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Background: Oxidative stress and cellular senescence (OSCS) have great impacts on the occurrence and progression of triple-negative breast cancer (TNBC). This study was intended to construct a prognostic model based on oxidative stress and cellular senescence related difference expression genes (OSCSRDEGs) for TNBC. Methods: The Cancer Genome Atlas (TCGA) databases and two Gene Expression Omnibus (GEO) databases were used to identify OSCSRDEGs. The relationship between OSCSRDEGs and immune infiltration was examined using single-sample gene-set enrichment analysis (ssGSEA), ESTIMATE, and the CIBERSORT algorithm. Least absolute shrinkage and selection operator (LASSO) regression analyses, Cox regression and Kaplan-Meier analysis were employed to construct a prognostic model. Receiver operating characteristic (ROC) curves, nomograms, and decision curve analysis (DCA) were used to evaluate the prognostic efficacy. Gene Set Enrichment Analysis (GSEA) Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to explore the potential functions and mechanism. Results: A comprehensive analysis identified a total of 27 OSCSRDEGs, out of which 15 genes selected for development of a prognostic model. A high degree of statistical significance was observed for the riskscores derived from this model to accurately predict TNBC Overall survival. The decision curve analysis (DCA) and ROC curve analysis further confirmed the superior accuracy of the OSCSRDEGs prognostic model in predicting efficacy. Notably, the nomogram analysis highlighted that DMD exhibited the highest utility within the model. In comparison between high and low OSCScore groups, the infiltration abundance of immune cells was statistically different in the TCGA-TNBC dataset. Conclusion: These studies have effectively identified four essential OSCSRDEGs (CFI, DMD, NDRG2, and NRP1) and meticulously developed an OSCS-associated prognostic model for individuals diagnosed with TNBC. These discoveries have the potential to significantly contribute to the comprehension of the involvement of OSCS in TNBC.
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Objective: To explore the effects and possible mechanisms of the drug pair Cornus officinalis and Radix achyranthis bidentatae (SYR-NX) on improving hypertensive kidney damage. Method: SYR-NX, a formulation of Cornus officinalis and Radix Achyranthis Bidentatae with a dose ratio 1:2.5, was used in this experiment. We investigated the effects of SYR-NX on spontaneously hypertensive rats (SHR) fed with a high-salt diet and Human Kidney-2 (HK2) cells exposed to hypoxia. After 8 weeks of treatment with SYR-NX, blood pressure was tested, and ß 2-Microglobulin(ß2-MG), blood creatinine (S-cr), endothelial nitric oxide synthase (eNOS), nicotinamide adenine dinucleotide phosphate (NADPH), M2 pyruvate kinase (PKM2), adenosine triphosphate (ATP), pyruvate, lactate, connective tissue growth factor (CTGF) and tumor necrosis factor-α (TNF-α)were measured. HK2 cells pre-treated with SYR-NX were cultured in a three-gas hypoxic incubator chamber (5 % CO2, 1 % O2, 94 % N2) for 12 h, and then eNOS, PKM2, NADPH, ATP, pyruvate, lactate, CTGF and TNF-α were assessed. Results: SYR-NX significantly reduced SBP, DBP, ß2-MG, S-cr, PKM2, pyruvate, lactate, CTGF and TNF-α, and increased eNOS, NADPH, and ATP. Conclusion: SYR-NX can regulate metabolic reprogramming through eNOS and improves hypertensive kidney injury.
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Objective: Many young male cancer patients experience reproductive concerns. Self-disclosure might be able to improve patients' perceived social support and reproductive concerns. Nevertheless, these relationships have not yet been confirmed among young male cancer patients. This study aims to investigate the level of reproductive concerns and to identify the mediating role of perceived social support between self-disclosure and reproductive concerns among young male cancer patients in China by developing a structural model. Methods: This study was a quantitative, cross-sectional design. We used the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement guidelines to report this study. A total of 369 young male cancer survivors were recruited by convenience sampling from two tertiary hospitals in Taiyuan, Shanxi, China. Data were collected using a "general data questionnaire", "distress disclosure index" (DDI), "perceived social support scale" (PSSS), and "reproductive concerns after cancer-male" (RCAC-M) via the WeChat mini program "Questionnaire Star" and paper questionnaire. Descriptive statistics, Pearson correlation analyses, and structural equation models were adopted to analyze the data. Results: Reproductive concerns were at moderate levels and negatively associated with self-disclosure (r = -0.619, P < 0.01) and perceived social support (r = -0.599, P < 0.01). Self-disclosure indirectly influenced reproductive concerns (-0.328â¼-0.159, P < 0.001) through perceived social support. Conclusions: Self-disclosure and perceived social support are closely associated with reproductive concerns in young male cancer patients, and perceived social support is a mediator between self-disclosure and reproductive concerns. Healthcare providers could reduce reproductive concerns by enhancing self-disclosure and improving perceived social support. Trial registration: This study was registered on ClinicalTrials.gov on June 13, 2023 (NCT05914181).
