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The practical applications of aqueous zinc-ion batteries (AZIBs) have been restricted by the fast growth of Zn dendrites and severe side reactions at the Zn/electrolyte interface. Herein, a multifunctional additive, L-leucine (Leu), is incorporated into a mild acidic electrolyte to stabilize the Zn anode. The Leu molecule, featuring both carboxyl and amino groups, exhibits strong interactions with Zn2+, which can reshape the solvation structure of Zn2+ and facilitate the uniform electrodeposition of Zn. Simultaneously, the Leu molecule exhibits preferential adsorption onto the Zn surface, effectively isolating it from direct contact with water, thus suppressing unwanted side reactions. Consequently, the Znâ¥Cu asymmetric cell exhibits a high and stable coulombic efficiency of 99.5% at a current density of 5 mA cm-2 for 1100 h. Importantly, the capacity retention of the Znâ¥NH4V4O10 full cell based on the Leu electrolyte reaches 80% after 1200 cycles at a current density of 2 A g-1. The successful application of the low-cost Leu effectively enhances the cycling stability of the AZIBs and accelerates their applications.
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In March 2023, our pediatric intensive care unit (PICU) retrospectively examined six cases of pediatric necrotizing tracheobronchitis (NTB), focusing on co-infections with influenza A virus (IAV) and Staphylococcus aureus (S. aureus). This study aimed to elucidate NTB's clinical characteristics, diagnostics, and therapeutic approaches. Diagnostics included symptom assessment, microbiological testing that confirmed all patients were positive for IAV H1N1 with a predominant S. aureus co-infection, and bronchoscopy. The patients predominantly exhibited fever, cough, and dyspnea. Laboratory analysis revealed decreased lymphocyte counts and elevated infection markers like C-reactive protein and procalcitonin. Chest computed tomography (CT) scans detected tracheobronchial obstructions in half of the cases, while bronchoscopy showed severe mucosal congestion, edema, necrosis, and purulent-hemorrhagic exudates. Treatments encompassed comprehensive strategies like oxygen therapy, intubation, bronchoscopic interventions, thoracentesis, oseltamivir, and a regimen of antibiotics. Our findings suggested potential correlations between clinical markers, notably lymphocyte count and procalcitonin, and clinical interventions such as the number of rescues and intensive care unit (ICU) duration. This research highlights the importance of early detection and the role of bronchoscopy and specific markers in assessing NTB, advocating for continued research in larger cohorts to better understand its clinical trajectory and refine treatment approaches for this challenging pediatric disease.
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Bronquitis , Coinfección , Gripe Humana , Infecciones Estafilocócicas , Staphylococcus aureus , Traqueítis , Humanos , Coinfección/diagnóstico , Masculino , Femenino , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/complicaciones , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , Preescolar , Traqueítis/diagnóstico , Traqueítis/microbiología , Traqueítis/complicaciones , Bronquitis/diagnóstico , Bronquitis/microbiología , Bronquitis/complicaciones , Estudios Retrospectivos , Staphylococcus aureus/aislamiento & purificación , Lactante , Niño , Broncoscopía/métodos , Unidades de Cuidado Intensivo Pediátrico , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Necrosis , Virus de la Influenza A/aislamiento & purificaciónAsunto(s)
Glomerulonefritis por IGA , Glomeruloesclerosis Focal y Segmentaria , Humanos , Glomerulonefritis por IGA/patología , Glomerulonefritis por IGA/clasificación , Glomeruloesclerosis Focal y Segmentaria/patología , Glomeruloesclerosis Focal y Segmentaria/clasificación , Glomeruloesclerosis Focal y Segmentaria/diagnóstico , Glomérulos Renales/patología , BiopsiaRESUMEN
Aims/Background Kawasaki disease is an acute inflammatory condition primarily affecting the young children. It can lead to coronary artery abnormalities, which can worsen the prognosis. Early diagnosis of coronary disease is crucial for the effective treatment and the prognosis evaluation. To explore the clinical significance of ultrasound examination characteristics, peripheral blood red cell distribution width, and changes in N-terminal pro-brain natriuretic peptide levels for the early detect coronary artery abnormality in children with Kawasaki disease. Methods The case-control study was conducted. 85 Kawasaki disease patients diagnosed in our hospital from January 2020 to December 2023 were selected as the Kawasaki disease group. 