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Doxorubicin (DOX)-mediated cardiotoxicity can impair the clinical efficacy of chemotherapy, leading to heart failure (HF). Given the importance of circRNAs and miRNAs in HF, this paper intended to delineate the mechanism of the circular RNA 0006332 (circ -0,006,332)/microRNA (miR)-143/Toll-like receptor 2 (TLR2) axis in doxorubicin (DOX)-induced HF. The binding of miR-143 to circ -0,006,332 and TLR2 was assessed with the dual-luciferase assay, and the binding between miR-143 and circ -0,006,332 was determined with FISH, RIP, and RNA pull-down assays. miR-143 and/or circ -0,006,332 were overexpressed in rats and cardiomyocytes, followed by DOX treatment. In cardiomyocytes, miR-143 and TLR2 expression, cell viability, LDH release, ATP contents, and levels of IL-1ß, IL-18, TNF-α, and pyroptosis-related molecules were examined. In rats, cardiac function, serum levels of cardiac enzymes, apoptosis, myocardial fibrosis, and levels of IL-1ß, IL-18, TNF-α, TLR2, and pyroptosis-related molecules were detected. miR-143 diminished TLR2 expression by binding to TLR2, and circ -0,006,332 bound to miR-143 to downregulate miR-143 expression. miR-143 expression was reduced and TLR2 expression was augmented in DOX-induced cardiomyocytes. miR-143 inhibited DOX-induced cytotoxicity by suppressing pyroptosis in H9C2 cardiomyocytes. In DOX-induced rats, miR-143 reduced cardiac dysfunction, myocardial apoptosis, myocardial fibrosis, TLR2 levels, and pyroptosis. Furthermore, overexpression of circ -0,006,332 blocked these effects of miR-143 on DOX-induced cardiomyocytes and rats. Circ -0,006,332 stimulates cardiomyocyte pyroptosis by downregulating miR-143 and upregulating TLR2, thus promoting DOX-induced cardiac injury.
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Doxorrubicina , MicroRNAs , Miócitos Cardíacos , Piroptose , RNA Circular , Receptor 2 Toll-Like , Animais , Doxorrubicina/efeitos adversos , MicroRNAs/genética , MicroRNAs/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 2 Toll-Like/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Piroptose/efeitos dos fármacos , RNA Circular/genética , RNA Circular/metabolismo , Ratos , Masculino , Ratos Sprague-Dawley , Cardiotoxicidade/metabolismo , Cardiotoxicidade/genética , Cardiotoxicidade/etiologia , Transdução de Sinais/efeitos dos fármacosRESUMO
The product of red cell distribution width (RDW) and mean corpuscular volume (MCV) has been identified as an indicator of target organ damage in cases of hypertension. However, the role of the RDW-MCV product in assessing carotid alteration, renal damage, and left ventricular hypertrophy in patients with hypertension has not been elucidated. In this cross-sectional study, a total of 1115 participants with hypertension were included. The RDW and MCV at admission were measured using an automated hematology analyzer. Organ damage was determined by the left ventricular mass index (LVMI), carotid intima-media thickness, and estimated glomerular filtration rate. The prevalence rates of carotid alteration and left ventricular hypertrophy were 57.0% and 18.0%, respectively. A higher RDW-MCV product and RDW were observed in hypertensive patients who developed carotid alteration. After adjusting for potential confounding factors, the correlations of the RDW-MCV product (Pâ =â .285) and RDW (Pâ =â .346) with carotid alteration were not significant. Moreover, the analysis of variance showed no significant correlation between RDW and LVMI (Pâ =â .186). However, the RDW-MCV product was higher in individuals with a high LVMI compared to those with a normal LVMI. Multivariable linear regression analysis revealed that the RDW-MCV product was independently associated with the LVMI (ßâ =â 2.519, 95% CI: 0.921-4.116; Pâ =â .002), but not the estimated glomerular filtration rate (ßâ =â -0.260, 95% CI: -2.031-1.511; Pâ =â .773). An elevated RDW-MCV product may be a predictor for left ventricular hypertrophy in patients with hypertension.
