RESUMO
Candida albicans is an opportunistic human fungal pathogen that causes superficial and systemic infections, particularly in immunocompromised individuals. In response to C. albicans infection, innate immune cells of the host produce and accumulate reactive oxygen species (ROS), which can lead to irreversible damage and apoptosis of fungal cells. Several transcription factors involved in this oxidative stress response have been identified; however, a systematic study to identify the transcription factors that mediate the oxidative stress response has not yet been conducted. Here, we screened a comprehensive transcription factor mutant library consisting of 211 transcription factor deletion mutant strains in the presence and absence of hydrogen peroxide (H2O2), a potent ROS inducer, and identified five transcription factors (Skn7, Dpb4, Cap1, Dal81, and Stp2) that are sensitive to H2O2. Genome-wide transcriptional profiling revealed that H2O2 induces a discrete set of differentially regulated genes among the five identified transcription factor mutant strains. Functional enrichment analysis identified KEGG pathways pertaining to glycolysis/gluconeogenesis, amino sugar and nucleotide sugar metabolism, and ribosome synthesis as the most enriched pathways. GO term analysis of the top common differentially expressed genes among the transcription factor mutant strains identified hexose catabolism and iron transport as the most enriched GO terms upon exposure to H2O2. This study is the first to systematically identify and characterise the transcription factors involved in the response to H2O2. Based on our transcriptional profiling results, we found that exposure to H2O2 modulates several downstream genes involved in fungal virulence. Overall, this study sheds new light on the metabolism, physiological functions, and cellular processes involved in the H2O2-induced oxidative stress response in C. albicans.
Assuntos
Candida albicans , Fatores de Transcrição , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Estresse Oxidativo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão GênicaRESUMO
BACKGROUND: Candida glabrata which belongs to normal microbiota, has caused significant concern worldwide due to its high prevalence and drug resistance in recent years. C. glabrata has developed many strategies to evade the clearance of the host immune system, thereby causing persistent infection. Although coping with the induced DNA damage is widely acknowledged to be important, the underlying mechanisms remain unclear. RESULTS: The present study provides hitherto undocumented evidence of the importance of the regulatory subunits of CgCK2 (CgCkb1 and CgCkb2) in response to DNA damage. Deletion of CgCKB1 or CgCKB2 enhanced cellular apoptosis and DNA breaks and led to cell cycle delay. In addition, deficiencies in survival upon phagocytosis were observed in Δckb1 and Δckb2 strains. Consistently, disruption of CgCKB1 and CgCKB2 attenuated the virulence of C. glabrata in mouse models of invasive candidiasis. Furthermore, global transcriptional profiling analysis revealed that CgCkb1 and CgCkb2 participate in cell cycle resumption and genomic stability. CONCLUSIONS: Overall, our findings suggest that the response to DNA damage stress is crucial for C. glabrata to survive in macrophages, leading to full virulence in vivo. The significance of this work lies in providing a better understanding of pathogenicity in C. glabrata-related candidiasis and expanding ideas for clinical therapies.
Assuntos
Candida glabrata , Candidíase , Animais , Camundongos , Candida glabrata/genética , Candida glabrata/metabolismo , Virulência/genética , Fagocitose , MacrófagosRESUMO
BACKGROUND: Stroke is one of the leading causes of death worldwide, especially in developing countries. In China, there is an urgent need to educate people about stroke awareness and the importance of using emergency medical services (EMS) quickly after a stroke has occurred. OBJECTIVE: We sought to explore the effects of the Stroke 1-2-0 Prehospital Stroke Education System based on the experience of a general practitioner team. METHOD: We prospectively enrolled 119 community general practitioners to be trained in the procedures advocated by the Stroke 1-2-0 Prehospital Stroke Education System. The training content included early detection of ischemic stroke, first aid for stroke, and intravenous thrombolysis; The effects of the training were later evaluated via a before-and-after comparison. The 119 enrolled physicians formed a Stroke 1-2-0 lecturer group and taught stroke knowledge to community residents. The group remained active for 6 months, during which the medical treatment data of stroke patients (i.e., stroke onset time, prehospital delay, whether an ambulance was called, and whether thrombolytic therapy was performed) in each of 5 jurisdictions were recorded for the month before (January 2021) and that after (August 2021) the 6-month community education program. Finally, the effects of the community education program were evaluated. RESULTS: The participants' understanding of intravenous thrombolysis in the treatment of acute ischemic stroke improved significantly after the training as compared with their earlier understanding (96% vs. 78.99%; P < .001), and their understanding of the time window for intravenous thrombolysis increased from 26.05% before to 72% (P < .001) after the training. Most of the participants (90% vs. 67.23%; P < .001) said that they would immediately call the 120 emergency number of China's emergency phone system if they encountered individuals who appeared to be victims of acute stroke. A total of 82 stroke patients were seen before and 67 after the community education program. As for the use of the emergency call system, more patients with stroke activated that system after the program versus before (21.95% vs. 37.31%; P = .04). The 3-hour arrival rate after the program was nearly three times higher than that before the program (62.69% vs. 19.51%; P < .001). Also, regarding receiving thrombolysis after the occurrence of a stroke, the program triggered a substantial increase compared with the total earlier (19.4% vs. 6.1%; P = .013). CONCLUSION: We found that the Stroke 1-2-0 Prehospital Stroke Education System significantly improved community residents' knowledge regarding stroke.
