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Small extracellular vesicles (sEV) derived from diverse natural killer (NK) cell lines have proven their exceptional antitumor activities. However, sEV from human primary NK cells, especially memory-like NK cells, are rarely utilized for cancer treatment. In this study, we obtained sEV from IL-12, IL-15 and IL-18 cultured human memory-like NK cells (mNK-sEV) that showed strong cytokine-secretory ability. It was uncovered that mNK-sEV entered cancer cells via macropinocytosis and induced cell apoptosis via caspase-dependent pathway. Compared to sEV from conventionally cultured NK cells (conNK-sEV), mNK-sEV inhibited tumor growth to a greater extent. Concomitantly, pharmacokinetics and biodistribution results validated a higher accumulation of mNK-sEV than conNK-sEV in tumors of xenografted murine models. Notably, elevated containment of granulysin (GNLY) within mNK-sEV, at least in part, may contribute to the enhanced therapeutic effect. Herein our results present that mNK-sEV can be a novel class of therapeutic reagent for effective cancer treatment.
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Apoptosis , Citocinas , Vesículas Extracelulares , Células Asesinas Naturales , Neoplasias , Animales , Vesículas Extracelulares/metabolismo , Humanos , Células Asesinas Naturales/efectos de los fármacos , Ratones , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Citocinas/metabolismo , Apoptosis/efectos de los fármacos , Distribución Tisular , Ensayos Antitumor por Modelo de Xenoinjerto , Pinocitosis/efectos de los fármacos , Femenino , Ratones Endogámicos BALB C , Antígenos de Diferenciación de Linfocitos TRESUMEN
Objective: To investigate the metabolic outcomes of primary aldosteronism (PA) patients receiving adrenalectomy (ADX) or spironolactone treatment and the contributing factors to the metabolic outcomes. Methods: The clinical data of 70 patients with aldosterone-producing adenoma (APA) and 86 patients with idiopathic hyperaldosteronism (IHA) were retrospectively analyzed. All subjects received confirmatory diagnosis of APA or IHA at the Department of Endocrinology and Metabolism, West China Hospital between March 2018 and October 2020. APA patients underwent ADX, while IHA patients were given spironolactone, a mineralocorticoid receptor antagonist (MRA). After ADX or spironolactone treatment, the outcomes of the metabolic indicators and the inter-group differences between the APA patients and IHA patients were studied. Results: There was no significant difference between the baseline data of the APA group and those of the IHA group in terms of age, sex, duration of hypertension, maximum systolic blood pressure (SBP-max), maximum diastolic blood pressure (DBP-max), body mass index (BMI), fasting blood glucose (FBG), lipid parameters, and renal function. IHA patients had higher waist circumference, serum potassium, and plasma renin activity (PRA) than those of the APA patients (all P<0.05). All patients showed significant improvement in blood pressure, blood potassium, and plasma aldosterone at follow-up. However, they also showed increased triglycerides (TG) accompanied by deterioration in renal function (P≤0.001). Multiple regression showed that TG levels were associated with spironolactone treatment for IHA patients and post-treatment BMI and creatinine levels. Furthermore, APA patients showed improvement in their FBG after ADX (P=0.041), while IHA patients showed elevated levels of FBG after spironolactone treatment (P=0.037). Conclusion: After treatment, PA patients still may experience abnormal lipid metabolism and deteriorating renal function. Spironolactone therapy may give rise to worse glucolipid metabolism than ADX therapy does.
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Hiperaldosteronismo , Hipertensión , Humanos , Espironolactona/uso terapéutico , Aldosterona , Hiperaldosteronismo/tratamiento farmacológico , Hiperaldosteronismo/cirugía , Hiperaldosteronismo/complicaciones , Adrenalectomía , Estudios Retrospectivos , PotasioRESUMEN
The pathogenesis of necrotizing enterocolitis (NEC) is severe inflammatory injury in preterm infants, which resulted from macrophage polarization. Nuclear factor-κB (NF-κB) is implicated to be involved in macrophage polarization. We here evaluated the essential role of NF-κB in macrophage polarization in NEC in human samples from neonates with NEC and the mouse experimental NEC model. Enhanced intestinal macrophage (IM) infiltration was presented in human neonates with NEC, the majority of which were M1 macrophages. Meanwhile, NF-κB was activated in the IMs in human NEC samples. NF-κB inhibition by BAY promoted the M1 to M2 macrophage polarization. Furthermore, glutaredoxin-1 (Grx1) deficiency promoted M2 polarization via NF-κB inactivation from the lipopolysaccharide-induced proinflammatory macrophages. The IMs isolated from Grx1- / - mice presented with decreases in total numbers and less macrophage differentiation. Grx1- / - derived IM were effective in the increased survival in experimental NEC through inflammation blocking. Our study provides evidence that NF-κB inactivation by Grx1 depletion contributed to the alleviation of NEC via inhibiting M1 macrophage polarization. The modulation to alternative macrophages in the intestines may provide a promising benefits for NEC treatment.
