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INTRODUCTION: It is important to predict adverse outcomes in febrile children with hematology/oncology diseases. Procalcitonin (PCT) is a promising biomarker for the prediction of infection severity, but further studies have revealed its performance in excluding adverse outcomes of infection. IL-6 and IL-10 were reported to have a close association with those infection outcomes. The aim of the study was to investigate the performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal PCT. METHODS: This was a retrospective study conducted in a tertiary children's hospital in China over the past ten years. Inflammatory biomarkers, including IL-6, IL-10, PCT and C-reactive protein (CRP), were detected at the onset of infection. Separate analyses were conducted in patients with neutropenia and without neutropenia. RESULTS: In total, 5987 febrile cases were enrolled. For patients with neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with bloodstream infection (BSI), gram-negative bacteremia (GNB) and severe sepsis (SS), but only IL-6 and IL-10 were predictive of GNB and SS. For patients without neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with BSI, GNB and SS, but no biomarkers were predictive of adverse outcomes. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis in patients with neutropenia. CONCLUSIONS: IL-6 and IL-10 could be predictors for GNB and SS in febrile patients with neutropenia and had some association with unfavorable outcomes in febrile patients without neutropenia. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis.
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Bacteriemia , Bronquite , Febre de Causa Desconhecida , Hematologia , Neoplasias , Neutropenia , Sepse , Criança , Humanos , Pró-Calcitonina , Interleucina-6/metabolismo , Interleucina-6/uso terapêutico , Prognóstico , Interleucina-10/uso terapêutico , Calcitonina , Estudos Retrospectivos , Biomarcadores , Proteína C-Reativa/análise , Sepse/diagnóstico , Sepse/complicações , Bacteriemia/complicações , Neoplasias/complicações , Neutropenia/complicaçõesRESUMO
Severe sepsis and septic shock are life-threatening for pediatric hematology and oncology patient receiving chemotherapy. Th1/Th2 cytokines, C-reactive protein (CRP), and procalcitonin (PCT) are all thought to be associated with disease severity. The aim of this study was to prospectively verify the utility of Th1/Th2 cytokines and compare them with PCT and CRP in the prediction of adverse outcomes. Data on patients were collected from January 1, 2011, to December 31, 2020. Blood samples were taken for Th1/Th2 cytokine, CRP, and PCT measurements at the initial onset of infection. Severe infection (SI) was defined as severe sepsis or septic shock. Th1/Th2 cytokine levels were determined by using flow cytometric bead array technology. In total, 7,735 febrile episodes were included in this study. For SI prediction, the AUCs of IL-6, IL-10 and TNF-α were 0.814, 0.805 and 0.624, respectively, while IL-6 and IL-10 had high sensitivity and specificity. IL-6 > 220.85 pg/ml and IL-10 > 29.95 pg/ml had high odds ratio (OR) values of approximately 3.5 in the logistic regression. Within the subgroup analysis, for bloodstream infection (BSI) prediction, the AUCs of IL-10 and TNF-α were 0.757 and 0.694, respectively. For multiorgan dysfunction syndrome (MODS) prediction, the AUC of CRP was 0.606. The AUC of PCT for mortality prediction was 0.620. In conclusion, IL-6 and IL-10 provide good predictive value for the diagnosis of SI. For children with SI, IL-10 and TNF-α are associated with BSI, while CRP and PCT are associated with MODS and death, respectively.
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Hematologia , Neoplasias , Sepse , Choque Séptico , Criança , Humanos , Pró-Calcitonina , Citocinas , Proteína C-Reativa , Interleucina-10 , Interleucina-6 , Fator de Necrose Tumoral alfa , BiomarcadoresRESUMO
Noise is one of the most common environmental hazards to which people are exposed,and the exposure to noise can cause not only hearing but also non-hearing damage.Although noise under safety limits may not affect the auditory system,it can cause changes in stress hormone levels,which is harmful to health.However,the current studies about the impact of noise on health mainly focus on the auditory system,and little is known about the relationship between noise and stress hormone levels.Therefore,this paper reviews the studies involving noise exposure and stress hormone levels,aiming to provide ideas for strengthening the prevention and control of noise hazards.