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Índices de Eritrócitos , Hipertensão , Humanos , Estudos Transversais , Hipertrofia Ventricular Esquerda , Espessura Intima-Media Carotídea , Hipertensão/complicações , Hipertensão/epidemiologiaRESUMO
BACKGROUND: Growing evidence suggests that symptoms associated with post-COVID-19 condition (also known as long COVID) can affect multiple organs and systems in the human body, but their association with viral persistence is not clear. The aim of this study was to investigate the persistence of SARS-CoV-2 in diverse tissues at three timepoints following recovery from mild COVID-19, as well as its association with long COVID symptoms. METHODS: This single-centre, cross-sectional cohort study was done at China-Japan Friendship Hospital in Beijing, China, following the omicron wave of COVID-19 in December, 2022. Individuals with mild COVID-19 confirmed by PCR or a lateral flow test scheduled to undergo gastroscopy, surgery, or chemotherapy, or scheduled for treatment in hospital for other reasons, at 1 month, 2 months, or 4 months after infection were enrolled in this study. Residual surgical samples, gastroscopy samples, and blood samples were collected approximately 1 month (18-33 days), 2 months (55-84 days), or 4 months (115-134 days) after infection. SARS-CoV-2 was detected by digital droplet PCR and further confirmed through RNA in-situ hybridisation, immunofluorescence, and immunohistochemistry. Telephone follow-up was done at 4 months post-infection to assess the association between the persistence of SARS-CoV-2 RNA and long COVID symptoms. FINDINGS: Between Jan 3 and April 28, 2023, 317 tissue samples were collected from 225 patients, including 201 residual surgical specimens, 59 gastroscopy samples, and 57 blood component samples. Viral RNA was detected in 16 (30%) of 53 solid tissue samples collected at 1 month, 38 (27%) of 141 collected at 2 months, and seven (11%) of 66 collected at 4 months. Viral RNA was distributed across ten different types of solid tissues, including liver, kidney, stomach, intestine, brain, blood vessel, lung, breast, skin, and thyroid. Additionally, subgenomic RNA was detected in 26 (43%) of 61 solid tissue samples tested for subgenomic RNA that also tested positive for viral RNA. At 2 months after infection, viral RNA was detected in the plasma of three (33%), granulocytes of one (11%), and peripheral blood mononuclear cells of two (22%) of nine patients who were immunocompromised, but in none of these blood compartments in ten patients who were immunocompetent. Among 213 patients who completed the telephone questionnaire, 72 (34%) reported at least one long COVID symptom, with fatigue (21%, 44 of 213) being the most frequent symptom. Detection of viral RNA in recovered patients was significantly associated with the development of long COVID symptoms (odds ratio 5·17, 95% CI 2·64-10·13, p<0·0001). Patients with higher virus copy numbers had a higher likelihood of developing long COVID symptoms. INTERPRETATION: Our findings suggest that residual SARS-CoV-2 can persist in patients who have recovered from mild COVID-19 and that there is a significant association between viral persistence and long COVID symptoms. Further research is needed to verify a mechanistic link and identify potential targets to improve long COVID symptoms. FUNDING: National Natural Science Foundation of China, National Key R&D Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and New Cornerstone Science Foundation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/diagnóstico , COVID-19/virologia , Estudos Transversais , SARS-CoV-2/isolamento & purificação , Masculino , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Adulto , Estudos de Coortes , Idoso , Pulmão/virologiaRESUMO
Background: Doxorubicin (Dox) can induce cardiotoxicity, thereby restricting the utility of this potent drug. Herein, the study ascertained the mechanism of the N6-methyladenosine (m6A) demethylase fat mass and obesity-associated protein (FTO) in pyroptosis and inflammation during Dox-induced heart failure (HF). Methods: Serum samples were collected from HF patients for detection of the expression of FTO and toll-like receptor 4 (TLR4). Dox-treated H9C2 cardiomyocytes were chosen for in vitro HF modeling, followed by measurement of FTO and TLR4 expression. Cardiomyocytes were detected for viability, apoptosis, spatial distribution of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), and the levels of lactic dehydrogenase, inflammatory factors, oxidative stress markers, and pyroptosis-related proteins. The m6A levels of mRNA were examined. RNA immunoprecipitation (RIP) and mRNA stability measurement were used to determine mRNA and protein expression, and RNA m6A dot blot and methylated-RIP assay were performed to detect m6A methylation levels. The expression of p-NF-κB p65 and p-IκB-α was measured by western blotting. Results: In the serum of HF patients, FTO was elevated while TLR4 was decreased. Dox treatment reduced FTO expression and increased m6A methylation levels and TLR4 expression in H9C2 cells. Overexpression of FTO and knockdown of TLR4 reduced apoptosis, cytotoxicity, inflammation, pyroptosis, oxidative stress, NLRP3 co-localization, and fluorescence intensity in Dox-induced H9C2 cells. Mechanistically, FTO resulted in reduced binding activity of YTHDF1 to TLR4 mRNA via m6A demethylation of TLR4, thus declining TLR4, p-NF-κB p65, and p-IκB-α expression. TLR4 knockdown counteracted the effects of FTO knockdown on Dox-induced H9C2 cells. Conclusions: FTO alleviated Dox-induced HF by blocking the TLR4/NF-κB pathway.
