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OBJECTIVE: Colorectal adenomas are an important precancerous lesion of colorectal adenoma with a high incidence. This study aims to explore new prognostic targets for colorectal adenomas through bioinformatics techniques. MATERIALS AND METHODS: In this study, data from 29 colonic adenomas and 38 normal colonic mucosa in GSE37364 were analyzed to screen for differentially expressed genes (DEGs). Then, batch survival analysis, construction of risk model, mutation analysis, Cox regression analysis and expression analysis were performed on DEGs to determine the hub genes of this study. Finally, immune correlation analysis and cell experiments were carried out on the hub gene to explore its potential mechanism. RESULTS: In our study, a total of 431 up-regulated and 809 down-regulated differentially expressed genes (DEGs) were identified. Among these, Unc-5 Netrin Receptor D (UNC5D) emerged as a pivotal gene associated with colorectal adenoma. Notably, UNC5D expression levels were found to be significantly higher in normal tissues compared to colorectal adenoma tissues. Furthermore, our analysis demonstrated that UNC5D showed promising diagnostic potential for patients with colon adenocarcinoma. In vitro experiments revealed that the overexpression of UNC5D had a profound impact on the behavior of colorectal tumor cells. Specifically, it led to a substantial reduction in the proliferation, motility, and invasion of these tumor cells. Additionally, UNC5D was shown to exert control over STAT1/STAT3 phosphorylation, which in turn regulated the expression of PD-L1 in response to interferon (IFN) stimulation. These findings highlight the significant role of UNC5D in modulating immune responses and the development of colorectal adenoma. UNC5D emerges as a potential diagnostic biomarker and an attractive immunotherapeutic target in the context of colorectal malignancies. These results call for further exploration of UNC5D-based strategies for the diagnosis and treatment of colorectal adenoma and adenocarcinoma. CONCLUSIONS: In addition to having the potential to be used as a diagnostic biomarker and an immunotherapeutic target in colorectal malignancies, UNC5D is necessary for the growth of colorectal adenomas. Additionally, UNC5D controlled STAT1/STAT3 phosphorylation to suppress the growth of colorectal cancers by regulating IFN-induced PD-L1 expression.
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Adenocarcinoma , Adenoma , Neoplasias Colorretais , Receptores de Superfície Celular , Humanos , Adenocarcinoma/genética , Adenoma/genética , Antígeno B7-H1/genética , Biomarcadores , Proliferação de Células , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Receptores de Superfície Celular/genéticaRESUMO
Objectives: To investigate the risk factors and short-term prognosis of early pulmonary hypertension (PH) in preterm infants. Methods: A retrospective case-control study was performed in preterm infants (gestational age <32 weeks) in the neonatal intensive care unit (NICU) of the Children's Hospital, Zhejiang University School of Medicine from January 2012 to December 2019. Eighty preterm infants with a diagnosis of PH between 3 and 14 days (early PH group) were matched in gestational age and sex with the controls (1â¶2) of the same period in NICU. Perinatal clinical records, complications, echocardiography and early outcomes were collected. Characteristics and outcomes were compared between the two groups with t-test, nonparametric test or Chi-square test. Multivariate Logistic regression was used to analyze the predictive factors of early PH. Results: The gestational age of the early PH group and the control group were both (27.9±1.4) weeks, and 52 (65.0%) and 104 (65.0%) were males in each group, respectively. Univariate analysis showed that birth weights were lower in the early PH group than those in the control group (1 030 (850, 1 200) vs. 1 110 (1 000, 1 278) g, Z=-3.27, P=0.001). The early PH group had higher rates of pregnancy-induced hypertension, prolonged rupture of membranes (PROM) >1 week, born by caesarean, small for gestational age (SGA), 1 and 5 min Apgar score ≤7 scores, neonatal respiratory distress syndrome (RDS) and hemodynamic significant patent ductus arteriosus (hsPDA) (12.5% (10/80) vs. 3.8% (6/160), 11.2% (9/80) vs. 3.8% (6/160), 48.8% (39/80) vs. 28.8% (46/160), 10.0% (8/80) vs. 1.9% (3/160), 70.8% (51/72) vs. 51.7% (74/143), 50.0% (36/72) vs. 20.3% (29/143), 88.8% (71/80) vs. 59.4% (95/160), 85.0% (68/80) vs. 22.5% (36/160), χ2=6.56, 5.12, 3.31, 8.05, 7.17, 20.05, 21.58, 84.84, all P<0.05). Multivariate Logistic regression analysis showed that the independent predictive factors of early PH were PROM >1 week, SGA, 5 min Apgar score ≤7 scores, nenonatal RDS and hsPDA (OR=10.40, 18.61, 4.47, 4.13, 20.10, 95%CI 1.93-56.12, 2.82-122.76, 1.91-10.46, 1.50-11.39, 8.28-48.80, all P<0.05),respectively. Infants with early PH had higher incidence of bronchopulmonary dysplasia (BPD), BPD associated PH, severe intraventricular hemorrhage (IVH), extrauterine growth retardation (EUGR), laser treatment for retinopathy of prematurity (ROP) and mortality than the controls (all P<0.05). The duration of invasive mechanical ventilation was also longer in the early PH group than that in the control group (P<0.05). Conclusions: Risk of early PH will be increased in preterm infants with PROM >1 week, SGA, 5 min Apgar score ≤7 scores, and comorbidities of nenonatal RDS and hsPDA. Early PH is associated with increased mortality, BPD, BPD associated PH, severe IVH, EUGR and laser treatment for ROP.