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Objective: To examine the dose-response relationship between specific types of exercise for alleviating Timed up and Go (TUG) in Parkinson's disease PD. Design: Systematic review and Bayesian network meta-analysis. Data sources: PubMed, Medline, Embase, PsycINFO, Cochrane Library, and Web of Science were searched from inception until February 5th, 2024. Study analysis: Data analysis was conducted using R software with the MBNMA package. Effect sizes of outcome indicators were expressed as mean deviation (MD) and 95% confidence intervals (95% CrI). The risk of bias in the network was evaluated independently by two reviewers using ROB2. Results: A total of 73 studies involving 3,354 PD patients. The text discusses dose-response relationships in improving TUG performance among PD patients across various exercise types. Notably, Aquatic (AQE), Mix Exercise (Mul_C), Sensory Exercise (SE), and Resistance Training (RT) demonstrate effective dose ranges, with AQE optimal at 1500 METs-min/week (MD: -8.359, 95% CI: -1.398 to -2.648), Mul_C at 1000 METs-min/week (MD: -4.551, 95% CI: -8.083 to -0.946), SE at 1200 METs-min/week (MD: -5.145, 95% CI: -9.643 to -0.472), and RT at 610 METs-min/week (MD: -2.187, 95% CI: -3.161 to -1.278), respectively. However, no effective doses are found for Aerobic Exercise (AE), Balance Gait Training (BGT), Dance, and Treadmill Training (TT). Mind-body exercise (MBE) shows promise with an effective range of 130 to 750 METs-min/week and an optimal dose of 750 METs-min/week (MD: -2.822, 95% CI: -4.604 to -0.996). According to the GRADE system, the included studies' overall quality of the evidence was identified moderate level. Conclusion: This study identifies specific exercise modalities and dosages that significantly enhance TUG performance in PD patients. AQE emerges as the most effective modality, with an optimal dosage of 1,500 METs-min/week. MBE shows significant benefits at lower dosages, catering to patients with varying exercise capacities. RT exhibits a nuanced "U-shaped" dose-response relationship, suggesting an optimal range balancing efficacy and the risk of overtraining. These findings advocate for tailored exercise programs in PD management, emphasizing personalized prescriptions to maximize outcomes.Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024506968).
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Background: Extensive research has been conducted on the correlation between adipose tissue and the risk of malignant lymphoma. Despite numerous observational studies exploring this connection, uncertainty remains regarding a causal relationship between adipose tissue and malignant lymphoma. Methods: The increase or decrease in adipose tissue was represented by the height of BMI. The BMI and malignant lymphoma genome-wide association studies (GWAS) used a summary dataset from the OPEN GWAS website. Single-nucleotide polymorphisms (SNPs) that met the criteria of P <5e-8 and LD of r2 = 0.001 in the BMI GWAS were chosen as genetic instrumental variants (IVs). Proxy SNPs with LD of r2 > 0.8 were identified, while palindromic and outlier SNPs were excluded. Mendelian randomization (MR) analysis used five methods, including inverse-variance weighted (IVW) model, weighted median (WM), MR-Egger, simple mode, and weighted mode. Sensitivity assessments included Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis. Participants randomly selected by the National Center for Health Statistics (NHANSE) and newly diagnosed HL patients at Fujian Medical University Union Hospital were used for external validation. Results: The results of the MR analysis strongly supported the causal link between BMI and Hodgkin's lymphoma (HL). The research demonstrated that individuals with lower BMI face a significantly increased risk of developing HL, with a 91.65% higher risk (ORIVW = 0.0835, 95% CI 0.0147 - 0.4733, P = 0.005). No signs of horizontal or directional pleiotropy were observed in the MR studies. The validation results aligned with the results from the MR analysis (OR = 0.871, 95% CI 0.826 - 0.918, P< 0.001). And there was no causal relationship between BMI and non-Hodgkin's lymphoma (NHL). Conclusions: The MR analysis study demonstrated a direct correlation between lower BMI and HL. This suggested that a decrease in adipose tissue increases the risk of developing HL. Nevertheless, further research is essential to grasp the underlying mechanism of this causal association comprehensively.