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Background: Sirtuin 2 (SIRT2) and galectin-3 have been shown to protect the heart against fibrosis. However, their impacts on radiation-induced myocardial fibrosis (RIMF) remain to be elucidated. To deepen this understanding, the current study sought to explore the effects of SIRT2 and galectin-3 on RIMF and the underlying mechanisms. Methods: Galectin-3 knockout mice were obtained, and a radiation-induced heart damage (RIHD) mouse model was induced by local radiation exposure to the heart. Lentivirus transfection was then performed, and heart function, fibrosis of heart tissues, and levels of SIRT2, galectin-3, and fibrosis-related markers collagen type-I/-III and matrix metalloproteinase (MMP)2/MMP9 were respectively assessed by echocardiography, hematoxylin-eosin and Masson staining, reverse transcription-quantitative polymerase chain reaction, Western blot, and immunofluorescence staining. Additionally, Western blot and chromatin immunoprecipitation were used to test H3K27 acetylation levels and the binding of H3K27ac to galectin-3, respectively. Results: After radiation exposure, heart tissues from the galectin-3 knockout mice had a smaller fibrotic area compared to normal mice, with reduced expression levels of collagen type-I/-III and MMP2/MMP9. SIRT2 was down-regulated and galectin-3 was up-regulated after RIHD treatment. The histone deacetylase inhibitor sirtinol promoted galectin-3 expression and H3K27 acetylation in a time-dependent manner, and increased H3K27ac enrichment in the galectin-3 promoter. Overexpression of SIRT2 down-regulated H3K27ac, collagen type-I/-III, and MMP2/MMP9 expression levels, and reduced the fibrotic area in mouse heart tissues. However, these effects were reversed by the additional overexpression of galectin-3. Conclusions: SIRT2 facilitates deacetylation of H3K27 to inhibit galectin-3 transcription, thus ameliorating RIMF in mice.
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BACKGROUND: It is not uncommon to encounter retrograde microcatheter-uncrossable lesions in retro-recanalization of Chronic Total Occlusion (CTO) cases, existing solutions were time-consuming or complicated to operate. Therefore, the present study aimed to propose and evaluate the feasibility, safety of a novel technique termed Active Pulling retrograde microcatheter crossing Technique (APT) during retrograde CTO percutaneous coronary intervention (PCI). METHODS: We retrospectively collected retrograde CTO-PCI cases from February 2017 to April 2023, only cases with the retrograde wire successfully crossed the CTO lesion were analyzed. The baseline clinical characteristics, angiographic characteristics, procedural details, and in-hospital major adverse cardiac events (MACEs) were compared. RESULTS: A total of 80 CTO cases were divided into the APT group and the non-APT group according to whether the APT was applied in the procedure. The APT group had a higher rate of device success than the non-APT group (100% vs. 85%, P = 0.013), with shorter duration (5.3 ± 3.8 vs. 18.6 ± 5.9 min, P < 0.001) and a smaller number of retrograde microcatheters were used (P < 0.001). In the APT group, the average air kerma radiation exposure was lower (2.7 ± 1.2 vs. 4.3 ± 1.7 Gy, P < 0.001), the fluoroscopy time (69.0 ± 15.0 vs. 88.1 ± 18.9 min, P < 0.001) and the procedure time (116.2 ± 22.2 vs. 131.6 ± 28.7 min, P = 0.009) was shorter than the non-APT group. The technical success rate of both groups reached 100% while the procedure success rate was higher in the APT group than the non-APT group (100% vs. 85%, P = 0.13). CONCLUSIONS: The APT is an easy and safe technique that can greatly improve procedural efficiency without adding other instruments, and allows the retrograde microcatheter to quickly crossing the CTO body after successful retrograde wire externalization.
