsis. Methods: Flow cytometry was used to assess peripheral B cell subsets from patients with sepsis on the first and seventh days following admission, as well as 111 healthy controls. The patients were divided into survivors and non-survivors, based on 28-day prognosis. Results: The analysis showed abnormal distribution and selective depletion of B cells and its subsets in the early stages of sepsis. On day 1, compared with survivors, non-survivors showed significant decreases in the proportion and absolute count of transitional (Tr) B cells, reductions in the proportion of CD5+ B cells, and increases in the proportion of double-negative (DN) B cells. On day 7, the proportions and absolute counts of Tr and CD5+ B cells significantly decreased whereas the proportion of DN B cells significantly increased in non-survivors. Ninety-four survivors and 15 non-survivors were included in our paired-sample rank-sum test. Compared to day 1, only the survivors showed significant increases in absolute B, Tr B, and CD5+ B cell counts by day 7. Multivariate Cox regression analysis showed that the proportion of DN B cells on day 1 (hazard ratio = 1.092 [95% confidence interval: 1.035-1.152], P = 0.001) was a risk factor for mortality, and Kaplan-Meier survival curve analysis showed that patients with proportions of DN B cells > 11.81% on day 1 had poorer prognoses. Receiver operating characteristic curve analysis showed that B cell subset parameters could predict mortality (area under the receiver operating characteristic curve [AUC], 0.741) and enhanced the prognostic value of the Acute Physiology and Chronic Health Evaluation II score (AUC, 0.840). Conclusion: Our study revealed that deficiencies of B, Tr B, and CD5+ B cells, as well as a persistent increase in the proportion of DN B cells, were associated with poor prognosis-and that B cell subsets showed predictive value to mortality. These results provide new insights into the roles of B cell subsets in sepsis, as well as ways to better manage its progression and predict its course.

Assuntos

Subpopulações de Linfócitos B , Sepse , Humanos , Masculino , Feminino , Sepse/imunologia , Sepse/mortalidade , Sepse/diagnóstico , Sepse/sangue , Prognóstico , Pessoa de Meia-Idade , Idoso , Subpopulações de Linfócitos B/imunologia , Contagem de Linfócitos , Curva ROC , Citometria de Fluxo , Adulto , Biomarcadores

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PURPOSE: We evaluated the efficacy and safety of roxadustat, a first-in-class hypoxia-inducible factor prolyl hydroxylase inhibitor, for chemotherapy-induced anemia (CIA) in patients with nonmyeloid malignancies receiving multicycle treatments of chemotherapy. PATIENTS AND METHODS: In this open-label, noninferiority phase III study conducted at 44 sites in China, 159 participants age ≥18 years with CIA nonmyeloid malignancy and CIA were randomly assigned (1:1) to oral roxadustat or subcutaneous recombinant human erythropoietin-α (rHuEPO-α) three times a week for 12 weeks. Roxadustat starting dosages were 100, 120, and 150 mg three times a week for participants weighing 40-<50, 50-60, and >60 kg, respectively. rHuEPO-α starting dosage for all participants was 150 IU/kg three times a week. Both roxadustat and rHuEPO-α dosages could be modified. The primary end point was least-squares mean (LSM) change in hemoglobin (Hb) concentration from baseline to the concentration averaged over weeks 9-13. RESULTS: Of the 159 participants randomly assigned, 140 were included in the per-protocol set (roxadustat, n = 78; rHuEPO-α, n = 62). The LSM (95% two-sided CI) change from baseline to weeks 9-13 in Hb concentration was 17.1 (13.58 to 20.71) g/L with roxadustat and 15.4 (11.34 to 19.50) g/L with rHuEPO-α (mean difference [95% CI], 1.7 [-3.39 to 6.84]). The lower bound of the one-sided 97.5% CI for the treatment difference (‒3.4 g/L) was greater than the predefined noninferiority margin of ‒6.6 g/L, establishing noninferiority. Noninferiority was supported by five of six key secondary end points. Rates of adverse events were generally comparable between treatments and consistent with previous findings. CONCLUSION: Roxadustat was noninferior to rHuEPO-α in treating CIA in participants with nonmyeloid malignancies receiving multicycle treatments of myelosuppressive chemotherapy. The oral formulation of roxadustat may potentially increase compliance.

