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Cardiovascular diseases (CVDs) impose a significant burden worldwide. Despite the elucidation of the etiology and underlying molecular mechanisms of CVDs by numerous studies and recent discovery of effective drugs, their morbidity, disability, and mortality are still high. Therefore, precise risk stratification and effective targeted therapies for CVDs are warranted. Recent improvements in single-cell RNA sequencing and spatial transcriptomics have improved our understanding of the mechanisms and cells involved in cardiovascular phylogeny and CVDs. Single-cell RNA sequencing can facilitate the study of the human heart at remarkably high resolution and cellular and molecular heterogeneity. However, this technique does not provide spatial information, which is essential for understanding homeostasis and disease. Spatial transcriptomics can elucidate intracellular interactions, transcription factor distribution, cell spatial localization, and molecular profiles of mRNA and identify cell populations causing the disease and their underlying mechanisms, including cell crosstalk. Herein, we introduce the main methods of RNA-seq and spatial transcriptomics analysis and highlight the latest advances in cardiovascular research. We conclude that single-cell RNA sequencing interprets disease progression in multiple dimensions, levels, perspectives, and dynamics by combining spatial and temporal characterization of the clinical phenome with multidisciplinary techniques such as spatial transcriptomics. This aligns with the dynamic evolution of CVDs (e.g., "angina-myocardial infarction-heart failure" in coronary artery disease). The study of pathways for disease onset and mechanisms (e.g., age, sex, comorbidities) in different patient subgroups should improve disease diagnosis and risk stratification. This can facilitate precise individualized treatment of CVDs.
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Head and neck cancer (HNC) is the sixth most common type of cancer worldwide, and head and neck squamous cell carcinoma (HNSCC) accounts for 90% of HNC cases. Furthermore, HNSCC accounts for 400,000 cancer-associated deaths worldwide each year. However, at present there is an absence of a versatile biomarker that can be used for diagnosis, prognosis evaluation and as a therapeutic target for HNSCC. In the present study, bioinformatics analysis was used to assess the relationship between hub genes and the clinical features of patients with HNSCC. The findings from the bioinformatics analysis were then verified using clinical samples and in vitro experiments. A total of 51 overlapping genes were identified from the intersection of differentially expressed genes and co-expressed genes. The top 10 hub genes were obtained from a protein-protein interaction network of overlapping genes. Among the hub genes, only secretoglobin family 1A member 1 (SCGB1A1) was significantly associated with both overall and disease-free survival. Specifically, upregulated SCGB1A1 expression levels were associated with prolonged overall and disease-free survival. Moreover, the SCGB1A1 expression levels were negatively correlated with drug sensitivity. Notably, it was demonstrated that SCGB1A1 was involved in tumor immunoreaction by affecting the infiltration of cells and checkpoint regulation of immune cells. Additionally, it was shown that SCGB1A1 regulated multiple key cancer-related signaling pathways, including extracellular matrix receptor interaction, transforming growth factor-ß and tumor metabolism signaling pathways. Based on the results of the present study, SCGB1A1 may serve as a novel biomarker for predicting the diagnosis, prognosis and therapeutic effectiveness of certain drugs in patients with HNSCC. Moreover, SCGB1A1 may serve as a potential therapeutic target for the management of HNSCC.
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Highland barley non-starch polysaccharides (HBNP), particularly ß-glucans, are known for their health-promoting effects, including modulation of glycemic response and enhancement of gut health. This study investigated the impact of different HBNP fractions on the properties and digestibility of high-glycemic index rice starch. HBNP was segmented into five fractions (HBNP-15, HBNP-30, HBNP-45, HBNP-60, and HBNP-75) using gradient ethanol precipitation, and these fractions exhibited varying molecular weights, monosaccharide compositions, and ß-glucan contents. All fractions reduced rice starch's pasting viscosity, with 1â¯% HBNP-75 leading to a 99.1â¯% decrease in final viscosity. Morphological and size distribution analyses showed that HBNP fractions limited granule swelling and disrupted starch's continuous phase structure. HBNPs also reduced starch digestibility and increased the formation of resistant starch from 10â¯% to 28â¯%. These results suggest potential uses for HBNP fractions in developing low-glycemic starch-based foods.