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Displasia Broncopulmonar , Permeabilidade do Canal Arterial , Hipertensão Pulmonar , Doenças do Recém-Nascido , Síndrome do Desconforto Respiratório do Recém-Nascido , Retinopatia da Prematuridade , Displasia Broncopulmonar/complicações , Estudos de Casos e Controles , Hemorragia Cerebral , Criança , Feminino , Idade Gestacional , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Gravidez , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
Objective: To compare the clinical diagnosis and outcomes of preterm infants with bronchopulmonary dysplasia (BPD) under two different diagnostic criteria. Methods: A retrospective study was performed in 157 preterm infants who were admitted to Neonatal Intensive Care Unit of the Children's Hospital, Zhejiang University School of Medicine from January 2015 to December 2018. Enrolled infants, with gestational age <32 weeks and survived >14 days, met the 2001 National Institute of Child Health and Human Development(NICHD) definition of moderate and severe BPD or died between 14 days of postnatal age and 36 weeks owing to persistent parenchymal lung disease and respiratory failure. The severities of BPD were revaluated according to the 2018 revised definition of BPD proposed by NICHD. Characteristics and outcomes of these infants were compared with the two different diagnostic criteria with t-test, nonparametric test or Chi-square test. Results: In the 157 enrolled infants (100 males), severities of BPD were classified as moderate in 62, severe in 84 and unclassifiable in 11 according to the 2001 NICHD criteria, while grade â in 51, â ¡ in 29, â ¢ in 66 and â ¢A in 11 infants respectively according to the 2018 NICHD criteria. Duration of oxygen therapy, positive pressure ventilation and endotracheal intubation in grade â ¡infants of 2018 criteria were much longer than that in moderate infants of 2001 criteria (80 (65, 95) vs. 65 (59, 77) d, 52 (38, 58) vs.30 (19, 48) d, 10 (2, 17) vs.4 (0, 12) d, Z=-2.995, -3.750, -2.073, all P<0.05). Mortality of moderate and severe infants in 2001 criteria was 10.3% (15/146), while mortality of BPD in 2018 criteria was 16.6% (26/157). Mortality of grade â ¢ and â ¢A BPD in 2018 criteria was much higher than mortality of severe BPD in 2001 criteria (33.8% (26/77) vs. 17.9%(15/84), χ(2)=5.357, P<0.05). Conclusion: Definition and classification of BPD based on 2001 NICHD criteria may cause missed or unclassified cases, resulting in the underestimation of the morbidity and mortality of infants with severe BPD.