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Tecido Adiposo , Índice de Massa Corporal , Estudo de Associação Genômica Ampla , Doença de Hodgkin , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Humanos , Doença de Hodgkin/genética , Predisposição Genética para Doença , Feminino , Masculino , Fatores de Risco , Adulto , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: This study aimed to explore the effect of narrative nursing on improving the negative emotions, sleep quality, and quality of life of patients with moderate to severe cancer pain. METHODS: A total of 80 patients with moderate to severe cancer pain who had been hospitalized in the lymphoma oncology department in our hospital from March 2019 to September 2021 were selected as the study subjects and randomly divided into the conventional nursing and narrative nursing groups, with 40 cases in each group. A conventional nursing intervention was conducted for one group, and narrative nursing was provided for the second group in addition to the conventional nursing. The anxiety and depression, sleep quality, quality of life, and satisfaction with pain management of the patients in the two groups were compared before and after the intervention. RESULTS: In the narrative nursing group, the self-rating anxiety scale and self-rating depression scale scores were significantly lower than those in the conventional nursing group after the intervention (P < 0.05). The scores for sleep quality, sleep duration, sleep efficiency, and daytime dysfunction and the total Pittsburgh Sleep Quality Index scores were significantly lower in the narrative nursing group compared with the conventional care group (P < 0.05). The scores for the physical function, living ability, social adaptation, and psychological status items in the Quality of Life Questionnaire Core 30 were significantly higher in the narrative nursing group than in the conventional care group (P < 0.05). The patients' satisfaction with pain management was higher in the narrative nursing group than in the conventional care group (P < 0.05). CONCLUSION: Narrative nursing can alleviate the negative emotions of anxiety and depression in patients with moderate to severe cancer pain and improve their sleep quality, quality of life, and pain management satisfaction.
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Colorectal cancer (CRC) is a common malignant tumor that occurs in the colon. Gut microbiota is a complex ecosystem that plays an important role in the pathogenesis of CRC. Our previous studies showed that the soluble dietary fiber of foxtail millet (FMB-SDF) exhibited significant antitumor activity in vitro. The present study evaluated the anticancer potential of FMB-SDF in the azoxymethane (AOM)- and dextran sodium sulfate (DSS)-induced mouse CRC models. The results showed that FMB-SDF could significantly alleviate colon cancer symptoms in mice. Further, we found that FMB-SDF consumption significantly altered gut microbiota diversity and the overall structure and regulated the abundance of some microorganisms in CRC mice. Meanwhile, KEGG pathway enrichment showed that FMB-SDF can also alleviate the occurrence of colon cancer in mice by regulating certain cancer-related signaling pathways. In conclusion, our findings may provide a novel approach for the prevention and biotherapy of CRC.
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Bactérias , Neoplasias Colorretais , Fibras na Dieta , Microbioma Gastrointestinal , Setaria (Planta) , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Neoplasias Colorretais/prevenção & controle , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/metabolismo , Camundongos , Setaria (Planta)/química , Fibras na Dieta/metabolismo , Fibras na Dieta/farmacologia , Humanos , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Azoximetano , Camundongos Endogâmicos C57BLRESUMO
Noninvasive prenatal diagnosis (NIPD) for autosomal recessive nonsyndromic hearing loss (ARNSHL) has been rarely reported until recent years. Additionally, the existing method can not be used for challenging genome loci (eg, copy number variations, deletions, inversions, or gene recombinants) or on families without proband genotype. This study assessed the performance of relative haplotype dosage analysis (RHDO)-based NIPD for identifying fetal genotyping in pregnancies at risk of ARNSHL. Fifty couples carrying pathogenic variants associated with ARNSHL in either GJB2 or SLC26A4 were recruited. The RHDO-based targeted linked-read sequencing combined with whole gene coverage probes was used to genotype the fetal cell-free DNA of 49 families who met the quality control standard. Fetal amniocyte samples were genotyped using invasive prenatal diagnosis (IPD) to assess the performance of NIPD. The NIPD results showed 100% (49/49) concordance with those obtained through IPD. Two families with copy number variation and recombination were also successfully identified. Sufficient specific informative single-nucleotide polymorphisms for haplotyping, as well as the fetal cell-free DNA concentration and sequencing depth, are prerequisites for RHDO-based NIPD. This method has the merits of covering the entire genes of GJB2 and SLC26A4, qualifying for copy number variation and recombination analysis with remarkable sensitivity and specificity. Therefore, it has clinical potential as an alternative to traditional IPD for ARNSHL.