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Cateteres Cardíacos , Angiografia Coronária , Oclusão Coronária , Estudos de Viabilidade , Intervenção Coronária Percutânea , Humanos , Estudos Retrospectivos , Masculino , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/terapia , Feminino , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/efeitos adversos , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Doença Crônica , Fatores de Tempo , Miniaturização , Cateterismo Cardíaco/instrumentação , Cateterismo Cardíaco/efeitos adversos , Desenho de Equipamento , Fatores de RiscoRESUMO
BNIP3 is reported to be involved in hypoxia-induced mitochondrial defect and cell death in cardiomyocytes. However, little is known about the specific function and molecular mechanism of BNIP3-mediated mitophagy in myocardial ischemia-reperfusion injury (MIRI). Herein, this study explored the mechanism regulating BNIP3-modulated mitophagy in MIRI. Rat cardiomyocytes (H9c2 cells) underwent transfection and hypoxia/reoxygenation (H/R) treatment, followed by cell viability and apoptosis detection. Gain-of-function assays were conducted in rats before MIRI modeling, followed by the monitoring of cardiac changes and the evaluation of cardiac function, myocardial infarction area, and apoptosis in myocardial tissues. The levels of creatine kinase MB (CK-MB), cardiac troponin I (cTnI), lactic dehydrogenase (LDH), reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), p62, and LC3 II/LC3 I were tested in rat serum or H9c2 cells. The co-localization of LC3 and TOMM20 was analyzed. The interaction of BNIP3 with YTHDF2 was assessed. H/R treatment decreased cell viability and p62 and SOD levels while elevating cell apoptosis, the levels of CK-MB, cTnI, LDH, MDA, ROS, and LC3 II/LC3 I, the number of autophagosomes, and the co-localization of LC3 and TOMM20 in cardiomyocytes, which were neutralized by downregulating BNIP3 or upregulating YTHDF2. Moreover, upregulation of YTHDF2 repressed myocardial injury and mitophagy in MIRI rats. Mechanistically, YTHDF2 mediated BNIP3 expression by recognizing methylated BNIP3. Upregulation of BNIP3 counteracted the suppressive effect of YTHDF2 overexpression on H/R-induced injury and mitophagy in cardiomyocytes. The RNA methylation reading protein YTHDF2 ameliorated MIRI by downregulating BNIP3 via m6A modification.