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Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/terapia , Displasia Broncopulmonar/mortalidade , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Pulmão , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Objective: To evaluate the efficacy and safety of Oryz-Aspergillus enzyme and pancreatin tablets (Combizym(®)) in the treatment of postprandial distress syndrome (PDS) in the elderly, compared with gastrointestinal motility drugs. Methods: A prospective randomized controlled trial was designed and registered in the China Clinical Trials Registry (ChiCTR-IPR-16008185). The elderly patients with PDS were randomly divided into three groups, including Mosapride group with Mosapride citrate tablets 5 mg 3 times per day for 2 weeks; Combizym(®) group with Combizym tablets 244 mg 3 times per day for 2 weeks; combined treatment group with both drugs and same doses for 2 weeks. The modified Nepean dyspepsia index (NDSI) score, discomfort intensity score and PDS score were calculated on patients before treatment, at the end of first and second week of treatment, as well as 4 weeks after treatment finished, respectively. Adverse effects were evaluated. Results: A total of 323 patients from 16 tertiary hospitals in China were enrolled in this study. Among them, 105 patients were in Mosapride group, 109 in Combizym(®) group and 109 in combined treatment group. There were 148 males (45.8%) and 175 females (54.2%) with median age 71.4±9.0 years (60-100 years). Baseline characteristics of three groups were comparable. After treatment, the NDSI scores in three groups all decreased significantly (P<0.001), while they were similar between groups (P>0.05). The discomfort intensity score and PDS score in three groups showed a significant reduction after treatment (P<0.001), especially in the combined treatment group. Compared with Mosapride group, the scores in Combizym(®) group decreased significantly after one or two weeks [discomfort intensity score: after one week, 4.0(2.5, 8.0) vs. 6.0(3.0, 10.0); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 6.0); all P<0.05. PDS score: after one week, 6.0(3.0, 9.0) vs. 7.0(3.5, 10.5); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 7.0); all P<0.05]. The efficacy rate in all patients after first week of treatment was over 15.0%. The efficacy rates after two weeks were 55.2%, 68.8% and 73.4% in Mosapride group, Combizym(®) group and combined treatment group, respectively. After two week treatment, the efficacy rates in Combizym(®) group (P=0.041) and combined group (P=0.006) were higher than that of Mosapride group. The recurrence rate of Mosapride group was 9.5%, which was significantly higher than that of Combizym(®) group (1.8%, P<0.05) and combined treatment group (1.8%, P<0.05). There were no serious adverse effects in the three groups. Conclusions: The efficacy of Oryz-Aspergillus enzyme and pancreatin tablets is comparable with that of Mosapride in elderly PDS patients, with fewer adverse effects and low recurrence rate. Combination regimen indicates better efficacy than that of Oryz-Aspergillus enzyme and pancreatin tablets or Mosapride alone.
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Benzamidas/uso terapêutico , Dispepsia/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Motilidade Gastrointestinal/efeitos dos fármacos , Glicosídeo Hidrolases/uso terapêutico , Morfolinas/uso terapêutico , Pancreatina/uso terapêutico , Peptídeo Hidrolases/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Benzamidas/efeitos adversos , China , Combinação de Medicamentos , Dispepsia/diagnóstico , Dispepsia/patologia , Feminino , Fármacos Gastrointestinais/efeitos adversos , Glicosídeo Hidrolases/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Morfolinas/efeitos adversos , Pancreatina/efeitos adversos , Peptídeo Hidrolases/efeitos adversos , Período Pós-Prandial , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Post-discharge optimal growth and nutritional intake have beneficial effects for neurodevelopment in preterm very low birth weight infants (VLBWIs) with extrauterine growth retardation (EUGR). The present study aimed to compare the effects of a nutrient-dense formula (NDF) to a post-discharge formula (PDF) on post-discharge growth of preterm VLBWIs with EUGR. METHODS: Forty-eight preterm VLBWIs with EUGR at discharge were randomised to receive NDF (100 kcal per 100 mL; 2.6 g protein per 100 mL) or PDF (74 kcal per 100 mL; 1.95 g protein per 100 mL) for 1-6 months until body weight reached the 50th percentile on growth charts with corrected age. Volume, nutrient intake, anthropometry and biochemistry data were collected. RESULTS: Volume intake was lower in the NDF group than the PDF group during the first 2 months of feeding (P = 0.039 and 0.018, respectively).There were no significant differences in volume intake during months 2-6 of feeding. Energy, protein, carbohydrate and fat intake were higher in the NDF group during months 1-6 of feeding. There were no significant differences in weight, length, and head circumference Z-scores during months 1-6 between the two groups. The â³length Z-score from discharge to month 6 was significantly higher in the NDF group than the PDF group (P = 0.043). No differences existed between the two groups with respect to biochemistry. CONCLUSIONS: After discharge, preterm VLBWIs with EUGR fed a NDF gain anthropometric parameter Z-scores similar to those for a PDF within 6 months of follow-up. A NDF leading to gain in length requires further follow-up.