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Stress damage caused by early weaning and its possible mechanism have been studied mainly in young mammals, but rarely in altrices, especially in squabs. The study aimed to investigate the possible molecular mechanism of intestinal epithelial barrier damage caused by early weaning in squabs through determining the intestinal permeability, the ultrastructure of villous epithelium, the contents of ileal cytokines, and the protein relative expression of tight-junction proteins, TLRs and their mediated key factors in inflammatory signaling pathways. A total of 192 newly hatched squabs were randomly divided into 2 groups, 1 group was weaned and fed artificial pigeon milk from d 7, and the other group continued to be fed by the parent pigeons. The ileal mucosa and serum of 8 replicates were collected at 1, 4, 7, 10, and 14 d after weaning. The results indicated that early weaning could reduce the growth performance of squabs and damage the intestinal epithelial barrier, which is characterized by down-regulating the protein expression of claudin-1/3, up-regulating the protein expression of claudin-2, promoting the secretion of pro-inflammatory factors, inhibiting the secretion of anti-inflammatory factors, and increasing the permeability of the intestinal barrier. The specific mechanism of stress damage might be the activation of TLR2/4-MyD88-ERK/JNK inflammatory signaling pathway leading to the increase levels of IL-6 and TNF-α.
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Carotenoids belonging to the class of tetraterpenoids have extensive applications in medicine, food, nutrition, cosmetics, and feed. Among them, lutein and zeaxanthin can prevent macular degeneration in the elderly, which is very important for protecting vision. Here, we introduce the first metabolomic analysis of Sphingopyxis sp. USTB-05, aiming to shed light on the biosynthesis of carotenoids. Sphingopyxis sp. USTB-05 has the complete methylerythritol 4-phosphate (MEP) pathway and carotenoid biosynthesis pathway, especially involved in the bioconversion of zeaxanthin, violaxanthin, and astaxanthin. Metabolomic profiling identified seven carotenes and six xanthophylls synthesized by Sphingopyxis sp. USTB-05. Zeaxanthin, in particular, was found to be the most abundant, with a content of 37.1 µg/g dry cells. Collectively, the results presented herein greatly enhance our understanding of Sphingopyxis sp. USTB-05 in carotenoids biosynthesis, and thus further accelerate its fundamental molecular investigations and biotechnological applications.
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Carotenoides , Metabolómica , Carotenoides/metabolismo , Metabolómica/métodos , Sphingomonadaceae/metabolismo , Vías Biosintéticas , Xantófilas/metabolismo , MetabolomaRESUMEN
BACKGROUND: Renal insufficiency (RI) is a key factor affecting the prognosis of multiple myeloma (MM) patients. Because the benefit of daratumumab for treating MM patients with RI remains unclear, our objective was to evaluate the efficacy of daratumumab on MM patients with RI. METHODS: We conducted a systematic search of the PubMed, EMBASE, and Cochrane Library databases as of October 24, 2023. Two independent reviewers screened the article titles, abstracts, and full text to identify the randomized controlled trials (RCTs) meeting the inclusion and exclusion criteria. Meta-analyses were performed using RevMan version 5.4. Outcomes of interest were progression-free survival (PFS), overall survival (OS), complete response or better (≥CR), and minimal residual disease (MRD) negativity, all calculated as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: A total of 10 RCTs with 5003 patients were included. Add-on daratumumab improved PFS and OS among newly diagnosed MM (NDMM) patients with RI (HR 0.48 [95% CI: 0.36, 0.64, I2 = 65%] and HR 0.63 [95% CI: 0.48, 0.82, I2 = 0%]) as well as relapsed/refractory MM (RRMM)-RI patients, compared with the control group (HR 0.46 [95% CI: 0.37, 0.58, I2 = 0%] and HR 0.68 [95% CI: 0.51, 0.92, I2 = 0%]). In terms of the renal status, the efficacy of add-on daratumumab for MMRI patients was similar to that for MM patients with normal renal function. A prolonged PFS benefit for add-on daratumumab treatment versus the control was evident across all RRMM-RI subgroups, and the benefits tended to increase with the follow-up time. CONCLUSIONS: Our results indicate that MM patients with RI could benefit from a daratumumab-added regimen regardless of MM status. Additional high-quality RCTs are still warranted to confirm our findings.