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OBJECTIVES: Doxorubicin (DOX) can contribute to severe myocardial injury, and bone marrow stromal cells (BMSC)-exosomes (Exos) improves acute myocardial infarction. Hence, this research investigated whether BMSC-Exos alleviated DOX-induced myocardial injury. METHODS: BMSC-derived Exos were isolated and identified, and the optimal concentration of DOX was confirmed. H9C2 cells were treated with DOX and BMSC-Exos or in combination with the protein kinase B (AKT) inhibitor. Reactive oxygen species (ROS) and JC-1 were detected to assess oxidative stress (OS) and mitochondrial membrane damage, respectively. In addition, the expression of pyroptosis-related molecules was measured. The expression of phosphatidylinositol 3 kinase (PI3K)-AKT pathway-related proteins and the phosphorylation and acetylation of forkhead box O1 (Foxo1) in the cell nucleus and cytoplasm were tested. Last, interactions between Foxo1 and gasdermin D (GSDMD) were assessed. RESULTS: BMSC-Exo treatment increased viability and mitochondrial membrane potential and reduced lactic dehydrogenase release and ROS levels in DOX-treated H9C2 cells. Furthermore, the addition of BMSC-Exos suppressed DOX-induced activation and upregulation of NLRP3 and apoptosis-associated speck-like protein containing A CARD (ASC) and in vitro cleavage of caspase-1, GSDMD, interleukin (IL)-1ß, and IL-18 proteins. Additionally, BMSC-Exo treatment enhanced the expression of phosphorylated (p)-PI3K, p-AKT, and p-mTOR in DOX-treated H9C2 cells and the levels of phosphorylated Foxo1 in the cytoplasm of DOX-treated H9C2 cells. Foxo1 was enriched in the promoter region of GSDMD. Moreover, the AKT inhibitor API-2 annulled the effects of BMSC-Exos on OS, pyroptosis, and Foxo1 phosphorylation in DOX-treated H9C2 cells. CONCLUSIONS: BMSC-Exos phosphorylated Foxo1 and inactivated Foxo1 transcription via the PI3K-AKT pathway to diminish GSDMD expression, thus restraining DOX-induced pyroptosis and OS of myocardial cells.
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Exossomos , Gasderminas , Células-Tronco Mesenquimais , Doxorrubicina/toxicidade , Exossomos/metabolismo , Estresse Oxidativo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt , Piroptose , Espécies Reativas de Oxigênio/metabolismo , Ratos , Animais , Gasderminas/genéticaRESUMO
The potential mechanism of miRNA released from adipose-derived stem cell (ADSC)-derived micro vesicle (MV) onthe modulation of proliferation, migration and invasion of endothelial cells were explored. In this study, miR-210 level was detected by qT-PCR. Alix, VEGF and RUNX3 expressions were detected by Western blot. The proliferation, migration and invasion of human umbilical vein endothelial cells (HUVECs) were observed by MTT assay and Transwell assay. Luciferase reporter gene assay was conducted to validate the targeting activity of MVs-released miR-210 on RUNX3. We found hypoxia significantly increased the expression of MVs-released miR-210. MVs released from ADSCsin hypoxic group significantly promoted the proliferation, migration and invasion of HUVECs. Overexpression of miR-210 significantly upregulated VEGF expression, and promoted the proliferation, migration and invasion of HUVECs. Besides, RUNX3 was identified as the direct of miR-210 in HUVECs. Overexpression of miR-210 decreased RUNX3 expression and promoted the proliferation, migration and invasion of HUVECs, while overexpression of RUNX3 inhibited these promotion effects. In vivo experiment showed that MVs derived from ADSCs under hypoxia increased miR-210 level and capillary density, and inhibition of miR-210 decreased capillary density. We also found MVs downregulated RUNX3 expression, and inhibition of miR-210 upregulated RUNX3 expression. Therefore, miR-210 released from ADSCs-derived MVs promoted proliferation, migration and invasion of HUVECs by targeting RUNX3, which revealed one of the mechanisms of ADSCs-derived MVs on the promotion of proliferation, migration and invasion of HUVECs. ABBREVIATIONS: ADSC, adipose-derived stem cell; MV, micro vesicle; HUVECs, human umbilical vein endothelial cells; RUNX3, Runtrelatedtranscription factor-3.