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INTRODUCTION: This study aimed to investigate the correlation between serum interleukin (IL)-17A levels and responsiveness to intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD) patients. METHODS: A retrospective analysis on data from 192 KD patients admitted to the Anqing Municipal Hospital between January 2021 and January 2024 was conducted. Patients were categorized into IVIG-nonresponsive and IVIG-sensitive groups as per the treatment outcomes. Outcome measures included serum IL-17A levels, left coronary artery (LCA) Z scores, and relevant laboratory parameters. Logistic regression analysis was performed to identify predictive factors for IVIG responsiveness, and diagnostic performance was assessed using receiver operating characteristic (ROC) curves and calculation of the area under the curve (AUC). RESULTS: A total of 40 IVIG-nonresponsive cases and 152 IVIG-sensitive cases were included. Prior to intervention, IVIG-nonresponsive patients had significantly higher serum IL-17A levels compared to IVIG-sensitive patients, with a statistically significant difference. After intervention, serum IL-17A levels significantly decreased in IVIG-sensitive patients while remaining elevated in IVIG-nonresponsive patients. IVIG-nonresponsive patients exhibited significantly higher levels of C-reactive protein (CRP), white blood cell count (WBC), NE, and ALT compared to IVIG-sensitive patients, whereas no significant differences in LCA Z scores between the two groups existed. Multivariable logistic regression analysis identified pre-IL-17A, CRP, WBC, and ALT as independent predictors of IVIG-nonresponsiveness in KD. When pre-IL-17A was ≥39.96 pg/mL, the specificity and sensitivity for predicting IVIG-nonresponsive KD were 63.9% and 71.9%, respectively, with an AUC of 0.637. The combined diagnosis of IL-17A, CRP, WBC, and ALT yielded an AUC of 0.780. CONCLUSION: Serum IL-17A levels were remarkably elevated in IVIG-nonresponsive KD patients both before and after intervention. A serum IL-17A level (≥39.96 pg/mL) demonstrated good predictive profile for IVIG-nonresponsive KD, and combining IL-17A with CRP, WBC, and ALT improved diagnostic performance.

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Fracture risk among individuals with diabetes poses significant clinical challenges due to the multifaceted relationship between diabetes and bone health. Diabetes not only affects bone density but also alters bone quality and structure, thereby increases the susceptibility to fractures. Given the rising prevalence of diabetes worldwide and its associated complications, accurate prediction of fracture risk in diabetic individuals has emerged as a pressing clinical need. This study aims to investigate the factors influencing fracture risk among diabetic patients. We propose a framework that combines Lasso feature selection with eight classification algorithms. Initially, Lasso regression is employed to select 24 significant features. Subsequently, we utilize grid search and 5-fold cross-validation to train and tune the selected classification algorithms, including KNN, Naive Bayes, Decision Tree, Random Forest, AdaBoost, XGBoost, Multi-layer Perceptron (MLP), and Support Vector Machine (SVM). Among models trained using these important features, Random Forest exhibits the highest performance with a predictive accuracy of 93.87%. Comparative analysis across all features, important features, and remaining features demonstrate the crucial role of features selected by Lasso regression in predicting fracture risk among diabetic patients. Besides, by using a feature importance ranking algorithm, we find several features that hold significant reference values for predicting early bone fracture risk in diabetic individuals.

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The neurological complications of influenza affect mainly the pediatric Asian population. In the category of influenza-associated encephalopathy, acute necrotizing encephalopathy (ANE) is a rapidly progressive and fulminant brain disorder associated with significant neurological sequelae and mortality. To date, only a few adult cases of influenza-associated ANE have been reported. We describe a 44-year-old woman who presented with rapid progression of consciousness impairment and recurrent generalized convulsions. Influenza was diagnosed three days prior to presentation, and infection with influenza A (H3N2) pdm09 was subsequently confirmed. A diagnosis of ANE was made based on the presence of characteristic brain MRI findings, the exclusion of central nervous system infection, and an elevated serum interleukin-6 level. Pulse steroid therapy followed by tocilizumab was initiated, which led to clinical stabilization and improvement. Genetic testing revealed that the patient carried heterozygous human leukocyte antigen DQB1 03:03 and DRB1 09:01 genotypes. An analysis of the adult cases of influenza-associated ANE in the literature and the present case revealed a wide range of ages (22-71 years), a short interval (median 3 days) between the clinical onset of influenza and ANE, and a high overall mortality rate (32%). The thalamus was the most frequent (91%) location of the lesions. Our report highlights the importance of identifying this devastating but treatable neurological complication of influenza in adults, especially those of Asian descent. As a cytokine storm is the most accepted pathogenic mechanism for ANE, cytokine-directed therapies may be promising treatments for which further investigation is warranted.