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Anticuerpos Monoclonales , Mieloma Múltiple , Insuficiencia Renal , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/complicaciones , Mieloma Múltiple/mortalidad , Humanos , Anticuerpos Monoclonales/uso terapéutico , Insuficiencia Renal/etiología , Insuficiencia Renal/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Stress-induced hyperglycemia (SIH) is associated with poor outcomes in cardiogenic shock (CS), and there have been inconsistent results among patients with or without diabetes mellitus (DM). The glycemic gap (GG) is derived by subtracting A1c-derived average glucose from blood glucose levels; it is a superior indicator of SIH. We aimed to explore the role of GG in the outcomes of patients with CS. METHODS: Data on patients diagnosed with CS were extracted from the MIMIC-IV v2.0 database to investigate the relationship between GG and 30-day mortality (Number of absolute GG subjects = 359; Number of relative GG subjects = 357). CS patients from the Second Affiliated Hospital of Wenzhou Medical University were enrolled to explore the correlation between GG and lactic acid (Number of absolute GG subjects = 252; Number of relative GG subjects = 251). Multivariate analysis, propensity score-matched (PSM) analysis, inverse probability treatment weighting (IPTW), and Pearson correlation analysis were applied. RESULTS: Absolute GG was associated with 30-day all-cause mortality in CS patients (HRadjusted: 1.779 95% CI: 1.137-2.783; HRPSM: 1.954 95% CI: 1.186-3.220; HRIPTW: 1.634 95% CI: 1.213-2.202). The higher the absolute GG level, the higher the lactic acid level (ßadjusted: 1.448 95% CI: 0.474-2.423). A similar trend existed in relative GG (HRadjusted: 1.562 95% CI: 1.003-2.432; HRPSM: 1.790 95% CI: 1.127-2.845; HRIPTW: 1.740 95% CI: 1.287-2.352; ßadjusted:1.294 95% CI: 0.369-2.219). Subgroup analysis showed that the relationship existed irrespective of DM. The area under the curve of GG combined with the Glasgow Coma Scale (GCS) for 30-day all-cause mortality was higher than that of GCS (absolute GG: 0.689 vs. 0.637; relative GG: 0.688 vs. 0.633). GG was positively related to the triglyceride-glucose index. Kaplan-Meier curves revealed that groups of higher GG with DM had the worst outcomes. The outcomes differed among races and GG levels (all P < 0.05). CONCLUSIONS: Among patients with CS, absolute and relative GGs were associated with increased 30-day all-cause mortality, regardless of DM. The relationship was stable after multivariate Cox regression analysis, PSM, and IPTW analysis. Furthermore, they reflect the severity of CS to some extent. Hyperlactatemia and insulin resistance may underlie the relationship between stress-induced hyperglycemia and poor outcomes in CS patients. They both improve the predictive efficacy of the GCS.