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Tecido Adiposo/citologia , Movimento Celular , Micropartículas Derivadas de Células/metabolismo , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , MicroRNAs/metabolismo , Células-Tronco/citologia , Movimento Celular/genética , Proliferação de Células/genética , Humanos , MicroRNAs/genéticaRESUMO
AIMS: Endothelial-to-mesenchymal transition (EndMT) contribute to diabetic cardiac fibrosis, the underlying mechanisms are poorly understood. In the study, we aimed to investigate the role of miR-328 in EndMT mediated by high glucose (HG) and the signaling pathways implicated in human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: EndMT of HUVECs was determined by immunofluorescent staining and western blot of the markers CD31 and α-SMA. Real-time polymerase chain reaction was used to detect mRNA expression of miR-328 and transforming growth factor ß1 (TGF-ß1). SB431542 was used to study the relation of miR-328 and TGF-ß1 during EndMT induced by HG. Over-expression and inhibition of miR-328 were achieved by transduction of miR-328 and antagomiR-328. The effects of miR-328 on expression of type I and III collagen, p-MEK1/2, p-ERK1/2 were examined by Western blot. KEY FINDINGS: The level of miR-328 was significantly up-regulated in HG-induced EndMT. MiR-328 showed the independent capability of inducing EndMT, which was not related to TGF-ß1, and this effect was abrogated by antagomiR-328. MiR-328 affected type I collagen in a time- and dose-dependent manner and enhanced protein expression of type I and III collagens. Further investigation displayed that a significantly higher expression of p-MEK1/2 and p-ERK1/2 in HUVECs transduced with miR-328, and a lower expression of p-MEK1/2 and p-ERK1/2 in cells transduced with antagomiR-328. SIGNIFICANCE: These results suggest a novel role for miR-328 in HG-induced EndMT, MEK1/2-ERK1/2 pathway is likely to be involved in the associated effects. Our findings may suggest antagomiR-328 as an alternative agent in prevention of HG-induced EndMT.
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Endotélio/metabolismo , Transição Epitelial-Mesenquimal , Células Endoteliais da Veia Umbilical Humana/citologia , MicroRNAs/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glucose/farmacologia , Humanos , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Exposure to fine particulate matter (PM2.5) pollution is associated with increased morbidity and mortality from respiratory diseases. However, few population-based studies have been conducted to assess the alterations in circulating pulmonary proteins due to long-term PM2.5 exposure. METHODS: We designed a two-stage study. In the first stage (training set), we assessed the associations between PM2.5 exposure and levels of pulmonary damage markers (CC16, SP-A and SP-D) and lung function in a coke oven emission (COE) cohort with 558 coke plant workers and 210 controls. In the second stage (validation set), significant initial findings were validated by an independent diesel engine exhaust (DEE) cohort with 50 DEE exposed workers and 50 controls. RESULTS: Serum CC16 levels decreased in a dose response manner in association with both external and internal PM2.5 exposures in the two cohorts. In the training set, serum CC16 levels decreased with increasing duration of occupational PM2.5 exposure history. An interquartile range (IQR) (122.0µg/m3) increase in PM2.5 was associated with a 5.76% decrease in serum CC16 levels, whereas an IQR (1.06µmol/mol creatinine) increase in urinary 1-hydroxypyrene (1-OHP) concentration was associated with a 5.36% decrease in serum CC16 levels in the COE cohort. In the validation set, the concentration of serum CC16 in the PM2.5 exposed group was 22.42% lower than that of the controls and an IQR (1.24µmol/mol creatinine) increase in urinary 1-OHP concentration was associated with a 12.24% decrease in serum CC16 levels in the DEE cohort. CONCLUSIONS: Serum CC16 levels may be a sensitive marker for pulmonary damage in populations with high PM2.5 exposure.
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Lesão Pulmonar Aguda , Biomarcadores/sangue , Exposição por Inalação/análise , Material Particulado/efeitos adversos , Uteroglobina/sangue , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/induzido quimicamente , China , Estudos de Coortes , Humanos , Exposição por Inalação/efeitos adversos , Tamanho da PartículaRESUMO
AIM: To investigate the species distribution and antifungal susceptibility profiles of yeast isolates causing invasive infections across Beijing. MATERIALS & METHODS: A total of 1201 yeast isolates recovered from blood and other sterile body fluids were correctly identified by matrix-assisted laser desorption/ionization TOF MS supplemented by DNA sequencing. Antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute broth microdilution method. RESULTS: Candida (95.5%) remained the most common yeast species isolated; Candida albicans (38.8%) and Candida parapsilosis (22.6%) were the leading species of candidemia. Azole resistances were mainly observed in Candida glabrata and Candida tropicalis isolates. CONCLUSION: This study outlined the epidemiologic data of invasive yeast infections and highlighted the need for continuous monitoring of azole resistances among C. glabrata and C. tropicalis isolates in Beijing.
