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Design-based STEM learning is believed to be an effective cross-disciplinary strategy for promoting children's cognitive development. Yet, its impact on executive functions, particularly for disadvantaged children, still need to be explored. This study investigated the effects of short-term intensive design-based STEM learning on executive function among left-behind children. Sixty-one Grade 4 students from a school dedicated to the left-behind children in China were sampled and randomly assigned to an experimental group (10.70 ± 0.47 years old, n = 30) or a control group (10.77 ± 0.43 years old, n = 31). The experimental group underwent a two-week design-based STEM training program, while the control group participated in a 2-week STEM-related reading program. Both groups were assessed with the brain activation from 4 brain regions of interest using functional near-infrared spectroscopy (fNIRS) and behavioral measures during a Stroop task before and after the training. Analysis disclosed: (i) a significant within-group time effect in the experimental group, with posttest brain activation in Brodmann Area 10 and 46 being notably lower during neutral and word conditions; (ii) a significant between-group difference at posttest, with the experimental group showing considerably lower brain activation in Brodmann Area 10 and Brodmann Area 46 than the control group; and (iii) a significant task effect in brain activity among the three conditions of the Stroop task. These findings indicated that this STEM learning effectively enhanced executive function in left-behind children. The discrepancy between the non-significant differences in behavioral performance and the significant ones in brain activation implies a compensatory mechanism in brain activation. This study enriches current theories about the impact of Science, Technology, Engineering, and Mathematics (STEM) learning on children's executive function development, providing biological evidence and valuable insights for educational curriculum design and assessment.
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Función Ejecutiva , Aprendizaje , Espectroscopía Infrarroja Corta , Humanos , Función Ejecutiva/fisiología , Masculino , Femenino , Espectroscopía Infrarroja Corta/métodos , Niño , Aprendizaje/fisiología , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Lectura , Matemática , Test de Stroop , Lateralidad Funcional/fisiología , ChinaRESUMEN
Background and Aim: Acute-on-chronic liver failure (ACLF) has a high mortality rate. The role of granulocyte colony-stimulating factor (G-CSF) in ACLF remains controversial. Monocytes/macrophages are core immune cells, which are involved in the initiation and progression of liver failure; however, the effect of G-CSF on monocytes/macrophages is unclear. The study aimed to verify the clinical efficacy of G-CSF and explore the effect of it on monocytes in hepatitis B virus (HBV)-related ACLF (HBV-ACLF) paitents. Methods: We performed a large randomized controlled clinical trial for the treatment of HBV-ACLF using G-CSF. A total of 111 patients with HBV-ACLF were prospectively randomized into the G-CSF group (5 µg/kg G-CSF every day for 6 days, then every other day until day 18) or the control group (standard therapy). All participants were followed up for at least 180 days. The relationship between monocyte count and mortality risk was analyzed. The effect of G-CSF on the phenotype and function of monocytes from patients with HBV-ACLF was evaluated using flow cytometry in vivo and in vitro experiments. Results: The survival probability of the G-CSF group at 180 days was higher than that of the control group (72.2% vs. 53.8%, P = 0.0142). In the G-CSF-treated group, the monocyte counts on days 0 and 7 were independently associated with an evaluated mortality risk in the fully adjusted model (Model 3) [at day 0: hazard ratio (HR) 95% confidence interval (CI): 15.48 (3.60, 66.66), P = 0.0002; at day 7: HR (95% CI): 1.10 (0.50, 2.43), P=0.8080]. Further analysis showed that after treatment with G-CSF in HBV-ACLF patients, the expression of M1-like markers (HLA-DR and CD86) in monocytes decreased (HLA-DR: P = 0.0148; CD86: P = 0.0764). The expression of MerTK (M2-like marker) increased (P = 0.0002). The secretion of TNF-α, IL-6, and IL-10 from monocytes decreased without lipopolysaccharide (LPS) stimulation (TNF-α: P < 0.0001; IL-6: P= 0.0025; IL-10: P = 0.0004) or with LPS stimulation (TNF-α: P = 0.0439; P = 0.0611; IL-10: P = 0.0099). Similar effects were observed in vitro experiments. Conclusion: G-CSF therapy confers a survival benefit to patients with HBV-ACLF. G-CSF can promote the anti-inflammatory/pro-restorative phenotype (M2-like) transition of monocytes, which may contribute to the recovery of ACLF.Clinical Trial Registration Number: ClinicalTrials.gov, identifier (NCT02331745).