100 healthy children who received physical examination in the Department of Child Healthcare during the same period were selected as control group. The cardiac ultrasound indicators, erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, N-terminal pro-brain natriuretic peptide of two groups were compared. The Kawasaki disease group was further divided into the coronary artery lesion group and the non-coronary artery lesion group based on whether coronary artery lesions occurred in the Kawasaki disease patients. The differences of above indicators were compared. Results The left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of the Kawasaki disease group were all higher than those of the control group (p < 0.05). There was no significant difference in left ventricular ejection fraction between Kawasaki disease group and control group (p > 0.05). The erythrocyte sedimentation rate, C-reactive protein, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease group were all higher than those of control group (p < 0.05). The left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of Kawasaki disease patients with coronary artery lesions were all higher than those of Kawasaki disease patients without coronary artery lesions (p < 0.05). The left ventricular ejection fraction of Kawasaki disease patients with coronary artery lesions was lower than that of Kawasaki disease patients without coronary artery lesions (p < 0.05). The erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease patients with coronary artery lesions were all higher than those of Kawasaki disease patients without coronary artery lesions, and the differences were statistically significant (p < 0.05). After treatment, the left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of Kawasaki disease patients with coronary artery lesions significantly decreased (p < 0.05), and the left ventricular ejection fraction significantly increased (p < 0.05). The erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease patients with or without coronary artery lesions significantly decreased after treatment compared with before treatment in the same group (p < 0.05). Conclusion Kawasaki disease patients with coronary artery lesions exhibit significantly increased coronary artery vessel diameter, as well as elevated red cell distribution width and N-terminal pro-brain natriuretic peptide concentration. The combined use of ultrasound combined with red cell distribution width and N-terminal pro-brain natriuretic peptide examination can assist in determining whether Kawasaki disease patients have coronary artery lesions and assessing the clinical treatment effect.
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Ecocardiografía , Índices de Eritrocitos , Síndrome Mucocutáneo Linfonodular , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Humanos , Síndrome Mucocutáneo Linfonodular/sangre , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/fisiopatología , Péptido Natriurético Encefálico/sangre , Masculino , Femenino , Estudios de Casos y Controles , Preescolar , Lactante , Fragmentos de Péptidos/sangre , Sedimentación Sanguínea , Niño , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Biomarcadores/sangre , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismoRESUMEN
Anti-interferon-γ monoclonal antibody emapalumab and JAK1/2 inhibitors ruxolitinib have been widely reported for the treatment of hemophagocytic lymphohistiocytosis (HLH) recently. These targeted drugs have fewer side effects and may provide new options for patients with HLH who are refractory to previous treatment or intolerant to chemotherapy. Herein, we reported a case of Epstein-Barr virus-related HLH, which did not respond well to HLH-94 plus ruxolitinib and developed severe fungal infection. The disease was successfully controlled after a combination therapy of emapalumab, ruxolitinib, and dexamethasone.
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Anticuerpos Monoclonales , Dexametasona , Infecciones por Virus de Epstein-Barr , Linfohistiocitosis Hemofagocítica , Nitrilos , Pirazoles , Pirimidinas , Humanos , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/etiología , Linfohistiocitosis Hemofagocítica/virología , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Quimioterapia Combinada , Masculino , Herpesvirus Humano 4 , Femenino , Anticuerpos NeutralizantesRESUMEN
The CCT gene family is present in plants and is involved in biological processes such as flowering, circadian rhythm regulation, plant growth and development, and stress resistance. We identified 87, 62, 46, and 40 CCTs at the whole-genome level in B. napus, B. rapa, B. oleracea, and A. thaliana, respectively. The CCTs can be classified into five groups based on evolutionary relationships, and each of these groups can be further subdivided into three subfamilies (COL, CMF, and PRR) based on function. Our analysis of chromosome localization, gene structure, collinearity, cis-acting elements, and expression patterns in B. napus revealed that the distribution of the 87 BnaCCTs on the chromosomes of B. napus was uneven. Analysis of gene structure and conserved motifs revealed that, with the exception of a few genes that may have lost structural domains, the majority of genes within the same group exhibited similar structures and conserved domains. The gene collinearity analysis identified 72 orthologous genes, indicating gene duplication and expansion during the evolution of BnaCCTs. Analysis of cis-acting elements identified several elements related to abiotic and biotic stress, plant hormone response, and plant growth and development in the promoter regions of BnaCCTs. Expression pattern and protein interaction network analysis showed that BnaCCTs are differentially expressed in various tissues and under stress conditions. The PRR subfamily genes have the highest number of interacting proteins, indicating their significant role in the growth, development, and response to abiotic stress of B. napus.