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Alelos , Conexina 26 , Haplótipos , Transportadores de Sulfato , Humanos , Transportadores de Sulfato/genética , Feminino , Gravidez , Polimorfismo de Nucleotídeo Único , Teste Pré-Natal não Invasivo/métodos , Conexinas/genética , Diagnóstico Pré-Natal/métodos , Variações do Número de Cópias de DNA , Surdez/genética , Surdez/diagnóstico , Genótipo , Masculino , Genes Recessivos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Proteínas de Membrana Transportadoras/genéticaRESUMO
Background: Cell division cycle protein 45 (CDC45) has been demonstrated to play vital roles in the progression of various malignancies. However, the clinical significance of CDC45 in gastric cancer (GC) remains unreported. Method: In this study, we employed the TCGA database and the TCGA & GTEx dataset to compare the mRNA expression levels of CDC45 between gastric cancer tissues and adjacent or normal tissues (p < 0.05 was considered statistically significant), which was further validated in multiple datasets including GSE13911, GSE29272, GSE118916, GSE66229, as well as RT-qPCR. Furthermore, we harnessed the Human Protein Atlas (HPA) to evaluate the protein expression of CDC45, which was subsequently verified through immunohistochemistry (IHC). To ascertain the diagnostic utility of CDC45, receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were calculated in TCGA database, and further validated it in TCGA & GTEx and GSE66229 datasets. The Kaplan-Meier method was used to reveal the prognostic importance of CDC45 in The Cancer Genome Atlas (TCGA) database and authenticated through the GSE66229, GSE84433, and GSE84437 datasets. Through cBioPortal, we identified co-expressed genes of CDC45, and pursued enrichment analysis. Additionally, we availed gene set enrichment analysis (GSEA) to annotate the biological functions of CDC45. Results: Differential expression analysis revealed that CDC45 was significantly upregulated at both the mRNA and protein levels in GC (all p < 0.05). Remarkably, CDC45 emerged as a promising prognostic indicator and a novel diagnostic biomarker for GC. In a comprehensive the drug susceptibility analysis, we found that patients with high expression of CDC45 had high sensitivity to various chemotherapeutic agents, among which 5-fluorouracil, docetaxel, cisplatin, and elesclomol were most evident. Furthermore, our findings suggested a plausible association between CDC45 and immune cell infiltration. Enrichment analysis revealed that CDC45 and its associated genes may play crucial roles in muscle biofunction, whereas GSEA demonstrated significant enrichment of gene sets pertaining to G protein-coupled receptor ligand binding and G alpha (i) signaling events. Conclusion: Our study elucidates that upregulation of CDC45 is intricately associated with immune cell infiltration and holds promising potential as a favorable prognostic marker and a novel diagnostic biomarker for GC.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Biomarcadores , Cisplatino , Docetaxel , RNA Mensageiro/genética , Proteínas de Ciclo Celular/genéticaRESUMO
Uranyl ions (UO22+) are recognized as important indicators for monitoring sudden nuclear accidents. However, the interferences coexisting in the complicated environmental matrices impart serious constraints on the reliability of current on-site monitoring methods. Herein, a novel ratiometric method for the highly sensitive and selective detection of UO22+ is reported based on a [Eu(diaminoterephthalic acid)] (Eu-DATP) metal-organic framework. Benefiting from the unique chemical structure of Eu-DATP, energy transfer from DATP to UO22+ was enabled, resulting in the up-regulated fluorescence of UO22+ and the simultaneous down-regulated fluorescence of Eu3+. The limit of detection reached as low as 2.7 nM, which was almost 2 orders of magnitude below the restricted limit in drinking water set by the United States Environmental Protection Agency (130 nM). The Eu-DATP probe showed excellent specificity to UO22+ over numerous interfering species, as the intrinsic emissions of UO22+ were triggered. This unprecedentedly high selectivity is especially beneficial for monitoring UO22+ in complicated environmental matrices with no need for tedious sample pretreatment, such as filtration and digestion. Then, by facilely equipping a Eu-DATP-based sampler on a drone, remotely controlled sampling and on-site analysis in real water samples were realized. The concentrations of UO22+ were determined to be from 16.5 to 23.5 nM in the river water of the Guangzhou downtown area, which was consistent with the results determined by the gold-standard inductively coupled plasma mass spectrometry. This study presents a reliable and convenient method for the on-site analysis of UO22+.