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Insuficiencia Hepática Crónica Agudizada , Insuficiencia Hepática Crónica Agudizada/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Antígenos HLA-DR , Virus de la Hepatitis B , Humanos , Interleucina-10 , Interleucina-6 , Lipopolisacáridos , Monocitos , Factor de Necrosis Tumoral alfaRESUMEN
BACKGROUND: Ankylosing spondylitis (AS) is a chronic progressive inflammatory disease that mainly affects the spine and sacroiliac joints. To the best of our knowledge, AS with acute myocardial infarction (AMI) has rarely been reported. Here, we report an unusual case of AS with AMI in a young patient. CASE SUMMARY: A 37-year-old man was admitted to the Department of Rheumatology and Immunology of our hospital on March 14, 2020, for low back pain. Further evaluation with clinical examinations, laboratory tests, and imaging resulted in a diagnosis of AS. Treatment with a non-steroidal anti-inflammatory drug and a tumor necrosis factor inhibitor partially improved his symptoms. However, his back pain persisted. After 6 wk of treatment, he was admitted to the emergency room of another hospital in this city for sudden-onset severe chest pain consistent with a diagnosis of AMI. Angiography revealed severe narrowing of the coronary arteries. Surgical placement of two coronary stents completely relieved his back pain. CONCLUSION: AS can cause cardiovascular diseases, including AMI. It is important to consider the cardiovascular risks in the management of AS.
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Gypenoside (GP), the main active ingredient of Gynostemma pentaphyllum, possesses a variety of pharmacological capacities including anti-inflammation, anti-oxidation, and anti-tumor. However, the effects of GP on IL-1ß-stimulated human osteoarthritis (OA) chondrocytes are still unknown. Therefore, this study aimed to investigate the anti-inflammatory effects of GP on IL-1ß-stimulated human OA chondrocytes and explore the possible mechanism. Our results showed that GP dose-dependently inhibited IL-1ß-induced NO and PGE2 production in human OA chondrocytes. In addition, treatment of GP inhibited the expression of MMP3 and MMP13, which was increased by IL-1ß. Finally, we found that pretreatment of GP obviously suppressed NF-κB activation in IL-1ß-stimulated human OA chondrocytes. Taken together, the results demonstrated that GP has chondro-protective effects, at least in part, through inhibiting the activation of NF-κB signaling pathway in human OA chondrocytes. Thus, these findings suggest that GP may be considered as an alternative therapeutic agent for the management of OA patients.
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Condrocitos/metabolismo , Interleucina-1beta/metabolismo , Osteoartritis/metabolismo , Transducción de Señal/efectos de los fármacos , Anciano , Células Cultivadas , Condrocitos/patología , Femenino , Gynostemma , Humanos , Inflamación/metabolismo , Inflamación/patología , Masculino , Metaloproteinasa 13 de la Matriz/biosíntesis , Metaloproteinasa 3 de la Matriz/biosíntesis , Persona de Mediana Edad , FN-kappa B/metabolismo , Osteoartritis/patología , Extractos Vegetales/farmacologíaRESUMEN
Liver failure is a life-threatened serious disease with many complications and high mortality rate. Stem cells have been applied to replacement therapy, gene therapy and tissue engineering for its capacity of self-renewal and multi-lineage differentiation. To investigate the bioactivity of the peripheral blood hematopoietic stem cells (PBHSC) in patients with acute-on-chronic liver failure, we isolated CD34+ cells from peripheral blood of patients with acute-on-chronic liver failure and healthy controls. After cultured it in serum-free medium (SFEM), we studied the bioactivity of CD34+ cells by observing the morphology, recording growth curve, detecting cell cycle and cell apoptosis. CD34+ cells and culture solution were collected at the time points of 3, 5, 7, 10, 12 and 14 days, and the levels of hepatocyte growth factor (HGF), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in culture solution were detected by ELISA. Also, the expressions of pyruvate kinase muscle isoenzyme 2 (PKM2), integrin-ß1 and liver-type pyruvate kinase (LPK) were detected by RT-PCR and immunofluorescence. Our results showed the bioactivity of CD34+ cells from patients with acute-on-chronic liver failure was identified to be similar with that from healthy controls. HGF, MMP-9, TNF-α and IL-6 were found in cell culture medium. RT-PCR and immunofluorescence results indicated that PKM2, Integrin-ß1 expressed on CD34+ cells from patients with acute-on-chronic liver failure. In conclusion, bioactivity of CD34+ cells of patients with acute-on-chronic liver failure was demonstrated to be normal, which could secrete HGF, MMP-9, TNF-α and IL-6, promote the growth of hepatocytes, and differentiate along a direction to hepatocyte lineage.
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BACKGROUND AND AIMS: Acute kidney injury (AKI) is a life-threatening complication in patients with acute-on-chronic liver failure (ACLF) of underlying cirrhosis. However, the characteristics of AKI in these patients have not been clarified. Our aim was to determine the incidence and risk factors of AKI and the association between AKI severity and 180-day transplant-free survival. METHODS: We performed a retrospective cohort analysis of patients with ACLF of underlying cirrhosis in a single center from January 2009 through December 2014. AKI was defined by the criteria proposed by International Club of Ascites (ICA). The incidence and risk factors of AKI development and its relationship to 180-day transplant-free survival rates were evaluated. RESULTS: Of 1032 patients with ACLF of underlying cirrhosis, 121 (11.72 %) had AKI at admission, and 319 (30.9 %) developed AKI during hospitalization. We established a logistic regression model including four independent factors with AKI development: MELD score [odds ratio (OR), 1.1; 95 % confidence interval (CI), 1.07-1.14], presence of ascites (OR, 3.80; 95 % CI, 2.13-6.78), sepsis/infection (OR, 2.25; 95 % CI, 1.66-3.03) and acute variceal bleed (OR, 1.78; 95 % CI, 1.00-3.19). The area under receiver operating characteristics of the model in internal and external validations were 0.95 and 0.85, respectively. Patients with mild-A AKI had a higher 180-day transplant-free survival rate (23.8 %) than patients with mild-B AKI (19.0 %) or marked AKI (5.9 %) (all p < 0.001). AKI patients with a peak value of sCr <1.5 mg/dl had higher 180-day transplant-free survival rates compared to those with a peak value of sCr â§1.5 mg/dl (23.8 % vs. 14.7 %, p < 0.001). CONCLUSIONS: We developed a clinical risk model for predicting development of AKI with great accuracy. Combining the ICA-AKI criteria and the peak value of sCr with 1.5 mg/dl provides a good prognostic method for patients with ACLF of underlying cirrhosis.
