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1.
Immunobiology ; 227(6): 152290, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36279621

RESUMO

PURPOSE: To determine the association of a combined ratio change of inflammatory biomarkers at 72 h after admission on sepsis severity and prognosis from pulmonary infections. METHODS: Data on adult patients diagnosed with sepsis, or septic shock were retrospectively analyzed. Patients were divided into two groups, according to their outcome of hospitalization. Blood specimens were obtained on admission (T0) and 72 h (T72) after therapy. Acute Physiology And Chronic Health Evaluation Score (APACHEII) and Sequential Organ Failure Assessment Score (SOFA) were statistically analyzed on admission. Survivors discharged from hospital were classified into different subgroups according to the change in biomarkers at T72, and compared for different clinical prognosis. RESULTS: Our study showed that IL-6, IL-8, IL-10 and TNF-a could predict the severity of sepsis at T0, since they showed a positive correlation with APACHEII or SOFA score. Another important finding was that survivors discharged from hospital whose ratio change with IL-10, i.e: IL-10/IL-6, IL-10/IL-8, IL-10/TNF-a ≤ 0 exhibited significantly greater 9-month overall survival. We also observed that patients with increased IL-6 after 72 h showed similar improved survival. CONCLUSION: Our findings suggested that a combined ratio change of inflammatory biomarkers was an effective predictor for sepsis severity and prognosis.


Assuntos
Pneumonia , Sepse , Adulto , Humanos , Interleucina-10 , Estudos Retrospectivos , Interleucina-6 , Interleucina-8 , Sepse/diagnóstico , Prognóstico , Biomarcadores , Curva ROC , Unidades de Terapia Intensiva
2.
BMC Infect Dis ; 21(1): 921, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488665

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is threatening the world with the symptoms of seasonal influenza. This study was conducted to investigate the patient characteristics and clinical value of blood markers to assess the severity of coronavirus disease 2019 (COVID-19). METHODS: 187 patients, diagnosed with COVID-19 (non-severe and severe cases) and admitted to hospital between January 27th and March 8th of 2020, were enrolled in the present study. RESULTS: A higher proportion of clinical symptoms, including cough, expectoration, myalgia, and fatigue were observed in the non-severe group. The level of white blood cell count, neutrophils, CRP, IL-6 and IL-8 were significantly increased, while the platelet count was remarkedly decreased in the severe group. The risk model based on lymphocyte, IL-6, IL-8, CRP and platelet counts had the highest area under the receiver operator characteristic curve (AUROC). The baseline of IL-6, IL-8 and CRP was positively correlated with other parameters except in the cases of lymphocyte, hemoglobin and platelet counts. The baseline of the platelet count was negatively correlated with other parameters except in the lymphocyte and hemoglobin counts. Additionally, there was no connection between the severity of COVID-19 and cultures of blood, sputum or catheter secretion. CONCLUSIONS: The present study suggested that high leucocyte and low platelets counts were independent predictive markers of the severity of COVID-19.


Assuntos
COVID-19 , Área Sob a Curva , Biomarcadores , Humanos , Contagem de Linfócitos , Contagem de Plaquetas , Estudos Retrospectivos , SARS-CoV-2
3.
Cell Death Dis ; 12(5): 463, 2021 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-33966039

RESUMO

Resistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Oxaliplatina/uso terapêutico , Fatores de Transcrição/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Antineoplásicos/farmacologia , Neoplasias Colorretais/genética , Humanos , Oxaliplatina/farmacologia
4.
Front Med (Lausanne) ; 8: 786414, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35004751

RESUMO

Objective: To explore the efficacy of anticoagulation in improving outcomes and safety of Coronavirus disease 2019 (COVID-19) patients in subgroups identified by clinical-based stratification and unsupervised machine learning. Methods: This single-center retrospective cohort study unselectively reviewed 2,272 patients with COVID-19 admitted to the Tongji Hospital between Jan 25 and Mar 23, 2020. The association between AC treatment and outcomes was investigated in the propensity score (PS) matched cohort and the full cohort by inverse probability of treatment weighting (IPTW) analysis. Subgroup analysis, identified by clinical-based stratification or unsupervised machine learning, was used to identify sub-phenotypes with meaningful clinical features and the target patients benefiting most from AC. Results: AC treatment was associated with lower in-hospital death risk either in the PS matched cohort or by IPTW analysis in the full cohort. A higher incidence of clinically relevant non-major bleeding (CRNMB) was observed in the AC group, but not major bleeding. Clinical subgroup analysis showed that, at admission, severe cases of COVID-19 clinical classification, mild acute respiratory distress syndrome (ARDS) cases, and patients with a D-dimer level ≥0.5 µg/mL, may benefit from AC. During the hospital stay, critical cases and severe ARDS cases may benefit from AC. Unsupervised machine learning analysis established a four-class clustering model. Clusters 1 and 2 were non-critical cases and might not benefit from AC, while clusters 3 and 4 were critical patients. Patients in cluster 3 might benefit from AC with no increase in bleeding events. While patients in cluster 4, who were characterized by multiple organ dysfunction (neurologic, circulation, coagulation, kidney and liver dysfunction) and elevated inflammation biomarkers, did not benefit from AC. Conclusions: AC treatment was associated with lower in-hospital death risk, especially in critically ill COVID-19 patients. Unsupervised learning analysis revealed that the most critically ill patients with multiple organ dysfunction and excessive inflammation might not benefit from AC. More attention should be paid to bleeding events (especially CRNMB) when using AC.

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