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Enterocolitis Necrotizante , FN-kappa B , Animales , Modelos Animales de Enfermedad , Enterocolitis Necrotizante/patología , Glutarredoxinas , Humanos , Recién Nacido , Recien Nacido Prematuro , Lipopolisacáridos/farmacología , Macrófagos/patología , RatonesRESUMEN
BACKGROUND: Management of primary aldosteronism (PA) has become a research hotspot in the field of endocrinology. To obtain reliable research evidence, it is necessary to establish a high-quality PA research database. METHODS: The establishment of PA research database involved two steps. Firstly, patients with confirmation of PA diagnosis between 1 Jan 2009 to 31 Aug 2019 at West China Hospital were identified and data were extracted. Secondly, patients with confirmatory testing for PA will be enrolled into a prospective cohort. Data will be prospectively collected based on the case report forms since 1 Sep 2019. We evaluated the quality of research database through assessment of quality of key variables. RESULTS: Totally, 862 patients diagnosed as PA were identified, of which 507 patients who had positive confirmatory testing for PA were included into the retrospective database. Among 862 patients diagnosed as PA, the mean systolic blood pressure (SBP) was 156.1 (21.7) mmHg, mean diastolic blood pressure (DBP) was 97.2 (14.5) mmHg. Among included patients, the mean serum potassium level was 2.85 (IQR, (2.47-3.36) mmol/L, and the mean plasma aldosterone concentration (PAC) was 28.1 (IQR, 20.0-40.4) ng/dL. The characteristics of patients with positive confirmatory testing for PA were similar. Validation of data extracting and linking showed the accuracy were 100%. Evaluation of missing data showed that the completeness of BMI (95.9%), SBP (99.4%) and DBP (99.4%) were high. CONCLUSION: Through integrating retrospective and prospective cohort of PA, a research database of PA with high quality and comprehensive data can be established. We anticipate that the research database will provide a high level of feasibility for management of PA in China.
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Investigación Biomédica/métodos , Bases de Datos Factuales , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/epidemiología , Adulto , Anciano , Investigación Biomédica/normas , Bases de Datos Factuales/normas , Femenino , Humanos , Hiperaldosteronismo/terapia , Masculino , Persona de Mediana Edad , Alta del Paciente/normas , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
OBJECTIVE: We prospectively investigated the accuracy of the seated saline suppression test (SSST) in 113 patients with hypertension (including 93 primary aldosteronism [PA] and 20 essential hypertension patients) in the Department of Endocrinology and Metabolism. METHODS: Each patient underwent a recumbent saline suppression test (RSST) and SSST. The accuracy of the SSST for a confirmative PA diagnosis and subtype classification was evaluated and compared with the RSST. RESULTS: The area under the receiver operating characteristic (ROC) curve of plasma aldosterone concentration (PAC) for the SSST was significantly greater than that for the RSST (0.945±0.0199 vs. 0.828 ± 0.0404; P<.05). The ROC analysis showed that the optimal PAC cut-off values were 12.94 ng/dL for the SSST (sensitivity 86.02%, specificity 95%; Youden index [YI] 0.810) and 12.04 ng/dL for the RSST (sensitivity 83.15%, specificity 57%; YI 0.401). The optimal PAC cut-off value for classifying aldosterone-producing adenoma and idiopathic hyperaldosteronism was 18.12 ng/dL for the SSST (sensitivity 73.5%, specificity 79.5%). No patients experienced adverse events during the SSST. CONCLUSION: The SSST is safe and convenient for PA diagnosis. The accuracy of the SSST for a confirmatory diagnosis of PA was better than that of the RSST. The SSST is a reliable alternative for PA confirmation in Chinese individuals. ABBREVIATIONS: APA = aldosterone-producing adenoma; ARR = aldosterone to renin ratio; AVS = adrenal vein sampling; CT = computed tomography; EH = essential hypertension; IHA = idiopathic hyperaldosteronism; MRI = magnetic resonance imaging; PA = primary aldosteronism; PAC = plasma aldosterone concentration; PRA = plasma renin activity; ROC = receiver operating characteristic; RSST = recumbent saline suppression test; SSST = seated saline suppression test; YI = Youden index.