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Lesión Renal Aguda/epidemiología , Insuficiencia Hepática Crónica Agudizada/epidemiología , Cirrosis Hepática/epidemiología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/mortalidad , Insuficiencia Hepática Crónica Agudizada/complicaciones , Adulto , China/epidemiología , Estudios de Cohortes , Femenino , Humanos , Incidencia , Trasplante de Riñón/estadística & datos numéricos , Cirrosis Hepática/complicaciones , Modelos Logísticos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
The aim of this study was to investigate the differentiation potential of induced pluripotent stem cells (iPSCs) derived from human foreskin fibroblasts (HFFs) into hepatocyte-like cells (HLCs). The iPSCs were firstly induced by transduction of OCT4, SOX2, KLF4, and c-MYC into HFFs using retrovirus. Afterwards, expressions of pluripotency factors were identified by semiquantitative reverse transcription-polymerase chain reaction and immunofluorescence staining, and karyotype, embryoid, and teratoma were observed by microscope. Then, iPSCs were gradually differentiated into endoderm cells, hepatic progenitor cells, and mature HLCs by special culture medium. During this process, differentiation efficiency into each kind of cells was evaluated by detecting SOX17, HNF4a, and ALB using flow cytometry, respectively. Besides, enzyme-linked immunosorbent assay was conducted to detect the secretion of ALB in iPSC-induced HLCs and quantitative reverse transcription-polymerase chain reaction was performed to detect the expression levels of hepatocyte-specific genes. The iPSCs were successfully induced by HFFs, which exhibited typical embryonic stem cells morphology, positive alkaline phosphatase staining, normal diploid karyotype, and positive expression of various pluripotency factors. Meanwhile, spherical embryoid and teratoma with 3 germ layers were formed by iPSCs. The iPSCs were consecutively induced into endoderm cells, hepatic progenitor cells and mature HLCs, and the differentiation efficiency was 55.7 ± 2.9%, 45.7 ± 4.8%, and 35.0 ± 3.9%, respectively. Besides, the secretion of ALB and expression of various hepatocyte-specific genes was highly detected in iPSC-induced HLCs. The iPSCs were successfully derived from HFFs and then differentiated into HLCs, which proved a new source for hepatocyte transplantation. HIGHLIGHTS: HFFs were successfully induced into iPSCs by transduction of OCT4, SOX2, KLF4, and c-MYC. Positive expressions of various pluripotency factors were exhibited in HFFs-induced iPSCs. The iPSCs were consecutively induced into endoderm cells, hepatic progenitor cells, and mature HLCs. Various hepatocyte-specific genes were highly expressed in iPSC-induced HLCs.
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Diferenciación Celular , Fibroblastos/citología , Prepucio/citología , Hepatocitos/citología , Células Madre Pluripotentes Inducidas/citología , Albúminas/metabolismo , Cuerpos Embrioides/citología , Fibroblastos/metabolismo , Técnica del Anticuerpo Fluorescente , Regulación de la Expresión Génica , Hepatocitos/metabolismo , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Cariotipificación , Factor 4 Similar a Kruppel , MasculinoRESUMEN
BACKGROUND: Hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) refers to acute deterioration occurring in patients with chronic hepatitis B infected liver diseases. An abnormality in NK cells mediated cellular immunity is believed to be a contributing factor. We aimed to evaluate the characteristic of NK cells in the peripheral blood of HBV related ACLF. METHODS: Flow cytometric method was used to detect the absolute numbers and subgroups of NK cells, and analyze the cytotoxicity and killing ability of NK cells in patients with HBV-ACLF. RESULTS: The results showed that peripheral numbers of NK cells were decreased in patients with HBV-ACLF, but not statistically significant. The cytotoxic CD56dimCD16bright NK cells were significantly decreased in HBV infected patients, especially ACLF patients. The CD56brightCD16- subgroup was expanded in patients with CHB and the CD56dimCD16- subgroup was expanded in patients with ACLF. The activating receptors of NKG2D, NKp30, NKp44, and NKp46 were increased in patients with ACLF. The inhibitory receptors of CD158a were increased, though the CD158b was decreased in patients of ACLF. The function of NK cells including cytotoxicity and killing activity were both downregulated in patients with ACLF and CHB. Even if after IL-12/15 stimulation, INF-γ and TNF-α produced by patients with ACLF were still less than those produced by healthy controls. CONCLUSIONS: Patients with HBV-ACLF had lower numbers and decreased functions of cytotoxic NK cells.