Assuntos
Serviços Médicos de Emergência , Clínicos Gerais , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Terapia Trombolítica/métodosRESUMO
BACKGROUND: Initiation of early antithrombotic therapy after acute ischemic stroke (AIS) is crucial. We aimed to investigate whether early antithrombotic therapy influences early neurological deterioration (END) in AIS patients with postinterventional cerebral hyperdensity (PCHD) immediately after mechanical thrombectomy (MT). METHODS: We retrospectively analyzed 108 consecutive anterior circulation AIS patients with PCHD immediately after MT. All patients were divided into END group and non-END group and END was defined as an increase of four points or more on the postinterventional National Institutes of Health Stroke Scale (NIHSS) score within the first 72 h after MT. Early antithrombotic therapy was defined as patients with PCHD who received antithrombotic therapy within 24 h after MT. Statistical analyses were performed to evaluate the association between early antithrombotic therapy and the risk of END. RESULTS: Among 108 patients, 27 (25%) patients developed END. Multivariate regression analysis revealed that early use of antithrombotic therapy (OR = 0.229, 95%CI = 0.083-0.626, P = 0.004) was an independent protector of END and postinterventional low density shadow exceeding 1/3 of the vascular territory (OR = 4.000, 95%CI = 1.157-13.834, P = 0.029) was an independent risk factor for END. CONCLUSION: Antithrombotic therapy within 24 h after MT maybe associated with the reduced risk of END in anterior circulation AIS patients with PCHD.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/complicações , Isquemia Encefálica/complicações , Fibrinolíticos/uso terapêutico , Estudos Retrospectivos , Trombectomia/efeitos adversos , AVC Isquêmico/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: The gut microbiome plays a pivotal role in the progression of sepsis. However, the specific mechanism of gut microbiota and its metabolites involved in the process of sepsis remains elusive, which limits its translational application. METHOD: In this study, we used a combination of the microbiome and untargeted metabolomics to analyze stool samples from patients with sepsis enrolled at admission, then microbiota, metabolites, and potential signaling pathways that might play important roles in disease outcome were screened out. Finally, the above results were validated by the microbiome and transcriptomics analysis in an animal model of sepsis. RESULTS: Patients with sepsis showed destruction of symbiotic flora and elevated abundance of Enterococcus, which were validated in animal experiments. Additionally, patients with a high burden of Bacteroides, especially B. vulgatus, had higher Acute Physiology and Chronic Health Evaluation II scores and longer stays in the intensive care unit. The intestinal transcriptome in CLP rats illustrated that Enterococcus and Bacteroides had divergent profiles of correlation with differentially expressed genes, indicating distinctly different roles for these bacteria in sepsis. Furthermore, patients with sepsis exhibited disturbances in gut amino acid metabolism compared with healthy controls; namely, tryptophan metabolism was tightly related to an altered microbiota and the severity of sepsis. CONCLUSION: Alterations in microbial and metabolic features in the gut corresponded with the progression of sepsis. Our findings may help to predict the clinical outcome of patients in the early stage of sepsis and provide a translational basis for exploring new therapies.
Assuntos
Microbioma Gastrointestinal , Microbiota , Sepse , Animais , Ratos , Microbioma Gastrointestinal/fisiologia , Metaboloma , Metabolômica , Sepse/microbiologia , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND: Clostridioides difficile infection (CDI) is a leading cause of nosocomial diarrhea. Patients receiving enteral nutrition (EN) in the intensive care unit (ICU) are potentially at high risk of CDI. In the present study, we assessed the risk factors and intestinal microbiome of patients to better understand the occurrence and development of CDI. METHODS: Patients were screened for C. difficile every week after starting EN, and their clinical records were collected for risk factor identification. Fecal samples were analyzed using 16S rRNA sequencing to evaluate the intestinal microbiota. RESULTS: Overall incidence of CDI was 10.7% (18/168 patients). History of cerebral infarction was significantly associated with CDI occurrence (OR, 9.759; 95% CI, 2.140-44.498), and treatment with metronidazole was identified to be protective (OR, 0.287; 95% CI, 0.091-0.902). Patients with EN had lower bacterial richness and diversity, accompanied by a remarkable decrease in the abundance of Bacteroides, Prevotella_9, Ruminococcaceae, and Lachnospiraceae. Of these patients, acquisition of C. difficile resulted in a transient increase in microbial diversity, along with consistent alterations in the proportion of some bacterial taxa, especially Ruminococcaceae and Lachnospiraceae. Upon initiation of EN, patients who were positive for C. difficile later showed an enhanced load of Bacteroides, which was negatively correlated with the abundance of C. difficile when CDI developed. CONCLUSION: ICU patients receiving EN have a high prevalence of CDI and a fragile intestinal microbial environment. History of cerebral infarction and prior treatment with metronidazole are considered as vital risk and protective factors, respectively. We propose that the emergence of CDI could cause a protective alteration of the intestinal microbiota. Additionally, Bacteroides loads seem to be closely related to the occurrence and development of CDI.