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Assistência ao Convalescente/métodos , Transtornos do Crescimento/dietoterapia , Fórmulas Infantis , Recém-Nascido Prematuro/crescimento & desenvolvimento , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Antropometria , China , Feminino , Transtornos do Crescimento/fisiopatologia , Humanos , Lactente , Fórmulas Infantis/análise , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Masculino , Nutrientes/administração & dosagem , Alta do Paciente , Resultado do Tratamento , Aumento de PesoRESUMO
OBJECTIVE: MiRNAs have been verified to play a role in the development and progression of prostate cancer (PCa). However, the role of miR-492 in PCa has not been mentioned. We aim to detect the expression of miR-492 in PCa and explore its underlying mechanism. PATIENTS AND METHODS: The relative expression of miR-492 in PCa tissue samples to normal prostate tissues was detected using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The level of miR-492 in PCa-derived cell lines compared with the normal prostate cell line was also measured. Cell counting kit-8 (CCK-8) and colony formation assays were employed to investigate the cell proliferation ability. Transwell assay and wound-healing assays were utilized to explore the cell invasion and migration abilities. Luciferase assay and Western blot were utilized to explore the underlying mechanism of miR-492 in PCa cells. RESULTS: MiR-492 expressed significantly higher in PCa tissues than that in the normal tissues. Its expression level was also over-expressed in PCa cells compared with that in the normal cells. The up-regulation of miR-492 promoted the growth, invasion, and migration of the cells, while down-regulation had the opposite effects. SOCS2 was identified as a potential target for miR-492 in PCa. Silencing of SOCS2 could neutralize the inhibitory function of miR-492 inhibitor in PCa cells. CONCLUSIONS: This study demonstrated that miR-492 was over-expressed in PCa and exerted tumor-promoting function in PCa cells via repressing SOCS2 expression. This might provide a new sight for future accurate therapy for PCa.
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Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/fisiologia , Neoplasias da Próstata/fisiopatologia , Proteínas Supressoras da Sinalização de Citocina/biossíntese , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Humanos , Masculino , MicroRNAs/biossíntese , Invasividade Neoplásica/fisiopatologia , Neoplasias da Próstata/metabolismoRESUMO
Objective: To study the clinical effect of probiotics in the treatment of non-alcoholic fatty liver disease (NAFLD). Methods: A total of 200 patients with NAFLD were randomly divided into 4 groups: control group (routine treatment group) and combined treatment group A, B and C. Each group had equal patients. The control group received orally polyene phosphatidylcholine capsules; whereas combined group A, B and C were given orally the live "combined Bifidobacterium Lactobacillus and Enterococcus powder" , "two live combined Bacillus subtilis and Enterococcus" , and the both probiotics respectively. The duration of treatment was 1 month. Laboratory parameters were evaluated before treatment and thirtieth day after treatment, including cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase (AST), fasting blood glucose (FPG), serum high molecular weight adiponectin (HMW-APN) and serum TNFα. Meanwhile the faece sample was collected for routine test and bacterial culture. Liver ultrasound scan was done in all patients. Results: In terms of blood lipids and blood glucose, each group improved after treatment with significant differences (P<0.05) except for HDL-C. As for liver function, serum ALT and AST decreased after treatment in each group; especially in combined group C which were lower than those of control group [(33.7±7.6) U/L vs. (45.0±8.5) U/L; (22.0±1.6) U/L vs. (29.4±3.7) U/L; P<0.05]. TNFα levels decreased after treatment in each group, in addition the values in combined group C was significantly lower than that of control group[(0.51±0.27) µg/L vs. (0.82±0.28) µg/L, P<0.05]. Serum HMW-APN increased after treatment in each group, and the HMW-APN in combined C group was significantly higher than that of control group[(9.28±3.72) µg/L vs. (7.87±3.96)µg/L, P<0.05]. (5) After treatment, all groups showed improvement of fatty liver by ultrasound, but the difference between groups was not statistically significant. (6) Compared with before treatment, fecal flora in combined groups was all reduced (P<0.01), but it was comparable before and after treatment in control group. Conclusions: Probiotics improve intestinal microecological system in NAFLD patients via inhibiting TNFα and enhancing adiponectin, possibly resulting in regulating blood glucose, lipid metabolism, and protecting liver injury from NAFLD.