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Insuficiencia Hepática Crónica Agudizada/metabolismo , Insuficiencia Hepática Crónica Agudizada/virología , Hepatitis B Crónica/complicaciones , Células Asesinas Naturales/metabolismo , Adulto , Anciano , Antígeno CD56/metabolismo , Regulación hacia Abajo , Femenino , Citometría de Flujo , Virus de la Hepatitis B , Humanos , Interferón gamma/metabolismo , Masculino , Persona de Mediana Edad , Receptores de IgG/metabolismo , Receptores Gatillantes de la Citotoxidad Natural/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Adulto JovenRESUMEN
BACKGROUND AND AIMS: The role of NK cells on inducing liver injury in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) is not well understood. The aim of this study was to determine the cytotoxicity of tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-expressed NK cells from HBV-ACLF patients and facilitate a better understanding of the immune pathogenesis of HBV-ACLF. METHODS: Peripheral blood samples were obtained from HBV-ACLF patients, mild chronic hepatitis B (CHB) patients and healthy controls (HC). Circulating NK cells phenotype was determined using flow cytometry. Serum cytokine concentrations were ascertained using the CBA Inflammation kit. Cell apoptosis was analyzed using the FITC-annexin V Apoptosis Detection Kit. RESULTS: Peripheral NK cells from HBV-ACLF expressed higher levels of TRAIL than those from CHB and HC. Expression of TRAIL on NK cells was correlated positively with serum IL-6 and IL-8 concentrations in HBV-ACLF patients, which is further confirmed by cytokines stimulation in vitro. NK cells caused a significant increase of apoptotic hepatocytes, and further increased the frequency of apoptosis in IL-6 and IL8-stimulated hepatocytes; the apoptosis was then inhibited partially by an anti-TRAIL monoclonal antibody. CONCLUSION: These results suggested that inflammation cytokines elevated in patients with HBV-ACLF may promote NK cell mediated cytotoxicity through TRAIL pathway.
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Insuficiencia Hepática Crónica Agudizada/sangre , Citotoxicidad Inmunológica , Hepatitis B Crónica/sangre , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Insuficiencia Hepática Crónica Agudizada/virología , Adulto , Anticuerpos Monoclonales/farmacología , Apoptosis , Estudios de Casos y Controles , Caspasas/metabolismo , Línea Celular , Técnicas de Cocultivo , Femenino , Hepatitis B Crónica/complicaciones , Hepatocitos/fisiología , Humanos , Interleucina-6/sangre , Interleucina-6/farmacología , Interleucina-8/sangre , Interleucina-8/farmacología , Células Asesinas Naturales/efectos de los fármacos , Leucocitos Mononucleares/efectos de los fármacos , Masculino , Persona de Mediana Edad , Fenotipo , Transducción de Señal , Ligando Inductor de Apoptosis Relacionado con TNF/antagonistas & inhibidoresRESUMEN
UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: To investigate thyroid function in patients with acute-on-chronic liver failure (ACLF) caused by hepatitis B virus infection and to determine whether thyroid hormone levels can be used as prognostic markers for assessing severity and prognosis of ACLF patients. We enrolled 75 patients with ACLF and70 patients with chronic hepatitis B (CHB). Continual serum samples were collected during hospitalization from the ACLF patients. The serum thyroid hormone levels (triiodothyronine [T3], thyroxine [T4], free (F)-T3, FT4, and thyroid stimulation hormone [TSH]) were measured by chemiluminescence. The Model for End-stage Liver Disease (MELD) score was used to assess severity. RESULTS: ACLF patients showed significantly (p < 0.001) lower values of serum T3, T4, FT3/FT4 and TSH than CHB patients. The T3, T4, and TSH levels in ACLF patients were negatively correlated with the MELD score (T3: r = -0.495, p < 0.001; T4: r = -0.281, p < 0.001; TSH: r = -0.498, p < 0.001), suggesting that serum thyroid hormone levels reflect disease severity. At 1 year, 31 patients died. The T3 (p = 0.016), T4 (p = 0.008), and TSH (p = 0.003) levels in non-survivors were significantly lower than in survivors. The serum TSH level was a significant factor for predicting mortality in ACLF patients (optimal cutoff value = 0.38 IU/mL). The cumulative survival rate was decreased significantly when the serum TSH level was < 0.38 IU/mL (39.2%, p < 0.001). CONCLUSION: Serum TSH level may be a useful indicator for assessing severity and prognosis in ACLF patients.