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Brassica napus , Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Familia de Multigenes , Filogenia , Proteínas de Plantas , Brassica napus/genética , Brassica napus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Cromosomas de las Plantas/genética , Estrés Fisiológico/genética , Evolución Molecular , Mapeo CromosómicoRESUMEN
ABSTRACT: Over the past decade, mitochondrial dysfunction has been investigated as a key contributor to acute and chronic kidney disease. However, the precise molecular mechanisms linking mitochondrial damage to kidney disease remain elusive. The recent insights into the cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthetase (cGAS)-stimulator of interferon gene (STING) signaling pathway have revealed its involvement in many renal diseases. One of these findings is that mitochondrial DNA (mtDNA) induces inflammatory responses via the cGAS-STING pathway. Herein, we provide an overview of the mechanisms underlying mtDNA release following mitochondrial damage, focusing specifically on the association between mtDNA release-activated cGAS-STING signaling and the development of kidney diseases. Furthermore, we summarize the latest findings of cGAS-STING signaling pathway in cell, with a particular emphasis on its downstream signaling related to kidney diseases. This review intends to enhance our understanding of the intricate relationship among the cGAS-STING pathway, kidney diseases, and mitochondrial dysfunction.
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ADN Mitocondrial , Enfermedades Renales , Proteínas de la Membrana , Mitocondrias , Nucleotidiltransferasas , Transducción de Señal , Humanos , Transducción de Señal/fisiología , Nucleotidiltransferasas/metabolismo , Mitocondrias/metabolismo , Enfermedades Renales/metabolismo , ADN Mitocondrial/metabolismo , ADN Mitocondrial/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/fisiología , AnimalesRESUMEN
Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease (CKD) on a global scale, with its incidence witnessing a consistent annual rise, thereby imposing a substantial burden on public health. The pathogenesis of DKD is primarily rooted in metabolic disorders and inflammation. Recent years have seen a surge in studies highlighting the regulatory impact of energy metabolism on innate immunity, forging a significant area of research interest. Within this context, fibroblast growth factor 21 (FGF21), recognized as an energy metabolism regulator, assumes a pivotal role. Beyond its role in maintaining glucose and lipid metabolism homeostasis, FGF21 exerts regulatory influence on innate immunity, concurrently inhibiting inflammation and fibrosis. Serving as a nexus between energy metabolism and innate immunity, FGF21 has evolved into a therapeutic target for diabetes, nonalcoholic steatohepatitis, and cardiovascular diseases. While the relationship between FGF21 and DKD has garnered increased attention in recent studies, a comprehensive exploration of this association has yet to be systematically addressed. This paper seeks to fill this gap by summarizing the mechanisms through which FGF21 operates in DKD, encompassing facets of energy metabolism and innate immunity. Additionally, we aim to assess the diagnostic and prognostic value of FGF21 in DKD and explore its potential role as a treatment modality for the condition.