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Adenoma Corticosuprarrenal , Hiperaldosteronismo , Hipertensión , Aldosterona , Pueblo Asiatico , Humanos , Hiperaldosteronismo/diagnóstico , Hipertensión/diagnóstico , ReninaRESUMEN
OBJECTIVE: To investigate the the feasibility and diagnostic efficiencyvalue of different screening indexesmethods for screening primary aldosteronism (PA). METHODS: The clinical data of 499 patients with PA and 479 patients with essential hypertension diagnosed from Jan. 2009 to Dec. 2018 were retrospectively analyzed. The diagnostic performance of different screening indexs was compared by plotting receiver operating characteristic curves (ROC). RESULTS: The area under the ROC curve ( AUC) of the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR) was greater than that of the ratio of the upright PAC to the angiotensin â ¡ (AT-â ¡) (AA2R), upright PRA, upright PAC, supine ARR, and lowest blood potassium ( P<0.05). The AUC of logistic regression model was greater than that of upright ARR (96.3% vs. 94.6%, P<0.05). There was no significant difference in AUC between decision tree model and upright ARR (94.1% vs. 94.6%, P>0.05). In the test set, the AUC difference between the logistic regression model and the decision tree model was not statistically significant (96.3% vs. 94.1%, P > 0.05). The calibration curve of the logistic regression model is closer to the 45 ° line, and the consistency between the prediction probability and the actual probability of the logistic regression model is better than that of the decision tree model. CONCLUSION: For the screening of PA, upright ARR seems to be the best single screening index, while AA2R (radioimmunoassay) is not recommended. The diagnostic efficacy of logistic regression model including upright PAC, PRA and lowest blood potassium is better than that of single upright ARR.
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Hiperaldosteronismo , Hipertensión , Aldosterona , Humanos , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/diagnóstico , Hipertensión/etiología , Renina , Estudios RetrospectivosRESUMEN
Hypoxic pulmonary vasoconstriction (HPV) can be modulated by Rho/Rho kinase signaling, which can alter HPV vascular function via regulating myosin light chain phosphorylation, in a manner generally believed to be Ca2+-independent. We hypothesized that the RhoA/ROCK signaling pathway also can regulate HPV vascular function via a Ca2+-dependent mechanism, signaling through the functional transient receptor potential canonical (TRPC) channels. In this study, male BALB/c mice were exposed to normoxic or 10% oxygen (hypoxic) conditions for six weeks, after which systolic pressure and right ventricular hypertrophy were assessed. Transient intracellular calcium was monitored using a fluorescence imaging system. Muscle tension was measured with a contractile force recording system, and protein expression was assessed by immunoblotting. We found that the expressions of RhoA and ROCK were increased in mouse pulmonary arteries (PAs) under conditions of chronic hypoxia. Inhibition of the RhoA/ROCK signaling pathway prevented the development of hypoxic pulmonary hypertension (HPH), as evidenced by significantly reduced PA remodeling and pulmonary vasoconstriction. Immunoblotting results revealed that inhibition of the RhoA/ROCK signaling pathway significantly decreased the expression of HIF-1α. Knockdown of HIF-1α down-regulated the expression and function of the TRPC1 and TRPC6 channels in PASMCs under conditions of hypoxia. Contraction of the PAs and a Ca2+ influx into PASMCs through either receptor- or store-operated Ca2+ channels were also increased after hypoxia. However, RhoA/ROCK inhibitors markedly attenuated these changes. These results indicate that inhibition of the RhoA/ROCK signaling pathway ameliorates HPH via HIF-1α-dependent functional TRPCs.
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1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , Amidas/farmacología , Antihipertensivos/farmacología , Presión Arterial/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Hipertensión Arterial Pulmonar/prevención & control , Piridinas/farmacología , Canales Catiónicos TRPC/metabolismo , Quinasas Asociadas a rho/antagonistas & inhibidores , Proteína de Unión al GTP rhoA/metabolismo , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , Animales , Señalización del Calcio , Línea Celular , Modelos Animales de Enfermedad , Hipoxia/complicaciones , Hipoxia/enzimología , Hipoxia/fisiopatología , Masculino , Ratones Endogámicos BALB C , Músculo Liso Vascular/enzimología , Músculo Liso Vascular/fisiopatología , Miocitos del Músculo Liso/enzimología , Hipertensión Arterial Pulmonar/enzimología , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/fisiopatología , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/enzimología , Arteria Pulmonar/fisiopatología , Canales Catiónicos TRPC/genética , Canal Catiónico TRPC6/genética , Canal Catiónico TRPC6/metabolismo , Vasoconstricción/efectos de los fármacos , Quinasas Asociadas a rho/metabolismo , Proteína de Unión al GTP rhoA/genéticaRESUMEN
Cardiac dysfunction is a vital complication during endotoxemia (ETM). Accumulating evidence suggests that enhanced glycolytic metabolism promotes inflammatory and myocardial diseases. In this study, we performed deep mRNA sequencing analysis on the hearts of control and lipopolysaccharide (LPS)-challenged mice (40â¯mg/kg, i.p.) and identified that the glycolytic enzyme, 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase 3 (PFKFB3) might play an indispensable role in ETM-induced cardiac damage. Quantitative real-time PCR validated the transcriptional upregulation of PFKFB3 in the myocardium of LPS-challenged mice and immunoblotting and immunostaining assays confirmed that LPS stimulation markedly increased the expression of PFKFB3 at the protein level both in vivo and in vitro. The potent antagonist 3-(3pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) was used to block PFKFB3 activity in vivo (50â¯mg/kg, i.p.) and in vitro (10⯵M). Echocardiographic analysis and TUNEL staining showed that 3PO significantly alleviated LPS-induced cardiac dysfunction and apoptotic injury in vivo. 3PO also suppressed the LPS-induced secretion of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6 and lactate in the serum, in addition to lactate in the myocardium. PFKFB3 inhibition also diminished the nuclear translocation and phosphorylation of transcription factor nuclear factor-κB (NF-κB) in both adult cardiomyocytes and HL-1 cells. Furthermore, immunoblotting analysis showed that 3PO inhibited LPS-induced apoptotic induction in cardiomyocytes. Taken together, these findings demonstrate that PFKFB3 participates in LPS-induced cardiac dysfunction via mediating inflammatory and apoptotic signaling pathway.