Assuntos
Infecções por Clostridium/dietoterapia , Nutrição Enteral/normas , Microbioma Gastrointestinal/fisiologia , Idoso , China , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/patogenicidade , Infecções por Clostridium/fisiopatologia , Diarreia/dietoterapia , Diarreia/etiologia , Nutrição Enteral/métodos , Feminino , Humanos , Incidência , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: With the increasing number of cancer treatments, the emergence of multidisciplinary teams (MDTs) provides patients with personalized treatment options. In recent years, artificial intelligence (AI) has developed rapidly in the medical field. There has been a gradual tendency to replace traditional diagnosis and treatment with AI. IBM Watson for Oncology (WFO) has been proven to be useful for decision-making in breast cancer and lung cancer, but to date, research on gastric cancer is limited. OBJECTIVE: This study compared the concordance of WFO with MDT and investigated the impact on patient prognosis. METHODS: This study retrospectively analyzed eligible patients (N=235) with gastric cancer who were evaluated by an MDT, received corresponding recommended treatment, and underwent follow-up. Thereafter, physicians inputted the information of all patients into WFO manually, and the results were compared with the treatment programs recommended by the MDT. If the MDT treatment program was classified as "recommended" or "considered" by WFO, we considered the results concordant. All patients were divided into a concordant group and a nonconcordant group according to whether the WFO and MDT treatment programs were concordant. The prognoses of the two groups were analyzed. RESULTS: The overall concordance of WFO and the MDT was 54.5% (128/235) in this study. The subgroup analysis found that concordance was less likely in patients with human epidermal growth factor receptor 2 (HER2)-positive tumors than in patients with HER2-negative tumors (P=.02). Age, Eastern Cooperative Oncology Group performance status, differentiation type, and clinical stage were not found to affect concordance. Among all patients, the survival time was significantly better in concordant patients than in nonconcordant patients (P<.001). Multivariate analysis revealed that concordance was an independent prognostic factor of overall survival in patients with gastric cancer (hazard ratio 0.312 [95% CI 0.187-0.521]). CONCLUSIONS: The treatment recommendations made by WFO and the MDT were mostly concordant in gastric cancer patients. If the WFO options are updated to include local treatment programs, the concordance will greatly improve. The HER2 status of patients with gastric cancer had a strong effect on the likelihood of concordance. Generally, survival was better in concordant patients than in nonconcordant patients.
Assuntos
Tomada de Decisão Clínica/métodos , Oncologia/métodos , Equipe de Assistência ao Paciente/normas , Neoplasias Gástricas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Clostridioides difficile is considered the main pathogen responsible for hospital-acquired infections. This prospective study determined the prevalence, molecular epidemiological characteristics, and risk factors for C. difficile infection (CDI) and C. difficile colonization (CDC) among patients in the intensive care unit (ICU) of a large-scale tertiary hospital in China, with the aim of providing strategies for efficient CDI and CDC prevention and control. METHODS: Stool samples were collected and anaerobically cultured for C. difficile detection. The identified isolates were examined for toxin genes and subjected to multilocus sequence typing. Patients were classified into CDI, CDC, and control groups, and their medical records were analyzed to determine the risk factors for CDI and CDC. RESULTS: Of the 800 patients included in the study, 33 (4.12%) and 25 (3.12%) were identified to have CDI and CDC, respectively. Associations with CDI were found for fever (OR = 13.993), metabolic disorder (OR = 7.972), and treatment with fluoroquinolone (OR = 42.696) or combined antibiotics (OR = 2.856). CDC patients were characterized by prolonged hospital stay (OR = 1.137), increased number of comorbidities (OR = 36.509), respiratory diseases (OR = 0.043), and treatment with vancomycin (OR = 18.168). Notably, treatment with metronidazole was found to be a protective factor in both groups (CDI: OR = 0.042; CDC: OR = 0.013). Eighteen sequence types (STs) were identified. In the CDI group, the isolated strains were predominantly toxin A and toxin B positive (A + B+) and the epidemic clone was genotype ST2. In the CDC group, the dominant strains were A + B+ and the epidemic clone was ST81. CONCLUSIONS: The prevalences of CDC and CDI in our ICU were relatively high, suggesting the importance of routine screening for acquisition of C. difficile. Future prevention and treatment strategies for CDC and CDI should consider hospital stay, enteral nutrition, underlying comorbidities, and use of combined antibiotics. Moreover, metronidazole may be a protective factor for both CDI and CDC, and could be used empirically.
