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OBJECTIVES: This study was designed to determine the incidence, contributing factors, and prognostic implications of acute kidney injury (AKI) recovery patterns in patients who experienced AKI after valve replacement surgery (VRS). DESIGN: A retrospective cohort study was conducted. SETTING: The work took place in a postoperative care center in a single large-volume cardiovascular center. PARTICIPANTS: Patients undergoing VRS between January 2010 and December 2019 were enrolled. INTERVENTION: Patients were categorized into three groups based on their postoperative AKI status: non-AKI, AKI with early recovery (less than 48 hours), and persistent AKI. MEASUREMENT AND MAIN RESULTS: The primary outcome was in-hospital major adverse clinical events. The secondary outcomes included in-hospital and 1-year mortality. A total of 4,161 patients who developed AKI following VRS were included. Of these, 1,513 (36.4%) did not develop postoperative AKI, 1,875 (45.1%) experienced AKI with early recovery, and 773 (18.6%) had persistent AKI. Advanced age, diabetes, New York Heart Association III-IV heart failure, moderate-to-severe renal dysfunction, anemia, and AKI stages 2 and 3 were identified as independent risk factors for persistent AKI. In-hospital major adverse clinical events occurred in 59 (3.9%) patients without AKI, 88 (4.7%) with early AKI recovery, and 159 (20.6%) with persistent AKI (p < 0.001). Persistent AKI was independently associated with an increased risk of in-hospital adverse events and 1-year mortality. In contrast, AKI with early recovery did not pose additional risk compared with non-AKI patients. CONCLUSIONS: In patients who develop AKI following VRS, early AKI recovery does not pose additional risk compared with non-AKI. However, AKI lasting more than 48 hours is associated with an increased risk of in-hospital and long-term adverse outcomes.
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OBJECTIVE: To identify different key genes and pathways between males and females by studying differentially expressed genes (DEGs). METHODS: The gene expression data of GSE123568 were downloaded from GEO database, including osteonecrosis of the femoral head (ONFH) samples from 3 females and 7 males, and DEGs between different gender were identified with R software. Protein-protein interaction (PPI) network was constructed to further analyze the interactions between overlapping DEGs, and finally, GO, KEGG and gene set enrichment analysis (GSEA) were conducted for enrichment analysis. RESULTS: 131 DEGs were identified between ONFH females and ONFH males, including 76 up-regulated genes and 55 down-regulated genes. And 10 hub genes were identified in PPI network, including SLC4A1, GYPA, CXCL8, IFIT1, GBP5, IFI44, IFI44L, IFIT3, KEL and AHSP. Functional enrichment analysis revealed that these genes were mainly enriched in cGMP-PKG signaling pathway, Fatty acid degradation, Non-alcoholic fatty liver disease, Systemic lupus erythematosus, Hematopoietic cell lineage and NO-cGMP-PKG signaling. CONCLUSIONS: NO-cGMP-PKG signaling may play an important role in the occurrence and development of ONFH. SLC4A1, GYPA, CXCL8, GBP5 and AHSP may be key genes associated with gender difference in the progression of ONFH, which may be ideal targets or prognostic markers for the treatment of ONFH.
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Cabeça do Fêmur , Osteonecrose , Fatores Sexuais , Feminino , Humanos , Masculino , Biologia Computacional , Osteonecrose/genéticaRESUMO
OBJECTIVES: The present study aimed to identify different key genes and pathways between postmenopausal females and males by studying differentially expressed genes (DEGs). METHODS: GSE32317 and GSE55457 gene expression data were downloaded from the GEO database, and DEGs were discovered using R software to obtain overlapping DEGs. The interaction between overlapping DEGs was further analyzed by establishing the protein-protein interaction (PPI) network. Finally, GO and KEGG were used for enrichment analysis. RESULTS: 924 overlapping DEGs between postmenopausal women and men with osteoarthritis (OA) were identified, including 674 up-regulated genes and 249 down-regulated ones. And 10 hub genes were identified in the PPI network, including BMP4, KDM6A, JMJD1C, NFATC1, PRKX, SRF, ZFX, LAMTOR5, UFD1L and AMBN. The findings of the functional enrichment analysis suggested that these genes were predominantly expressed in MAPK signaling pathway as well as the Thyroid hormone signaling pathway, indicating that those two pathways may be involved in onset and disease progression of OA in postmenopausal patients. CONCLUSION: BMP4, KDM6A, JMJD1C, PRKX, ZFX and LAMTOR5 are expected to play crucial roles in disease development in postmenopausal patients and may be ideal targets or prognostic markers for the treatment of OA.