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Biomarcadores , Glucemia , Hemoglobina Glucada , Hiperglucemia , Ácido Láctico , Choque Cardiogénico , Humanos , Choque Cardiogénico/mortalidad , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/sangre , Choque Cardiogénico/terapia , Choque Cardiogénico/etiología , Masculino , Femenino , Estudios Retrospectivos , Glucemia/metabolismo , Persona de Mediana Edad , Anciano , Biomarcadores/sangre , Factores de Riesgo , Factores de Tiempo , Hiperglucemia/diagnóstico , Hiperglucemia/mortalidad , Hiperglucemia/sangre , Pronóstico , Hemoglobina Glucada/metabolismo , Ácido Láctico/sangre , China/epidemiología , Bases de Datos Factuales , Valor Predictivo de las Pruebas , Medición de Riesgo , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidadRESUMEN
Background: Neuromuscular blocking agents (NMBAs) are primarily used during surgical procedures to facilitate endotracheal intubation and optimize surgical conditions. This study aimed to explore the adverse event signals of NMBAs, providing reference for clinical safety. Methods: This study collected reports of atracurium, cisatracurium, rocuronium, and vecuronium as primary suspect drugs in The US Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the third quarter of 2023. The adverse events (AEs) reported in the study were retrieved based on the Preferred Terms (PTs) of the Medical Dictionary for Regulatory Activities. In addition, we conducted disproportionality analysis on relevant reports using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. A positive signal was generated when both algorithms show an association between the target drug and the AE. Results: A total of 11,518 NMBA-related AEs were reported in the FAERS database. The most AEs of rocuronium were collected. NMBA-related AEs involved 27 different system organs (SOCs), all of the four NMBAs had positive signals in "cardiac disorders," "immune system disorders," "respiratory, thoracic and mediastinal disorders" and "vascular disorders." At the PTs level, a total of 523 effective AEs signals were obtained for the four NMBAs. AEs labled in the instructions such as anaphylaxis (include anaphylactic reaction and anaphylactic shock), bronchospasm, respiratory arrest and hypotension were detected positive signals among all NMBAs. In addition, we also found some new AEs, such as ventricular fibrillation for the four NMBAs, hyperglycaemia for atracurium, kounis syndrome and stress cardiomyopathy for rocuronium, hepatocellular injury for cisatracurium, hyperkalaemia for vecuronium. To further investigated the AEs associated with serious clinical outcomes, we found that cardiac arrest and anaphylaxis were the important risk factors for death due to NMBAs. Conclusion: NMBA-related AEs have a significant potential to cause clinically severe consequences. Our study provides valuable references for the safety profile of NMBAs, and considering the limitations of the FAERS database, further clinical data are needed to validate the findings of this study.
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To explore the clinical characteristics of patients infected with SARS-CoV-2 nationwide, especially the effect factors of asymptomatic infection and disappearance of clinical symptoms. A total of 66,448 COVID-19 patients in China who have been diagnosed by nucleic acid test or rapid antigen test were surveyed online (December 24, 2022 to January 16, 2023). Our cross-sectional study used descriptive analyses and binary Logistics regression model to assess the correlation between the clinical characteristics and relative factors, including age, gender, pre-existing conditions, reinfection, vaccination and treatment. A total of 64,515 valid questionnaires were collected. Among included participants, 5969 of which were asymptomatic. The symptoms were mainly upper respiratory symptoms, including dry and itchy throat (64.16%), sore throat (59.95%), hoarseness (57.90%), nasal congestion (53.39%). In binary Logistics regression model, we found that male, no pre-existing conditions, reinfection and vaccination have positive correlations with the appearance of asymptomatic COVID-19 patients. In Cox proportional-hazards regression model, considering all clinical symptoms disappeared in 14 days as outcome, we found that ≤ 60 years old, male, no pre-existing conditions, vaccination and adopted treatment have positive correlations with rapid amelioration of clinical symptoms in COVID-19 patients. The clinical symptoms of the participants were mainly upper respiratory symptoms which were according with the infection of Omicron variant. Factors including age, gender, pre-existing conditions and reinfection could influence the clinical characteristics and prognosis of COVID-19 patients. Importantly, vaccination has positive significance for the prevention and treatment of COVID-19. Lastly, the use of Chinese medicine maybe beneficial to COVID-19 patients, however, reasonable guidance is necessary.