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Candidíase Invasiva/epidemiologia , Candidíase Invasiva/microbiologia , Testes de Sensibilidade Microbiana/métodos , Leveduras/efeitos dos fármacos , Leveduras/isolamento & purificação , Adolescente , Adulto , Idoso , Anfotericina B/farmacologia , Antifúngicos , Pequim/epidemiologia , Candida/efeitos dos fármacos , Candida/genética , Candida/isolamento & purificação , Candida/patogenicidade , Candida albicans/efeitos dos fármacos , Candida albicans/genética , Candida albicans/isolamento & purificação , Candida albicans/patogenicidade , Candida glabrata/efeitos dos fármacos , Candida glabrata/genética , Candida glabrata/isolamento & purificação , Candida glabrata/patogenicidade , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/genética , Candida parapsilosis/isolamento & purificação , Candida parapsilosis/patogenicidade , Candida tropicalis/efeitos dos fármacos , Candida tropicalis/genética , Candida tropicalis/isolamento & purificação , Candida tropicalis/patogenicidade , Candidemia/epidemiologia , Candidemia/microbiologia , Criança , Pré-Escolar , Farmacorresistência Fúngica/efeitos dos fármacos , Equinocandinas/farmacologia , Monitoramento Epidemiológico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA , Triazóis/farmacologia , Leveduras/genética , Leveduras/patogenicidade , Adulto JovemRESUMO
BACKGROUND: Accumulating evidence suggests that increased red cell distribution width (RDW) and mean corpuscular volume (MCV) were both poor prognostic factors for patients with cardiovascular diseases. Recently, the multiplicative interaction between RDW and MCV has been observed for predicting mortality in elderly patients without anemia; however, the relationship between the product of RDW-MCV and hypertension-induced target organ damage (TOD) has not been evaluated. METHODS: We performed a cross-sectional study in 1115 hypertensive patients. RDW and MCV were determined using automated hematology analyzers. Prevalence of TOD was evaluated by estimated glomerular filtration rate, carotid intima-media thickness, and left ventricular mass index. RESULTS: The prevalence of TOD was observed to be increased with the RDW or product of RDW-MCV quartiles. Moreover, RDW, MCV and product of RDW-MCV were significantly higher in patients with TOD compared to those without TOD. According to two logistic regression models, the associations of RDW and MCV with TOD were lost after adjustment for other factors. However, product of RDW-MCV remains an independent predictor of TOD, with per 0.4 fL increase in the product of RDW-MCV associated with a 16% increased risk of TOD (P=.012). CONCLUSIONS: The inclusion of MCV by calculating the product of RDW-MCV appears to enhance the association of RDW with TOD.
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Índices de Eritrócitos/fisiologia , Hipertensão , Idoso , Espessura Intima-Media Carotídea , Estudos Transversais , Feminino , Taxa de Filtração Glomerular/fisiologia , Ventrículos do Coração/fisiopatologia , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: The morning heart rate surge (MHRS) and morning blood pressure surge (MBPS) may be responsible for the high prevalence of cardiovascular events during the morning period. The clinical significance of the MBPS has been well established, but that of the MHRS remains unclear. Thus, we evaluated the association between the MHRS and target organ damage (TOD). METHODS: A cross-sectional study of 580 hypertensive patients was performed. MHRS and heart rate variability (HRV) were analyzed by 24 h electrocardiogram. TOD was assessed by estimated glomerular filtration rate, carotid intima-media thickness (IMT), and left ventricular mass index. RESULTS: The prevalence of TOD tended to decrease with sleep-trough MHRS (first to fourth quartiles: 71%, 70.3%, 58.6%, and 52.7%, respectively) or prewaking MHRS quartiles (first to fourth quartiles: 65.3%, 73.6%, 61.4%, and 54.2%, respectively), whereas the opposite trend was observed for standard deviation of all normal NN intervals (SDNN). Moreover, sleep-trough MHRS, prewaking MHRS, SDNN, and SDNN index were significantly lower in patients with TOD than in those without TOD. According to four logistic regression models, the associations of prewaking MHRS, SDNN, and SDNN index with TOD were lost after adjustment for age and BP. Patients in the first (≤11.125 bpm) and second sleep-trough MHRS quartiles (11.125-15.75 bpm) had a 1.95-2.06-fold increased risk of TOD compared with those in the fourth quartile (p < 0.05). CONCLUSION: A blunted sleep-trough MHRS, which may serve as a surrogate marker for autonomic imbalance, was independently associated with TOD in primary hypertensive patients.