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Apoptosis , Endotoxemia/enzimología , Cardiopatías/enzimología , Mediadores de Inflamación/metabolismo , Miocitos Cardíacos/enzimología , Fosfofructoquinasa-2/metabolismo , Animales , Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Línea Celular , Modelos Animales de Enfermedad , Endotoxemia/inducido químicamente , Endotoxemia/patología , Endotoxemia/prevención & control , Inhibidores Enzimáticos/farmacología , Regulación Enzimológica de la Expresión Génica , Cardiopatías/inducido químicamente , Cardiopatías/patología , Cardiopatías/prevención & control , Lipopolisacáridos , Masculino , Ratones Endogámicos C57BL , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Fosfofructoquinasa-2/antagonistas & inhibidores , Fosfofructoquinasa-2/genética , Piridinas/farmacología , Transducción de SeñalRESUMEN
BACKGROUND/AIMS: CTLA-4 polymorphisms are associated with susceptibility to various cancers, but the results are often conflicting. Hence, we performed a comprehensive meta-analysis to quantitatively investigate the association between CTLA-4 polymorphisms (rs231775, rs4553808ï¼rs5742909, rs3087243 or rs733618) and cancer risk. METHODS: Data were collected from PubMed and Web of Science. A total of 67 case-control studies were selected for quantitative analysis. Stata (Version 12) software was used to calculate the odds ratio (OR) and 95% confidence interval (CI) to evaluate the strength of the associations. Subgroup meta-analysis was conducted based on ethnicity and cancer type. Heterogeneity tests, sensitivity analysis, and publication bias assessments were also performed. RESULTS: rs231775, rs4553808 and rs5742909 but not rs3087243 and rs733618 were significantly related to cancer risk. In analyses stratified by ethnicity, both rs231775 and rs4553808 were significant susceptibility polymorphisms in an Asian population but not in a Caucasian population. Moreover, there were stronger associations between the rs231775 polymorphism and increased risk of bone, breast, liver, head and neck and pancreatic cancers. Additionally, rs4553808 was associated with significantly increased susceptibility to breast cancer and head and neck cancer. CONCLUSION: rs231775, rs4553808 and rs5742909 may be used as predictive genetic biomarkers for cancer predisposition. Combined detection of CTLA-4 SNPs could be a useful tool for prediction of cancer susceptibility in clinical practice.
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Antígeno CTLA-4/genética , Neoplasias/genética , Polimorfismo de Nucleótido Simple , Pueblo Asiatico/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Neoplasias/epidemiología , Sesgo de Publicación , Población Blanca/genéticaRESUMEN
BACKGROUND/AIMS: Relevant markers of cancer stem cells (CSCs) may serve as commonly used biomarkers of ovarian cancer (OC). However, their actual clinicopathological and prognostic significance remains inconclusive. Thus, we conducted a meta-analysis to quantitatively evaluate the association between the expression of CSC-relevant markers (ALDH1, CD117, CD133, and CD44) and OC. METHODS: We used an odds ratio (OR) and a hazard ratio (HR) with a 95% confidence interval (CI) to estimate the effects by analyzing 52 studies from a literature search. Heterogeneity and sensitivity were evaluated, as well. Publication bias was assessed using funnel plots and Egger tests. RESULTS: ALDH1 expression was statistically associated with FIGO stage (OR=1.872, 95%CI=1.14-3.076, P=0.013) and lymph invasion (OR=2.78, 95%CI=1.08-7.152, P=0.034). CD117 expression was significantly associated with FIGO stage (OR=2.01, 95%CI=1.35-2.98, P=0.001). CD133 expression was correlated with FIGO stage (OR=3.410, 95%CI=2.196-5.294, P< 0.001) and differentiation grade (OR=2.672, 95%CI=1.354-5.272, P=0.005). CD44s was related to chemotherapy resistance (OR=3.218, 95%CI=1.148-9.016, P=0.026). Furthermore, overexpression of ALDH1 (HR=1.494, 95%CI=1.207-1.849, P< 0.001), CD117 (HR=1.395, 95%CI=1.025-1.898, P=0.034) or CD44s (HR=1.725, 95%CI=1.135-2.623, P=0.011) was associated with poor OS. Further, overexpression of both ALDH1 (HR=1.524, 95%CI=1.158-2.007, P=0.003) and CD44s (HR=2.12, 95%CI=1.692-2.657, P< 0.001) was correlated with worse DFS. CONCLUSION: CSC markers are useful predictive or prognostic biomarkers for OC in clinical assessments. Combined detection of CSC marker expression may be a powerful tool for prognostic predictions in clinical practice for patients with OC.