Assuntos

Influenza Humana , Leucoencefalite Hemorrágica Aguda , Humanos , Adulto , Feminino , Influenza Humana/complicações , Influenza Humana/virologia , Leucoencefalite Hemorrágica Aguda/virologia , Leucoencefalite Hemorrágica Aguda/patologia , Imageamento por Ressonância Magnética , Vírus da Influenza A Subtipo H3N2/genética , Encéfalo/patologia , Encéfalo/diagnóstico por imagem , Anticorpos Monoclonais Humanizados

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In Candida albicans, Cdr1 pumps azole drugs out of the cells to reduce intracellular accumulation at detrimental concentrations, leading to azole-drug resistance. Milbemycin oxime, a veterinary anti-parasitic drug, strongly and specifically inhibits Cdr1. However, how Cdr1 recognizes and exports azole drugs, and how milbemycin oxime inhibits Cdr1 remain unclear. Here, we report three cryo-EM structures of Cdr1 in distinct states: the apo state (Cdr1Apo), fluconazole-bound state (Cdr1Flu), and milbemycin oxime-inhibited state (Cdr1Mil). Both the fluconazole substrate and the milbemycin oxime inhibitor are primarily recognized within the central cavity of Cdr1 through hydrophobic interactions. The fluconazole is suggested to be exported from the binding site into the environment through a lateral pathway driven by TM2, TM5, TM8 and TM11. Our findings uncover the inhibitory mechanism of milbemycin oxime, which inhibits Cdr1 through competition, hindering export, and obstructing substrate entry. These discoveries advance our understanding of Cdr1-mediated azole resistance in C. albicans and provide the foundation for the development of innovative antifungal drugs targeting Cdr1 to combat azole-drug resistance.

Assuntos

Antifúngicos , Azóis , Candida albicans , Microscopia Crioeletrônica , Proteínas Fúngicas , Proteínas de Membrana Transportadoras , Candida albicans/efeitos dos fármacos , Candida albicans/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/antagonistas & inibidores , Antifúngicos/farmacologia , Antifúngicos/química , Azóis/farmacologia , Azóis/química , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/ultraestrutura , Farmacorresistência Fúngica , Fluconazol/farmacologia , Sítios de Ligação

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Enhancement of Connexin43 (Cx43) and ferroptosis are respectively associated with the exacerbation of myocardial ischemia-reperfusion injury (MIRI) in diabetes. Myocardial vulnerability to ischemic insult has been shown to vary during early and later phases of diabetes in experimental settings. Whether or not Connexin43 (Cx43) and ferroptosis interplay during MIRI in diabetes is unknown. We, thus, aimed to investigate whether or not the content of myocardial Cx43 may be attributable to myocardial vulnerability to MIRI at different stages of diabetes and also to explore the potential interplay between Cx43 and ferroptosis in this pathology. Age-matched control and subgroups of Streptozotocin-induced diabetic mice were subjected to MIRI induced by 30 minutes coronary artery occlusion and 2 hours reperfusion respectively at 1, 2 and 5 weeks of diabetes. Rat cardiac H9C2 cells were exposed to high glucose (HG) for 48h in the absence or presence of Cx43 gene knockdown followed by hypoxia/reoxygenation (HR) respectively for 6 and 12 hours. Post-ischemic myocardial infarct size was reduced in 1 and 2 weeks DM mice concomitant with enhanced GPX4 and reduced cardiac Cx43 and ferroptosis as compared to control. By contrast, cardiac GPX4 was significantly reduced while Cx43 increased at DM 5 weeks (D5w) which was correspondent to significant increases in ferroptosis and myocardial infarction. Post-ischemic cardiac function was improved in 1 and 2 weeks but worsened in 5w DM mice as compared with non-diabetic control. GAP19 (Cx43 inhibitor) significantly attenuated ferroptosis and reduced myocardial infarction in D5w mice. Erastin (ferroptosis activator) reversed the cardioprotective effect of GAP19. In vitro, HR significantly reduced cell viability accompanied with reduced GPX4 but elevated Cx43 expression, MDA production and ferroptosis. Cx43 gene knockdown in H9C2 resulted in a significant increase in GPX4, reduction in MDA and ferroptosis, and subsequently reduced post-hypoxic cell viability. The beneficial effects of Cx43 gene knock-down was minified or eliminated by Erastin. It is concluded that Cx43 overexpression exacerbates MIRI under diabetic conditions via promoting ferroptosis, while its down-regulation at early state of diabetes is attributable to enhanced myocardial tolerance to MIRI.