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Biologia Computacional , Osteoartrite , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Histona Desmetilases , Humanos , Histona Desmetilases com o Domínio Jumonji , Masculino , Osteoartrite/genética , Osteoartrite/metabolismo , Oxirredutases N-Desmetilantes , Caracteres SexuaisRESUMO
Background: Bloodstream infection (BSI) are prone to circulation disorders, which portend poor outcome. The central venous-to-arterial carbon dioxide difference (Pcv-aCO2) is a biomarker for circulation disorders, but the prognostic value of Pcv-aCO2 in BSI patients remains unclear. This study was to investigate the association of Pcv-aCO2 with adverse events in BSI patients. Methods: The patients with BSI between August 2014 and August 2017 were prospectively enrolled. Clinical characteristic and laboratory results were collected. We analyzed the association of the level of Pcv-aCO2 with clinical variables and 28-day mortality. Results: A total of 152 patients were enrolled. The Pcv-aCO2 was positively correlated with white blood cell count (r=0.241, p=0.003), procalcitonin (r=0.471, p<0.001), C-reactive protein (r=0.192, p=0.018), lactate (r=0.179, p=0.027), Sequential Organ Failure Assessment (r=0.318, p<0.001) and Acute Physiology And Chronic Health Evaluation II score (r=0.377, p<0.001), while that was negatively correlated with central venous oxygen saturation (r=-0.242, p<0.001) and platelet (r=-0.205, p=0.011). Kaplan-Meier curves demonstrated that patients with Pcv-aCO2 >6mmHg had a worse prognosis than those without (log rank=32.10, p<0.001). Multivariate analysis showed Level of Pcv-aCO2 was an independent risk factor for 28-day mortality (HR: 3.10, 95% CI: 1.43-6.74, p=0.004). The area under the receiver operating characteristic curve of Pcv-aCO2 for prediction of 28-day mortality in patients with BSI was 0.794. Pcv-aCO2>6 mmHg had 81.1% sensitivity and 78.8% specificity for predicting 28-day mortality. Conclusion: Pcv-aCO2 may be a simple and valuable biomarker to assessment of 28-day mortality in patients with BSI.
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Dióxido de Carbono/sangue , Sepse/mortalidade , Idoso , Idoso de 80 Anos ou mais , Gasometria/estatística & dados numéricos , Feminino , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Masculino , Prognóstico , Estudos Prospectivos , Curva ROC , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Sepse/sangue , Sepse/terapiaRESUMO
Ischemia postconditioning (PTC) can reduce myocardial ischemia/reperfusion injury. However, the effectiveness of PTC cardioprotection is reduced or lost in diabetes and the mechanisms are largely unclear. Hyperglycemia can induce overexpression of inducible nitric oxide synthesis (iNOS) in the myocardium of diabetic subjects. However, it is unknown whether or not iNOS especially its overexpression plays an important role in the loss of cardioprotection of PTC in diabetes. C57BL6 and iNOS-/- mice were treated with streptozotocin to induce diabetes. Part of diabetic C57BL6 mice were also treated with an iNOS specific inhibitor, 1400â¯W. Mice were subjected to myocardial ischemia/ reperfusion with/without PTC. The hemodynamic parameters, plasma levels of cardiac troponin T (cTnT), TNF-α, IL-6 and nitric oxide (NO) were monitored. The myocardial infarct size, superoxide anion (O2-) generation, nitrotyrosine production and apoptosis were measured. The expression of phosphorylated Akt, endothelial NOS (eNOS), iNOS and Erk1/2 in ischemic heart were detected by immunoblot analysis. In diabetic C57BL6 and iNOS-/- mice, the post-ischemic hemodynamics were impaired, the cTnT, TNF-α, IL-6 level, myocardial infarct size, apoptotic index, O2- and nitrotyrosine generation were increased and the Akt/eNOS signal pathways were inhibited. PTC improved hemodynamic parameters, reduced cTnT level, myocardial infarct size, apoptotic index, O2- and nitrotyrosine generation and activated Akt/eNOS and Erk1/2 signal pathways in both non-diabetic C57BL6 and iNOS-/- mice as well as diabetic iNOS-/- mice, but not in diabetic C57BL6 mice. PTC also increased NO production in both non-diabetic and diabetic C57BL6 and iNOS-/- mice, and enhanced iNOS expression in non-diabetic C57BL6 mice. 1400â¯W restored the cardioprotection of PTC in diabetic C57BL6 mice. Our data demonstrated that PTC reduced myocardial ischemia/reperfusion injury in non-diabetic mice but not C57BL6 diabetic mice. Deletion of iNOS restored the cardioprotection of PTC in diabetic mice. Our findings suggest that iNOS plays a key role in the reduction of cardioprotection of PTC in diabetes and may provide a therapeutic target for diabetic patients.