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Biomarcadores de Tumor/metabolismo , Células Madre Neoplásicas/metabolismo , Neoplasias Ováricas/patología , Antígeno AC133/genética , Antígeno AC133/metabolismo , Familia de Aldehído Deshidrogenasa 1 , Biomarcadores de Tumor/genética , Bases de Datos Factuales , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Femenino , Humanos , Receptores de Hialuranos/genética , Receptores de Hialuranos/metabolismo , Isoenzimas/genética , Isoenzimas/metabolismo , Oportunidad Relativa , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Retinal-Deshidrogenasa/genética , Retinal-Deshidrogenasa/metabolismo , Tasa de SupervivenciaRESUMEN
BACKGROUND: Atherosclerosis is characterized by chronic inflammation in vascular wall. Previous studies suggest that Kuwanon G (KWG) exerts anti-inflammatory activities. However, the effect of KWG on atherosclerosis remains unexplored. AIMS: To explore whether KWG affects macrophage foam cell formation in vitro and atherogenesis in vivo. METHODS: RAW 264.7 macrophages were stimulated with ox-LDL for 24h to induce foam cell formation and treated with KWG. Foam cell formation was determined by ORO staining and enzymatic analysis. Pro-inflammatory cytokines mRNA levels were tested by Real-time PCR method. Further molecular mechanism was investigated using Western blot. In vivo, ApoE-/- mice were fed with high-fat diet and intraperitoneally injected with KWG. Atherosclerotic lesion was accessed by H&E and ORO staining. Plaque composition was evaluated by immunohistochemistry and Sirius Red staining. Serum lipid profile and inflammatory cytokines were evaluated by enzymatic method and ELISA. RESULTS: KWG significantly decreased intracellular lipid accumulation and inflammatory cytokines mRNA levels in macrophages through enhancing LXRα-ABCA1/ABCG1 pathway and inhibiting NFκB activation. Administrated with KWG remarkably reduced the atherosclerotic lesion areas and macrophage content in the plaque of high-fat diet fed ApoE-/- mice. KWG also reduced hyperlipidemia and serum inflammatory cytokines in vivo. CONCLUSION: Taken together, these data highlight that KWG can attenuate atherosclerosis through inhibiting foam cell formation and inflammatory response.
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Transportador 1 de Casete de Unión a ATP/biosíntesis , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/biosíntesis , Aterosclerosis/metabolismo , Flavonoides/farmacología , Receptores X del Hígado/biosíntesis , Macrófagos/metabolismo , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Aterosclerosis/etiología , Aterosclerosis/prevención & control , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Dieta Alta en Grasa/efectos adversos , Relación Dosis-Respuesta a Droga , Flavonoides/uso terapéutico , Macrófagos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Células RAW 264.7 , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiologíaRESUMEN
OBJECTIVE: To compare two means of performing therapeutic plasma exchange (TPE) in patients with liver failure. METHOD: This open-label monocentric randomized trial, conducted in a single prestigious general healthcare facility, recruited liver failure patients with an indication to receive artificial liver support therapy for TPE. All patients underwent TPE procedures and were administered in a random sequence: heparin-free or systemic heparinization with unfractionated heparin. The primary endpoint was completion of TPE sessions, and the secondary endpoints included the safety and efficacy. RESULTS: In the period of the studying, there were 164 patients being recruited in and underwent total of 398 randomized TPEs: 168 with unfractionated heparin and 230 with heparin-free. In unfractionated heparin group, there were 3 cases (1.79%) being interrupted due to uncontrollable intraoperative pulmonary hemorrhages and gastrointestinal bleeding. In heparin-free group, 228 (99.13%) were completed successfully and 2 of them (0.87%) were switched from heparin-free to unfractionated heparin eventually. No significant differences were found between the two groups for either RRs or IRs (Pâ¯>â¯0.05). CONCLUSION: Heparin-free regimen is feasible and safer than systemic heparinization with unfractionated heparin in the process of TPEs in patients with liver failure.