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Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/terapia , Probióticos , Adiponectina , Alanina Transaminase/sangue , Alanina Transaminase/efeitos dos fármacos , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/efeitos dos fármacos , Glicemia , Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/metabolismo , Humanos , Metabolismo dos Lipídeos , Lipídeos , Probióticos/uso terapêutico , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: This study is to investigate the effect of low concentration hydrogen peroxide (H2O2) on the proliferation of gastric cancer AGS cell line in vitro and the mechanism. MATERIALS AND METHODS: AGS cells were treated with different low concentrations of H2O2 (1, 0.1, 0.01, and 0.001 µm) for 48 hours. The effect of H2O2 concentration gradient on the activity of AGS cell activities was detected by methyl thiazolyl tetrazolium (MTT) method. The expression of the epidermal growth factor receptor (EGFR) and its downstream signaling pathway extracellular signal-regulated kinase (ERK) protein in H2O2 was detected by Western blot method; moreover, the effect of H2O2 on intracellular reactive oxygen species (ROS) in AGS cells was observed under the fluorescence microscope and quantitative analysis by flow cytometry. The effect of H2O2 on the level of c-myc mRNA in AGS cells was also detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: MTT detection results showed that 1 µm and 0.1 µm H2O2 at 48h can effectively promote the proliferation of AGS cells (p<0.05). The Western blot results showed that after 48 hours of low concentration of H2O2 treatment of AGS cells, the EGFR protein levels and ERK protein phosphorylation levels increased significantly (p<0.05). Fluorescence microscopy and flow cytometry showed that the low concentration of H2O2 increased the intracellular reactive oxygen species (ROS). RT-PCR results showed the levels of c-myc mRNA in AGS cells treated with a low concentration of H2O2 were significantly increased (p<0.05) and EGFR blocking agent AG1478 can resist the above effects. CONCLUSIONS: Low concentration of H2O2 can significantly promote the proliferation of AGS cells by activating EGFR/ERK signaling pathway.
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Receptores ErbB , Peróxido de Hidrogênio/farmacologia , Neoplasias Gástricas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , HumanosRESUMO
Objective: To evaluate the effectiveness and safety of the use of noninvasive high-frequency oscillation ventilation (nHFOV) in very low birth weight infants. Method: A total of 36 cases received nHFOV between January 2016 and October 2016 in Children's Hospital, Zhejiang University School of Medicine, including 24 males and 12 females, with the gestational age of (27.5±2.5) weeks and birth weight of(980±318)g. The data of the ventilator settings, side effects, and changes of the respiratory function before and after nHFOV were collected and analyzed retrospectively. Nonparametric tests or t tests or χ(2) tests were used. Result: Thirty-two (89%) out of the 36 cases successfully avoided intubation or re-intubation after using of nHFOV. nHFOV was used as the rescue treatment after failure of other noninvasive ventilation in 17 cases, and as the prophylactical treatment preventing re-intubation after extubation in the remaining 19 cases. There were significant decreases in the incidences of apnea and desaturation(SpO(2)<0.85), the level of PaCO(2, )and the FiO(2) 24 h after the initiation of the nHFOV as the rescue therapy((1.2±1.1)vs.(6.3±2.1)episodes , (1.1±1.2) vs.(4.3±1.5) episodes, (43±8) vs.(56±10) mmHg, 0.30±0.07 vs. 0.39±0.11, respectively; 1 mmHg=0.133 kPa, t=7.562, 8.913, 4.179, 3.437 respectively, all P<0.01). No significant changes were found in FiO(2) and PaCO(2) levels 24 h after initiation of nHFOV as the prophylactical therapy after extubation (0.42±0.12 vs.0.40±0.10, (49±8)vs.(48±7)mmHg, t=0.872 and 0.501 respectively, both P>0.05), except for the significant decreases in the mean airway pressure ((7.9±2.6)vs.(9.6±1.6)cmH(2)O, 1 cmH(2)0=0.098 kPa, t=2.198, P=0.041). There were 4 cases suffered from nasal septum injury, while no other nHFOV related complications were noted. Conclusion: nHFOV can be applied in preterm infants as a rescue treatment after the failure of other noninvasive ventilation, or prophylactically used in patients who have high risk of re-intubation.