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Audição , Ruído , Humanos , Ruído/efeitos adversos , HormôniosRESUMO
During interventional procedures,subjects are exposed to direct and scattered X-rays.Establishing diagnostic reference levels is an ideal way to optimize the radiation dose and reduce radiation hazard.In recent years,diagnostic reference levels in interventional radiology have been established in different countries.However,because of the too many indicators for characterizing the radiation dose,the indicators used to establish diagnostic reference levels vary in different countries.The research achievements in this field remain to be reviewed.We carried out a retrospective analysis of the definition,establishment method,application,and main factors influencing the dose difference of the diagnostic reference level,aiming to provide a basis for establishing the diagnostic reference level for interventional procedures in China.
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Níveis de Referência de Diagnóstico , Radiologia Intervencionista , Humanos , Radiologia Intervencionista/métodos , Doses de Radiação , Estudos Retrospectivos , RadiografiaRESUMO
BACKGROUND AND PURPOSE: The insidious onset of Parkinson's disease (PD) makes early diagnosis difficult. Notably, idiopathic rapid eye movement sleep behavior disorder (iRBD) was reported as a prodrome of PD, which may represent a breakthrough for the early diagnosis of PD. However, currently there is no reliable biomarker for PD diagnosis. Considering that α-synuclein (α-Syn) and neuroinflammation are known to develop prior to the onset of clinical symptoms in PD, it was hypothesized that plasma total exosomal α-Syn (t-exo α-Syn), neural-derived exosomal α-Syn (n-exo α-Syn) and exosomal apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) may be potential biomarkers of PD. METHODS: In this study, 78 PD patients, 153 probable iRBD patients (pRBD) and 63 healthy controls (HCs) were recruited. α-Syn concentrations were measured using a one-step paramagnetic particle-based chemiluminescence immunoassay, and ASC levels were measured using the Ella system. RESULTS: It was found that t-exo α-Syn was significantly increased in the PD group compared to the pRBD and HC groups (p < 0.0001), whilst n-exo α-Syn levels were significantly increased in both the PD and pRBD groups compared to HCs (p < 0.0001). Furthermore, although no difference was found in ASC levels between the PD and pRBD groups, there was a positive correlation between ASC and α-Syn in exosomes. CONCLUSIONS: Our results suggest that both t-exo α-Syn and n-exo α-Syn were elevated in the PD group, whilst only n-exo α-Syn was elevated in the pRBD group. Additionally, the adaptor protein of inflammasome ASC is correlated with α-Syn and may facilitate synucleinopathy.
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Exossomos , Doença de Parkinson , Transtorno do Comportamento do Sono REM , Humanos , Transtorno do Comportamento do Sono REM/metabolismo , alfa-Sinucleína , Doença de Parkinson/diagnóstico , Exossomos/metabolismo , BiomarcadoresRESUMO
BACKGROUND: We aimed to explore the association between long-term exposure to particulate matter ≤ 2.5 µm (PM2.5) and metabolic syndrome (MetS) and its components including fasting blood glucose (FBG), blood pressure, triglyceride (TG), high-density lipoprotein cholesterol (HDL-c) and waist circumference among adults and elderly in south China. METHODS: We surveyed 6628 participants in the chronic disease and risk factors surveillance conducted in 14 districts of Guangdong province in 2015. MetS was defined based on the recommendation by the Joint Interim Societies' criteria. We used the spatiotemporal land-use regression (LUR) model to estimate the two-year average exposure of ambient air pollutants (PM2.5, PM10, SO2, NO2, and O3) at individual levels. We recorded other covariates by using a structured questionnaire. Generalized linear mixed model was used for analysis. RESULTS: A 10-µg/m3 increase in the two-year mean PM2.5 exposure was associated with a higher risk of developing MetS [odd ratio (OR): 1.17, 95% confidence interval (CI): 1.01, 1.35], increased risk of fasting blood glucose level. (OR: 1.18, 95% CI: 1.02, 1.36), and hypertriglyceridemia (OR: 1.36, 95% CI: 1.18, 1.58) in the adjusted/unadjusted models (all P < 0.05). We found significant interaction between PM2.5 and the region, exercise on the high TG levels, and an interaction with the region, age, exercise and grain consumption on FBG (P interaction < 0.05). CONCLUSIONS: Long-term exposure to PM2.5 was associated with MetS, dyslipidemia and FBG impairment. Efforts should be made for environment improvement to reduce the burden of MetS-associated non-communicable disease.
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Poluentes Atmosféricos , Síndrome Metabólica , Adulto , Idoso , Poluentes Atmosféricos/efeitos adversos , Glicemia/metabolismo , China/epidemiologia , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Material Particulado/efeitos adversos , TriglicerídeosRESUMO
We present an erratum to our recent work [Appl. Opt.60, 10862 (2021)APOPAI0003-693510.1364/AO.440435] that corrects errors in Fig. 4 and the body of the paper. The corrections do not affect the results and conclusions of the original paper.