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Fallo Hepático/terapia , Intercambio Plasmático/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Augmented reality (AR) technology is used to reconstruct three-dimensional (3D) images of hepatic and biliary structures from computed tomography and magnetic resonance imaging data, and to superimpose the virtual images onto a view of the surgical field. In liver surgery, these superimposed virtual images help the surgeon to visualize intrahepatic structures and therefore, to operate precisely and to improve clinical outcomes. DATA SOURCES: The keywords "augmented reality", "liver", "laparoscopic" and "hepatectomy" were used for searching publications in the PubMed database. The primary source of literatures was from peer-reviewed journals up to December 2016. Additional articles were identified by manual search of references found in the key articles. RESULTS: In general, AR technology mainly includes 3D reconstruction, display, registration as well as tracking techniques and has recently been adopted gradually for liver surgeries including laparoscopy and laparotomy with video-based AR assisted laparoscopic resection as the main technical application. By applying AR technology, blood vessels and tumor structures in the liver can be displayed during surgery, which permits precise navigation during complex surgical procedures. Liver transformation and registration errors during surgery were the main factors that limit the application of AR technology. CONCLUSIONS: With recent advances, AR technologies have the potential to improve hepatobiliary surgical procedures. However, additional clinical studies will be required to evaluate AR as a tool for reducing postoperative morbidity and mortality and for the improvement of long-term clinical outcomes. Future research is needed in the fusion of multiple imaging modalities, improving biomechanical liver modeling, and enhancing image data processing and tracking technologies to increase the accuracy of current AR methods.
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Enfermedades de las Vías Biliares/cirugía , Procedimientos Quirúrgicos del Sistema Biliar/métodos , Hepatectomía/métodos , Laparoscopía/métodos , Hepatopatías/cirugía , Modelación Específica para el Paciente , Procedimientos Quirúrgicos Robotizados/métodos , Enfermedades de las Vías Biliares/diagnóstico por imagen , Humanos , Imagenología Tridimensional , Hepatopatías/diagnóstico por imagen , Imagen por Resonancia Magnética , Interpretación de Imagen Radiográfica Asistida por Computador , Tomografía Computarizada por Rayos XRESUMEN
The biodegradation of nonylphenol (NP) and octylphenol (OP) isomers by laccase has attracted increasing concerns. However, the interaction mechanism between these isomers and laccase remains unclear, especially for fungal laccase. In this work, molecular docking was employed to study this issue. The results indicated that the structural characteristic of alkyl chain (position and branching degree) affected the interactions between Trametes versicolor (T. versicolor) laccase and isomers. The binding affinity between them was closely related to the position and branching degree of alkyl chain in isomers. The binding affinities between linear isomers and T. versicolor laccase were para-position < meta-position < ortho-position. For selected branched 4-NP, the isomers with bulky α-substituent in alkyl chain had higher binding affinities. In addition, hydrophobic contacts between T. versicolor laccase and NP or OP isomers were necessary, while H-bonds were optional. The isomers with similar structure may have more common residues involved in hydrophobic contacts. The H-bonds of selected NPs and OPs were all connected with phenolic hydroxyl. These findings provide an insight into detailed interaction mechanism between T. versicolor laccase and isomers of NP and OP. It is helpful to broaden the knowledge of degradation technology of NPs and OPs and provide theoretical basis on biological remediation of these contaminants.
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Basidiomycota/enzimología , Proteínas Fúngicas/química , Lacasa/química , Simulación del Acoplamiento Molecular , Fenoles/químicaRESUMEN
BACKGROUND: With rapid urbanization in China, an increasing number of rural adults have migrated to cities to seek job opportunities, leaving their school-aged children behind. These left-behind children (LBC) without one or both parents usually receive less attention from their caregivers. Whether the parental migration affects the children's oral health is not well understood. This study aimed to explore the differences in dental caries status and oral health-related behaviors between children with different parental migration experiences in a rural area of Southern China. METHODS: A cross-sectional study was conducted in Luchuan County of Guangxi Province in 2015. A total of 1085 school children aged 8-12 participated in this study. Participants' demographic characteristics, parental migration information, and eating and oral hygiene habits were collected using a self-administered questionnaire. Dental caries of permanent teeth was examined using the decayed, missing, and filled tooth (DMFT) index recommended by the World Health Organization. Dental caries experience and oral health-related behaviors were compared between LBC and non-LBC, as well as children with different experiences of parental migrations. The impact of various parental migration attributes on LBC oral health outcomes was examined by univariate and multivariate analyses. RESULTS: Among the school-aged children examined, 60.9% of them were LBC. Only 29.7% of the children brushed their teeth regularly; 86.5% of them did not know what fluoride toothpaste was. Caries prevalence was 51.4% for LBC and 40.8% for non-LBC (p < 0.001). The LBC experienced a greater DMFT mean (1.20 ± 1.59) compared to the non-LBC (0.85 ± 1.30) (p < 0.001). Oral health-related behaviors were not significantly different between LBC and non-LBC. Dental caries experience and oral health-related behaviors were not related to the type or duration of parental migration. Multiple regression analyses showed that parental migration was one of significant predictors of children's caries outcome; LBC had a higher risk to caries than non-LBC (95% CI =1.26, 2.09). CONCLUSIONS: These findings indicate that parental migration could be a significant risk factor for caries development among 8- to 12-year-old school children in rural China.
