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1.
Neuroimage ; : 116315, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669409

RESUMO

Non-invasive quantitative imaging of cerebral oxygen metabolism (CMRO2) in small animal models is crucial to understand the role of oxidative metabolism in healthy and diseased brains. In this study, we developed a multimodal method combining near-infrared spectroscopy (NIRS) and MRI to non-invasively study oxygen delivery and consumption in the cortex of mouse and rat models. The term CASNIRS is proposed to the technique that measures CMRO2 with ASL and NIRS. To determine the reliability of this method, CMRO2 values were compared with reported values measured with other techniques. Also, the sensitivity of the CASNIRS technique to detect changes in CMRO2 in the cortex of the animals was assessed by applying a reduction in core temperature, which is known to reduce CMRO2. Cerebral blood flow (CBF) and CMRO2 were measured in five mice and five rats at a core temperature of 37 °C followed by another measurement at 33 °C. CMRO2 was 7.8 ±â€¯1.8 and 3.7 ±â€¯0.9 (ml/100 g/min, mean ±â€¯SD) in mice and rats respectively. These values are in good agreement with reported values measured by 15O PET, 17O NMR, and BOLD fMRI. In hypothermia, we detected a significant decrease of 37% and 32% in CMRO2 in the cortex of mice and rats, respectively. Q10 was calculated to be 3.2 in mice and 2.7 in rats. In this study we showed that it is possible to assess absolute values of metabolic correlates such as CMRO2, CBF and oxygen extraction fraction (OEF) noninvasively in living brain of mice and rats by combining NIRS with MRI. This will open new possibilities for studying brain metabolism in patients as well as the many mouse/rat models of brain disorders.

2.
Opt Express ; 27(20): 29297-29308, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684666

RESUMO

We investigate theoretically the generation and enhancement of sum sideband in a quadratically coupled optomechanical system with parametric interactions. It is shown that the generation of frequency components at the sum sideband stems from the nonlinear optomechanical interactions via two-phonon processes in the quadratically coupled optomechanical system, while an optical parametric amplifier (OPA) inside the system can considerably improve the sum sideband generation (SSG). The dependence of SSG on the system parameters, including the power of the control field, the frequency detuning of the probe fields and the nonlinear gain of OPA are analyzed in detail. Our analytic calculation indicates that the SSG can be obtained even under weak driven fields and greatly enhanced via meeting the matching conditions. The effect of SSG may have potential applications for achieving measurement of electric charge (or other weak forces) with higher precision and on-chip manipulation of light propagation.

3.
J Vasc Res ; : 1-10, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31715615

RESUMO

AIM: Glucose fluctuations may be responsible for, or further the onset of arterial hypertension, but the exact mechanisms remain unclear. The purpose of this study was to investigate the mechanisms behind and related to aortic fibrosis and aortic stiffening induced by glucose fluctuations. METHODS: Sprague-Dawley rats were injected with streptozotocin (STZ) and randomly divided into three treatment groups: controlled STZ-induced diabetes (C-STZ); uncontrolled STZ-induced diabetes (U-STZ); and STZ-induced diabetes with glucose fluctuations (STZ-GF). After 3 weeks, rat blood pressure (BP) was tested, and aortic fibrosis was detected by using the Masson trichrome staining technique. Levels of p38 mitogen-activated protein kinase (p38 MAPK), runt-related transcription factor 2 (Runx2), collagen type 1 (collagen I), and NADPH oxidases were determined by Western blot.Rat vascular smooth muscle cells in vitro were used to explore underlying mechanisms. RESULTS: The systolic BP of diabetic rats in the C-STZ, U-STZ, and STZ-GF groups was 127.67 ± 6.53, 150.03 ± 5.24, and 171.63 ± 3.53 mm Hg, respectively (p< 0.05). The mean BP of diabetic rats in the three groups was 91.20 ± 10.07, 117.29 ± 4.28, and 140.58 ± 2.14 mm Hg, respectively (p< 0.05). The diastolic BP of diabetic rats in the three groups was 73.20 ± 12.63, 101.93 ± 5.79, and 125.37 ± 4.62 mm Hg, respectively (p< 0.05). The ratios of fibrosis areas in the aortas of the three groups were 11.85 ± 1.23, 29.00 ± 0.87, and 48.36 ± 0.55, respectively (p< 0.05). The expressions of p38 MAPK, Runx2, and collagen I were significantly increased in the STZ-GF group. In vitro, applications of inhibitors of reactive oxygen species (ROS) and p38 MAPK successfully reversed glucose fluctuations that would have possibly induced aortic fibrosis. CONCLUSIONS: Blood glucose fluctuations aggravate aortic fibrosis via affecting the ROS/p38 MAPK /Runx2 signaling pathway.