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Diabetes Mellitus Experimental/enzimologia , Pós-Condicionamento Isquêmico , Miocárdio/enzimologia , Óxido Nítrico Sintase Tipo II/metabolismo , Animais , Apoptose , Glicemia/metabolismo , Peso Corporal , Citocinas/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Mediadores da Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Óxido Nítrico/metabolismo , Superóxidos/metabolismo , Troponina T/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo , Função VentricularRESUMO
BACKGROUND: Lung ultrasound and echocardiography are mainly applied in critical care and emergency medicine. However, the diagnostic value of cardiopulmonary ultrasound in elderly patients with acute respiratory distress syndrome (ARDS) is still unclear. METHODS: Consecutive patients admitted to ICU with the diagnosis of suspected ARDS based on clinical grounds were enrolled. Cardiopulmonary ultrasound was performed as part of monitoring on day 1, day 2 and day 3. On each day a bedside ultrasound was performed to examine the lungs and calculate the Left Ventricular Ejection Fraction (LVEF). On day 3, a thoracic CT was performed on each patient as gold standard for ARDS imaging diagnosis. According to the results from CT scan, patients were grouped into ARDS group or Non-ARDS group. The relation between the cardiopulmonary ultrasound results on each day and the results of CT scan was analyzed. RESULTS: Fifty one consecutive patients aged from 73 to 97 years old were enrolled. Based on CT criteria, 33 patients were classified into the ARDS group, while 18 patients were included in non-ARDS group. There was no significant difference between the two groups in baseline characteristics, including gender, age, underlying disease, comorbidities, APACHE II score, SOFA score, and PaO2/FiO2 ratio (P > 0.05). Lung ultrasound (LUS) examination results were consistent with the CT scan results in diagnosis of pulmonary lesions. The Kappa values were 0.55, 0.74 and 0.82 on day 1, day 2 and day 3, respectively. The ROC analysis showed that the sensitivity, specificity and area under curve of ROC (AUROC) for lung ultrasound in diagnose ARDS were 0.788,0.778,0.783;0.909,0.833,0.871;0.970,0.833,0.902 on day 1, day 2 and day 3, respectively. However, cardiopulmonary ultrasound performed better in diagnosing ARDS in elderly patients. The sensitivity, specificity and AUROC were 0.879,0.889,0.924;0.939,0.889,0.961;and 0.970,0.833,0.956 on day 1, day 2 and day 3, respectively. The combined performances of cardiopulmonary ultrasound, N-terminal pro-brain natriuretic peptide (NT-proBNP), and PaO2/FiO2 ratio improved the specificity of the diagnosis of ARDS in elderly patients. CONCLUSIONS: LUS examination results were consistent with the CT scan results in diagnosis of pulmonary lesions. Cardiopulmonary ultrasound has a greater diagnostic accuracy in elderly patients with ARDS, compared with LUS alone. The combined performances of cardiopulmonary ultrasound, NT-proBNP, and PaO2/FiO2 increased the specificity of the diagnosis of ARDS in elderly patients.