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Infecciones Asintomáticas , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/diagnóstico , COVID-19/virología , Masculino , Femenino , China/epidemiología , Estudios Transversales , Persona de Mediana Edad , Adulto , Infecciones Asintomáticas/epidemiología , SARS-CoV-2/aislamiento & purificación , Anciano , Adulto Joven , AdolescenteRESUMEN
Physical exercise is widely recognized for its benefits to individuals' general health, yet its implications for in-role and extrarole job performance, especially on demanding workdays, have rarely been explored. This oversight is concerning as high work demands can deter employees from exercising when they are unaware that exercise can improve their job performance on demanding workdays. In this research, we draw on the effort-recovery model to propose that daily physical exercise not only promotes next-day well-being but also enhances next-day in-role job performance and extrarole organizational citizenship behavior (OCB) by fostering positive affect and work engagement the following day. Moreover, these benefits of daily physical exercise are more pronounced on days with high rather than low work demands. Results from two experience sampling studies generally support our hypotheses, revealing that daily physical exercise contributes to next-day well-being, both self- and leader-rated in-role job performance and self-rated, but not leader-rated, extrarole OCB, through the sequential mediation of next-morning positive affect and next-day work engagement. Furthermore, these benefits of physical exercise are more evident on days when employees face high overall work demands (Study 1) and in particular on days with high-hindrance demands but on days with low-challenge demands (Study 2). (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Objectives: This study aimed to summarize the existing literature on risk factors for arrhythmias after chemotherapy in cancer patients. To provide reliable evidence for treating arrhythmias after chemotherapy in oncology patients by assessing multiple biasing factors in the literature and quantifying the risk factors. Methods: The risk factors for arrhythmia following tumor chemotherapy were systematically collected from various reputable databases, including PubMed, Cochrane Library, MEDLINE, EMBASE, and multiple Chinese databases, covering the period from inception to May 2023. Two independent reviewers performed rigorous article screening, data extraction, and assessment of research quality. Data analysis was conducted using Review Manager 5.4 software, ensuring a standardized and robust approach to evaluate the gathered evidence. Results: The analysis of chemotherapy-induced arrhythmias included 16 articles, encompassing 14,785 cancer patients. Among the patients, 3295 belonged to the arrhythmia group, while 11,490 were in the non-arrhythmia group. These studies identified 12 significant risk factors associated with arrhythmias following chemotherapy in cancer patients. The findings of the analysis are as follows. General patient characteristics: The incidence of post-chemotherapy arrhythmias was 14.33 times higher in oncology patients aged ≥60 years compared to patients <60 years of age [OR = 14.33, 95%CI (8.51, 24.13), Pï¼0.00001]. Patients with a smoking history exhibited a 1.67-fold higher risk of arrhythmia after chemotherapy [OR = 1.67, 95%CI (1.24, 2.25), P = 0.0007]. However, there was no significant correlation between gender and body mass index (BMI) with arrhythmia after chemotherapy in oncology patients (P = 0.52; P = 0.19). Disease-related factors: Patients with a history of hypertension, diabetes, and cardiovascular disease had a 1.93-fold, 1.30-fold, and 1.76-fold increased risk of arrhythmia after chemotherapy, respectively [OR = 1.93, 95%CI (1.66, 2.24), Pï¼0.00001; OR = 1.30, 95%CI (1.10, 2.52), P = 0.002; OR = 1.76, 95%CI (1.51, 2.05), Pï¼0.00001]. Additionally, the incidence of arrhythmia increased 1.97 times in patients with electrolyte and acid-base balance disorders following chemotherapy [OR = 1.97, 95%CI (1.41, 2.76), Pï¼0.00001]. Chemotherapy-related factors: Seven articles examined the association between chemotherapy drugs and post-chemotherapy arrhythmias. The results indicated that oncology patients were 3.03 times more likely to develop arrhythmias with chemotherapy drugs compared to non-chemotherapy drugs [OR = 3.03, 95%CI (2.59, 3.54), Pï¼0.00001]. Notably, anthracyclines and fluorouracil chemotherapy demonstrated a 2.98-fold and 3.35-fold increased risk of arrhythmia after chemotherapy, respectively [OR = 2.98, 95%CI (2.51, 3.03), Pï¼0.00001; OR = 3.35, 95%CI (2.20, 5.10), Pï¼0.00001]. The risk of arrhythmia after chemotherapy was 1.72 times higher in patients with chemotherapy cycles longer than 4 weeks than those with cycles shorter than 4 weeks [OR = 1.72, 95%CI (1.30, 2.28), P = 0.0001]. Conclusion: The occurrence of arrhythmia after chemotherapy in cancer patients was significantly associated with the patient's age, history of smoking, history of hypertension, history of diabetes, history of cardiovascular disease, chemotherapy drug use, and cycle. However, further high-quality evidence is needed to support these results.