4.
Clin Lab ; 65(11)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31710436

RESUMO

BACKGROUND: Although some recent studies have shown that small nucleolar RNA host gene 6 (SNHG6) was associated with clinical outcomes in malignant tumors, the results remain insufficient and inconsistent. Therefore, we performed this meta-analysis to clarify whether SNHG6 can serve as a prognostic biomarker in cancer. METHODS: We conducted a detailed search of the following online databases for all eligible studies: PubMed, Web of Science, and Embase. A meta-analysis was performed using Stata 12.0 software. The Cancer Genome Atlas (TCGA) dataset was further utilized to verify the results. RESULTS: Compared to corresponding normal tissues, SNHG6 expression was significantly up-regulated in most types of solid tumors. A total of 1,535 patients from eighteen studies were included in this study to investigate the correlation of SNHG6 with overall survival and clinicopathological parameters by pooled hazard ratio (HR) and odds ratio (OR) in cancer. Our results manifested that altered SNHG6 expression was markedly related with worse overall survival (HR = 1.88, 95% CI: 1.56 - 2.19, p = 0.000) among tumor patients. Levels of SNHG6 were closely associated with tumor size (OR = 1.95, 95% CI: 1.18 - 3.20, p = 0.009), tumor invasion (OR = 3.22, 95% CI: 2.08 - 4.98, p = 0.000), lymph node metastasis (OR = 2.62, 95% CI: 1.36 - 5.04, p = 0.004), distant metastasis (OR = 5.01 95% CI: 3.11 - 8.09, p = 0.000), and tumor stage (OR = 2.97 95% CI: 2.31 - 3.82, p = 0.000), but not related to histological differentiation (OR = 1.40, 95% CI: 0.77 - 2.52, p = 0.27) in cancer. CONCLUSIONS: High expression level of SNHG6 was correlated with more advanced clinicopathological features and poor prognosis and might be a potential molecular marker for cancer prognosis.

5.
Hum Mol Genet ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31691812

RESUMO

Integration of genome-wide association study (GWAS) signals with expression quantitative trait loci (eQTL) studies enables identification of candidate genes. However, evaluating whether nearby signals may share causal variants, termed colocalization, is affected by the presence of allelic heterogeneity, different variants at the same locus impacting the same phenotype. We previously identified eQTLs in subcutaneous adipose tissue from 770 participants in the METSIM study and detected 15 eQTL signals that colocalized with GWAS signals for waist-hip ratio (WHRadjBMI) from the GIANT consortium. Here, we reevaluated evidence of colocalization using two approaches, conditional analysis and the Bayesian test COLOC, and show that providing COLOC with approximate conditional summary statistics at multi-signal GWAS loci can reconcile disagreements in colocalization classification between the two tests. Next, we performed conditional analysis on the METSIM subcutaneous adipose tissue data to identify conditionally distinct, or secondary, eQTL signals. We used the two approaches to test for colocalization with WHRadjBMI GWAS signals and evaluated the differences in colocalization classification between the two tests. Through these analyses, we identified four GWAS signals colocalized with secondary eQTL signals for FAM13A, SSR3, GRB14, and FMO1. Thus, at loci with multiple eQTL and/or GWAS signals, analyzing each signal independently enabled additional candidate genes to be identified.