Assuntos
Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/epidemiologia , Unidades de Terapia Intensiva , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/metabolismo , China/epidemiologia , Clostridioides difficile/genética , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/prevenção & controle , Comorbidade , Enterotoxinas/metabolismo , Feminino , Genótipo , Humanos , Tempo de Internação , Masculino , Programas de Rastreamento , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Prevalência , Estudos Prospectivos , Fatores de RiscoRESUMO
A Gram-stain-negative, aerobic, coccoid to small rod-shaped bacterium, designated X1T, was isolated from sludge collected from the vicinity of a pesticide manufacturer in Nantong, Jiangsu Province, China. Based on 16S rRNA gene sequence analysis, strain X1T belonged to the genus Cupriavidus, and was most closely related to Cupriavidus taiwanensis LMG 19424T (99.1 % 16S rRNA gene sequence similarity) and Cupriavidus alkaliphilus LMG 26294T (98.9 %). Strain X1T showed 16S rRNA gene sequence similarities of 97.2-98.2 % with other species of the genus Cupriavidus. The major cellular fatty acids of strain X1T were C16 : 0, C16 : 1ω7c and/or iso-C15 : 0 2-OH (summed feature 3), C18 : 1ω7c and C17 : 0 cyclo, and the major respiratory quinone was ubiquinone Q-8. The major polar lipids of strain X1T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, aminophospholipid, phospholipid and hydroxyphosphatidylethanolamine. The DNA G+C content was 66.6 mol%. The DNA-DNA relatedness values of strain X1T with the five reference strains C. taiwanensis LMG 19424T, C. alkaliphilus LMG 26294T, Cupriavidus necator LMG 8453T, Cupriavidus gilardii LMG 5886T and 'Cupriavidus yeoncheonense' KCTC 42053 were lower than 70 %. The results obtained from phylogenetic analysis, phenotypic characterization and DNA-DNA hybridization indicated that strain X1T should be proposed to represent a novel species of the genus Cupriavidus, for which the name Cupriavidus nantongensis sp. nov. is proposed. The type strain is X1T (=KCTC 42909T=LMG 29218T).
Assuntos
Clorpirifos/metabolismo , Cupriavidus/classificação , Filogenia , Esgotos/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , Cupriavidus/genética , Cupriavidus/isolamento & purificação , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ubiquinona/químicaRESUMO
In this study, a highly effective chlorpyrifos (CP)-degrading bacterium (termed strain X1) was isolated from the sludge of drain outlet of a chlorpyrifos manufacturer. Strain X1 was identified as Cupriavidus taiwanensis based upon the analysis of the 16S rDNA gene and biochemical characteristics, which is capable of transforming CP into 3,5,6-trichloro-2-pyridinol (TCP), and the resulting TCP was further metabolized when performed in an aqueous medium. Degradation experiments were carried out under different conditions at the range of pH (5.0â¼9.0) and temperature (22â¼42 °C), and the optimized pH and temperature were 7.0 and 32 °C respectively. Biotransformation of high concentration of CP was also determined; 400 mg l(À1) of CP was completely transformed within 36 h; approximately 95% of CP was removed within 48 h when concentration of CP was up to 500 mg l(À1) . A genomic library was successfully constructed to clone the gene encoding the CP hydrolase, and a positive transformant with clear hydrolytic zones was obtained and analyzed. The insert gene sequence exhibited close relationship with 99% similar to opdB gene encoding parathion hydrolase, whereas, transformant failed in degrading the accumulated TCP. These results highlight the potential of this bacterium to be used in the cleanup of CP.