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INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by excessive production of inflammatory cytokines and multiple organs injury. Ruxolitinib, an oral selective JAK1/2 inhibitor, has recently shown efficacy and safety in the treatment of secondary HLH, which may be an alternative to intensive chemotherapy. CASE REPORT: We report a case of a 2-year-old boy who presented to our institution with recurrent fever and acute renal failure. We made the diagnosis of Epstein-Barr virus related HLH based on the HLH-2004 protocol, and gave the treatment of ruxolitinib instead of etoposide. MANAGEMENT AND OUTCOME: The patient received dexamethasone and continuous renal replacement therapy due to renal failure, but he still had fever and anuria. Given that the use of etoposide may deteriorate renal function, ruxolitinib was administered instead of etoposide. After 5 days of ruxolitinib treatment, the patient's fever was resolved and renal function also gradually recovered 14 days later. DISCUSSION: Currently, dexamethasone, etoposide and cyclosporine A are the main drugs in HLH treatment. However, cytotoxic chemotherapy can temporally deteriorate organ damage and induce serious myelosuppression, which makes clinicians hesitate to implement these regimens. Ruxolitinib has shown efficacy in treating HLH without much toxicity in clinical trials. Thus, we suggest that ruxolitinib constitutes a treatment option for secondary HLH complicated by severe renal damage which may reduce toxic effects compared with intense chemotherapy.
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Injúria Renal Aguda , Infecções por Vírus Epstein-Barr , Linfo-Histiocitose Hemofagocítica , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Pré-Escolar , Etoposídeo/uso terapêutico , Herpesvirus Humano 4 , Humanos , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Masculino , Nitrilas , Pirazóis , PirimidinasRESUMO
OBJECTIVES: To analyse the patterns of transition of health burden for 110 causes of death by stratification of age, sex and geographic regions in Guangdong between 2005 and 2015. METHODS: We analysed the age-specific, sex-specific, region-specific mortality in Guangdong based on assembled databases. County-level surveillance data were calculated to inform city-level changes. RESULTS: The age-standardised mortality of all causes, non-communicable diseases (NCDs), communicable diseases, maternal diseases, neonatal diseases, malnutrition and injury declined progressively. Despite declining mortality of NCDs, the overall burden of disease was dominated by NCDs (ie, cerebrovascular disease, chronic obstructive pulmonary disease) that still accounted for 86.93% and 88.12% of death in 2005 and 2015, respectively. Considerable variations across geographic regions were observed (lowest in Pearl River Delta and highest in west Guangdong). There was a modest shift to transport injuries at younger ages and unintentional injuries in the elderly. CONCLUSIONS: We have documented a dramatic change in the overall mortality and age-specific, sex-specific and cause-specific mortality in Guangdong province between 2005 and 2015. The significant burden of NCDs remains a major healthcare issue despite the notable progress in reducing mortality in Guangdong, China. Our findings highlight important unmet needs to refine healthcare services by taking into account the inequity of age, sex and geographic regions. Identification of the 'treatable' risk factors and improved disease surveillance should be continuously improved to minimised the overall and cause-specific mortality.
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Transição Epidemiológica , Doenças não Transmissíveis , Idoso , Causas de Morte , China/epidemiologia , Feminino , Saúde Global , Humanos , Recém-Nascido , Masculino , MortalidadeRESUMO
BACKGROUND AND AIMS: Free and bioavailable 25-hydroxyvitamin D (25OHD) are emerging measurements of vitamin D status. It remains unclear whether circulating free or bioavailable 25OHD are relevant to hepatocellular carcinoma (HCC) prognosis. Our aim was to test the hypothesis that bioavailable 25OHD may be a better serum biomarker of vitamin D status than total 25OHD on the association with HCC survival. APPROACH AND RESULTS: We included 1,031 newly diagnosed, previously untreated patients with HCC from the Guangdong Liver Cancer Cohort enrolled between September 2013 and April 2017. Serum total 25OHD levels were measured using an electrochemiluminescence immunoassay. Serum-free 25OHD levels were measured using a two-step enzyme-linked immunosorbent assay. Bioavailable 25OHD levels were calculated from measured free 25OHD and albumin using a previously validated equation. Primary outcomes were liver cancer-specific (LCSS) and overall survival (OS). Cox proportional hazards models were performed to calculate the multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 726 days, 430 patients had deceased, including 393 deaths from HCC. In multivariable analyses, higher bioavailable 25OHD levels were significantly associated with better survival, independent of nonclinical and clinical prognostic factors including serum C-reactive protein, Barcelona Clinic Liver Cancer stage, and cancer treatment. The multivariable-adjusted HRs in the highest versus lowest quartile of bioavailable 25OHD levels were 0.69 (95% CI: 0.51, 0.93; P for trend = 0.014) for LCSS and 0.71 (95% CI: 0.53, 0.94; P for trend = 0.013) for OS. In contrast, neither total nor free 25OHD levels were associated with LCSS or OS. CONCLUSIONS: Higher bioavailable, rather than total, 25OHD levels were independently associated with improved survival in a population-based HCC cohort, suggesting a potential utility of bioavailable 25OHD in HCC prognosis.