6.
Cell Death Dis ; 10(11): 843, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31695022

RESUMO

Doxorubicin is conventionally used in chemotherapy against hepatocellular carcinoma (HCC), but acquired resistance developed during long-term therapy limits its benefits. Autophagy, a conserved catabolic process for cellular self-protection and adaptation to the changing environment, is regarded as a potential clinical target to overcome doxorubicin resistance. In this study, the potential role of miR-223 in modulating doxorubicin-induced autophagy and sensitivity were evaluated in four transfected human HCC cell lines, and the in vivo relevance was assessed using a mouse xenograft model of HCC. We found that the well-defined miR-223 is expressed at low levels in doxorubicin treated HCC cells and that miR-223 overexpression inhibits the doxorubicin-induced autophagy that contributes to chemoresistance. Blockade of autophagic flux by chloroquine resulted in the failure of miR-223 inhibitor to suppress doxorubicin sensitivity of HCC cells. We further identified FOXO3a as a direct downstream target of miR-223 and primary mediator of the regulatory effect of miR-223 on doxorubicin-induced autophagy and chemoresistance in HCC cells. Finally, we confirmed the enhancement of doxorubicin sensitivity by agomiR-223 in xenograft models of HCC. These findings establish a novel miRNA-based approach for autophagy interference to reverse doxorubicin resistance in future chemotherapy regimens against human HCC.

7.
J Immunol ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31704883

RESUMO

Duck Tembusu virus (DTMUV) is a newly emerged causative agent of avian disease. The protease-dependent immune evasion of flaviviruses has been reported; however, the molecular details of this process are unclear. In this study, we found that DTMUV nonstructural protein 2B-3, a NS2B3 protease, can inhibit IFN-ß production. DTMUV NS2B3 inhibited RIG-I-, MDA5-, MAVS-, and STING-directed IFN-ß transcription, but not TBK1- and IRF7-mediated induction of IFN-ß. Further analysis showed that DTMUV NS2B3 could cleave duck STING (duSTING); the cleavage was dependent on the protease activity of NS2B3. Moreover, the STING cleavage event occurred in a not-strictly-species-specific manner. The scissile bond of duSTING cleaved by NS2B3 was mapped between the R84 and G85 residues. The ability of NS2B3 to reduce duSTING cleavage-resistant mutant-mediated IFN-ß, and ISG production was significantly reduced, demonstrating that duSTING cleavage is essential for NS2B3-induced suppression of type I IFN responses. Remarkably, the binding of NS2B3 to duSTING, which is a prerequisite for cleavage, was found to depend on NS2B, but not NS3, the cofactor of the enzyme. Unexpectedly, we found that the region between aa residues 221-225 of duSTING, distal from the site of the scissile bond, was essential for the binding of NS2B3 to duSTING and/or the cleavage of duSTING by NS2B3. Thus, we identified the molecular mechanism by which DTMUV subverts the host innate immunity using its protease. More importantly, our study provides insight into NS2B3-mediated STING cleavage events in general.