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Diabetes Mellitus , Nefropatías Diabéticas , Factores de Crecimiento de Fibroblastos , Humanos , Inflamación/metabolismo , Inmunidad Innata , Metabolismo EnergéticoRESUMEN
Objective: The aim of this study is to investigate the clinical value of radiomics based on non-enhanced head CT in the prediction of hemorrhage transformation in acute ischemic stroke (AIS). Materials and methods: A total of 140 patients diagnosed with AIS from January 2015 to August 2022 were enrolled. Radiomic features from infarcted areas on non-enhanced CT images were extracted using ITK-SNAP. The max-relevance and min-redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) were used to select features. The radiomics signature was then constructed by multiple logistic regressions. The clinicoradiomics nomogram was constructed by combining radiomics signature and clinical characteristics. All predictive models were constructed in the training group, and these were verified in the validation group. All models were evaluated with the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: Of the 140 patients, 59 experienced hemorrhagic transformation, while 81 remained stable. The radiomics signature was constructed by 10 radiomics features. The clinicoradiomics nomogram was constructed by combining radiomics signature and atrial fibrillation. The area under the ROC curve (AUCs) of the clinical model, radiomics signature, and clinicoradiomics nomogram for predicting hemorrhagic transformation in the training group were 0.64, 0.86, and 0.86, respectively. The AUCs of the clinical model, radiomics signature, and clinicoradiomics nomogram for predicting hemorrhagic transformation in the validation group were 0.63, 0.90, and 0.90, respectively. The DCA curves showed that the radiomics signature performed well as well as the clinicoradiomics nomogram. The DCA curve showed that the clinical application value of the radiomics signature is similar to that of the clinicoradiomics nomogram. Conclusion: The radiomics signature, constructed without incorporating clinical characteristics, can independently and effectively predict hemorrhagic transformation in AIS patients.
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Aqueous zinc-ion batteries (AZIBs) have demonstrated great potential for large-scale energy storage. However, their practical applications have been restricted by fast Zn dendrite growth and severe side reactions at the Zn/electrolyte interface. Herein, sodium gluconate is incorporated into a mild acidic electrolyte as a multifunctional additive to stabilize the Zn anode. Experiments and theoretical calculations reveal that the SG additive can induce planar growth of Zn along its (002) direction, thereby inhibiting Zn dendrite growth. This dendrite inhibition effect is attributed to the preferential adsorption of Zn2+ on the Zn (002) plane, while the Zn (100) and (101) planes are shielded by gluconate ions. Consequently, Zn||Zn symmetric cells with the electrolyte additive exhibit significantly prolonged cycle lives of 2000 h at 1 mA cm-2, 1 mA h cm-2 and 900 h at 5 mA cm-2, 2.5 mA h cm-2. Futhermore, the Zn||NH4V4O10 full cell retains 95% of its initial capacity after 2000 cycles at a current density of 5 A g-1 with an average CE of nearly 100%. This work offers a cost-effective strategy to enhance the electrochemical performance of AZIBs.
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BACKGROUND RASopathies involve mutations in genes that encode proteins participating in the RAS-mitogen-activated protein kinase pathway and are a collection of multisystem disorders that clinically overlap. Variants in the SHOC2 gene have been reported in Noonan-like syndrome, which include distinct facial features, short stature, congenital cardiac defects, developmental delays, bleeding disorders, and loose anagen hair. This report is of a 7-year-old girl with the c.4A>G (p.Ser2Gly) variant of the SHOC2 gene, consistent with Noonan-like syndrome, with loose anagen hair, presenting with thrombotic thrombocytopenic purpura and autoimmune hemolytic anemia. CASE REPORT The child had a medical history of 7 hospitalizations at our institution. At the age of 2 months, she underwent surgical correction for ventricular and atrial septal defects. At the age of 2 years, tonsil and adenoid removal surgery was performed, followed by surgery for otitis media at age 5 years. At 7 years, she was hospitalized for the simultaneous occurrence of thrombotic thrombocytopenic purpura and autoimmune hemolytic anemia. The patient displayed short stature and mild intellectual disability. Notable facial features included sparse hair, mild frontal bossing, and low-set ears. Antinuclear antibody levels demonstrated a significant gradual shift. Through trio whole-exome sequencing, a c.4A>G (p.Ser2Gly) variation in the SHOC2 gene was identified. CONCLUSIONS Given the clinical information and genetic testing results, the patient's condition appeared to closely be a type of RASopathy. This report has highlighted the importance of physical, developmental, and genetic testing in children presenting with dysmorphism, developmental delay, and hematological abnormalities.