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Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Vitamina D/análogos & derivados , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Vitamina D/sangueRESUMO
Recent experiments reported that the complicated translocation dynamics of a looped DNA chain through a nanopore can be detected by ionic current blockade profiles. Inspired by the experimental results, we systematically study the translocation dynamics of a looped polymer, formed by three building blocks of a loop in the middle and two tails of the same length connected with the loop, by using Langevin dynamics simulations. Based on two entering modes (tail-leading and loop-leading) and three translocation orders (loop-tail-tail, tail-loop-tail, and tail-tail-loop), the translocation of the looped polymer is classified into six translocation pathways, corresponding to different current blockade profiles. The probabilities of the six translocation pathways are dependent on the loop length, polymer length, and pore radius. Moreover, the translocation times of the entire polymer and the loop are investigated. We find that the two translocation times show different dependencies on the translocation pathways and on the lengths of the loop and the entire polymer.
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Nanoporos , DNA , Polímeros , ProbabilidadeRESUMO
The alkali atom concentration plays an important role in the performance of a diode pumped alkali vapor laser (DPAL). At the rubidium DPAL operational region, the alkali concentration is as high as 1013-1014cm-3, which is "optically thick," or opaque, for the 780 nm or 795 nm doublet D lines when the traditional scanning absorption spectrum method is used for concentration measurement. To solve this problem, we propose the use of a probe laser of 420 nm, which corresponds to the 52S1/2 to 62P3/2 transition and has a lower absorption cross section compared to the D-line doublet. Due to the moderate absorption strength at a fixed 420 nm probe wavelength, we realized fast, online measurement of the Rb concentration in a real-world DPAL. By combining it with the quasi-two-level model, we further provided the population distribution in the lower three energy levels. This fast, online diagnostic method could be well applied in DPAL concentration measurement, and could show the dynamics of a laser's performance.
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BACKGROUND: The epidemiological evidence of traumatic brain injury (TBI) and spinal cord injury (SCI) mortality in mainland China is lacking. We aimed to assess the trends of TBI and SCI mortality, and their association with sex, age, location and external causes of injury in south China. METHODS: Mortality data were derived from the Disease Surveillance Points (DSPs) system of Guangdong province between 2014 and 2018. We examined the trends in mortality with Cochran-Armitage trend test, and the association between the socio-demographic factors and the TBI and SCI mortality by using negative binomial models. Subgroup analysis was performed by stratifying the external causes of TBI and SCI. RESULTS: The age-standardized TBI mortality remained relatively stable (from 11.6 to 15.4 per 100,000), while the SCI mortality increased by 148.3% from 2014 to 2018. Compared with females and urban residents, the adjusted mortality rate ratios of males and rural residents were 2.3 and 2.0 for TBI, and 2.2 and 4.6 for SCI, respectively. TBI and SCI mortality increased substantially with age. Motor vehicle crashes and falls were the leading causes of TBI mortality in residents aged under 75 years and over 75 years, respectively. Falls were the most important external cause for SCI death of all ages. CONCLUSIONS: Being male, rural and elderly residents are at higher risk of dying from TBI and SCI. The substantial burden of TBI and SCI caused by road traffic crashes and falls has called for the urgent need to improve injury prevention, pre-hospital aid, hospital treatment and recovery.