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Insuficiencia Hepática Crónica Agudizada/sangre , Tirotropina/sangre , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/mortalidad , Insuficiencia Hepática Crónica Agudizada/virología , Adulto , Área Bajo la Curva , Biomarcadores/sangre , Femenino , Estado de Salud , Indicadores de Salud , Hepatitis B/complicaciones , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Índice de Severidad de la Enfermedad , Tiroxina/sangre , Triyodotironina/sangreRESUMEN
BACKGROUND & AIMS: HBV-related acute-on-chronic liver failure (HBV-ACLF) is a severe liver disease which results in a high mortality in China. To early predict the prognosis of the patients may prevent the complications and improve the survival. This study was aimed to develop a new prognostic index to estimate the survival related to HBV-ACLF. METHODS: Consecutive patients with HBV-ACLF were included in a prospective observational study. Serum Cystatin C concentrations were measured by using the particle-enhanced immunonephelometry assay. All of the patients were followed for at least 3 months. Cox regression analysis was carried out to identify which factors were predictive of mortality. The area under the receiver operating characteristic curve (AUC) was used to evaluate the efficacy of the variates for early predicting mortality. RESULTS: Seventy-two patients with HBV-ACLF were recruited between January 2012 and January 2013. Thirty patients died (41.7%) during 3-months followed up. Cox multivariate regression analysis identified serum cystatin C (CysC) and total bilirubin (TBil) were independent factors significantly (P < 0.01) associated with survival. Our results further showed that new prognostic index (PI) combining serum CysC with TBil was a good indicator for predicting the mortality of patients with HBV-ACLF. Specifically, the PI had a higher accuracy than the CTP, MELD, or MELD-Na scoring for early prediction short-term survival of HBV-ACLF patients with normal levels of serum creatinine (Cr). The survival rate in low risk group (PI < 3.91) was 94.3%, which was markedly higher than those in the high-risk group (PI ≥ 3.91) (17.4%, P < 0.001). CONCLUSION: We developed a new prognostic index combining serum CysC with TBil which early predicted the short-term mortality of HBV-ACLF patients.
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Insuficiencia Hepática Crónica Agudizada/etiología , Insuficiencia Hepática Crónica Agudizada/mortalidad , Bilirrubina/sangre , Cistatina C/sangre , Hepatitis B/sangre , Hepatitis B/complicaciones , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Causas de Muerte , Femenino , Estudios de Seguimiento , Hepatitis B/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Curva ROC , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
BACKGROUND: To develop a relatively simple and effective and low-risk operation, aortic root wrapped procedure, to treat aortic root aneurysm or ectasia. METHODS: From June 2008 to September 2010, 15 patients were accepted for aortic root wrapped angioplasty procedure, Marfan's syndrome with aortic root ectasia in 2 cases, and aortic sinus aneurysm with middle to severe aortic valve stenosis and/or regurgitation in 13 cases. The diameter of aortic valve annulus was 25.43 ± 2.34 mm (range = 22-32 mm) and the diameter of aortic sinus was 50.45 ± 7.32 mm (range = 45-60 mm). All patients underwent aortic root wrapped angioplasty procedures with artificial blood vessel combined with aortic valve plasty or replacement with tissue valve prosthesis. RESULTS: Fifteen patients survived well, and the perioperative mortality was 0%. Cardiopulmonary bypass time was 82.31 ± 16.34 minutes (range = 55-128 minutes). Predischarge echocardiography check result showed trace aortic regurgitation in 3 cases and normal aortic valve function in 12 cases. Compared with preoperative echocardiography results, the aortic annulus diameter (22.63 ± 1.25 mm [range = 21-25 mm]) decreased significantly (P < .01) and the aortic sinus diameter (36.86 ± 7.41 mm [range = 30-41 mm]) decreased significantly (P < .001). Follow-up results: All 15 patients survived well, and heart function (New York Heart Association classification) of the patients are all class I. The late mortality was 0%. CONCLUSION: Aortic root wrapped procedures combined with aortic valve plastic or replacement operation is an alternative surgical procedure in patients with aortic sinus aneurysm and aortic valve disease.
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Angioplastia/métodos , Aneurisma de la Aorta/cirugía , Implantación de Prótesis Vascular/métodos , Seno Aórtico/cirugía , Adolescente , Adulto , Angioplastia/mortalidad , Angioplastia/estadística & datos numéricos , Aneurisma de la Aorta/diagnóstico por imagen , Implantación de Prótesis Vascular/mortalidad , Implantación de Prótesis Vascular/estadística & datos numéricos , Niño , Ecocardiografía , Femenino , Humanos , Masculino , Síndrome de Marfan , Persona de Mediana Edad , Seno Aórtico/diagnóstico por imagen , Adulto JovenRESUMEN
With cancer being a major cause of death worldwide, microRNAs (miRNAs) have been investigated as novel and non-invasive biomarkers for cancer diagnosis. Recently, microRNA-21 (miR-21) attracts much attention for its aberrant expression and has been widely studied in various cancers. However, the inconsistent results from studies make it hard to evaluate the diagnostic value of miR-21 in cancer diagnosis, which lead us to conduct this meta-analysis. We conducted a comprehensive literature search in the Medline, Embase, PubMed, CNKI, and Web of Science before July 1, 2014. STATA 12.0 software was used for calculation and statistical analysis. The pooled sensitivity, specificity, positive and negative likelihood ratio (PLR, NLR), and diagnostic odds ratio (DOR) were used to assess the diagnostic performance of miR-21 for cancers. Seventy-three studies in 60 articles were involved in this meta-analysis, with a total of 4684 patients with cancer and 3108 controls. The overall parameters were calculated from all the included studies: sensitivity of 0.78 (95% confidence interval (CI) 0.74-0.81), specificity of 0.83 (95% CI 0.80-0.86), PLR of 4.5 (95% CI 3.8-5.4), NLR of 0.27 (95% CI 0.23-0.32); DOR of 17 (95% CI 12-23), and area under the curve (AUC) of 0.88 (95% CI 0.84-0.90). In addition, we performed subgroup analyses based on ethnicity, cancer types, and sample types. Results from subgroup analysis showed that cancer types and sample types were the sources of heterogeneity in our meta-analysis. The overall diagnostic value of miR-21 is not very high for cancer diagnosis; however, it is affected significantly by the types of cancer and specimen. MiR-21 has a relatively high diagnostic value for detecting breast cancer, and miR-21 assays based on plasma, serum, and tissue achieved relatively higher accuracy.