Assuntos
Clorpirifos/metabolismo , Cupriavidus/isolamento & purificação , Cupriavidus/metabolismo , Hidrolases/genética , Piridonas/metabolismo , Esgotos/microbiologia , Biodegradação Ambiental , Biotransformação , Cupriavidus/classificação , Cupriavidus/genética , DNA Ribossômico , Biblioteca Genômica , Hidrólise , FilogeniaRESUMO
BACKGROUND: The systemic inflammation score (SIS) has been utilised as a representative biomarker for evaluating nutritional and inflammation status. However, the predictive value of SIS has not been reported in patients with acute ischemic stroke (AIS). We aimed to evaluate whether SIS is associated with prognosis in stroke. METHODS: A total of 4801 patients with AIS were included in the study. The primary outcome was a modified Rankin Scale score>2 at the 3-month follow-up. A total of 4801 patients were randomly allocated into training (n=3361) and validation cohorts (n=1440) at a ratio of 7:3. Model performance was validated using the receiver operating characteristic (ROC) curve and calibration curve. Additionally, a comparison was made between the nomogram and the THRIVE score in regards to their respective predictive capabilities. RESULTS: Overall, 1091(32.5%) patients in the training cohort and 446 (31.0%) patients in the validation cohort experienced an unfavorable outcome. The multivariate logistic regression analysis revealed that a high SIS, age, NIHSS, diabetes and prior stroke were associated with unfavorable outcome. Our nomogram was developed based on the variables mentioned above. The area under the curve (AUC) of the training set and the validation set are 0.702 and 0.708, respectively, indicating that the model has modest agreement and discrimination. The results of AUC, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) showed that nomogram had significantly higher predictive value than THRIVE scores (all P<0.001). However, unlike the THRIVE publication, all patients who had undergone intravenous thrombolysis or endovascular thrombectomy therapy were excluded in our study. In consequence, our derived THRIVE scores cannot be compared to those in the original THRIVE study. CONCLUSION: The SIS exhibits potential as a simple prognostic biomarker, and the nomogram, which utilizes the SIS, may serve as a valuable tool for clinicians in the early identification of patients at heightened risk for unfavorable outcomes.
Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Prognóstico , AVC Isquêmico/diagnóstico , AVC Isquêmico/cirurgia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Terapia Trombolítica/métodos , Inflamação/diagnóstico , BiomarcadoresRESUMO
BACKGROUND: Lactate dehydrogenase to albumin ratio (LAR) is a comprehensive biomarker for anaerobiosis, inflammation, and nutritional status, but its prognostic value for ischemic stroke has rarely been reported. We aimed to prospectively investigate whether serum LAR is associated with the prognosis of ischemic stroke patients in a large-scale cohort study. MATERIALS AND METHODS: Serum LAR levels were measured among 6634 patients with ischemic stroke admitted at Minhang hospital from January 2018 to December 2022. The primary outcome was the composite of major disability and death (modified Rankin Scale score [mRS] ≥ 3) at 3-month follow up. Secondary outcomes included death and the ordered 7-level category score of mRS. Multivariate logistic regression and restricted cubic splines were adopted to evaluate the associations between serum LAR levels and adverse clinical outcomes of ischemic stroke. RESULTS: During 3 months of follow-up period, a total of 2125 patients experienced primary outcome. After multivariate adjustment, the highest quartile of serum LAR was associated with an increased risk of primary outcome (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.27-1.83; P for trend < 0.001). Each standard deviation higher log-transformed serum LAR resulted in a 20% (95% CI, 12%-28%) increased risk of primary outcome. Furthermore, multivariable-adjusted restricted cubic spline analyses showed a linear association between the serum LAR level with primary outcome (P for linearity < 0.001). Finally, the addition of serum LAR to conventional risk factors significantly improved risk predictive abilities for the primary outcome (net reclassification improvement [NRI]: 18.35%, P < 0.001; integrated discrimination improvement [IDI]: 0.35%, P < 0.001) at 3-month follow up in patients with ischemic stroke. CONCLUSION: High serum LAR level was independently associated with an increased risk of adverse clinical outcomes among patients with ischemic stroke, indicating that serum LAR may be a valuable prognostic biomarker for ischemic stroke.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/complicações , Isquemia Encefálica/complicações , AVC Isquêmico/complicações , Estudos de Coortes , Biomarcadores , Prognóstico , Fatores de Risco , Lactato DesidrogenasesRESUMO
BACKGROUND: The evidence for the association between white matter hyperintensity (WMH) severity and neurological deterioration (ND) in patients with single subcortical infarction (SSI) remains unclear and whether the association between them is modified by anterior circulation parent artery steno-occlusion (PAS) is unknown. Herein, we aimed to prospectively investigate the internal relevance. METHODS: In this prospective study, the severity of WMH and PAS were assessed in 288 consecutive patients with anterior circulation SSI arriving at our hospital, a tertiary teaching hospital affiliated with Fudan University, 24 h after onset from January 2017 to December 2018. The multivariable logistic regression model was used to estimate the association between WMH severity and the risk of ND within 7 days after stroke onset as well as the interactive effect between WMH severity and PAS on ND among patients with SSI. RESULTS: PAS modified the association between WMH severity and ND among patients with SSI (pinteraction = .029). After multivariate adjustment, the odds ratios of moderate-severe WMH associated with ND were 1.61 (95% CI, 0.50-5.19; ptrend = .428) for patients with PAS, and 0.37 (95% CI, 0.14-0.97; ptrend = .043) for those without PAS. Adding WMH severity to conventional risk factors improved risk prediction for ND in patients without PAS (net reclassification improvement: 48.2%, p = .005; integrated discrimination index: 2.5%, p = .004) but not in those with PAS. CONCLUSION: There was a modified effect of PAS on the association between WMH severity and ND within 7 days after stroke onset among patients with anterior circulation SSI, which deserves more research attention. WMH was negatively associated with ND in anterior circulation SSI patients without PAS.