Assuntos

Conexina 43 , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Ferroptose , Traumatismo por Reperfusão Miocárdica , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Animais , Ferroptose/genética , Conexina 43/metabolismo , Conexina 43/genética , Camundongos , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/genética , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Ratos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/genética , Masculino , Técnicas de Silenciamento de Genes , Humanos , Linhagem Celular , Miocárdio/patologia , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo

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This study investigates the therapeutic effectiveness of intranasal dantrolene nanoparticles in the Ryanodex formulation (DNRF) pretreatment to inhibit lipopolysaccharide (LPS)-induced depressive and anxiety behavior in mice. Both wild-type (WT) B6SJLF1/J and 5XFAD adult mice were pretreated with intranasal DNRF (5mg/kg), daily, Monday to Friday, 5 days per week, for 4 weeks. Then, mice were treated with intraperitoneal injection of LPS (5mg/kg) for one time. Behavioral tests for depression and anxiety were performed 24 hours after a one-time LPS injection. Biomarkers for inflammation (IL-1ß and IL-18) in blood were measured using enzyme-linked immunosorbent assay (ELISA). In both types of mice, intranasal DNRF significantly inhibited LPS-induced pathological elevation of IL-1ß and IL-18 in the blood. Intranasal DNRF abolished LPS-induced depression and anxiety behaviors behavior in both WT and 5XFAD mice, without obvious side effects, which was associated with its significant inhibition of pathological elevation of pyroptosis related cytokines in blood.

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Pomacea canaliculata, an invasive species native to South America, is recognized for its broad geographic distribution and adaptability to a variety of ecological conditions. The details concerning the evolution and adaptation of P. canaliculate remain unclear due to a lack of whole-genome resequencing data. We examined 173 P. canaliculata genomes representing 17 geographic populations in East and Southeast Asia. Interestingly, P. canaliculata showed a higher level of genetic diversity than other mollusks, and our analysis suggested that the dispersal of P. canaliculata could have been driven by climate changes and human activities. Notably, we identified a set of genes associated with low temperature adaptation, including Csde1, a cold shock protein coding gene. Further RNA sequencing analysis and reverse transcription quantitative polymerase chain reaction experiments demonstrated the gene's dynamic pattern and biological functions during cold exposure. Moreover, both positive selection and balancing selection are likely to have contributed to the rapid environmental adaptation of P. canaliculata populations. In particular, genes associated with energy metabolism and stress response were undergoing positive selection, while a large number of immune-related genes showed strong signatures of balancing selection. Our study has advanced our understanding of the evolution of P. canaliculata and has provided a valuable resource concerning an invasive species.