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In this work, a novel fluorinated magnetic microporous organic network (Fe3O4@FMON) was exquisitely designed and synthesized for highly efficient and selective magnetic solid phase extraction (MSPE) of fluorinated benzoylurea insecticides (BUs) from complex tea beverage samples. The Fe3O4@FMON exhibited good extraction for BUs via the pre-designed hydrophobic, π-π stacking, hydrogen bonding and specific FF interactions. A sensitive Fe3O4@FMON-based MSPE-HPLC-UV method with wide linear range (0.10-1000 µg L-1, R2 ≥ 0.996), low limits of detection (0.01-0.02 µg L-1), and large enrichment factors (85.6-98.0) for BUs from tea beverage samples was developed. By decorating F elements within MON's networks, the Fe3O4@FMON characterized good hydrophobicity and chemical stability, which could be reused at least 8 times without decrease of recoveries. This work demonstrated the great prospects of Fe3O4@FMON for enriching trace BUs from complex substrates and triggered the potential of FMON for sample pretreatment of fluorinated analytes.
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Halogenación , Insecticidas , Extracción en Fase Sólida , Té , Insecticidas/química , Insecticidas/aislamiento & purificación , Insecticidas/análisis , Té/química , Extracción en Fase Sólida/métodos , Extracción en Fase Sólida/instrumentación , Contaminación de Alimentos/análisis , Adsorción , Porosidad , Cromatografía Líquida de Alta Presión , Interacciones Hidrofóbicas e Hidrofílicas , Urea/química , Urea/aislamiento & purificaciónRESUMEN
BACKGROUND: This study performs a detailed bioinformatics and machine learning analysis to investigate the genetic foundations of membranous nephropathy (MN) in lung adenocarcinoma (LUAD). METHODS: In this study, the gene expression profiles of MN microarray datasets (GSE99339) and LUAD dataset (GSE43767) were downloaded from the Gene Expression Omnibus database, common differentially expressed genes (DEGs) were obtained using the limma R package. The biological functions were analyzed with R Cluster Profiler package according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Machine learning algorithms, including LASSO regression, support vector machine (SVM), Random Forest, and Boruta analysis, were applied to identify hubgenes linked to LUAD-associated MN. These genes' prognostic values were evaluated in the TCGA-LUAD cohort and validated through immunohistochemistry on renal biopsy specimens. RESULTS: A total of 36 DEGs in common were identified for downstream analyses. Functional enrichment analysis highlighted the involvement of the Toll-like receptor 4 pathway and several immune recognition pathways in LUAD-associated MN. COL3A1, PSENEN, RACGAP1, and TNFRSF10B were identified as hub genes in LUAD-associated MN using machine learning algorithms. ROC analysis demonstrated their effective discrimination of MN with high accuracy. Survival analysis showed that lung adenocarcinoma patients with higher expression of these genes had significantly reduced overall survival. In patients with lung adenocarcinoma-associated MN, RACGAP1, COL3A1, PSENEN, and TNFRSF10B were higher expressed in the glomerular, especially RACGAP1, indicating an important role in the pathogenesis of LUAD-associated membranous nephropathy. CONCLUSIONS: Our study underscores the critical role of RACGAP1, COL3A1, PSENEN, and TNFRSF10B in the development of LUAD-associated MN, providing important insights for future research and the development of potential therapeutic strategies.
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Adenocarcinoma del Pulmón , Biología Computacional , Glomerulonefritis Membranosa , Neoplasias Pulmonares , Aprendizaje Automático , Humanos , Glomerulonefritis Membranosa/genética , Glomerulonefritis Membranosa/inmunología , Adenocarcinoma del Pulmón/genética , Biología Computacional/métodos , Neoplasias Pulmonares/genética , Proteínas Activadoras de GTPasa/genética , Regulación Neoplásica de la Expresión Génica , Pronóstico , Masculino , Femenino , Perfilación de la Expresión Génica , Bases de Datos Genéticas , Persona de Mediana Edad , Colágeno Tipo IIIRESUMEN
Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.