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BACKGROUND: The emergence of severe sepsis is contingent upon the occurrence of a cytokine storm (CS), a multifaceted process intricately entwined with the temporal dimension, thereby rendering the infection response remarkably intricate. Consequently, it becomes imperative to discern and accurately identify the optimal timing for interventions, predicated upon the dynamic timeline of inflammatory changes. Moreover, the administration of exogenous low-dose pro-inflammatory agents has exhibited the potential to impede the relentless progression of the inflammatory cascade. Hence, the present study aims to scrutinize the impact of exogenous Local Inflammatory Response (eLIR) on the body surface in the context of the inflammatory cascade during sepsis, within a temporal framework, with a particular emphasis on the point of exacerbation of inflammation. METHODS: Rats were induced sterile sepsis by intraperitoneal injection of zymosan (ZY) at an appropriate dosage. The temporal progression of inflammatory changes and eLIR effects were described based on the trend of serum crucial inflammatory cytokines, tring to quest time-point of inflammatory aggravation in sepsis. Then, the varying degrees of surface inflammation caused by eLIR on this time point leading to the final effects on the inflammatory cascade response were explored. In addition, given the authentic pathological progression of sepsis, further observation was conducted on the impact of another intervention timing of eLIR on the inflammatory cascade. The survival rate was measured. Serum and organ related inflammatory cytokines were detected, and organ histopathology was investigated. RESULTS: In present study, a dosage of 600 mg/kg ZY was found to be optimal for the sterile sepsis model. Initiating eLIR 6 h prior to ZY injection, the maximum effect point of eLIR could be precisely align with the inflammatory aggravation point of sterile sepsis. Initiating eLIR at this time, 3 sessions of eLIR were found to be more effective than 1 or 2 sessions in mitigating inflammatory responses during the initial stage of inflammation and the peak of inflammation. Notably, the findings also suggested that this intervention improve survival rate. In addition, the anti-inflammatory efficacy has been substantially diminished by the prompt initiation of 3 sessions of eLIR immediately after ZY injection at the onset of sepsis. Similarly, the current findings did not demonstrate a statistically significant enhancement in survival rates with eLIR at this time point. CONCLUSIONS: Compared with the initial stage of inflammation, low-scale inflammation caused by a certain intensity of eLIR (3 sessions) on the body surface can more effectively pry the inflammation aggravation time-point, thereby shifting the pro-inflammatory to anti-inflammatory milieu, impeding the disproportionate cytokines release in inflammatory diseases, slowing down the inflammatory cascade, and improving the survival rate of sepsis.
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Síndrome da Liberação de Citocina , Sepse , Ratos , Animais , Síndrome da Liberação de Citocina/tratamento farmacológico , Citocinas , Inflamação/tratamento farmacológico , Sepse/complicações , Sepse/tratamento farmacológico , Anti-Inflamatórios/uso terapêuticoRESUMO
Age-associated B cells (ABCs) accumulate during infection, aging, and autoimmunity, contributing to lupus pathogenesis. In this study, we screened for transcription factors driving ABC formation and found that zinc finger E-box binding homeobox 2 (ZEB2) is required for human and mouse ABC differentiation in vitro. ABCs are reduced in ZEB2 haploinsufficient individuals and in mice lacking Zeb2 in B cells. In mice with toll-like receptor 7 (TLR7)-driven lupus, ZEB2 is essential for ABC formation and autoimmune pathology. ZEB2 binds to +20-kb myocyte enhancer factor 2b (Mef2b)'s intronic enhancer, repressing MEF2B-mediated germinal center B cell differentiation and promoting ABC formation. ZEB2 also targets genes important for ABC specification and function, including Itgax. ZEB2-driven ABC differentiation requires JAK-STAT (Janus kinase-signal transducer and activator of transcription), and treatment with JAK1/3 inhibitor reduces ABC accumulation in autoimmune mice and patients. Thus, ZEB2 emerges as a driver of B cell autoimmunity.
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Autoimunidade , Linfócitos B , Diferenciação Celular , Regulação da Expressão Gênica , Lúpus Eritematoso Sistêmico , Homeobox 2 de Ligação a E-box com Dedos de Zinco , Animais , Humanos , Camundongos , Autoimunidade/genética , Linfócitos B/citologia , Linfócitos B/metabolismo , Diferenciação Celular/genética , Linhagem da Célula/genética , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Fatores de Transcrição MEF2/genética , Fatores de Transcrição MEF2/metabolismo , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo , Haploinsuficiência , Envelhecimento/imunologia , Modelos Animais de Doenças , FemininoRESUMO
BACKGROUND: The combination of immune checkpoint inhibitors and anti-angiogenic agents has been proposed as a promising strategy to improve the outcome of advanced triple-negative breast cancer (TNBC). However, further investigation is warranted to elucidate the specific mechanisms underlying the effects of combination therapy and its potential as neoadjuvant therapy for early-stage TNBC. METHODS: In this study, we constructed humanized mouse models by engrafting the human immune system into severely immunodeficient mice and subsequently implanting TNBC cells into the model. The mice were treated with neoadjuvant combination therapy (bevacizumab combined with nivolumab), followed by in vivo imaging system to assess tumor recurrence and metastasis after surgery. The immune microenvironment of tumors was analyzed to investigate the potential mechanisms. Furthermore, we verified the impact of extending the interval before surgery or administering adjuvant therapy after neoadjuvant therapy on the prognosis of mice. RESULTS: Neoadjuvant combination therapy significantly inhibited tumor growth, prevented recurrence and metastasis by normalizing tumor vessels and inducing robust CD8+ T cell infiltration and activation in primary tumors (p < 0.001). In vivo experiments demonstrated that prolonging the interval before surgery or administering adjuvant therapy after neoadjuvant therapy did not enhance its efficacy. CONCLUSION: The preclinical study has demonstrated the therapeutic efficacy and mechanism of neoadjuvant combination therapy (nivolumab plus bevacizumab) in treating early TNBC.
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Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Terapia Neoadjuvante , Nivolumabe , Neoplasias de Mama Triplo Negativas , Microambiente Tumoral , Animais , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Bevacizumab/uso terapêutico , Bevacizumab/farmacologia , Bevacizumab/administração & dosagem , Terapia Neoadjuvante/métodos , Feminino , Humanos , Camundongos , Nivolumabe/uso terapêutico , Nivolumabe/farmacologia , Nivolumabe/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Prognóstico , Ensaios Antitumorais Modelo de Xenoenxerto , Modelos Animais de Doenças , Recidiva Local de Neoplasia/patologia , Linhagem Celular Tumoral , Camundongos SCIDRESUMO
Monitoring the residual dichlorvos (O,O-dimethyl-O-2,2-dichlorovinylphosphate, DDVP) in food has received extensive attention owing to its large consumption in agriculture. However, the previous sensing methods are not time-efficient enough due to the long incubation time for enzyme inhibition (tens of minutes to hours) or bottlenecked by the complicated procedures for senor fabrication. Herein, a novel sensing strategy is proposed based on the hydrolysis of DDVP into PO43-. By using alkaline phosphatase for hydrolysis, a certain portion of DDVP was transformed to PO43- within only 8 min. Then, the released PO43- was detected by a fluorescent terbium metal-organic framework (Tb-MOF). The coordination of the naked P-O groups to the metal nodes of the Tb-MOF disturbed the antenna effects of its ligands. Thus, DDVP was quantified by the decrease of the fluorescence of Tb ions. Based on this method, DDVP residues on plum surfaces were collected by swabs and successfully detected. The recovery of DDVP was determined in the range from 105 % to 115 %, demonstrating the quantification accuracy of this method. The detection limit reached 4.7 µM, which was lower than the restricted amount in fruit set by the National Standard of China. The present method provides an efficient and user-friendly way for the detection of DDVP and many other organophosphorus pesticides in food.
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Arsenic (As) is a metal with potentially toxic effects on different organisms. Hydrogen sulfide (H2S) plays a vital role in mitigating heavy metal toxicity by reducing oxidative stress in plants and animals. However, the role of H2S in alleviating arsenic toxicity in yeast cells remains unclear. In this study, the role of NaHS (exogenous physiological H2S) in alleviating As-induced yeast cell death was investigated. Yeast cells in the logarithmic phase were pretreated with 0.05 mmol/L NaHS for 6 h, and then incubated in the YPD medium with or without 1 mmol/L As. After 12 h of treatment, relative survival rate, H2S content, oxidative stress biomarkers, and antioxidant machinery were measured. Our results showed that sodium arsenite-induced yeast cell death and pretreatment with 0.05 mmol/L NaHS significantly alleviated sodium arsenite-induced cell death. Under sodium arsenite conditions, the levels of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) increased, accompanied by the inhibition of the catalase (CAT) activity and the downregulation of CTT1 expression. However, the activities of the superoxide dismutase (SOD) and glutathion peroxidase (GPX) increased, and the expression of SOD1 and GPX2 was markedly upregulated in the group treated with sodium arsenite. When yeast cells were pretreated with NaHS, the intracellular ROS and MDA levels decreased significantly, and the activities of SOD, CAT, and GPX increased significantly. This was associated with a significant increase in relative survival rate and H2S content compared to the arsenic treatment alone. Our findings indicate that NaHS alleviates sodium arsenite-induced yeast cell death, mainly by enhancing the antioxidant defense system.