Assuntos

Adaptação Fisiológica , Espécies Introduzidas , Caramujos , Sequenciamento Completo do Genoma , Animais , Caramujos/genética , Adaptação Fisiológica/genética , Evolução Molecular , Ásia , Variação Genética , Seleção Genética , Filogenia , Evolução Biológica

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Integrated fixed-film activated sludge (IFAS) system, an improvement of the activated sludge process, combines the advantages of both attached sludge (AS) and suspended sludge (SS). This study aimed to fully decipher the roles of AS and SS in simultaneous N and P removal in an IFAS system through metagenomic analysis. It was found that AS contributed about 84.04%, 97%, and 95.12% to exogenous NO3--N reduction, endogenous NO3--N reduction, and endogenous NO2--N reduction, respectively. Compared with AS, SS exhibited a greater contribution to anaerobic P release (69.06%) and aerobic P uptake (73.48%). Nitrate and nitrite reductase enzymes showed higher activities in AS, while the activities of exopolyphosphatase and alkaline phosphatase D were more active in SS. P content further indicated that in AS, only a small amount of P was stored in EPS, with most presented intracellularly. In SS, the amount of P stored in EPS was found to be higher. Metagenomic analysis revealed genes related to the synthesis and degradation of endogenous carbon were higher in AS, whereas the TCA cycle exhibited higher activity in SS. P removal-related genes (such as ppk2, ppx, and adk) was significantly higher in SS than in AS. The alteration of genes associated with nitrogen metabolism suggested that the microbes in AS had a higher capacity for nitrification and denitrification. In summary, the discrepancy in the roles of AS and SS in N and P removal in IFAS can be attributed to variations in enzyme activity, P storage in EPS, microbial community composition, and functional gene abundance.

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Detection and Dissection of Anomalous Tissue Domains (DDATD) from multi-sample spatial transcriptomics (ST) data provides unprecedented opportunities to characterize anomalous tissue domains (ATDs), revealing both population-level and individual-specific pathogenic factors for understanding pathogenic heterogeneities behind diseases. However, no current methods can perform de novo DDATD from ST data, especially in the multi-sample context. Here, we introduce STANDS, an innovative framework based on Generative Adversarial Networks which integrates three core tasks in multi-sample DDATD: detecting, aligning, and subtyping ATDs. STANDS incorporates multimodal-learning, transfer-learning, and style-transfer techniques to effectively address major challenges in multi-sample DDATD, including complications caused by unalignable ATDs, under-utilization of multimodal information, and scarcity of normal ST datasets necessary for comparative analysis. Extensive benchmarks from diverse datasets demonstrate STAND's superiority in identifying both common and individual-specific ATDs and further dissecting them into biologically distinct subdomains. STANDS also provides clues to developing ATDs visually indistinguishable from surrounding normal tissues.

Assuntos

Transcriptoma , Humanos , Transcriptoma/genética , Perfilação da Expressão Gênica/métodos , Algoritmos , Biologia Computacional/métodos

RESUMO

Plastics aging reduces resistance to microbial degradation. Plastivore Tenebrio molitor rapidly biodegrades polystyrene (PS, size: < 80 µm), but the effects of aging on PS biodegradation by T. molitor remain uncharacterized. This study examined PS biodegradation over 24 days following three pre-treatments: freezing with UV exposure (PS1), UV exposure (PS2), and freezing (PS3), compared to pristine PS (PSv) microplastic. The pretreatments deteriorated PS polymers, resulting in slightly higher specific PS consumption (602.8, 586.1, 566.7, and 563.9 mg PS·100 larvae-1·d-1, respectively) and mass reduction rates (49.6 %, 49.5 %, 49.2 %, and 48.7 %, respectively) in PS1, PS2, and PS3 compared to PSv. Improved biodegradation correlated with reduced molecular weights and the formation of oxidized functional groups. Larvae fed more aged PS exhibited greater gut microbial diversity, with microbial community and metabolic pathways shaped by PS aging, as supported by co-occurrence network analysis. These findings indicated that the aging treatments enhanced PS biodegradation by only limited extent but impacted greater on gut microbiome and bacterial metabolic genes, indicating that the T. molitor host have highly predominant capability to digest PS plastics and alters gut microbiome to adapt the PS polymers fed to them.