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Biomarcadores de Tumor/genética , MicroARNs/genética , Neoplasias/diagnóstico , Neoplasias/genética , Anciano , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To explore the function of the baseline model for end-stage liver disease (MELD) scores, MELD-Na scores and iMELD scores in short-term prognosis in the initial treatment of hepatitis B virus (HBV) related acute-on-chronic liver failure (ACLF) patients. METHODS: 232 HBV-related ACLF patients who received initial treatment in 302 Military Hospital of China from January 2011 to January 2013 were enrolled in this prospective clinical follow-up. The relationship between the baseline MELD scores, MELD-Na scores, iMELD scores and clinical outcomes were analyzed, and the value of these three models for short term prognosis was assessed. RESULTS: Finally the 12-week clinical follow-up was completed in 191 patients, with the completion rate of 82.33%. Eighty-five patients died, with the fatality rate of 44.50%. Compared with the survival group, in non-survival group, the baseline of MELD scores (26.65 ± 7.75 vs. 21.19 ± 5.42, t=-5.720, P=0.000), MELD-Na scores (29.16 ± 11.35 vs. 21.72 ± 6.33, t=-5.729, P=0.000), iMELD scores (47.19 ± 10.96 vs. 38.02 ± 7.01, t=-7.011, P=0.000), total bilirubin (TBil: 374.3 ± 150.1 µmol/L vs. 305.5 ± 147.1 µmol/L, t=-3.182, P=0.002), creatinine (Cr: 110.7 ± 90.1 µmol/L vs. 71.1 ± 35.1 µmol/L, t=-4.157, P=0.000) and international normalized ratio (INR: 2.3 ± 0.9 vs. 2.0 ± 0.6, t=-2.754, P=0.006) were significantly increased, but the baseline of serum Na⺠(132.8 ± 6.1 mmol/L vs. 136.7 ± 5.1 mmol/L, t=4.861, P=0.000) was significantly lowered. It was shown by Spearman correlation analysis that the baseline MELD scores, MELD-Na scores and iMELD scores all had positive correlation with the short-term prognosis of patients (r value was 0.398, 0.404, and 0.470, respectively, all P=0.000), the baseline of serum Na⺠had a negative correlation with the short-term prognosis of patients (r=-0.365, P=0.000). It was shown by receiver operating characteristic curve (ROC curve) that the cut-off scores of the baseline of MELD scores, MELD-Na scores and iMELD scores were 25.07, 25.43 and 43.11 respectively, and the area under ROC curve (AUC) of the baseline of MELD scores, MELD-Na scores and iMELD scores were 0.731, 0.735 and 0.773, respectively. The sensitivity of the three models was 55.3%, 57.7%, 63.5%, and the specificity was 84.9%, 84.0%, 84.9% respectively. The value of the three models had no difference in short-term prognostic prediction. According to the respective cut-off score, the three prediction models were divided into four groups, and all of them had differences in fatality rate on the whole (χ² for MELD scores was 34.740, P=0.000; χ² for MELD-Na scores was 36.861, P=0.000; χ² for iMELD scores was 50.127, P=0.000). The mortality was elevated gradually as the equation scores increased. CONCLUSIONS: The baseline of MELD scores, MELD-Na scores and iMELD scores can predict well the short-term prognosis of the initial treatment in HBV-related ACLF patients, and have relatively good clinical value for guiding therapy.