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Ventilação de Alta Frequência , Recém-Nascido de muito Baixo Peso , Extubação , Peso ao Nascer , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Ventilação não Invasiva , Estudos RetrospectivosRESUMO
OBJECTIVE: The aims of this study were to determine if characterization of serum concentrations of interferon-gamma inducible protein-10 (IP-10), fractalkine, and their receptors (CXCR3 and CX3CR1) were predictive of acute allograft rejection in kidney transplant recipients. METHODS: Kidney transplant recipients (n = 52) were enrolled in this study and divide into either the acute rejection (AR, n = 15) or non-acute rejection (NAR, n = 35) groups. Serum samples from recipients were collected 1 day prior to transplantation and on days 1, 3, 5, 7, and 9 post-transplantation. The accuracy of chemokine concentrations for predicting acute rejection episodes was evaluated using receiver operator characteristic (ROC) curves. RESULTS: AR was diagnosed in 15 patients based on histologic changes to renal biopsies. AR patients had significantly higher serum fractalkine, CXCR1, IP-10, and CXCR3 levels compared to levels observed in the NAR group and healthy controls. Fractalkine and IP-10 had the largest area under the ROC curve at 0.86 (95% confidence interval: 0.77-0.96). Following steroid therapy, chemokine levels decreased, which may serve to predict the therapeutic response to steroid therapy. CONCLUSION: Measuring serum levels of fractalkine, IP-10, and their receptors (especially the fractalkine/IP-10 combination) may serve as a noninvasive approach for the early diagnosis of renal allograft rejection.
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Biomarcadores/sangue , Quimiocina CX3CL1/sangue , Quimiocina CXCL10/sangue , Rejeição de Enxerto/diagnóstico , Transplante de Rim , Adulto , Idoso , Diagnóstico Precoce , Feminino , Rejeição de Enxerto/sangue , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Phase-change random-access memory (PCRAM) is one of the leading candidates for next-generation data-storage devices, but the trade-off between crystallization (writing) speed and amorphous-phase stability (data retention) presents a key challenge. We control the crystallization kinetics of a phase-change material by applying a constant low voltage via prestructural ordering (incubation) effects. A crystallization speed of 500 picoseconds was achieved, as well as high-speed reversible switching using 500-picosecond pulses. Ab initio molecular dynamics simulations reveal the phase-change kinetics in PCRAM devices and the structural origin of the incubation-assisted increase in crystallization speed. This paves the way for achieving a broadly applicable memory device, capable of nonvolatile operations beyond gigahertz data-transfer rates.
RESUMO
A new class of superlattice, crystalline amorphous superlattice (CASL), by alternatively depositing two semiconductor materials, is proposed. CASL displays three states depending on the component materials' phase: both polycrystalline phases, both amorphous phases, and one polycrystalline phase while another amorphous phase. Using materials capable of reversible phase transition, CASL can demonstrate reversibility among three states. GeTe/Sb(2)Te(3) CASL has been synthesized and proved by x-ray reflectometry and TEM results. The reversible transition among three states induced by electrical and laser pulse was observed. The changes in the optical absorption edge, electrical resistivity, thermal conductivity, and crystallization temperature as a function of layer thickness are interpreted as quantum or nanoeffects. The unique properties of CASL enable the design of materials with specific properties.
RESUMO
BACKGROUND AND PURPOSE: Our previous study showed that SM905, a novel artemisinin derivative, exhibited potent immunosuppressive activity. In this study, we evaluate preventive and therapeutic effect of SM905 on collagen-induced arthritis (CIA) in DBA/1 mice, and investigate its mechanisms both in inflammatory and autoimmune aspects of the disease. EXPERIMENTAL APPROACH: CIA was induced by type II bovine collagen (CII) in DBA/1 mice. SM905 was given orally either before (continuously 1 day before booster immunization) or after disease onset (continuously 14 days after booster immunization). Disease incidence and severity were monitored, mRNA expression of proinflammatory mediators was determined by real-time PCR, purified T cell proliferation was assessed using [(3)H]-thymidine incorporated assay, and T helper (Th) 17/Th1/Th2 type cytokine production was examined by ELISA. KEY RESULTS: Oral treatment with SM905 delayed disease onset, reduced arthritis incidence and severity, and suppressed the enhanced expression of pro-inflammatory cytokines, chemokines and chemokine receptors in draining lymph nodes. The CII-induced T cell proliferation and production of interleukin (IL)-17A by T cells were strikingly inhibited. Correspondingly, the mRNA expression of IL-17A and RORgamma t (a specific transcription factor for Th17) was also reduced. This effect was coupled with a striking reduction of IL-6 production, which has a critical role in Th17 development. In established arthritis, SM905 profoundly inhibited disease progression, reduced IL-17A and RORgamma t mRNA expression, and suppressed pro-inflammatory mediator expression in arthritic joints. CONCLUSIONS AND IMPLICATIONS: SM905 had beneficial effects on CIA by suppressing inflammatory and pathogenic Th17 responses.