Assuntos

Biodegradação Ambiental , Microbioma Gastrointestinal , Larva , Poliestirenos , Tenebrio , Animais , Tenebrio/metabolismo , Microbioma Gastrointestinal/fisiologia , Larva/metabolismo , Bactérias/metabolismo , Plásticos/metabolismo , Poluentes Químicos da Água/metabolismo

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BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with decreased heart rate variability (HRV) with an unclear intermediate mechanism. This study aimed to conduct mediation analysis to explore the impact of various adipose tissues on the relationship between T2DM and HRV. METHODS: A total of 380 participants were enrolled for analysis, including 249 patients with T2DM and 131 non-diabetic controls. The thicknesses of four adipose tissues (subcutaneous, extraperitoneal, intraperitoneal, and epicardial) were measured by abdominal ultrasound or echocardiography respectively. HRV was assessed by 24-hour Holter for monitoring both frequency domain indices (LF, HF, and LF/HF) and time domain indices (SDNN, SDANN, SDNN index, rMSSD and pNN50). Mediation analysis was used toexamine whether adipose tissues mediated the relationship between T2DM and each index of HRV. Then, a latent variable - HRV burden - was constructed by structural equation model with selected HRV indices to comprehensively assess the whole HRV. RESULTS: Compared to non-diabetic controls, patients with T2DM exhibited a significant reduction in indices of HRV, and a remarkable increase in the thicknesses of extraperitoneal, intraperitoneal, and epicardial adipose tissues. Mediation analysis found significant indirect effects of T2DM on six indices of HRV, including HF, SDNN, SDANN, SDNN index, rMSSD, and pNN50, which was mediated by epicardial adipose tissue rather than other adipose tissues, with the mediation proportions of 64.21%, 16.38%, 68.33%, 24.34%, 24.10% and 30.51%, respectively. Additionally, epicardial adipose tissue partially mediated the relationship between T2DM and reduced HRV burden (24.26%), which composed by SDNN, SDNN index, rMSSD, and pNN50. CONCLUSION: Epicardial adipose tissue partially mediated the relationship between T2DM and reduced HRV, which reinforces the value of targeting heart-specific visceral fat to prevent cardiac autonomic neuropathy in diabetes.

Assuntos

Adiposidade , Diabetes Mellitus Tipo 2 , Frequência Cardíaca , Humanos , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Idoso , Análise de Mediação , Eletrocardiografia Ambulatorial , Fatores de Risco , Adulto , Fatores de Tempo , Estudos Transversais , Tecido Adiposo/fisiopatologia , Tecido Adiposo/diagnóstico por imagem , Medição de Risco , Sistema Nervoso Autônomo/fisiopatologia , Gordura Intra-Abdominal/fisiopatologia , Gordura Intra-Abdominal/diagnóstico por imagem

RESUMO

BACKGROUND & AIMS: Malnutrition is prevalent among hospitalised patients, and increases the morbidity, mortality, and medical costs; yet nutritional assessments on admission are not routine. This study assessed the clinical and economic benefits of using an artificial intelligence (AI)-based rapid nutritional diagnostic system for routine nutritional screening of hospitalised patients. METHODS: A nationwide multicentre randomised controlled trial was conducted at 11 centres in 10 provinces. Hospitalised patients were randomised to either receive an assessment using an AI-based rapid nutritional diagnostic system as part of routine care (experimental group), or not (control group). The overall medical resource costs were calculated for each participant and a decision-tree was generated based on an intention-to-treat analysis to analyse the cost-effectiveness of various treatment modalities. Subgroup analyses were performed according to clinical characteristics and a probabilistic sensitivity analysis was performed to evaluate the influence of parameter variations on the incremental cost-effectiveness ratio (ICER). RESULTS: In total, 5763 patients participated in the study, 2830 in the experimental arm and 2933 in the control arm. The experimental arm had a significantly higher cure rate than the control arm (23.24% versus 20.18%; p = 0.005). The experimental arm incurred an incremental cost of 276.52 CNY, leading to an additional 3.06 cures, yielding an ICER of 90.37 CNY. Sensitivity analysis revealed that the decision-tree model was relatively stable. CONCLUSION: The integration of the AI-based rapid nutritional diagnostic system into routine inpatient care substantially enhanced the cure rate among hospitalised patients and was cost-effective. REGISTRATION: NCT04776070 (https://clinicaltrials.gov/study/NCT04776070).