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Coração/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Gasometria , Ecocardiografia , Feminino , Humanos , Pulmão/patologia , Masculino , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios XRESUMO
Circular RNAs (circRNAs) play important roles in many human diseases. However, their role in the development of severe sepsis, a condition that remains one of the main causes of death in intensive care units, has not yet been defined. In this study, we interrogated the molecular mechanisms of circRNAs in severe sepsis. We profiled the expression levels of 5,680 circRNAs in plasma extracted from blood samples of 9 severe sepsis cases or 9 controls (male, age 78 ± 7) using the Human circRNA Array. To enrich protein-coding genes hosting severe sepsis-related circRNAs, we conducted gene ontology and pathways analyses. Out of the identified 760 differentially expressed circRNAs, 404 were upregulated while 356 were downregulated (fold change [FC] ≥2 or ≤-2, and false discovery ratio <0.05). Circ-0008285 (located in exons of CDYL), showed significant upregulation in severe sepsis with an FC of 13.7, and Bonferroni-corrected P < 0.05/5. In silico analysis identified Circ-0008285 interacting microRNAs as well as protein-coding genes. We systematically investigated the differential expression pattern of circRNAs in severe sepsis. The circRNAs we identified might serve as potential biomarkers for diagnosis and prognosis of sepsis.
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Mouse models of myocardial ischemic preconditioning (IPC) and ischemic postconditioning (IPD) have proven to be very useful models of cardiovascular diseases. In 2010, Gao described a novel procedure without the aid of mechanical ventilation. However, the technique of heart externalization could not be applied to mouse models of IPC or IPD due to the limited time frame of the technique. We proposed a modified simple and safe method using lung recruitment and short-term ventilation to perform the procedure in mice with IPC or IPD. The mice were randomly divided into 4 groups: the modified groups, M-IPC and M-IPD, and the conventional groups, C-IPC and C-IPD. In the 2 modified groups, the mice were removed from the ventilator and allowed to resume breathing spontaneously upon completion of the lung recruitment and the rapid closure of the thorax. Our study demonstrated that the postoperative recovery time was significantly reduced for the modified groups compared with the 2 conventional groups. Moreover, the inflammatory damages were attenuated by the modified method compared with the conventional method. In addition, the modified method significantly increased the survival rates of mice with IPC or IPD. The modified method improved the survival rates of mouse models of myocardial ischemia.
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Modelos Animais de Doenças , Pós-Condicionamento Isquêmico/métodos , Precondicionamento Isquêmico Miocárdico/métodos , Isquemia Miocárdica/terapia , Animais , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/etiologia , Vasos Coronários , Incidência , Interleucina-6/sangue , Ligadura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/complicações , Isquemia Miocárdica/mortalidade , Isquemia Miocárdica/patologia , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Sepsis is associated with poor survival outcomes in patients with infective endocarditis (IE). However, the prognostic value of the Sepsis-1 and Sepsis-3 criteria of sepsis for IE patients is unclear. METHODS: A total of 1354 patients with IE was enrolled and classified into the sepsis and non-sepsis groups according to the Sepsis-1 and Sepsis-3. Multivariate regression analysis was performed to test the predictive performances of the Sepsis-1 and Sepsis-3 in assessing the risk of mortality in patients with IE. RESULTS: Sepsis was diagnosed in 347 (25.6%) patients according to the Sepsis-1 and 496 (36.6%) patients with the Sepsis-3. The in-hospital mortality rate was 11.5% in the Sepsis-1 group and 14.3% in the Sepsis-3 group. Kaplan-Meier survival curve analysis showed that both Sepsis-1 (Log-rank = 17.2, p < 0.001) and Sepsis-3 (Log-rank = 94.3, p < 0.001) were significantly associated with 6-month mortality. Multivariate regression analysis demonstrated that the Sepsis-3 was independently associated with the in-hospital mortality (odds ratio = 2.89, 95% CI 1.68-4.97, p < 0.001) and the 6-month mortality (hazard ratio = 3.24, 95% CI 2.08-5.04, p < 0.001). CONCLUSIONS: Sepsis-3 shows better predictive performance than Sepsis-1 criteria in assessing the risk of mortality in patients with IE.