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Artemisininas/farmacologia , Artrite Experimental/tratamento farmacológico , Animais , Artrite Experimental/fisiopatologia , Bovinos , Proliferação de Células/efeitos dos fármacos , Quimiocinas/efeitos dos fármacos , Quimiocinas/metabolismo , Colágeno Tipo II , Modelos Animais de Doenças , Progressão da Doença , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-17/metabolismo , Linfonodos/efeitos dos fármacos , Linfonodos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos DBA , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Receptores de Quimiocinas/efeitos dos fármacos , Receptores de Quimiocinas/metabolismo , Índice de Gravidade de Doença , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/metabolismoRESUMO
Phase change materials are widely used for date storage. The most widespread and important applications are rewritable optical disc and Phase Change Random Access Memory (PCRAM), which utilizes the light and electric induced phase change respectively. For decades, miniaturization has been the major driving force to increase the density. Now the working unit area of the current data storage media is in the order of nano-scale. On the nano-scale, extreme dimensional and nano-structural constraints and the large proportion of interfaces will cause the deviation of the phase change behavior from that of bulk. Hence an in-depth understanding of nanophase change and the related issues has become more and more important. Nanophase change can be defined as: phase change at the scale within nano range of 100 nm, which is size-dependent, interface-dominated and surrounding materials related. Nanophase change can be classified into two groups, thin film related and structure related. Film thickness and clapping materials are key factors for thin film type, while structure shape, size and surrounding materials are critical parameters for structure type. In this paper, the recent development of nanophase change is reviewed, including crystallization of small element at nano size, thickness dependence of crystallization, effect of clapping layer on the phase change of phase change thin film and so on. The applications of nanophase change technology on data storage is introduced, including optical recording such as super lattice like optical disc, initialization free disc, near field, super-RENS, dual layer, multi level, probe storage, and PCRAM including, superlattice-like structure, side edge structure, and line type structure. Future key research issues of nanophase change are also discussed.
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Dispositivos de Armazenamento em Computador , Armazenamento e Recuperação da Informação , Nanotecnologia/métodos , Computadores , Cristalização , Eletroquímica/métodos , Temperatura Alta , Cinética , Lasers , Modelos Estatísticos , Nanotecnologia/instrumentação , Tamanho da Partícula , Software , Temperatura , Fatores de TempoRESUMO
BACKGROUND AND PURPOSE: Artemisinin and its derivatives exhibit potent immunosuppressive activity. The purpose of the current study was to examine the immunosuppressive activity of artemether directly on T lymphocytes and to explore its potential mode of action. EXPERIMENTAL APPROACH: In vitro, T-cell proliferation was measured using [(3)H]-thymidine incorporation assay in cells stimulated with ConA, alloantigen and anti-CD3 antibody. CFSE-labeled cell division and cell cycle distribution were monitored by flow cytometry. In vivo, the effects of artemether were evaluated in delayed-type hypersensitivity (DTH) and purified T-cell responses to ovalbumin in ovalbumin-immunized mice. The activation of extracellular signal-regulated kinase1/2 (ERK1/2) and Raf1 were assessed by Western blot analysis and the activation of Ras was tested in pull-down assays. KEY RESULTS: We show that, in vitro, artemether suppressed ConA- or alloantigen-induced splenocyte proliferation, influenced production of the cytokines IL-2 and IFN-gamma and inhibited cell cycle progression through the G0/G1 transition. In vivo, administration of artemether attenuated CD4 T-cell-mediated DTH reaction, and suppressed antigen-specific T-cell response in immunized mice. Further experiments showed that, treatment with artemether impaired both antigen- and anti-CD3-induced phosphorylation of ERK. In primary T cells, artemether profoundly inhibited anti-CD3-induced phosphorylation of Raf1 and activation of Ras. CONCLUSIONS AND IMPLICATIONS: This study provided experimental evidence of the immunosuppressive effects of artemether directly on T cells both in vitro and in vivo. Its immunosuppressive mechanism involved inhibition of the activation of the Ras-Raf1-ERK1/2 protein kinase cascade in T cells.