Assuntos
Ventrículos do Coração , Hipertensão , Idoso , Monitorização Ambulatorial da Pressão Arterial/métodos , Espessura Intima-Media Carotídea , China/epidemiologia , Estudos Transversais , Eletrocardiografia/métodos , Feminino , Taxa de Filtração Glomerular , Frequência Cardíaca , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Fatores de RiscoRESUMO
BACKGROUND: FLT3-internal tandem duplication mutations (ITDs) are found in approximately 30% of patients with acute myeloid leukemia (AML) and are markers of poor prognosis. However, the characteristics of FLT3/ ITDs in Chinese AML patients have rarely been reported. The aim of this study was to analyze the frequency and characteristics of FLT3/ITDs in Chinese AML patients. METHODS: In the selected 152 cases of Chinese AML patients, capillary electrophoresis (CE) was used to analyze the frequency and characteristics of FLT3/ITDs. Next-generation sequencing was used to analyze the sequences of FLT3/ITDs positive patients. The differences of clinical features between FLT3/ITD positive group and FLT3/ITD negative group were estimated by statistical analysis. RESULTS: 42 cases (27.6%) were FLT3/ITDs-positive, in which 34 cases (81%) had a single duplication, and the remaining 8 cases (19%) had 2 or more ITDs. Median ITD size was 42 bp and median ITD allelic ratio was 0.25. Using next-generation sequencing, ITDs integrating in non-juxtamembrane (JM) domains were detected in 12 ITDs (24%) and in JM domains were detected in 38 ITDs (76%). Furthermore, duplication of at least one residue between Y591 and Y599 was detected in 48 (96%) of all 50 ITDs, and the insertion site was strongly correlated with ITD size: more C-terminal located inserted fragments were significantly longer. CONCLUSIONS: Our data provide further evidence of the heterogeneity of FLT3/ITDs among different subgroups in Chinese AML patients. ITDs varied widely, but hotspots were concentrated. These results also suggest that nextgeneration sequencing is a useful method for detection of FLT3/ITDs sequences.
Assuntos
Eletroforese Capilar/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Leucemia Mieloide Aguda/genética , Mutação , Sequências de Repetição em Tandem/genética , Tirosina Quinase 3 Semelhante a fms/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Severe acute respiratory syndrome (SARS) is an acute infectious disease of the respiratory system. Although a novel coronavirus has been identified as the causative agent of SARS, the pathogenic mechanisms of SARS are not understood. In this study, sera were collected from healthy donors, patients with SARS, patients with severe SARS, and patients with SARS in convalescence. The serum concentrations of interleukin-1 (IL-1), IL-4, IL-6, IL-8, IL-10, tumor growth factor beta (TGF-beta), tumor necrosis factor alpha (TNF-alpha), and gamma interferon (IFN-gamma) were measured by enzyme-linked immunosorbent assays (ELISA). The concentrations of IL-1 and TNF-alpha were not significantly different in different groups. The IL-6 concentration was increased in SARS patients and was significantly elevated in severe SARS patients, but the IL-6 concentrations were similar in convalescent patients and control subjects, suggesting that there was a positive relationship between the serum IL-6 concentration and SARS severity. The concentrations of IL-8 and TGF-beta were decreased in SARS patients and significantly reduced in severe SARS patients, but they were comparable in convalescent SARS patients and control subjects, suggesting that there was a negative relationship between the IL-8 and TGF-beta concentrations and SARS severity. The concentrations of IFN-gamma, IL-4, and IL-10 showed significant changes only in convalescent SARS patients. The IFN-gamma and IL-4 levels were decreased, while the levels of IL-10 were increased, and the differences between convalescent SARS patients and other patient groups were statistically significant. These results suggest that there are different immunoregulatory events during and after SARS and may contribute to our understanding of the pathogenesis of this syndrome.