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Metastasis to the lungs is a leading cause of death for breast cancer patients. Therefore, effective therapies are urgently needed to prevent and treat breast cancer lung metastasis In this study, we uncovered a mechanism by which NAD(P)H:quinone oxidoreductase 1 (NQO1) orchestrates lung metastasis. NQO1 stabilized and upregulated peptidyl-prolyl cis-trans isomerase A (PPIA), a chaperone that regulates protein conformation and activity, by preventing its oxidation at a critical cysteine residue C161. PPIA subsequently activated CD147, a membrane protein that facilitates cell invasion. Moreover, NQO1-induced secretion of PPIA modulated the immune landscape of both primary and lung metastatic sites. Secreted PPIA engaged CD147 on neutrophils and triggered the release of neutrophil extracellular traps (NET) and neutrophil elastase, which enhanced tumor progression, invasiveness and lung colonization. Pharmacological targeting of PPIA effectively inhibited NQO1-mediated breast cancer lung metastasis. These findings reveal a previously unrecognized NQO1-PPIA-CD147-NET axis that drives breast cancer lung metastasis. Inhibiting this axis is a potential therapeutic strategy to limit lung metastasis in breast cancer patients.
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Collaborative Metric Learning (CML) has recently emerged as a popular method in recommendation systems (RS), closing the gap between metric learning and collaborative filtering. Following the convention of RS, existing practices exploit unique user representation in their model design. This paper focuses on a challenging scenario where a user has multiple categories of interests. Under this setting, the unique user representation might induce preference bias, especially when the item category distribution is imbalanced. To address this issue, we propose a novel method called Diversity-Promoting Collaborative Metric Learning (DPCML), with the hope of considering the commonly ignored minority interest of the user. The key idea behind DPCML is to introduce a set of multiple representations for each user in the system where users' preference toward an item is aggregated by taking the minimum item-user distance among their embedding set. Specifically, we instantiate two effective assignment strategies to explore a proper quantity of vectors for each user. Meanwhile, a Diversity Control Regularization Scheme (DCRS) is developed to accommodate the multi-vector representation strategy better. Theoretically, we show that DPCML could induce a smaller generalization error than traditional CML. Furthermore, we notice that CML-based approaches usually require negative sampling to reduce the heavy computational burden caused by the pairwise objective therein. In this paper, we reveal the fundamental limitation of the widely adopted hard-aware sampling from the One-Way Partial AUC (OPAUC) perspective and then develop an effective sampling alternative for the CML-based paradigm. Finally, comprehensive experiments over a range of benchmark datasets speak to the efficacy of DPCML.
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Background: Pandy's test is used to assess the globulin level in cerebrospinal fluid (CSF). As a semi-quantitative manual method, the practicality and clinical value of Pandy's test has been challenged. Objective: We tend to summarize the relationship between CSF total protein (CSF-TP) quantification and Pandy's results, providing a formula to estimate Pandy's results merely by CSF-TP value. Methods: This retrospective study involved 1090 cases hospitalized in Huashan Hospital during 1/1/2023 to 20/4/2023. All samples were divided into six group based on their Pandy's results. Their corresponding CSF-TP quantitative results were subsequently analyzed and summarized. Another 364 patients were also gathered for verification. Results: The turbidity of samples won't affect examiners'ocular inspection and interpretation of Pandy's tests in positive groups. The results of Pandy's tests can be deduced based on CSF-TP quantitative results according to following rules: CSF-TP quantitative results 0-614 mg/L for Pandy negative (-), 615-1322 mg/L for extremely weak positive (±), 1323-2953 mg/L for weak positive (1+), 2954-6561 mg/L for medium positive results (2+), 6562-13007 mg/L for strong positive results (3+) and CSF-TP results >13007 for strongest positive (4+). The quantitative range above was experimentally verified as effective and correct by calculating the agreement rate through another 364 samples and the R ratio of each Pandy group was greater than 90 %. Conclusion: There is an excellent correlation between CSF-TP and Pandy's test. Therefore, CSF-TP quantification test through PROT Slides can be used to infer the results of Pandy's test to accelerate the abolish of this traditional manual test.