Assuntos
Substância Branca , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Idoso , Estudos Prospectivos , Imageamento por Ressonância Magnética , Índice de Gravidade de Doença , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , Infarto Cerebral/fisiopatologiaRESUMO
BACKGROUND: The double burden of malnutrition, defined as the coexistence of obesity and malnutrition, is an increasing global health concern and is unclear in patients after ischemic stroke. The current study explored the combined impacts of obesity and malnutrition on patients with ischemic stroke. METHODS: We conducted a single-center prospective cohort study with patients with ischemic stroke enrolled in Minhang Hospital in China between January 2018 and December 2022. Patients were stratified into four categories based on their obesity (defined by body mass index) and nutritional status (classified according to the Controlling Nutritional Status score): (1) nourished nonobese, (2) malnourished nonobese, (3) nourished obese, and (4) malnourished obese. The primary end points were poor outcomes and all-cause mortality at 3 months. RESULTS: A total of 3160 participants with ischemic stroke were included in our study, of which 64.7% were male and the mean age was 69 years. Over 50% of patients were malnourished. At 3-month follow-up, the malnourished nonobese had the worst outcomes (34.4%), followed by the malnourished obese (33.2%), nourished nonobese (25.1%), and nourished obese (21.8%; P < 0.001). In multivariable analyses, with nourished nonobese group as the reference, the malnourished nonobese group displayed poorer outcomes (odds ratio [OR], 1.395 [95% CI, 1.169-1.664], P < 0.001) and higher all-cause mortality (OR, 1.541 [95% CI, 1.054-2.253], P = 0.026), but only a nonsignificant increase in poor prognosis rate (33.2% vs. 25.1%, P = 0.102) and mortality (4.2% vs. 3.6%, P = 0.902) were observed in the malnourished obese group. CONCLUSION: A high prevalence of malnutrition is observed in the large population suffering from ischemic attack, even in the obese. Malnourished patients have the worst prognosis particularly in those with severe nutritional status regardless of obesity, while the best functional outcomes and the lowest mortality are demonstrated in nourished obese participants.
Assuntos
AVC Isquêmico , Desnutrição , Estado Nutricional , Obesidade , Humanos , Feminino , Masculino , Desnutrição/mortalidade , Desnutrição/epidemiologia , Desnutrição/complicações , Obesidade/complicações , Obesidade/mortalidade , Idoso , Prognóstico , Estudos Prospectivos , AVC Isquêmico/mortalidade , AVC Isquêmico/complicações , AVC Isquêmico/epidemiologia , Pessoa de Meia-Idade , China/epidemiologia , Índice de Massa Corporal , Fatores de Risco , Estudos de CoortesRESUMO
BACKGROUND: Poststroke cognitive impairment (PSCI) is a prevalent complication among stroke survivors. Although the systemic inflammatory response index (SIRI) has been shown to be a reliable predictor of a variety of inflammatory diseases, the association between the SIRI and PSCI is still unclear. Therefore, the purpose of this study was to investigate the relationship between SIRI and PSCI, and to design a nomogram to predict the risk of PSCI in acute ischemic stroke (AIS) patients. METHODS: A total of 1342 patients with AIS were included in the study. Using the Mini-Mental State Examination scale, patients were separated into PSCI and non-PSCI groups within 2 weeks of stroke. Clinical data and SIRI values were compared between the groups. We developed the optimal nomogram for predicting PSCI using multivariate logistic regression. Finally, the nomogram was validated using the receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA). RESULTS: In total, 690 (51.4%) patients were diagnosed with PSCI. After adjusting for potential confounders, the SIRI (OR = 1.226, OR: 1.095-1.373, p < .001) was shown to be an independent risk factor for PSCI in the logistic regression analysis. The nomogram based on patient gender, age, admission National Institutes of Health Stroke Scale scores, education, diabetes mellitus, and SIRI had good discriminative ability with an area under the curve (AUC) of 0.716. The calibration curve and Hosmer-Lemeshow test revealed excellent predictive accuracy for the nomogram. Finally, the DCA showed the good clinical utility of the model. CONCLUSION: Increased SIRI on admission is correlated with PSCI, and the nomogram built with SIRI as one of the predictors can help identify PSCI early.