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Emigrantes e Inmigrantes , Salud Bucal/estadística & datos numéricos , Niño , China/epidemiología , Estudios Transversales , Caries Dental/epidemiología , Emigrantes e Inmigrantes/estadística & datos numéricos , Femenino , Humanos , Masculino , Higiene Bucal/estadística & datos numéricos , Padres , Factores de Riesgo , Población Rural/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
In order to explore the correlation between the medicinal propertiesï¼efficacy and application in the same genetic relationshipï¼explain the scientific connotation of the medicinal properties and effects of traditional Chinese medicines(TCM)ï¼promote the academic development of the theory of traditional Chinese medicinesï¼and provide reference for the research and development of the traditional Chinese medicines of a same genus. In this paper, a literature study of ancient and modern works of Chinese herbal medicine was conducted to investigate the correlation between the properties, meridians tropism, efficacy and application of Alpinia officinarumï¼ A. katsumadaiï¼ Galangae Fructus and Alpinae Oxyphyllae Fructus, four kinds of Alpinia Chinese medicinesï¼The results showed that the similar properties of these four kinds of Alpinia Chinese medicines included that they were acrid, warm,and mainly getting into the spleen and stomach channels; the similar efficacies included that dispelling coldï¼relieving painï¼warming stomachï¼anti-nauseaï¼anti-diarrhealï¼reinforcing spleen to promote digestion and other effects; in application aspects, the similarities were that they were all mainly used in treatment of catching cold or spleen deficiency induced by abdominal painï¼vomitingï¼diarrhea,diet indigestion, etc. indicating that phylogenetic relationship was closely related with the herbal properties, efficacy and application. It is an effective way to exploreï¼collate and research traditional Chinese medicine by using plant phylogenetic relationships in exploring the internal relations and laws of TCM theoriesï¼material bases, pharmacological effects and clinical applications, also with a strong maneuverability to explain their scientific connotation.
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Alpinia , Medicamentos Herbarios Chinos , Meridianos , Medicina Tradicional China , FilogeniaRESUMEN
The marriage of biology with nanomaterials has significantly accelerated advancement of biological techniques, profoundly facilitating practical applications in biomedical fields. With unique optical properties (e.g., tunable broad excitation, narrow emission spectra, robust photostability, and high quantum yield), fluorescent quantum dots (QDs) have been reasonably functionalized with controllable interfaces and extensively used as a new class of optical probe in biological researches. In this review, we summarize the recent progress in synthesis and properties of QDs. Moreover, we provide an overview of the outstanding potential of QDs for biomedical research and innovative methods of drug delivery. Specifically, the applications of QDs as novel fluorescent nanomaterials for biomedical sensing and imaging have been detailedly highlighted and discussed. In addition, recent concerns on potential toxicity of QDs are also introduced, ranging from cell researches to animal models.
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Cadmio/análisis , Nanoestructuras , Puntos Cuánticos/química , Puntos Cuánticos/toxicidad , Animales , Investigación Biomédica/métodos , Técnicas Biosensibles/métodos , Sistemas de Liberación de Medicamentos/métodos , Colorantes Fluorescentes , Imagen Molecular/métodos , Nanoestructuras/efectos adversos , Puntos Cuánticos/metabolismoRESUMEN
OBJECTIVE: To investigate the ethnic differences in osteoporosis (OP) and body composition (BC) and their relationship in the Maonan, Mulam, Hmong, and Yao minorities in China. DESIGN: A total of 860 Maonan, Mulam, Hmong, and Yao women were included in this cross-sectional study. Demographic, health history, and lifestyle information was collected using questionnaires. BC was measured through bioelectrical impedance analysis, and bone mineral density (BMD) was assessed via calcaneal quantitative ultrasound. RESULTS: Compared with premenopausal women, postmenopausal women exhibited a lower fat-free mass (FFM), muscle mass (MM), limb muscle mass, and T-score but a higher waist-to-hip ratio and prevalence of OP in each minority (p < .05). After adjustment for age, Hmong women displayed the highest body mass index, fat mass, percentage of body fat, visceral fat, and subcutaneous fat contents, while Yao women presented the highest T-scores and lowest prevalence of OP among the four minorities (p < .05). Having a greater number of children and an older age were significant risk factors for OP in all ethnic groups (p < .05, OR > 1). In addition, our results revealed that FFM and MM exhibited exactly the same weak positive relationship with the T-score (r = 0.081, p < .05) after adjusting for menopausal status and age in all of the participants. Furthermore, significant ethnic differences in the relationship between BC and the T-score existed in the four minorities studied here. CONCLUSIONS: BC and OP prevalence varied by menopausal status and ethnic group, and ethnic-specific relationships between BC and BMD were present in the four minorities. More research is needed to further investigate the ethnic differences in BC, OP, and risk factors for lower BMD to develop targeted prevention strategies to reduce the burden of OP across different ethnic groups in China.