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Lesões Encefálicas Traumáticas , Traumatismos da Medula Espinal , Acidentes por Quedas , Idoso , Lesões Encefálicas Traumáticas/epidemiologia , Lesões Encefálicas Traumáticas/etiologia , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Traumatismos da Medula Espinal/epidemiologiaRESUMO
BACKGROUND: Guangdong province is dominated by three cultural regions: Canton, Hakka and Hoklo. However, little is known about the disease burden within these regions, particularly because different population,environmental and socioeconomic risk factors might cause different patterns of mortality, disability-adjusted life-years (DALY), life expectancy and healthy life expectancy (HALE). We aimed to compare the patterns of disease burden in Canton, Hakka and Hoklo regions between 2005 and 2015. METHOD: We calculated the mortality, YLL, YLD for 116 diseases for different cultural regions between 2005 and 2015. We calculated the DALYs for 116 causes as the sum of YLLs and YLDs. We estimated the life expectancy and HALE by using sex-specific mortality rates and YLDs for the three cultural regions. RESULTS: With a respective reduction of 22.3, 15.8 and 17.8% in 2015 compared with 2005, the age-standardized DALY rates in 2015 was 19,988.0, 14,396.5 and 20,436.6 in Hakka, Canton and Hoklo region. Canton region had a significantly lower mortality and DALYs in most diseases, followed by Hoklo and Hakka regions. The life expectancy and HALE at birth were highest in Canton region in both 2005 and 2015, than in Hoklo and Hakka region. CONCLUSIONS: Our findings call for improved public health care via the refinement of policy and effective measures for disease prevention. Understanding the environmental and culture-related risk factors of diseases in Hoklo and Hakka regions may help inform public health sectors to reduce the disease burden and the between-region inequality.
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Etnicidade/estatística & dados numéricos , Carga Global da Doença/estatística & dados numéricos , Expectativa de Vida/etnologia , Mortalidade/etnologia , Anos de Vida Ajustados por Qualidade de Vida , Adulto , Idoso , China/epidemiologia , Comparação Transcultural , Pessoas com Deficiência/estatística & dados numéricos , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores SocioeconômicosRESUMO
Copper and zinc are essential micronutrients, whose imbalance may be involved in the development and progression of cancer. However, the role of copper and/or zinc imbalance in the prognosis of hepatocellular carcinoma (HCC) is currently unclear. Our objective was to investigate the association between serum levels of copper, zinc and their ratio (copper/zinc) at diagnosis with HCC survival. We included 989 patients with incident HCC in this prospective cohort study, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study within 30 days of diagnosis between September 2013 and February 2017. Serum copper and zinc were measured using inductively coupled plasma mass spectrometry. Primary outcomes were liver cancer-specific survival (LCSS) and overall survival (OS). Cox proportional hazards models were used to calculate the multivariable hazard ratios (HRs) and 95% confidence interval (CI). Higher serum copper levels were strongly associated with worse LCSS (Q4 vs. Q1: HR = 1.87, 95% CI: 1.22-2.86; p < 0.01 for trend) and OS (Q4 vs. Q1: HR = 2.06, 95% CI: 1.36-3.11; p < 0.01 for trend). The calculated copper/zinc ratio was positively associated with LCSS (Q4 vs. Q1: HR = 1.31, 95% CI: 0.89-1.92; P = 0.04 for trend) and OS (Q4 vs. Q1: HR = 1.43, 95% CI: 0.99-2.08; P = 0.01 for trend). No overall associations were observed between serum zinc levels and LCSS or OS in the entire cohort. The results suggest that higher serum copper and copper in relation to zinc levels (i.e., higher copper/zinc ratio) may be associated with worse HCC survival, but serum zinc levels may be not associated with HCC survival.
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Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/mortalidade , Cobre/sangue , Neoplasias Hepáticas/mortalidade , Zinco/sangue , Adulto , Carcinoma Hepatocelular/sangue , China/epidemiologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Análise de SobrevidaRESUMO
The aim of this study is to systematically compare the performance of C-reactive protein (CRP), procalcitonin (PCT) and serum cytokines in identifying pediatric cancer patients with high-risk infection. A prospective observational study was performed from January 2014 through December 2016. Consecutive pediatric cancer patients who experienced febrile illness during hospitalization were enrolled. The CRP, PCT, interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were determined within 6â¯h of fever onset. A total of 3118 episodes of febrile illness were included, with 13.1% episodes documented as bloodstream infection (BSI) and 3.5% diagnosed as septic shock. Patients with BSI presented much higher levels of PCT, IL-6, IL-10 and TNF-α than patients with other types of fever and have much higher incidence of septic shock (11.2% vs. 2.3%, Pâ¯<â¯0.001). IL-6 and IL-10 showed better performance in identifying patients with gram-negative bacteremia (GNB) and septic shock than CRP and PCT, respectively. The area under the curve (AUCs) of receiver operating characteristic (ROC) curve for septic shock prediction were 0.65, 0.78, 0.89 and 0.87 for CRP, PCT, IL-6 and IL-10, respectively. Furthermore, elevation of IL-6 and IL-10 were strongly associated with the development of GNB and septic shock. Our results indicate that BSI, especially GNB, is a high-risk form of infection which results in high incidence of septic shock. IL-6 and IL-10 performance better than CRP and PCT in identifying patients with high-risk febrile illness.