Assuntos
Disfunção Cognitiva , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Área Sob a Curva , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Acidente Vascular Cerebral/complicações , Síndrome de Resposta Inflamatória SistêmicaRESUMO
Rapid and accurate clinical staging of pediatric patients with inflammatory bowel disease (IBD) is crucial to determine the appropriate therapeutic approach. This study aimed to identify effective, convenient biomarkers for staging IBD in pediatric patients. We recruited cohorts of pediatric patients with varying severities of IBD to compare the features of the intestinal microbiota and metabolites between the active and remitting disease stages. Metabolites with potential for staging were targeted for further assessment in both patients and colitis model mice. The performance of these markers was determined using machine learning and was validated in a separate patient cohort. Pediatric patients with IBD exhibited distinct gut microbiota structures at different stages of disease activity. The enterotypes of patients with remitting and active disease were Bacteroides-dominant and Escherichia-Shigella-dominant, respectively. The bile secretion pathway showed the most significant differences between the two stages. Fecal and serum bile acid (BA) levels were strongly related to disease activity in both children and mice. The ratio of primary BAs to secondary BAs in serum was developed as a novel comprehensive index, showing excellent diagnostic performance in stratifying IBD activity (0.84 area under the receiver operating characteristic curve in the primary cohort; 77% accuracy in the validation cohort). In conclusion, we report profound insights into the interactions between the gut microbiota and metabolites in pediatric IBD. Serum BAs have potential as biomarkers for classifying disease activity, and may facilitate the personalization of treatment for IBD.
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Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Animais , Criança , Camundongos , Ácidos e Sais Biliares , BiomarcadoresRESUMO
Introduction. The intestinal flora has become a promising new target in acute ischaemic stroke (AIS), and small intestinal bacterial overgrowth (SIBO) is a common pathological condition of the intestinal flora. Recently, the lactose hydrogen-methane breath test has emerged as a non-invasive and economical method for the detection of SIBO in AIS patients. Exploring the prevalence of SIBO and its associated risk factors will provide a clinical basis for the association between intestinal flora and AIS.Hypothesis/Gap Statement. Given that the prevalence of SIBO and its risk factors in patients with AIS remain to be studied, there is a need to investigate them.Aim. This study aimed to investigate the prevalence and risk factors of SIBO in patients with AISMethodology. Eighty patients tested for SIBO using the lactulose hydrogen-methane breath test were evaluated. Patients were divided into SIBO-positive and SIBO-negative groups according to the presence or absence of SIBO, respectively. The baseline characteristics and clinical biochemical indicators of the patients were compared between the two groups. The independent risk factors and predictive value of SIBO in AIS patients were determined using multivariate logistic regression and receiver operating characteristic (ROC) curve analyses.Results. Of the 80 consecutive patients with AIS, 23 (28.8â%) tested positive for SIBO. Triglyceride (TG) and homocysteine (Hcy) levels were identified as independent risk factors for SIBO in patients with AIS using multivariate logistic regression analysis (P<0.005). ROC curve analysis showed that the area under the curve (AUC) of TG was 0.690 (95â% CI 0.577-0.789, P=0.002). The sensitivity, specificity and optimal cut-off values were 95.7â%, 35.1â% and 1.14 mmol l-1, respectively. The AUC of Hcy was 0.676 (95â% CI 0.562-0.776, P=0.01). The sensitivity, specificity and optimal cut-off values were 73.9â%, 59.7â% and 14.1 µmol-1, respectively. When TG and Hcy levels were combined, the AUC increased to 0.764 (95â% CI 0.656-0.852, P<0.001). The specificity and sensitivity were 61.4 and 82.6â%, respectively. This showed that the combined detection of TG and Hcy levels had a higher predictive valueConclusion. The prevalence of SIBO in patients with AIS was 28.8â%. TG and Hcy levels are independent risk factors for SIBO in patients with AIS. Both markers had good predictive value for the occurrence of SIBO. In the future, we should actively utilize these indicators to prevent intestinal flora imbalance and the occurrence of SIBO.
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Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Intestino Delgado/microbiologia , Isquemia Encefálica/complicações , Isquemia Encefálica/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Fatores de Risco , Testes Respiratórios/métodos , Metano/análise , Hidrogênio/análiseRESUMO
Introduction: A crucial aspect of stroke progression is the inflammatory response. As novel inflammatory and prognostic markers, the systemic immune inflammation index (SII) and the systemic inflammation response index (SIRI) have recently been studied. The objective of our study was to evaluate the prognostic value of SII and SIRI in mild acute ischemic stroke (AIS) patients following intravenous thrombolysis (IVT). Methods: Our study screened the clinical data of patients with mild AIS admitted to the Minhang Hospital of Fudan University for retrospective analysis. The SIRI and SII were examined by the emergency laboratory before IVT. Functional outcome was evaluated 3 months after the onset of stroke using the modified Rankin Scale (mRS). mRS ≥ 2 was defined as an unfavorable outcome. The relationship between SIRI and SII and the 3-month prognosis was determined using both univariate and multivariate analysis. Receiver operating characteristic curve was performed to evaluate the predictive value of SIRI for AIS prognosis. Results: A total of 240 patients were included in this study. Both SIRI and SII were higher in the unfavorable outcome group than in the favorable outcome group [1.28 (0.70-1.88) vs. 0.79 (0.51-1.08), P < 0.001 and 531.93 (377.55-797.12) vs. 397.23 (263.32-577.65), P < 0.001]. Multivariate logistic regression analyses showed that SIRI was significantly associated with 3-month unfavorable outcome of mild AIS patients [odds ratio (OR) = 2.938, 95% confidence interval (CI) = 1.805-4.782, P < 0.001], conversely, SII had no prognostic value. When SIRI combined with the established clinical factors, the area under the curve (AUC) showed a significant improvement (0.773 vs. 0.683, P for comparison = 0.0017). Conclusions: Higher SIRI could be valuable in predicting poor clinical outcomes for patients with mild AIS following IVT.