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An apolipoprotein A-I mimetic peptide, D-4F, has been shown to improve vasodilation and inhibit atherosclerosis in hypercholesterolemic low-density lipoprotein receptor-null (LDLr(-/-)) mice. To study the metabolic variations of D-4F ininhibiting atherosclerosis, metabonomics, a novel system biological strategy to investigate the pathogenesis, was developed. Female LDLr(-/-) mice were fed a Western diet and injected with or without D-4F intraperitoneally. Atherosclerotic lesion formation was measured, whereas plasma metabolic profiling was obtained on the basis of ultra-high-performance liquid chromatography in tandem with time-of-flight mass spectrometry operating in both positive and negative ion modes. Data were processed by multivariate statistical analysis to graphically demonstrate metabolic changes. The partial least-squares discriminate analysis model was validated with cross-validation and permutation tests to ensure the model's reliability. D-4F significantly inhibited the formation of atherosclerosis in a time-dependent manner. The metabolic profiling was altered dramatically in hypercholesterolemic LDLr(-/-) mice, and a significant metabolic profiling change in response to D-4F treatment was observed in both positive and negative ion modes. Thirty-six significantly changed metabolites were identified as potential biomarkers. A series of phospholipid metabolites, including lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE), phosphatidylcholine (PC), phatidylethanolamine (PE), sphingomyelin (SM), and diacylglycerol (DG), particularly the long-chain LysoPC, was elevated dramatically in hypercholesterolemic LDLr(-/-) mice but reduced by D-4F in a time-dependent manner. Quantitative analysis of LysoPC, LysoPE, PC, and DG using HPLC was chosen to validate the variation of these potential biomarkers, and the results were consistent with the metabonomics findings. Our findings demonstrated that D-4F may inhibit atherosclerosis by regulating phospholipid metabolites specifically by decreasing plasma long-chain LysoPC.
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Apolipoproteína A-I/uso terapêutico , Aterosclerose/prevenção & controle , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Apolipoproteína A-I/administração & dosagem , Aterosclerose/etiologia , Biomarcadores/sangue , Biomarcadores/química , Cromatografia Líquida de Alta Pressão , Dieta Aterogênica/efeitos adversos , Feminino , Hipercolesterolemia/patologia , Hipercolesterolemia/fisiopatologia , Hipolipemiantes/administração & dosagem , Injeções Intraperitoneais , Lipídeos/química , Lisofosfatidilcolinas/sangue , Lisofosfatidilcolinas/química , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/prevenção & controle , Receptores de LDL/genética , Receptores de LDL/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Vasodilatadores/administração & dosagem , Vasodilatadores/uso terapêuticoRESUMO
OBJECTIVES: Hypernatremia often occurs in patients with brain death. This study summarizes its characteristics. METHODS: We recorded 57 patient's highest blood sodium value, as well as daily NT-proBNP, blood creatinine, and urine output. Further, we analyzed the time of the first rise in blood sodium, and the relationship between NT-proBNP, serum creatinine, urine output, and serum sodium. RESULTS: There was no hyponatremia in these patients, and only seven of the 53 patients registered blood sodium between 137 and 150 mmol/L. We found that blood sodium started to rise at 36.0 (28.5-52.3) h, reaching the highest value in 79.0 (54.0-126.0) h. Urine volume and creatinine have no correlation with serum sodium level, while NT-proBNP has a significant correlation with serum sodium level. CONCLUSION: It is necessary to conduct volume assessments and urine electrolyte testing on patients with brain death. BNP has a protective effect on water and electrolytes to prevent hypernatremia.
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Hipernatremia , Encéfalo , Morte Encefálica , Creatinina , Humanos , SódioRESUMO
BACKGROUND: The central venous-to-arterial carbon dioxide difference (Pcv-aCO2) is a biomarker for tissue perfusion, but the diagnostic value of Pcv-aCO2 in bacteria bloodstream infections (BSI) caused by gram-negative (GN) bacteria remains unclear. This study evaluated the expression levels and diagnostic value of Pcv-aCO2 and procalcitonin (PCT) in the early stages of GN bacteria BSI. METHODS: Patients with BSI admitted to the intensive care unit at Guangdong Provincial People's Hospital between August 2014 and August 2017 were enrolled. Pcv-aCO2 and PCT levels were evaluated in GN and gram-positive (GP) bacteria BSI patients. RESULTS: A total of 132 patients with BSI were enrolled. The Pcv-aCO2 (8.32 ± 3.59 vs 4.35 ± 2.24 mmHg p = 0.001) and PCT (30.62 ± 34.51 vs 4.92 ± 6.13 ng/ml p = 0.001) levels were significantly higher in the GN group than in the GP group. In the diagnosis of GN bacteria BSI, the area under the receiver operating characteristic curve (AUROC) for Pcv-aCO2 was 0.823 (95% confidence interval (CI): 0.746-0.900). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.90%, 88.00%, 74.07% and 78.21%, respectively. The AUROC for PCT was 0.818 (95% CI: 0.745-0.890). The sensitivity, specificity, PPV and NPV were 57.90%, 94.67%, 71.93% and 74.67%, respectively. CONCLUSIONS: Pcv-aCO2 and PCT have similar and high diagnostic value for the early diagnosis of BSI caused by GN bacteria.