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Anemia Hemolítica Autoinmune , Síndrome de Noonan , Púrpura Trombocitopénica Trombótica , Femenino , Humanos , Niño , Preescolar , Lactante , Fenotipo , Anemia Hemolítica Autoinmune/complicaciones , Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/genética , Síndrome de Noonan/genética , Mutación , Péptidos y Proteínas de Señalización Intracelular/genéticaRESUMEN
Lobular capillary hemangioma (LCH), previously known as pyogenic granuloma, is a benign vascular lesion commonly found within the oral and nasal cavities. However, it is rarely encountered within the trachea, especially in pediatric patients, where it manifests as hemoptysis, cough, and wheeze, and is frequently misdiagnosed as bronchitis or asthma. There is limited literature on the presentation, behavior, and management of tracheal LCH. Herein, we describe a rare case of tracheal LCH in an 11-year-old boy with a history of hemoptysis, which was successfully managed with arterial embolization followed by electrocautery loop snaring via flexible bronchoscopy. No complications occurred during and after the procedure. A review of the relevant literature is also provided. Our case is unique, given the therapeutic strategy utilized for pediatric tracheal LCH, and reminds physicians to be aware of tracheal LCH in the differential diagnosis for hemoptysis.
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Introduction: The primary factor for cardiovascular disease and upcoming cardiovascular events is atherosclerosis. Recently, carotid plaque texture, as observed on ultrasonography, is varied and difficult to classify with the human eye due to substantial inter-observer variability. High-resolution magnetic resonance (MR) plaque imaging offers naturally superior soft tissue contrasts to computed tomography (CT) and ultrasonography, and combining different contrast weightings may provide more useful information. Radiation freeness and operator independence are two additional benefits of M RI. However, other than preliminary research on MR texture analysis of basilar artery plaque, there is currently no information addressing MR radiomics on the carotid plaque. Methods: For the automatic segmentation of MRI scans to detect carotid plaque for stroke risk assessment, there is a need for a computer-aided autonomous framework to classify MRI scans automatically. We used to detect carotid plaque from MRI scans for stroke risk assessment pre-trained models, fine-tuned them, and adjusted hyperparameters according to our problem. Results: Our trained YOLO V3 model achieved 94.81% accuracy, RCNN achieved 92.53% accuracy, and MobileNet achieved 90.23% in identifying carotid plaque from MRI scans for stroke risk assessment. Our approach will prevent incorrect diagnoses brought on by poor image quality and personal experience. Conclusion: The evaluations in this work have demonstrated that this methodology produces acceptable results for classifying magnetic resonance imaging (MRI) data.
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We described a 14-year-old girl with acute lymphoblastic leukemia who developed disseminated mucormycosis during induction therapy. Disseminated Cunninghamella elegans infection was confirmed by histopathology, microbiological culture, and metagenomic next-generation sequencing analysis of skin tissue, blood, and cerebrospinal fluid. Subsequently, the patient received a combination of liposomal amphotericin B, posaconazole, and caspofungin for antifungal treatment, but eventually died because of severe fungal pneumonia, respiratory failure, and septic shock. Moreover, case reports of pulmonary mucormycosis in children published since 1959 were reviewed. In summary, metagenomic next-generation sequencing is an effective diagnostic method for Cunninghamella with high speed and sensitivity.
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Cunninghamella , Mucormicosis , Leucemia-Linfoma Linfoblástico de Células Precursoras , Femenino , Humanos , Niño , Adolescente , Mucormicosis/tratamiento farmacológico , Quimioterapia de Inducción , Antifúngicos/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológicoRESUMEN
BACKGROUND: Novel nonsteroidal mineralocorticoid receptor antagonists (MRAs) are noted for their potential cardiorenal benefits for patients with type 2 diabetes mellitus and chronic kidney diseases; however, the effect of this regimen on renal outcomes remains uncertain. METHODS: We performed a systematic review and meta-analysis of nonsteroidal MRAs focusing primarily on renal outcomes and safety in randomized, controlled trials. The MEDLINE, Embase, and Cochrane databases were systemically searched for trials published through April 2022. We included randomized, controlled trials assessing the effects of nonsteroidal MRAs on renal outcomes, as well as cardiovascular disease (CVD) effects in patients with chronic kidney disease (CKD). Summary estimates of risk ratios (RRs) reductions were calculated with a random-effects model. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to evaluate the certainty of evidence. This study is registered with PROSPERO under number CRD42022335464. FINDINGS: In total, 11 trials and 1 pooled analysis including a total of 17,517 participants were enrolled. Nonsteroidal MRAs reduced renal composite endpoints by 17 % [HR = 0.83, 95 % (0.75, 0.91); low quality] with 16 % in kidney failure (high quality), 23 % in ESRD (high quality), 20 % in eGFR decreased to less than 15 mL/min/1.73 m2 (high quality), and 17 % with more than a 40 % decrease in eGFR (high quality); 14 % with cardiovascular composite endpoints [HR = 0.86, 95 % (0.78, 0.94); moderate quality]; and 13 % of all-cause mortality [HR = 0.87, 95 % (0.76, 0.98); moderate quality]. Nonsteroidal MRAs were also associated with additional benefits in lowering UACR levels (moderate quality) and lowering BP levels (moderate quality) compared with the control groups. However, nonsteroidal MRAs did not show a statistically significant effect on the risk of renal death (moderate quality), hospitalization for any cause (moderate quality) or change in GFR (low quality). Regarding safety, there was no significant difference in the risk of adverse events between the participants receiving nonsteroidal MRAs and the control group. INTERPRETATION: Nonsteroidal MRAs had a statistically beneficial effect on reducing the risk of the composite kidney outcome, the composite of cardiovascular outcomes, and all-cause mortality. Nonsteroidal MRAs were also associated with benefits of proteinuria remission and blood pressure lowering. Although these findings provided positive evidence for the use of nonsteroidal MRAs for cardiorenal protection in patients with or without CKD, the quality of this evidence is potentially uncertain.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Humanos , Antagonistas de Receptores de Mineralocorticoides/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Insuficiencia Renal Crónica/complicaciones , Enfermedades Cardiovasculares/complicaciones , RiñónRESUMEN
Tumor-infiltrating lymphocyte (TIL) is a class of cells with important immune functions and plays a crucial role in bladder cancer (BCa). Several studies have shown the clinical significance of TIL in predicting the prognosis and immunotherapy efficacy. TIL-related gene module was screened utilizing weighted gene coexpression network analysis. We screened eight TIL-related genes utilizing univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) Cox regression analysis, and multivariate Cox regression analysis. Then, we established a TIL-related signature model containing the eight selected genes and subsequently classified all patients into two groups, that is, the high-risk as well as low-risk groups. Gene mutation status, prognosis, immune cell infiltration, immune subtypes, TME, clinical features, and immunotherapy response were assessed among different risk subgroups. The results affirmed that the TIL-related signature model was a reliable predictor of overall survival (OS) for BCa and was determined as an independent risk factor for BCa patients in two cohorts. Moreover, the risk score was substantially linked to age, tumor staging, TNM stage, and pathological grade. And there were different mutational profiles, biological pathways, immune scores, stromal scores, and immune cell infiltration in the tumor microenvironment (TME) between the two risk groups. In particular, immune checkpoint genes' expression was remarkably different between the two risk groups, with patients belonging to the low-risk group responding better to immune checkpoint inhibition (ICI) therapy. In conclusion, our study demonstrates that the TIL-related model was a reliable signature in anticipating prognosis, immune status, and immunotherapy response, which can help in screening patients who respond to immunotherapy.
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Linfocitos Infiltrantes de Tumor , Neoplasias de la Vejiga Urinaria , Humanos , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Estimación de Kaplan-Meier , Pronóstico , Microambiente Tumoral/genética , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
BACKGROUND: Studies have shown that circular RNAs (circRNAs) have significant potential as novel molecular markers for the diagnosis, treatment, and prognosis of prostate carcinoma (PCa). However, the role and mechanism of circRNA hsa_circ_0102485 in PCa remains unclear. MATERIALS & METHODS: The real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to quantify hsa_circ_0102485 expression in PCa. The potential mechanisms and roles of hsa_circ_0102485 in tumor growth were explored using dual-luciferase-reporter and subcutaneous-xenograft assays, rescue experiments, and immunohistochemical staining. Clinical correlations were assessed by tissue-on-a-chip in-situ hybridization and Fisher's exact test. RESULTS: Hsa_circ_0102485 expression was decreased in PCa, and overexpression of hsa_circ_0102485 suppressed the proliferation, metastasis, invasion, and antiapoptotic abilities of PCa cells. MicroRNA 188-3p (MiR-188-3p) is a direct target of hsa_circ_0102485, and cotransfection of hsa_circ_0102485 in PCa cells overexpressing miR-188-3p inhibited its promotive effects. Hsa_circ_0102485 indirectly promotes the expression of AT-rich interaction domain 5B (ARID5B) and androgen receptor (AR) by sponging miR-188-3p and inhibiting PCa cell growth. Correlation analysis showed that hsa_circ_0102485 expression in PCa was not significantly correlated with the age, International Society of Urologic Pathologists (ISUP) grade, Gleason score, or lymph node metastasis status of PCa patients. CONCLUSION: Hsa_circ_0102485 plays an inhibitory role in PCa by regulating the Mir-188-3p/ARID5B/AR axis and may be a potential diagnostic biomarker and therapeutic target for PCa that requires further study.