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Clostridioides difficile is a pathogen contributing to increased morbidity and mortality of patients with inflammatory bowel disease (IBD). To determine how C. difficile affects the severity of colitis, we constructed a dextran sulfate solution-induced colitis model challenged with C. difficile. Without antibiotic administration, C. difficile led to transient colonization in mice with colitis, but still significantly enhanced disease severity as assessed by weight loss, histopathological damages, and inflammatory cytokine concentrations. Because this effect is independent of toxin production as shown by infection with a non-toxigenic strain, we focused on changes in the gut microbiota. The microbiota altered by C.difficile, featured with reduced proportions of g_Prevotellaceae_UCG-001 and g_Muribaculaceae, were confirmed to contribute to disease severity in colitis mice via fecal microbiota transplantations. The inflamed colon showed neutrophil accumulation by flow cytometric analysis and myeloperoxidase immunochemical staining. There was enrichment of upregulated genes in leukocyte chemotaxis or migration as shown by RNA sequencing analysis. The isolated neutrophils from C. difficile-infected mice with colitis showed a robust migratory ability and had enhanced expression of cytokines and chemokines. We observed a detrimental role of neutrophils in the progress of disease by hindering neutrophil recruitment with the CXCR2 inhibitor SB225002. Furthermore, neutrophil recruitment appeared to be regulated by interleukin (IL)-1ß, as inhibition of IL-1ß production by MCC950 markedly ameliorated inflammation with decreased neutrophil accumulation and neutrophil-derived chemokine expression. In conclusion, our study provides information on the complicated interaction between microbiota and immune responses in C. difficile-induced inflammation in mice with colitis. Our findings could help determine potential therapeutic targets for patients with IBD concurrent with C. difficile infection.
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Clostridioides difficile , Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Camundongos , Animais , Clostridioides difficile/metabolismo , Sulfato de Dextrana/toxicidade , Clostridioides/metabolismo , Infiltração de Neutrófilos , Colo/metabolismo , Inflamação/patologia , Citocinas/metabolismo , Doenças Inflamatórias Intestinais/patologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BLRESUMO
Background: Platelet activation in the early stage of pancreatitis is the key step developing into pancreatic necrosis. Studies suggested that vitamin C (Vit C) can inhibit platelet activity by targeting CXCL12/CXCR4 pathway. High-dose Vit C were showed to reduce pancreatic necrosis in severe acute pancreatitis (SAP) but the mechanism remains unclear. Here we speculate high-dose Vit C reduce pancreatic necrosis by inhibiting platelet activation through downregulating CXCL12/CXCR4 pathway. Methods: The pancreatic microcirculation of rats was observed by intravital microscopy. The platelet activity of SAP rats treated with or without high-dose Vit C was analyzed by platelet function test. Besides, the activity of platelets preincubated with high-dose Vit C or vehicle from SAP patients was also evaluated. Then, the TFA (CXCR4 agonist) and rCXCL12 were used to neutralize the effect of high-dose Vit C in SAP rats treated with high-dose Vit C. Meanwhile, the levels of enzymes and inflammatory cytokines in rat plasma, and rats' pancreatic histopathology and mortality were assessed. Results: Platelets from animals and patients with SAP are more sensitive to agonists and are more easily activated. Administration of high-dose Vit C significantly ameliorated excessive activation of platelets in SAP rats, ultimately increasing the microvessel density and inducing microthrombus and blood stasis; these results were consistent with clinical sample analysis. Moreover, high-dose Vit C significantly inhibited the release of amylase, lipase, TNF-α, and IL-6 in SAP rat plasma, reducing pancreatic damage and the mortality of SAP rats. However, using TFA and rCXCL12 significantly reversed the effect of high-dose Vit C on excessive activation of platelets, aggravating microcirculation impairment and pancreatic damage. Conclusion: The present study suggests that high-dose Vit C can ameliorate pancreatic necrosis by improving microcirculation disorders of SAP. For the first time, the underlying mechanism is related with inhibiting platelet activation through the CXCL12/CXCR4 pathway.