Assuntos

Inteligência Artificial , Análise Custo-Benefício , Hospitalização , Desnutrição , Avaliação Nutricional , Humanos , Masculino , Feminino , Inteligência Artificial/economia , Idoso , Pessoa de Meia-Idade , Desnutrição/diagnóstico , Desnutrição/economia , Hospitalização/economia , Estado Nutricional , Idoso de 80 Anos ou mais , Adulto

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Psoriasis is a recurrent autoimmune disease characterized by seasonal and latitudinal variations. Double-stranded DNA (dsDNA) is a crucial component of nucleic acids and nucleosomes that provoke innate immune responses. Given the potential influence of climate on immunity and the development of autoimmune diseases, a comprehensive quantitative analysis of dsDNA levels in the population is warranted. In this case-control study conducted from 2016 to 2020, 10,110 psoriasis patients and matched controls from 12 regions in China were included. This study examined variations in serum dsDNA levels based on season and latitude. The results revealed significant associations between geographical location, climatic conditions, and season with serum dsDNA concentration. Individuals residing in Northern China exhibited significantly higher serum dsDNA levels compared to those in the South (1.00 vs. 0.96 ng/ml), and those in medium latitude regions had higher levels than their counterparts in areas with extreme latitudes (0.98 vs. 0.96 ng/ml). Furthermore, individuals in regions with low to medium ultraviolet exposure demonstrated higher serum dsDNA concentrations than those in areas with high ultraviolet levels (1.03 vs. 0.93 ng/ml), and individuals in winter showed higher levels than those in summer (1.03 vs. 0.92 ng/ml). Factors such as sex, UV index, humidity, and sunshine duration were inversely related to serum dsDNA levels, while age and daylight hours showed a positive association. These findings suggest that meteorological and climatic factors play a role in influencing serum dsDNA levels.

RESUMO

Recalcitrant structure of cell walls restricts the extraction of bioactive components from edible plants. In this study, the impacts of steam explosion (SE) on the release and transformation of flavonoids in Astragali Radix (AR) were evaluated. Results revealed that SE destroyed the compact structure of cell walls. Furthermore, the porous network was reformed due to the degradation of hemicelluloses and water-soluble components. The maximum extraction contents of ethanol-soluble and water-soluble flavonoids of 6.34 and 1.48 mg/g were obtained from the pretreated AR (1.5 MPa, 5 min), which were 5.22 and 2.88 times higher than those obtained from the untreated AR, respectively. SE not only released bound flavonoids from cell walls by cleaving glycoside or ester bonds, but also transformed some flavonoid glycosides into aglycones through deglycosylation. In conclusion, SE can reduce mass transfer hindrance and facilitate flavonoid transformation, thus providing a green and facile processing method for traditional edible plants.

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Gout is a heterogeneous disease caused by the deposition of monosodium urate crystals in joints, but its pathogenesis is currently poorly understood. The discovery of novel biomarkers is necessary for the early detection and diagnosis of gout. The present study aimed to characterize the metabolic profile of patients with gout using metabolomics, and to uncover the underlying pathological mechanisms leading to gout development. Serum samples were collected from 49 healthy participants and 47 patients with gout. Using ultra-high-performance liquid chromatography Orbitrap Exploris mass spectrometer non-target metabolomics technology, with a variable importance in the projection >1 and a false discovery rate adjusted P<0.05 was used, while a biomarker panel was screened using receiver operating characteristic (ROC) analysis. The potential differentially expressed markers related to gout were identified by ROC analysis, and the erythrocyte sedimentation rate, uric acid, alanine transaminase, aspartate aminotransferase, creatinine, triglyceride, total cholesterol, high-density lipoprotein and low-density lipoprotein levels were significantly different in the group of patients with gout compared with those in healthy individuals. A total of 186 differentially expressed metabolites were identified, with 156 differential metabolites upregulated and 30 downregulated in the patients with gout compared with healthy individuals. Pathway analysis demonstrated that D-glutamine and D-glutamate metabolism may serve key roles in gout. Compared with healthy people, the indolelactic acid (ILA) level of patients with gout was significantly higher. ILA may serve as a potential biomarker for the diagnosis of gout and could be used to detect or predict gout progression in the future.