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Insuficiencia Hepática Crónica Agudizada/diagnóstico , Enfermedad Hepática en Estado Terminal , Modelos Teóricos , Insuficiencia Hepática Crónica Agudizada/etiología , Insuficiencia Hepática Crónica Agudizada/virología , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Hepatitis B/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Adulto JovenRESUMEN
AIM: To investigate the clinical features, response to corticosteroids, and prognosis of autoimmune hepatitis (AIH)-induced liver failure in China. METHODS: A total of 22 patients (19 female and 3 male; average age 51 ± 15 years) with AIH-induced liver failure treated in our hospital from 2004 to 2012 were retrospectively analyzed. Clinical, biochemical and pathological characteristics of the 22 patients and responses to corticosteroid treatment in seven patients were examined retrospectively. The patients were divided into survivor and non-survivor groups, and the clinical characteristics and prognosis were compared between the two groups. The t test was used for data analysis of all categorical variables, and overall survival was calculated by the Kaplan-Meier method. RESULTS: At the time of diagnosis, mean IgG was 2473 ± 983 mg/dL, with three (18.8%) patients showing normal levels. All of the patients had elevated serum levels of antinuclear antibody (≥ 1:640). Liver histology from one patient showed diagnostic pathological changes, including massive necrosis and plasma cell infiltration. Four patients survived (18.2%) and 18 died (81.8%) without liver transplantation. The results showed that patients with low admission Model for End-Stage Liver Disease (MELD) scores (21.50 ± 2.08 vs 30.61 ± 6.70, P < 0.05) and corticosteroid therapy (100% vs 16.7%, P < 0.05) had better prognosis. A total of seven patients received corticosteroid therapy, of whom, four responded and survived, and the other three died. Survivors showed young age, shorter duration from diagnosis to corticosteroid therapy, low MELD score, and absence of hepatic encephalopathy at the time of corticosteroid administration. Six patients who were administered corticosteroids acquired fungal infections but recovered after antifungal therapy. CONCLUSION: Early diagnosis and corticosteroid therapy are essential for improving the prognosis of patients with AIH-induced liver failure without liver transplantation.
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Corticoesteroides/uso terapéutico , Hepatitis Autoinmune/tratamiento farmacológico , Fallo Hepático/tratamiento farmacológico , Adulto , Anciano , Biomarcadores/sangre , China , Diagnóstico Precoz , Femenino , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/mortalidad , Humanos , Estimación de Kaplan-Meier , Fallo Hepático/diagnóstico , Fallo Hepático/inmunología , Fallo Hepático/mortalidad , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND/AIMS: To observe the clinical safety of bioartificial liver supporting system constructed by human hepatoma cell line. METHODOLOGY: Seventeen patients with liver failure were treated with C3A-cell-constructed bioartificial liver supporting system, contrasting the difference of biochemical results and imaging data with 9 patients treated with non-bioartificial liver during 5-year treatment. RESULTS: 11 cases of Treatment Group survived at 3 months' follow-up, among whom 2 cases underwent hepatic transplantation. 9 cases without hepatic transplantation survived in 5-year follow-up, and 1 of them was found to occur focal liver lesion at the 5th years, and had hepatic lobectomy. Pathological prompt: hepatocellular carcinoma with moderate differentiation. Totally 4 patients in Control Group survived after 3 months' follow-up, including 1 patient of hepatic transplantation. All the 3 patients without hepatic transplantation survived the last 5-year follow-up, with basically normal biochemical indicators and no focal liver lesion were found by imaging examination. CONCLUSIONS: It was safe to use bioartificial liver constructed by tumor cell line C3A to treat liver failure.
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Carcinoma Hepatocelular/metabolismo , Fallo Hepático/terapia , Neoplasias Hepáticas/metabolismo , Hígado Artificial , Ingeniería de Tejidos/métodos , Adulto , Biomarcadores/metabolismo , Línea Celular Tumoral , Femenino , Humanos , Fallo Hepático/diagnóstico , Fallo Hepático/metabolismo , Fallo Hepático/mortalidad , Pruebas de Función Hepática , Trasplante de Hígado , Hígado Artificial/efectos adversos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: As most HBV-related acute-on-chronic liver failure (ACLF) have concurrent cirrhosis, it is important to clarify the association of viral factors with ACLF with or without cirrhosis. OBJECTIVES: The aim of this study was to analyze the association of HBV genotypes and mutations with ACLF development underlying different chronic liver diseases. PATIENTS AND METHODS: Eighty-seven ACLF patients including 29 patients with chronic hepatitis (ACLF-CHB) and 58 patients with liver cirrhosis (ACLF-LC) were enrolled. Age and sex matched patients with chronic hepatitis (CHB) and liver cirrhosis (LC) were enrolled as controls. The genotypes and mutations at HBV basic core promoter (BCP), precore (PC), and partial C regions were determined by nested PCR and direct sequencing. RESULTS: Our results revealed significantly higher incidences (P < 0.05) of genotype B with C1913A/G or A1846T in patients with ACLF-CHB than those with CHB; genotype C with C1913A/G or A1846T in patients with ACLF-CHB and ACLF-LC than those with CHB and LC, respectively. Multivariable analysis indicated that A1846T and C1913A/G mutations were independent factors for ACLF (OR = 2.86 and 5.93, respectively), suggesting an association between the mutations and development of ACLF. In addition, there were no significant differences in mutations at T1753V, A1762T, G1764A, G1896A, and G1899A which were found between either CHB and ACLF-CHB or LC and ACLF-LC patientsï¼ suggesting no associations of these mutations with ACLF development. CONCLUSIONS: Our findings suggest that CHB or LC patients infected with HBV A1846T and C1913A/G mutants are more susceptible to develop ACLF.
RESUMEN
This study investigated features and clinical implications of HBV mutations in patients with different clinical manifestations. In total, 516 patients were enrolled in this study, including 131 patients with acute hepatitis B, 239 patients with chronic hepatitis B, and 146 patients with acute-on-chronic liver failure. HBV genotypes and mutations were analyzed by direct sequencing of complete viral genomes. Genotypes B2, C1, C2, and D1 accounted for 22.2%, 1.6%, 74.6%, and 1.6%, respectively. Genotype B was more frequently detected in patients with acute hepatitis B than those with chronic hepatitis B and acute-on-chronic liver failure. Deletion mutations were detected mostly in preS1 and preS2 regions and the detection rates were 3.8%, 19.7%, and 24.7% for acute hepatitis B, chronic hepatitis B and acute-on-chronic liver failure patients, respectively. Incidences of point mutation T53C (preS1F53L), G1613A (polR841K), G1775A and A1762T + G1764A in the basal core promoter region, G1896A and G1899A in precore region and A2189C (coreI97L) in core region increased along with acute hepatitis B, chronic hepatitis B, and acute-on-chronic liver failure. The mutation G1896A was independently associated with poor survival of patients with acute-on-chronic liver failure. The gradual increase of viral mutation incidences was also observed in three HLA-A2-restricted cytotoxic T lymphocyte epitopes from HLA-A2-positive patients, that is env188-196 (5.8%, 10.1%, 22.5%), core107-115 (4.3%, 4.6%, 19.7%), and x92-100 (1.4%, 20.2%, 33.8%). In conclusion, certain viral mutations in various regions of HBV genome are associated with disease progression of HBV infection.
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ADN Viral/química , ADN Viral/genética , Variación Genética , Genoma Viral , Virus de la Hepatitis B/genética , Hepatitis B/patología , Hepatitis B/virología , Adulto , China , Epítopos de Linfocito T/genética , Femenino , Genotipo , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación , Análisis de Secuencia de ADNRESUMEN
The clinical use of a bioartificial liver (BAL) device strongly depends on the development of human liver cell lines. The aim of this study was to establish and assess the potential use of the stable HepG2 cell line expressing human augmenter of liver regeneration (hALR). The cDNA encoding hALR protein was inserted into pcDNA3.1 to generate pcDNA3.1/hALR, following which pcDNA3.1/hALR was transfected to HepG2 to establish a cell line that stably expressed hALR (HepG2 hALR). A total of 800 million HepG2 hALR cells were loaded into laboratory-scale BAL bioreactors and cultured for 4 days, during which time the parameters of hepatocyte-specific function and general metabolism were determined. The cell line that stably expressed human ALR was successfully established. The expression of recombinant hALR was higher in the HepG2 hALR cell line than in the HepG2 cell line based on immunofluorescence and immunoblot assays. In samples removed from the BAL bioreactor on day 4, compared to HepG2 cells, HepG2 hALR cells produced significantly more alpha-fetoprotein (127.3 %; P < 0.05) and urea (128.8 %; P < 0.05) and eliminated more glucose (135.7 %; P < 0.05); the level of human albumin was also higher (117 %) in HepG2 hALR cells, but the difference was not significant (P > 0.05). After 24 h of culture, the mean lidocaine removal rate was 65.1 and 57.3 % in culture supernatants of HepG2 hALR and HepG2 cell lines, respectively (P < 0.01). Based on these results, we conclude that HepG2 hALR cells showed liver-specific functionality when cultured inside the bioreactor and would therefore be a potential cell source for BAL.
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Técnicas de Cultivo de Célula/métodos , ADN Complementario/genética , Regeneración Hepática/genética , Hígado Artificial , Proteínas/genética , Transfección/métodos , Reactores Biológicos , Células Hep G2 , Humanos , Plásmidos/genéticaRESUMEN
Seronegative hepatitis--non-A, non-B, non-C, non-D, non-E hepatitis--is poorly characterized but strongly associated with serious complications. We collected 92 sera specimens from patients with non-A-E hepatitis in Chongqing, China between 1999 and 2007. Ten sera pools were screened by Solexa deep sequencing. We discovered a 3,780-bp contig present in all 10 pools that yielded BLASTx E scores of 7e-05-0.008 against parvoviruses. The complete sequence of the in silico-assembled 3,780-bp contig was confirmed by gene amplification of overlapping regions over almost the entire genome, and the virus was provisionally designated NIH-CQV. Further analysis revealed that the contig was composed of two major ORFs. By protein BLAST, ORF1 and ORF2 were most homologous to the replication-associated protein of bat circovirus and the capsid protein of porcine parvovirus, respectively. Phylogenetic analysis indicated that NIH-CQV is located at the interface of Parvoviridae and Circoviridae. Prevalence of NIH-CQV in patients was determined by quantitative PCR. Sixty-three of 90 patient samples (70%) were positive, but all those from 45 healthy controls were negative. Average virus titer in the patient specimens was 1.05 e4 copies/µL. Specific antibodies against NIH-CQV were sought by immunoblotting. Eighty-four percent of patients were positive for IgG, and 31% were positive for IgM; in contrast, 78% of healthy controls were positive for IgG, but all were negative for IgM. Although more work is needed to determine the etiologic role of NIH-CQV in human disease, our data indicate that a parvovirus-like virus is highly prevalent in a cohort of patients with non-A-E hepatitis.