Assuntos
Artemisininas/farmacologia , Proliferação de Células/efeitos dos fármacos , Hipersensibilidade Tardia/prevenção & controle , Imunossupressores/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Animais , Artemeter , Artemisininas/uso terapêutico , Complexo CD3/imunologia , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular , Concanavalina A/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Hipersensibilidade Tardia/induzido quimicamente , Hipersensibilidade Tardia/imunologia , Imunidade Celular/efeitos dos fármacos , Memória Imunológica/efeitos dos fármacos , Imunossupressores/uso terapêutico , Interferon gama/metabolismo , Interleucina-2/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mitógenos/farmacologia , Ovalbumina/imunologia , Fosforilação , Proteínas Proto-Oncogênicas c-raf/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fatores de Tempo , Proteínas ras/metabolismoRESUMO
OBJECTIVE: To determine the optimal venous tubing diameter for adult cardiopulmonary bypass (CPB) to improve gravity drainage and to reduce priming volume. METHODS: (A) Maximum bovine blood flow rates by gravity drainage were assessed in vitro for four different tubing diameters (1/2, 3/8, 5/16,1/4 inch) with three different lengths and various pre- and afterloads. Based on the results of (A) and multiple regression analyses, we developed equations to predict tubing sizes as a function of target flows. (C) The equations obtained in (B) were validated by ex vivo bovine experiments. (D) The clinically required maximal flows were determined retrospectively by reviewing 119 perfusion records at Zurich University. (E) Based on our model (B), the clinical patient and hardware requirements, the optimal venous tubing diameter was calculated. (F) The optimized venous tubing was evaluated in a prospective clinical trial involving 312 patients in Hangzhou. RESULTS: For a mean body surface area of 1.83+/-0.2 m(2), the maximal perfusion flow rate (D) achieved with 1/2-inch (=1.27 cm(2)) venous tubing was 4.62+/-0.57 l/min (range: 2.50-6.24 l/min). Our validated model (B,C) predicted 1.0 cm(2) as optimal cross-sectional area for the venous line. New tubing packs developed accordingly were used routinely thereafter. The maximal flow rate was 4.93+/-0.58 l/min (range: 3.9-7.0) in patients with a mean body surface area of 1.62+/-0.21 m(2). CONCLUSION: The new venous tubing with 1.0-cm(2) cross-sectional area improves the drainage in the vast majority of adult patients undergoing CPB and reduces the priming volume (-27 ml/m). Reduced hemodilution can prevent homologous transfusions if a predefined transfusion trigger level is not reached.
Assuntos
Ponte Cardiopulmonar/instrumentação , Adulto , Animais , Velocidade do Fluxo Sanguíneo , Bovinos , Desenho de Equipamento , Feminino , Hemorreologia , Humanos , Intubação/instrumentação , Masculino , Estudos ProspectivosRESUMO
A microscopic theory is developed to treat the ultrathin film of liquid crystals of molecules that have no cylindrical symmetry. The Hamiltonian is derived from the basic electrostatic interaction among electrons by considering the dipole-dipole and dipole-quadrupole interactions between nonchiral molecules. It exhibits the in-plane sixfold symmetry. From a unified model with the same interaction constants we are able to explain simultaneously the layer-thinning SmA-I transition, the anomalous multiplex heat capacity, the strong singularity in the HexB-SmA transition, and the coexistence of different phases. The theoretical calculations agree quantitatively with recent experimental results for the free-standing 54COOBC films.
RESUMO
A simple method is outlined for the calculation of the refractive-index profiles of both multimode and monomode planar optical waveguides. The method is an extension of the well-established IWKB method. The parameters required are the dispersion relation of the surface index changes and the effective indices at different wavelengths. As an example, the refractive-index profile of a monomode z-cut KTiOPO(4) planar waveguide fabricated by Rb(+):K(+) exchange is computed. Close agreement is obtained, indicating the practicality of this method. The method is also applicable to optical waveguides in other materials, such as LiNbO(3), LiTaO(3), and glass.