RESUMO

BACKGROUND: Vunakizumab, a novel anti-IL-17A antibody, has showed promising efficacy for moderate-to-severe plaque psoriasis in a phase 2 trial. OBJECTIVE: We conducted a double-blind, randomized phase 3 trial (NCT04839016) to further evaluate vunakizumab in this population. METHODS: 690 subjects were randomized (2:1) to receive vunakizumab 240 mg or placebo at weeks 0, 2, 4 and 8. At week 12, subjects on placebo were switched to vunakizumab 240 mg (weeks 12, 14, 16 and q4w thereafter). The co-primary endpoints were ≥90% improvement from baseline in the psoriasis area-and-severity index score (PASI 90) and a static Physicians Global Assessment score of 0/1 (sPGA 0/1) at week 12. RESULTS: At week 12, the vunakizumab group showed higher PASI 90 (76.8% vs 0.9%) and sPGA 0/1 (71.8% vs 0.4%) response rates, as well as higher PASI 75 (93.6% vs 4.0%), PASI 100 (36.6% vs 0.0%) and sPGA 0 (38.2% vs 0.0%) response rates (all two-sided P<0.0001 vs placebo). Efficacy was maintained through week 52 with continuous vunakizumab. Possible treatment-related serious adverse events occurred in 0.9% of vunakizumab-treated subjects. LIMITATIONS: Chinese subjects only; no active comparator. CONCLUSION: Vunakizumab demonstrated robust clinical response at week 12 and through week 52, with good tolerability in moderate-to-severe plaque psoriasis.

RESUMO

We proposed a novel fiber Mach-Zehnder interferometer (FMZI) that can perform an ultrahigh extinction ratio (ER), ultracompact, and ultra-broadband interference characteristics. The FMZI structure is based on an extremely tiny hollow core fiber (HCF) with a small diameter of 10 µm (named HCF10) connected with a beam splitter of a large core of 50 µm HCF (named HCF50). The refractive index (RI) of the air core is lower than that of the HCF cladding; a leaky-guided fiber waveguide (LGFW) occurs in such a short-section HCF10 waveguide to simultaneously have the core and cladding modes. To achieve better fringe visibility of the interference, the section of HCF50 assists in splitting the optical light into core and cladding beams launched into the HCF10 with appropriate intensities. Experimental and simulation results show that the optical characteristics of the proposed LGFW-FMZI are very similar. Based on the results of the study, the length of the HCF10 primarily influences the free spectral range (FSR) of the interference spectra, and the HCF50 splitter significantly controls the optimal extinction ratio (ER) of the interference fringes. By exactly adjusting the lengths of HCF10 and HCF50, the proposed fiber interferometers can perform the capability of an ultrahigh ER over 50 dB with the arbitrary FSR in the transmitted interference spectra over an ultra-broad wavelength range of 1250 nm to 1650 nm.

RESUMO

With the emergence of new variant strains resulting from high mutation rates and genome recombination, avian infectious bronchitis virus (IBV) has caused significant economic losses to the poultry industry worldwide. Little is known about the underlying mechanisms of IBV-host interactions, particularly how IBV utilizes host metabolic pathways for efficient viral replication and transmission. In the present study, the effects of the cell membrane, viral envelope membrane, and viperin-mediated cholesterol synthesis on IBV replication were explored. Our results revealed significant increase in cholesterol levels and the expression of viperin after IBV infection. Acute cholesterol depletion in the cell membrane and viral envelope membrane by treating cells with methyl-ß-cyclodextrin (MßCD) obviously inhibited IBV replication; thereafter, replenishment of the cell membrane with cholesterol successfully restored viral replication, and direct addition of exogenous cholesterol to the cell membrane significantly promoted IBV infection during the early stages of infection. In addition, overexpression of viperin effectively suppressed cholesterol synthesis, as well as IBV replication, whereas knockdown of viperin (gene silencing with siRNA targeting viperin, siViperin) significantly increased IBV replication and cholesterol levels, whereas supplementation with exogenous cholesterol to viperin-transfected cells markedly restored viral replication. In conclusion, the increase in viperin induced by IBV infection plays an important role in IBV replication by affecting cholesterol production, providing a theoretical basis for understanding the pathogenesis of IBV and discovering new potential antiviral targets.

Assuntos

Galinhas , Colesterol , Vírus da Bronquite Infecciosa , Replicação Viral , Vírus da Bronquite Infecciosa/fisiologia , Animais , Colesterol/metabolismo , Doenças das Aves Domésticas/virologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia