ABSTRACT
To explore the association and impact between viral myocarditis and mortality in patients with severe fever with thrombocytopenia syndrome. A dynamic analysis was conducted between fatal group and nonfatal group regarding the daily epidemiology data, clinical symptoms, and electrocardiogram (ECG), echocardiogram, and laboratory findings. Outcomes of patients with and without viral myocarditis were compared. The association between viral myocarditis and mortality was analyzed. Among 183 severe fever with thrombocytopenia syndrome patients, 32 were in the fatal group and 151 in the nonfatal group; there were 26 (81.25%) with viral myocarditis in the fatal group, 66 (43.70%) with viral myocarditis in the nonfatal group (p < 0.001), 79.35% of patients had abnormal ECG results. The abnormal rate of ECG in the fatal group was 100%, and in the nonfatal group was 74.83%. Univariate analysis found that the number of risk factors gradually increased on Day 7 of the disease course and reached the peak on Day 10. Combined with the dynamic analysis of the disease course, alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine kinase fraction, lactate dehydrogenase, hydroxybutyrate dehydrogenase, neutrophil count, serum creatinine, Na, Ca, carbon dioxide combining power, amylase, lipase, activated partial thromboplastin time and thrombin time had statistically significant impact on prognosis. The incidence of fever with thrombocytopenia syndrome combined with viral myocarditis is high, especially in the fatal group of patients. Viral myocarditis is closely related to prognosis and is an early risk factor. The time point for changes in myocarditis is Day 7 of the course of the disease.
Subject(s)
Myocarditis , Severe Fever with Thrombocytopenia Syndrome , Virus Diseases , Humans , Myocarditis/complications , Myocarditis/epidemiology , Prevalence , Virus Diseases/complications , Virus Diseases/epidemiology , Fever/epidemiology , Disease ProgressionABSTRACT
Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is a formidable pathogen responsible for severe intracranial infections post-craniotomy, exhibiting a mortality rate as high as 71%. Tigecycline (TGC), a broad-spectrum antibiotic, emerged as a potential therapeutic agent for MDR A. baumannii infections. Nonetheless, its clinical application was hindered by a short in vivo half-life and limited permeability through the blood-brain barrier (BBB). In this study, we prepared a novel core-shell nanoparticle encapsulating water-soluble tigecycline using a blend of mPEG-PLGA and PLGA materials. This nanoparticle, modified with a dual-targeting peptide Aß11 and Tween 80 (Aß11/T80@CSs), was specifically designed to enhance the delivery of tigecycline to the brain for treating A. baumannii-induced intracranial infections. Our findings demonstrated that Aß11/T80@CSs nanocarriers successfully traversed the BBB and effectively delivered TGC into the cerebrospinal fluid (CSF), leading to a significant therapeutic response in a model of MDR A. baumannii intracranial infection. This study offers initial evidence and a platform for the application of brain-targeted nanocarrier delivery systems, showcasing their potential in administering water-soluble anti-infection drugs for intracranial infection treatments, and suggesting promising avenues for clinical translation.
Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Humans , Tigecycline/pharmacology , Tigecycline/therapeutic use , Minocycline/pharmacology , Acinetobacter Infections/drug therapy , Drug Resistance, Multiple, Bacterial , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , WaterABSTRACT
Glucose metabolism plays an important role for formation of normal physiological state of organisms. However, association between altered glucose metabolism and toxicity of 6-PPD quinone (6-PPDQ) remains largely unknown. In 1-100 µg/L 6-PPDQ exposed Caenorhabditis elegans, we observed increased glucose content. After 6-PPDQ exposure (1-100 µg/L), expressions of F47B8.10 and fbp-1 governing gluconeogenesis were increased, and expressions of hxk-1, hxk-3, pfk-1.1, pyk-1, and pyk-2 governing glycolysis were decreased. Under 6-PPDQ exposure condition, glucose content could be changed by RNAi of F47B8.10, hxk-1, and hxk-3, key genes for gluconeogenesis and glycolysis. In 6-PPDQ exposed nematodes, RNAi of daf-16 and aak-2 elevated glucose content, increased expressions of F47B8.10 and/or fbp-1, and decreased expressions of hxk-1, hxk-3, and/or pfk-1.1. Additionally, lifespan and locomotion during aging were increased by RNAi of F47B8.10 and decreased by RNAi of hxk-1 and hxk-3 in 6-PPDQ exposed nematodes. Moreover, after 6-PPDQ exposure, RNAi of F47B8.10 decreased expressions of insulin peptide genes (ins-7 and daf-28) and insulin receptor gene daf-2 and increased expressions of daf-16 and aak-2. In 6-PPDQ exposed nematodes, RNAi of hxk-1 and hxk-3 further increased expressions of ins-7, daf-28, and daf-2 and decreased expressions of daf-16 and aak-2. Our results demonstrated important association between altered glucose metabolism and toxicity of 6-PPDQ in inducing lifespan reduction in organisms.
Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Glucose , Insulin , Longevity , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Animals , Longevity/drug effects , Glucose/metabolism , Insulin/metabolism , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/genetics , AMP-Activated Protein Kinases/metabolism , Signal Transduction/drug effects , Gluconeogenesis/drug effects , Glycolysis/drug effects , PQQ Cofactor , Forkhead Transcription FactorsABSTRACT
BACKGROUND: To investigate the relationship between interstitial maturity and prognosis of colorectal cancer. AIM: To examine the correlation between interstitial maturity and the prognosis of colorectal cancer. METHODS: The paper database PubMed, EMBASE, Cochranelibrary, Springerlink, CNKI, and Wanfang database were searched until December 2023. "tumor stroma maturity" "desmoplastic stroma reaction" "desmoplastic reaction" "stroma reaction" "degree of stroma reaction "" stroma classification" "stroma density" "colorectal cancer" "colon cancer" "rectal cancer" "prognosis" were searched for the search terms. Two system assessors independently screened the literature quality according to the inclusion exclusion criteria, Quality evaluation and data extraction were performed for the included literatures, and meta-analysis was performed for randomized control trials included at using Review Manager 5.2 software. RESULTS: Finally, data of 9849 patients with colorectal cancer from 19 cosets in 15 literatures were included, including 4339 patients with mature type (control group), 3048 patients with intermediate type (intermediate group) and 2456 patients with immature type (immature group). The results of meta-analysis showed: Relapse-free survival [hazard ratio (HR) = 2.66, 95% confidence interval (CI): 2.30-3.08; P < 0.00001], disease-free survival (HR = 3.68, 95%CI: 2.33-5.81; P < 0.00001) and overall survival (HR = 1.70, 95%CI: 1.53-1.87; P < 0.00001) were significantly lower than those in mature group (control group); relapse-free survival (HR = 1.36, 95%CI: 1.17-1.59; P < 0.0001) and disease-free survival rate (HR = 1.85, 95%CI: 1.53-2.24; P < 0.0001) was significantly lower than the mature group (control group). CONCLUSION: There is the correlation between tumor interstitial maturity and survival prognosis of colorectal cancer, and different degrees of tumor interstitial maturity have a certain impact on the quality of life of colorectal cancer patients.