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Bacteriemia , Infecções por Bactérias Gram-Negativas , Sepse , Humanos , Pró-Calcitonina , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/microbiologia , Curva ROC , Bactérias Gram-Negativas , Diagnóstico Precoce , Bactérias , Estudos Retrospectivos , Bacteriemia/diagnóstico , Bacteriemia/microbiologiaRESUMO
Therapeutic angiogenesis remains unsuccessful in coronary artery disease. It is known that plasma endothelium-derived microparticles (EMPs) are increased in coronary artery disease and that hypercholesterolemia can inhibit angiogenesis. We evaluated the relationship between EMPs and hypercholesterolemia in the impairment of angiogenesis. EMPs isolated from human umbilical vein endothelial cells were injected into low-density lipoprotein receptor-null (LDLr(-/-)) mice fed a Western diet for 2 wk and C57BL6 mice for 6 h or were directly added to the tissue culture media. Hearts isolated from mice were sectioned and cultured, and endothelial tube formation was measured. The expression and phosphorylation of endothelial NO synthase (eNOS) and the generation of NO in the hearts were determined. Angiogenesis was inhibited by pathophysiological concentrations of EMPs but not physiological concentrations of EMPs in hearts from C57BL6 mice. However, angiogenesis was inhibited by EMPs at both physiological and pathophysiological concentrations of EMPs in hearts from hypercholesterolemic LDLr(-/-) mice. Pathophysiological concentrations of EMPs decreased eNOS phosphorylation at Ser(1177) and NO generation without altering eNOS expression in hearts from C57BL6 mice. Both physiological and pathophysiological concentrations of EMPs decreased not only eNOS phosphorylation at Ser(1177) and NO generation, but eNOS expression in hypercholesterolemic hearts from LDLr(-/-) mice. These data demonstrated that pathophysiological concentrations of EMPs could inhibit angiogenesis in hearts by decreasing eNOS activity. EMPs and hypercholesterolemia mutually enhanced their inhibitory effect of angiogenesis by inducing eNOS dysfunction. Our findings suggest a novel mechanism by which hypercholesterolemia impairs angiogenesis.
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Micropartículas Derivadas de Células/fisiologia , Vasos Coronários/crescimento & desenvolvimento , Endotélio Vascular/citologia , Hipercolesterolemia/complicações , Neovascularização Fisiológica , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Células Cultivadas , Regulação para Baixo , Coração/fisiopatologia , Humanos , Hipercolesterolemia/patologia , Hipercolesterolemia/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Fisiológica/fisiologia , Receptores de LDL/genéticaRESUMO
circRNAs play important roles in regulating gene expression at both transcriptional and post transcriptional levels and involve in a variety of human diseases. But up to now, it is still unclear whether circRNAs are involved in the occurrence and development of sepsis induced acute respiratory distress syndrome (ARDS). In the present research, we collected lung tissues of sepsis induced ARDS patients (n = 3) and brain dead patients without ARDS (n = 3). From the results of genome-wide sequencing, a total of 272 significantly up-regulated and 231 significantly down-regulated circRNAs were obtained. Combining the previous sequencing results in the plasma of ARDS patients, 11 up-regulated and 3 down-regulated circRNAs simultaneously in plasma and lung tissues were identified. Pathway enrichment analysis showed that the co differentially expressed circRNAs might be involved in the regulation of ECM-receptor interaction and adherens junction etc. In conclusion, these data indicates that circRNAs may involve in the progression of sepsis induced ARDS.