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Proteína C-Reativa/análise , Febre/diagnóstico , Interleucina-10/sangue , Interleucina-6/sangue , Pró-Calcitonina/sangue , Adolescente , Bacteriemia/sangue , Bacteriemia/diagnóstico , Criança , Pré-Escolar , Feminino , Febre/sangue , Infecções por Bactérias Gram-Negativas/sangue , Infecções por Bactérias Gram-Negativas/diagnóstico , Humanos , Lactente , Interferon gama/sangue , Masculino , Estudos Prospectivos , Choque Séptico/sangue , Choque Séptico/diagnóstico , Fator de Necrose Tumoral alfa/sangueAssuntos
Anemia Aplástica , Transplante de Células-Tronco Hematopoéticas , Sistema de Registros , Transplante Homólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Anemia Aplástica/terapia , Anemia Aplástica/mortalidade , Anemia Aplástica/diagnóstico , Idoso , Masculino , Feminino , Pessoa de Meia-Idade , Resultado do Tratamento , China/epidemiologia , População do Leste AsiáticoRESUMO
Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.
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Carcinoma Hepatocelular/mortalidade , Ácido Fólico/sangue , Neoplasias Hepáticas/mortalidade , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , China , Feminino , Humanos , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos ProspectivosRESUMO
Autophagy, a form of cellular self-digestion by lysosome, is associated with various disease processes including cancers, and modulating autophagy has shown promise in the treatment of various malignancies. A number of natural products display strong antitumor activity, yet their mechanisms of action remain unclear. To gain a better understanding of how traditional Chinese medicine agents exert antitumor effects, we screened 480 natural compounds for their effects on autophagy using a high content screening assay detecting GFP-LC3 puncta in HeLa cells. Tubeimoside-1 (TBMS1), a triterpenoid saponin extracted from Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae), was identified as a potent activator of autophagy. The activation of autophagy by TBMS1 was evidenced by increased LC3-II amount and GFP-LC3 dots, observation of autophagosomes under electron microscopy, and enhanced autophagic flux. To explore the mechanisms underlying TBMS1-activated autophagy, we performed cheminformatic analyses and surface plasmon resonance (SPR) binding assay that showed a higher likelihood of the binding between Akt protein and TBMS1. In three human breast cancer cell lines, we demonstrated that Akt-mTOR-eEF-2K pathway was involved in TBMS1-induced activation of autophagy, while Akt-mediated downregulations of Mcl-1, Bcl-xl, and Bcl-2 led to the activation of apoptosis of the breast cancer cells. Inhibition of autophagy enhanced the cytotoxic effect of TBMS1 via promoting apoptosis. Our results demonstrate the role and mechanism of TBMS1 in activating autophagy, suggesting that inhibition of cytoprotective autophagy may act as a therapeutic strategy to reinforce the activity of TBMS1 against cancers.
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Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Recent evidence shows that raddeanin A (RA), an oleanane-type triterpenoid saponin extracted from Anemone raddeana Regel, exerts remarkable cytotoxicity against cancer cells in vitro and in vivo. In addition, RA has also been found to activate autophagy in human gastric cancer cells. In this study, we investigated the molecular mechanisms underlying RA-induced autophagy as well as the relationship between RA-induced autophagy and its cytotoxicity in human breast cancer cells in vitro. Treatment with RA (2-8 µmol/L) dose-dependently enhanced autophagy, as evidenced by increased LC3 levels in breast cancer cell lines T47D, MCF-7 and MDA-MB-231. Furthermore, the Akt-mTOR-eEF-2K signaling pathway was demonstrated to be involved in RA-induced activation of autophagy in the 3 breast cancer cell lines. Treatment with RA (2-10 µmol/L) dose-dependently induced apoptosis in the 3 breast cancer cell lines. Pretreatment with the autophagy inhibitor chloroquine (CQ, 20 µmol/L) significantly enhanced RA-caused cytotoxicity via promoting apoptosis. In conclusion, our results suggest that modulating autophagy can reinforce the cytotoxicity of RA against human breast cancer cells.