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Composición Corporal , Etnicidad/estadística & datos numéricos , Osteoporosis/etnología , Posmenopausia , Premenopausia , Adulto , Factores de Edad , Anciano , Índice de Masa Corporal , China/epidemiología , Estudios Transversales , Femenino , Humanos , Grasa Intraabdominal , Persona de Mediana Edad , Músculo Esquelético , Osteoporosis/epidemiología , Paridad , Grasa Subcutánea , Encuestas y Cuestionarios , Relación Cintura-CaderaRESUMEN
Background: There are currently no uniform treatments for post-stroke comorbid cognitive impairment and depression (PSCCID). Objective: To verify whether repetitive transcranial magnetic stimulation (rTMS) can improve PSCCID symptoms and explore the underlying roles of resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Thirty PSCCID patients were randomized in a 1â:â1 ratio to receive 4 weeks of rTMS (intervention group) or sham rTMS (control group) over the left dorsolateral prefrontal cortex (DLPFC). rs-fMRI was acquired to analyze the functional plasticity of brain regions at baseline and immediately after the last intervention. Results: Cognition, depression status, and neural electrophysiology were improved in both intervention and control groups after treatment (pâ=â0.015-0.042), and the intervention group had more significant improvement than the control group. Analysis of functional connectivities (FCs) within the default mood network (DMN) showed that the connection strength of the left temporal pole/left parahippocampal cortex and right lateral temporal cortex/right retrosplenial cortex in the intervention group were enhanced compared with its pre-intervention and that in the control group after treatment (pâ<â0.05), and the both FC values were positively correlated with MMSE scores (pâ<â0.001). The intervention group had stronger FCs within the DMN compared with the control group after treatment, and some of the enhanced FCs were correlated with the P300 latency and amplitude. Conclusions: rTMS over the left DLPFC is an effective treatment for improving both cognitive impairment and depression among patients with PSCCID. The enhanced FCs within the DMN may serve as a compensatory functional recombination to promote clinical recovery.
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Disfunción Cognitiva , Depresión , Imagen por Resonancia Magnética , Accidente Cerebrovascular , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Femenino , Masculino , Disfunción Cognitiva/terapia , Disfunción Cognitiva/etiología , Persona de Mediana Edad , Depresión/terapia , Anciano , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/psicología , Accidente Cerebrovascular/terapia , Resultado del Tratamiento , Corteza Prefontal DorsolateralRESUMEN
Objective: The primary objective of this study was to scrutinise the disparities in the diversity, structure, and function of the oral microbiome among caries-free children from the Zhuang and Han ethnic groups with a focus on the influence of ethnically distinct oral health behaviours on the composition of the oral microbiota. Methods: A questionnaire survey was conducted to assess oral health behaviours and dental plaque samples were collected from 96 Zhuang and Han children aged 4-5 years living in Guangxi, southern China for high-throughput sequencing. PCR amplification was performed for sequencing of the V4 region of the 16S rDNA gene, and second-generation sequencing was performed using the Illumina MiSeq platform to compare and analyse the diversity, structure and function of the microbiota. Results: Single-factor analysis revealed significant differences between the Zhuang and Han ethnic groups regarding juice consumption, the frequency of consuming sugar-sweetened food or beverages before bedtime, the age that individuals started toothbrushing, the frequency of toothbrushing and the frequency of parental assistance with toothbrushing (p < 0.001). The dominant phyla were Proteobacteria, Firmicutes, etc., and the dominant genera included Streptococcus and Neisseria. The dental plaques of the caries-free Zhuang and Han ethnic groups had similar core microbiomes, with no significant differences in the diversity and structure of the microbiota and no significant differences in the abundance of the dominant genera. In addition, no significant difference in metabolic function was observed between the Zhuang and Han ethnic groups. Conclusion: The core oral microbiota was consistent in caries-free Zhuang and Han children. Despite differences in dietary habits and oral hygiene behaviours between the Zhuang and Han ethnic groups, with a high frequency of sugary food intake but better oral health behaviours in the Zhuang group, there were no significant differences in the diversity, structure and function of the oral microbiota of caries-free children in the Zhuang and Han ethnic groups.