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Encéfalo/metabolismo , Regulação da Expressão Gênica , Pulmão/metabolismo , RNA Circular , Síndrome do Desconforto Respiratório/metabolismo , Sepse/metabolismo , Junções Aderentes , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Perfilação da Expressão Gênica , Genoma Humano , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA , Transdução de Sinais/genética , TranscriptomaRESUMO
PURPOSE: The relationship between circulating selenium and diabetes mellitus (DM) remains inconsistent. Therefore, the relationship between circulating selenium and DM was investigated in the present study. PATIENTS AND METHODS: All participants (aged ≥18 years) were included from the National Health and Nutrition Examination Survey (NHANES) 1999-2006. Selenium concentrations from the fasting serum samples were determined using inductively coupled mass spectrometry, then grouped into quartiles. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multivariate logistic regression analysis and the results were stratified by age and sex. RESULTS: A total of 2,903 (61.9±13.7 years old) participants (49.3% males) were enrolled, and 580 (19.97%) of them had DM. The mean levels of selenium were 136.4±19.6 µg/L. Patients with DM (138.76±20.02 vs 135.88±19.44, P=0.002) had higher selenium levels compared to those without DM. The OR for DM was 1.12 (95% CI=1.01-1.24; P=0.0270) for each 10 µg/L increment in selenium, and subjects in the highest quartile of selenium levels (>147.00 uµg/L) had 2.82 (95% CI=1.55-5.11; P=0.0007) times higher risk of DM compared to the lowest quartile of selenium levels. Subgroup analysis showed that selenium was independently associated with DM only in female aged <65 years. CONCLUSION: Circulating selenium levels were positively associated with the odds of DM, but difference in sex and age.
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Previous studies have suggested the beneficial effects of vitamin C in patients with sepsis. However, the results could not be reproduced in the subsequent studies. This meta-analysis aimed to reevaluate the value of vitamin C treatment in patients with sepsis. Electronic databases were searched from inception to August 2019 for the studies comparing the effect of vitamin C versus non-vitamin C infusion in patients with sepsis. Data from 10 studies (4 randomized controlled trials [RCTs] and 6 retrospective studies) involving 1671 patients (495 in the vitamin C treatment group and 1176 in the control group) were included. The use of vitamin C did not reduce the risk of 28-day (OR = 0.84, P = 0.611, I2 = 56.3%), intensive care unit (ICU; OR = 0.79, P = 0.319, I2 = 46.2%), or in-hospital mortality (OR = 0.76, P = 0.251, I2 = 51.0%). No difference in the duration of vasopressor usage and the length of ICU or hospital stay was present. The subgroup analysis for two RCTs suggested that vitamin C treatment showed reduced 28-day mortality (OR = 0.22, P = 0.014, I2 = 35.7%), whereas this beneficial effect did not occur in subgroup analysis for three retrospective studies (OR = 1.11, P = 0.527, I2 = 0%). Retrospective meta-analysis could not reveal the beneficial effect of vitamin C on patients with sepsis. Therefore, in order to clarify the role of vitamin C in sepsis the high-quality RCTs will be required in the future study.
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Ácido Ascórbico/uso terapêutico , Sepse/tratamento farmacológico , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/mortalidade , Fatores de Tempo , Resultado do Tratamento , Vasoconstritores/uso terapêuticoRESUMO
In this work, an effective hybrid strategy was developed for tandem conversion of biomass to furfurylamine with tin-based solid acid Sn-Maifanitum stone and recombinant Escherichia coli whole cells harboring ω-transaminase. 90.3 mM furfural was obtained from corncob (75 g/L) at 170 °C for 0.5 h over Sn-Maifanitum stone catalyst (3.5 wt%) in the aqueous media (pH 1.0), which could be further bioconverted into furfurylamine at 74.0% yield (based on biomass-derived furfural) within 20.5 h. Finally, an efficient recycling and reuse of Sn-Maifanitum stone catalyst and immobilized Escherichia coli AT2018 whole-cell biocatalyst was developed for the synthesis of furfurylamine from biomass in the one-pot reaction system.
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Biomassa , Furanos/metabolismo , Biocatálise , Biotransformação , Escherichia coli/metabolismo , Concentração de Íons de Hidrogênio , TemperaturaRESUMO
Objective To prepare a monoclonal antibody (mAb) against human CD33 by immunizing mice with recombinant vector and analyze its characteristics and clinical application. Methods The eukaryotic expression vector pcDNA3.1(+)/CD33 was constructed and used to immunize mice. The mouse monoclonal antibody against human CD33 was then harvested using the hybridoma technique. Its properties were evaluated and the clinical performance was validated. Results One hybridoma cell line capable of secreting mouse anti-human CD33 monoclonal antibody was successfully obtained, which was named HI33a for clone identification with a subclass of IgG2a, κ. Flow Cytometry analysis revealed that the antibody could stain myeloid cell lines but not lymphoid cell lines, and it could inhibit the binding of similar imported antibodies with HL-60 cells competitively. Western blotting verified that it could bind a Mr 67 000 membrane protein extracted from HL-60 cells, which was a strong indication of the characteristics of CD33 protein molecule. Labeled with PE fluorescein, CD33-PE was tested as an antibody reagent in comparison with other similar imported products. Its overall performance including the accuracy, linearity, and precision all met the industrial standard. Further clinical evaluation of 558 bone marrow samples showed that the results were highly consistent with those by the imported reagents used as controls. Conclusion A hybridoma cell line stably secreting anti-human CD33 mAb was prepared.