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Arsênio , Arsenitos , Sulfeto de Hidrogênio , Compostos de Sódio , Sulfetos , Animais , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Saccharomyces cerevisiae/metabolismo , Arsênio/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Morte CelularRESUMO
BACKGROUND: Spread of SARS-CoV-2 led to a global pandemic, and there remains unmet medical needs in the treatment of Omicron infections. VV116, an oral antiviral agent that has potent activity against SARS-CoV-2, was compared with a placebo in this phase 3 study to investigate its efficacy and safety in patients with mild-to-moderate COVID-19. METHODS: This multicentre, double-blind, phase 3, randomised controlled study enrolled adults in hospitals for infectious diseases and tertiary general hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio using permuted block randomisation to receive oral VV116 (0·6 g every 12 h on day 1 and 0·3 g every 12 h on days 2-5) or oral placebo (on the same schedule as VV116) for 5 days. Randomisation stratification factors included SARS-CoV-2 vaccination status and the presence of high-risk factors for progression to severe COVID-19. Inclusion criteria were a positive SARS-CoV-2 test, an initial onset of COVID-19 symptoms 3 days or less before the first study dose, and a score of 2 or more for any target COVID-19-related symptoms in the 24 h before the first dose. Patients who had severe or critical COVID-19 or who had taken any antiviral drugs were excluded from the study. The primary endpoint was the time to clinical symptom resolution for 2 consecutive days. Efficacy analyses were performed on a modified intention-to-treat population, comprising all patients who received at least one dose of VV116 or placebo, tested positive for SARS-CoV-2 nucleic acid, and did not test positive for influenza virus before the first dose. Safety analyses were done on all participants who received at least one dose of VV116 or placebo. This study was registered with ClinicalTrials.gov, NCT05582629, and has been completed. FINDINGS: A total of 1369 patients were randomly assigned to treatment groups and 1347 received either VV116 (n=674) or placebo (n=673). At the interim analysis, VV116 was superior to placebo in reducing the time to sustained clinical symptom resolution among 1229 patients (hazard ratio [HR] 1·21, 95% CI 1·04-1·40; p=0·0023). At the final analysis, a substantial reduction in time to sustained clinical symptom resolution was observed for VV116 compared with placebo among 1296 patients (HR 1·17, 95% CI 1·04-1·33; p=0·0009), consistent with the interim analysis. The incidence of adverse events was similar between groups (242 [35·9%] of 674 patients vs 283 [42·1%] of 673 patients). INTERPRETATION: Among patients with mild-to-moderate COVID-19, VV116 significantly reduced the time to sustained clinical symptom resolution compared with placebo, with no observed safety concerns. FUNDING: Shanghai Vinnerna Biosciences, Shanghai Science and Technology Commission, and the National Key Research and Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Adenosina , COVID-19 , Adulto , Humanos , SARS-CoV-2 , Vacinas contra COVID-19 , China/epidemiologia , Método Duplo-Cego , Adenosina/análogos & derivadosRESUMO
A 82-year-old man was admitted to hospital with fever, unresponsiveness, elevated hypersensitive C-reactive protein and neutrophile granulocyte. Ceftriaxone was administrated by intravenous dripping in the emergency room, but the effect was not satisfactory. Following his admission to the ward, cefoperazone sulbactam were given. Elizabethkingia meningoseptica was identified by blood culture and further confirmed by 16S rRNA sequencing. The lumbar puncture showed that cerebrospinal fluid pressure was 80 mmH2O (1 mmH2O=0.0098 kPa) and biochemical results were normal. After 11 days of cefoperazone sulbactam treatment, the patient was discharged with negative blood culture. The hypersensitive C-reactive protein and neutrophile granulocyte had also declined. The patient received levofloxacin tablets for anti-infection treatment for 14 d after discharge. No signs of infection were observed in three months' following up.