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Carcinoma , MicroARNs , Masculino , Humanos , ARN Circular/genética , MicroARNs/genética , MicroARNs/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Invasividad Neoplásica/genética , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Próstata/metabolismo , Línea Celular Tumoral , Biomarcadores , Carcinoma/genética , Proteínas de Unión al ADN/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Background: Necroptosis, a recently identified type of programmed necrotic cell death, is closely related to the tumorigenesis and development of cancer. However, it remains unclear whether necroptosis-associated long noncoding RNAs (lncRNAs) can be used to predict the prognosis of kidney renal clear cell carcinoma (KIRC). This work was designed to probe the possible prognostic worth of necroptosis-associated lncRNAs along with their impact on the tumor microenvironment (TME) in KIRC. Methods: The Cancer Genome Atlas (TCGA) database was used to extract KIRC gene expression and clinicopathological data. Pearson correlation analysis was used to evaluate necroptosis-associated lncRNAs against 159 known necroptosis-associated genes. To define molecular subtypes, researchers used univariate Cox regression analysis and consensus clustering, as well as clinical significance, TME, and tumor immune cells in each molecular subtype. We develop the necroptosis-associated lncRNA prognostic model using univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Patients were divided into high- and low-risk groups according to prognostic model. Moreover, comprehensive analyses, including prognostic value, gene set enrichment analysis (GSEA), immune infiltration, and immune checkpoint gene expression, were performed between the two risk groups. Finally, anticancer drug sensitivity analyses were employed for assessing associations for necroptosis-associated lncRNA expression profile and anticancer drug chemosensitivity. Results: Through univariate analysis, sixty-nine necroptosis-associated lncRNAs were found to have a significant relationship with KIRC prognosis. Two molecular clusters were identified, and significant differences were found with respect to clinicopathological features and prognosis. The segregation of patients into two risk groups was done by the constructed necroptosis-associated lncRNA model. The survival prognosis, clinical features, degree of immune cell infiltration, and expression of immune checkpoint genes of high-risk and low-risk groups were all shown to vary. Conclusions: Our study identified a model of necroptosis-associated lncRNA signature and revealed its prognostic role in KIRC. It is expected to provide a reference for the screening of KIRC prognostic markers and the evaluation of immune response.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , ARN Largo no Codificante , Carcinoma de Células Renales/patología , Humanos , Riñón/metabolismo , Neoplasias Renales/patología , Necroptosis/genética , Pronóstico , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: IgA nephropathy is the most common glomerular disease and is a common cause of progression to end-stage renal disease in patients with kidney diseases. Proteinuria levels are critical for the prognosis of patients with IgA nephropathy, but many patients are still unable to effectively control their proteinuria levels after receiving RAAS blockers. Antimalarial drugs have shown good efficacy in the treatment of kidney disease in previous studies; however, there have been no strictly designed randomized controlled trials to confirm the clinical efficacy of artesunate for treating IgA nephropathy patients. Therefore, we designed this clinical trial to compare the effect of artesunate versus placebo in patients with IgA nephropathy. METHODS: This study is a randomized, double-blind, three-group-parallel, placebo-controlled clinical trial. One hundred and twenty eligible IgA nephropathy patients at risk of progression will be randomly divided into the artesunate 100-mg group, artesunate 50-mg group, and placebo group. Changes in proteinuria and renal function will be measured 6 months after the intervention. The levels of Gd-IgA1 and anti-Gd-IgA1 in the patient's blood will also be tested to explore the possible immune mechanisms. DISCUSSION: Clinical evidence supporting artesunate treatment of IgA nephropathy is currently lacking, and we expect that the results of this trial will provide high-quality clinical evidence for artesunate as a treatment option for IgA nephropathy in the future. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000038104 . Registered on 10 September 2020.