Assuntos
Anticorpos Monoclonais/biossíntese , Hibridomas , Imunoglobulina G/biossíntese , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/antagonistas & inibidores , Animais , Especificidade de Anticorpos , Western Blotting , Humanos , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Background: The prognostic nutritional index (PNI) has been described as a simple risk-stratified tool for several diseases. We explored the predictive role of the PNI on coronavirus disease 2019 (COVID-19) severity. Methods: A total of 101 patients with COVID-19 were included in this retrospective study from January 2020 to March 2020. They were divided into two groups according to COVID-19 severity: non-critical (n = 56) and critical (n = 45). The PNI was calculated upon hospital admission: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm3). Critical COVID-19 was defined as having one of the following features: respiratory failure necessitating mechanical ventilation; shock; organ dysfunction necessitating admission to the intensive care unit (ICU). The correlation between the PNI with COVID-19 severity was analyzed. Results: The PNI was significantly lower in critically ill than that in non-critically ill patients (P < 0.001). The receiver operating characteristic curve indicated that the PNI was a good discrimination factor for identifying COVID-19 severity (P < 0.001). Multivariate logistic regression analysis showed the PNI to be an independent risk factor for critical illness due to COVID-19 (P = 0.002). Conclusions: The PNI is a valuable biomarker that could be used to discriminate COVID-19 severity.
RESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19)2 has emerged as a global pandemic. However, as effective treatments for this disease are still unclear, safe and efficient therapies are urgently needed. Qingfei Paidu decoction (QPD)3 is strongly recommended in the Chinese Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Provisional 6th Edition). However, clinical research data on the effects of QPD on COVID-19 are scarce. Our study aimed to explore the effects of combined treatment with QPD and Western medicine on COVID-19. METHODS: In this study, 63 patients with confirmed COVID-19 were analyzed. During the first 14 days of hospitalization, patients with deteriorating symptoms were administered QPD along with Western medicine therapy (the antiviral medicine selected from interferon, lopinavir, or arbidol). The clinical characteristics and blood laboratory indices (blood routine, inflammatory factors, and multi-organ biochemical indices) were examined, and the total lung severity scores were evaluated in each patient by reviewing chest computed tomography before treatment and at the end of treatment. RESULTS: Before QPD treatment, the combined treatment group showed higher blood C-reactive protein levels and more severe pulmonary inflammation and clinical symptoms than the Western medicine treatment group. Both groups met the discharge criteria after a similar length of hospitalization. At the end of treatment, circulating white blood cells, total lymphocyte count, and glutamic-oxaloacetic transaminase levels improved dramatically in both groups (Pâ¯<⯠0.05). In contrast, C-reactive protein, creatine kinase, creatine kinase-myocardial band, lactate dehydrogenase, and blood urea nitrogen levels were improved only in the combined treatment group (Pâ¯<⯠0.05), and C-reactive protein and creatine kinase were the most pronounced (Pâ¯<⯠0.01). Compared with baseline, at the end of treatment, the proportion of patients with normal values of C-reactive protein, total lymphocyte count, and lactate dehydrogenase were increased in the combined treatment group (P < 0.05), whereas no significant difference was observed in the Western medicine treatment group (Pâ¯>⯠0.05). CONCLUSION: The combination of QPD with Western medicine demonstrated significant anti-inflammatory effects compared with those of only Western medicine in patients with mild and moderate COVID-19; however, neither mortality nor length of hospitalization was affected. Moreover, the combined treatment tended to mitigate the extent of multi-organ impairment. Long-term randomized controlled trials with follow-up evaluations are required to confirm the results presented here.