Assuntos
Infecções por Flavobacteriaceae , Sepse , Masculino , Humanos , Idoso de 80 Anos ou mais , Proteína C-Reativa , Cefoperazona/uso terapêutico , Infecções por Flavobacteriaceae/diagnóstico , Infecções por Flavobacteriaceae/tratamento farmacológico , RNA Ribossômico 16S , Sulbactam/uso terapêuticoRESUMO
BACKGROUND: Effective pain management is closely related to nurses' knowledge, attitudes and empathy regarding pain. Nursing educators and managers should understand the relationship between nurses' pain management knowledge, attitudes and empathy level, and take targeted measures accordingly. Currently, there is limited study exploring the relationship between pain empathy and pain knowledge and attitudes among nurses in North China. OBJECTIVES: The purpose of this study was to investigate the level of nurses' pain management knowledge and attitudes and pain empathy, to analyze the factors influencing pain empathy, and to explore the relationship between these two variables. DESIGN: This study was a quantitative, descriptive-correlation design. SETTING AND PARTICIPANTS: The study population was registered nurses in North China, the sample included 177 registered nurses in North China. METHODS: Data were collected with the "General data questionnaire", "Knowledge and attitudes survey regarding pain" (KASRP) and the "Empathy for pain scale" (EPS) via Wechat mini program "Questionnaire Star". RESULTS: The 177 registered nurses completed the survey. The averege correct rate for KASRP was (51.94 ± 9.44)%, and none of the respondents achieved a percentage score of >80%. The mean score for pain empathy was (2.78 ± 0.78), the empathy reactions dimension was (2.99 ± 0.77), and the body and mind discomfort dimension was (2.71 ± 0.80). The results of multiple stepwise linear regression showed that whether they had received empathy training, whether they had greater trauma or severe pain and whether they had negative emotions were independent influencing factors for EPS scores. Pearson correlation analysis showed that KASRP scores were positively correlated with EPS scores (r = 0.242, P < 0.05). CONCLUSIONS: The pain knowledge and attitudes of nurses in North China are far from optimal. Nurses have a relatively low accuracy rate in areas such as medication knowledge, assessment of patient pain based on case studies, and handling PRN prescriptions. Nursing educators and administrators need to design some pain management courses in a targeted manner. Nurses' empathy for pain was at a moderate level. Pain empathy was positively correlated with pain knowledge and attitudes, suggesting that empathy for pain can be developed postnatally.
RESUMO
BACKGROUND: Exploration of the relationship between individual work immersion and perceived stress is critical for clinical nurses' effective psychological interventions and human resource management, as well as to alleviate nursing staff shortages. In order to further dissect the influencing factors of perceived stress among nursing staff, our study introduces the concepts of perfectionism and social connectedness to analyze the specific pathways that influence perceived stress in terms of an individual's intrinsic and external personality traits. This study provides relevant recommendations for the development of stress management measures for nursing staff. METHODS: This was a cross-sectional survey. 993 registered clinical nurses were included from four hospitals in Guangzhou through a convenience sampling method. Clinical nurses' work immersion, perceived stress, perfectionism, and social connectedness were investigated using questionnaires based on latent profile analysis. The relationships between variables were analyzed using t-tests, analysis of variance, Pearson's correlation analysis, latent profile analysis, and moderated mediation analysis. RESULTS: The results showed that (1) general influences on nurses' perceived stress included only child, labor relationship, labor allowance, and family support; (2) nurses' work immersion contained four subgroups: lowest (12.6%), medium-low (39.8%), medium-high (39.9%), and highest (7.7%); (3) positive and negative perfectionism played a mediating role between the association of work immersion and perceived stress; (4) social connectedness played a moderating role in the mediation model of perceived stress. CONCLUSIONS: Work immersion, perfectionism, and social connectedness have an important impact on clinical nurses' perceived stress. Nursing managers or leaders should pay attention to the differences of individual work immersion status, adopt reasonable stress management strategies, accurately identify positive perfectionist groups and strengthen the relationship between groups, so as to ensure the quality of nursing care, and reduce nursing turnover and alleviate the problem of staff shortage.
RESUMO
Two-dimensional (2D) conductive metal-organic frameworks (cMOFs) have emerged as powerful transducers for electrochemical sensing. However, electrochemical sensing in aqueous solutions remains at a very early stage for 2D cMOFs. Herein, the interfacial capacitances of a 2D cMOF are utilized for electrochemical sensing for the first time. Various redox-innocent compounds along with redox-active compounds in aqueous solutions are successfully detected based on the responses of two capacitance peaks at low voltages. The quantitative sensitivity to ascorbic acid is even an order of magnitude higher than the previous voltammetric method. Further investigation demonstrates that the responses are rooted in the pseudocapacitances of the 2D cMOF, i.e., the transitions among the multiple redox states of the ligands. The analytes are suggested to alert the d-p conjugation and exchange electrons with the 2D cMOF. These deep insights in response mechanisms represent an important step for promoting the application of 2D cMOFs in chemical sensing.