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Background: Membranous nephropathy (MN) is an autoimmune disease and represents the most prevalent type of renal pathology in adult patients afflicted with nephrotic syndrome. Despite substantial evidence suggesting a possible link between MN and cancer, the precise underlying mechanisms remain elusive. Methods: In this study, we acquired and integrated two MN datasets (comprising a single-cell dataset and a bulk RNA-seq dataset) from the Gene Expression Omnibus database for differential expression gene (DEG) analysis, hub genes were obtained by LASSO and random forest algorithms, the diagnostic ability of hub genes was assessed using ROC curves, and the degree of immune cell infiltration was evaluated using the ssGSEA function. Concurrently, we gathered pan-cancer-related genes from the TCGA and GTEx databases, to analyze the expression, mutation status, drug sensitivity and prognosis of hub genes in pan-cancer. Results: We conducted intersections between the set of 318 senescence-related genes and the 366 DEGs, resulting in the identification of 13 senescence-related DEGs. Afterwards, we meticulously analyzed these genes using the LASSO and random forest algorithms, which ultimately led to the discovery of six hub genes through intersection (PIK3R1, CCND1, TERF2IP, SLC25A4, CAPN2, and TXN). ROC curves suggest that these hub genes have good recognition of MN. After performing correlation analysis, examining immune infiltration, and conducting a comprehensive pan-cancer investigation, we validated these six hub genes through immunohistochemical analysis using human renal biopsy tissues. The pan-cancer analysis notably accentuates the robust association between these hub genes and the prognoses of individuals afflicted by diverse cancer types, further underscoring the importance of mutations within these hub genes across various cancers. Conclusion: This evidence indicates that these genes could potentially play a pivotal role as a critical link connecting MN and cancer. As a result, they may hold promise as valuable targets for intervention in cases of both MN and cancer.
Asunto(s)
Glomerulonefritis Membranosa , Humanos , Glomerulonefritis Membranosa/genética , Glomerulonefritis Membranosa/inmunología , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/metabolismo , Perfilación de la Expresión Génica , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/metabolismo , Biología Computacional/métodos , Pronóstico , Biomarcadores de Tumor/genética , Transcriptoma , Redes Reguladoras de Genes , Biomarcadores , Bases de Datos GenéticasRESUMEN
Malaria infection remains a serious threat to human health worldwide. Rapid and accurate detection technology is crucial for preventing malaria transmission and minimizing damage. We aimed to establish and validate a new rapid molecular detection method for malaria, called EasyNAT Malaria Assay, targeting Plasmodium vivax, Plasmodium falciparum, Plasmodium ovale, and Plasmodium malariae. The analytical performance of EasyNAT Malaria Assay was determined using positive materials. We identified 42 clinical samples as malaria positive and 95 negative samples. Each sample was examined by four methods: light microscopy, rapid diagnostic test, EasyNAT Malaria Assay, and digital PCR. Diagnostic accuracy and clinical performance were evaluated. The limit of detection (LOD)95% of EasyNAT Malaria was consistently 40 parasites/mL. It specifically amplified Plasmodium and performed with reliable repeatability and reproducibility. In 137 clinical samples, EasyNAT Malaria detected four more positive samples than microscopic examination and two more positive samples than rapid diagnostic test (RDT). One clinical sample was positive only under digital PCR. However, no significant differences statistically in sensitivity or specificity were observed. Compared with microscopy, the total, positive, and negative concordance rates of EasyNAT were 97.08%, 100%, and 95.79%, respectively. Enhanced diagnostic accuracy of EasyNAT Malaria in patients who had taken anti-malarial medication before their clinical appointment was observed. The EasyNAT Malaria Assay has good detection efficiency for clinical samples, presents a promising molecular detection tool in clinical practice, and is particularly suitable for rapid screening of high-risk populations in the emergency room. IMPORTANCE: This study established and validated EasyNAT Malaria Assay as a promising molecular detection tool for malaria screening of high-risk populations in clinical practice. This novel isothermal amplification method may effectively facilitate the rapid diagnosis of malaria and prevent its transmission.