8.
Environ Res ; 179(Pt B): 108809, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31678729

RESUMO

BACKGROUND: Exposure to ambient fine particles, particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5), is a public health concern. Concentrations of ambient PM2.5 have changed temporally in the past 10 years after a series of action policies for improving air quality were implemented in Taiwan. In this study, temporal changes in the relationship between PM2.5 and lung function among children were investigated. METHODS: A nationwide respiratory health survey was conducted among Taiwanese elementary and middle school students in 2011 and again in 2016-2017. A questionnaire was administered to students, for whom forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured using spirometry. During the study period, monthly concentrations of ambient PM2.5 were obtained from the monitoring stations of the Environmental Protection Administration. Lung function measurements were compared with ambient PM2.5 exposure using mixed-effects models. RESULTS: In the 2011 survey (mean PM2.5: 40.6 µg/m3), exposure to PM2.5 in the preceding 1-2 months was associated with a 2.2% decrease (95% confidence interval [CI]: -4.1%, -0.3%) in FVC and a 2.3% decrease (95% CI: -4.0%, -0.5%) in FEV1. By contrast, a significant relationship between PM2.5 concentrations and lung function was not observed in the 2016-2017 survey (mean PM2.5: 30.0 µg/m3). CONCLUSIONS: As improvement in air quality over time, the negative relationship between PM2.5 and childhood lung function tend to be not significant.

9.
Virol J ; 16(1): 134, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718685

RESUMO

BACKGROUND: Duck tembusu virus (DTMUV, genus Flaviviruses, family Flaviviridae) is an emerging flavivirus that can infect a wide range of cells and cell lines in vitro, though the initial step of virus invasion remains obscure. METHODS: In this study, drug treatments that including heparin, chondroitin sulfate, heparinase I, chondroitinase ABC and trypsin were applied to detect the influence of DTMUV absorption, subsequently, the copy number of viral genome RNA was analyzed by quantitative real-time PCR. The inhibition process of viral absorption or entry by heparin was determined by western blotting, and the cytotoxicity of drug treated cells was detected by cell counting kit-8. RESULTS: We found that the desulfation of glycosaminoglycans (GAGs) with sodium chlorate had a significant effect on the adsorption of DTMUV in both BHK21 and DEF cells. Based on this result, we incubated cells with a mixture of DTMUV and GAGs competition inhibitors or pre-treated cells with inhibitors, after incubation with the virus, the NS5 expression of DTMUV and viral titers were detected. The data suggested that heparin can significantly inhibit the absorption of DTMUV in a dose dependent manner but not at the step of viral entry in BHK21 and DEF cells. Meanwhile, heparinase I can significantly inhibit DTMUV attachment step. CONCLUSIONS: Our results clearly proved that heparin sulfate plays an important role in the first step of DTMUV entry, viral attachment, in both BHK21 and DEF cells, which sheds light on the entry mechanism of DTMUV.

10.
Virol J ; 16(1): 136, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727103

RESUMO

BACKGROUND: Goose parvovirus (GPV) is the etiological agent of Derzsy's disease and is fatal for gosling. Research on the molecular basis of GPV pathogenicity has been hampered by the lack of a reliable reverse genetics system. At present, the GPV infectious clone has been rescued by transfection in the goose embryo, but the growth character of it is unclear in vitro. METHODS: In this study, we identified the full-length genome of GPV RC16 from the clinical sample, which was cloned into the pACYC177, generating the pIRC16. The recombinant virus (rGPV RC16) was rescued by the transfection of pIRC16 into goose embryo fibroblasts (GEFs). The rescued virus was characterized by whole genome sequencing, indirect immunofluorescence assays (IFA) and western blot (WB) using rabbit anti-GPV Rep polyclonal antibody as the primary antibody. Previously, we found the 164 K, 165 K, and 167 K residues in the 160YPVVKKPKLTEE171 are required for the nuclear import of VP1 (Chen S, Liu P, He Y, et al. Virology 519:17-22). According to that, the GPV infectious clones with mutated K164A, K165A, or K167A in VP1 were constructed, rescued and passaged. RESULTS: The rGPV RC16 has been successfully rescued by transfection of pIRC16 into the GEFs and can proliferate in vitro. Furthermore, the progeny virus produced by pIRC16 transfected cells was infectious in GEFs. Moreover, mutagenesis experiments showed that the rGPV RC16 with mutated 164 K, 165 K and 167 K in VP1 could not proliferate in GEFs based on the data of IFA and WB in parental virus and progeny virus. CONCLUSIONS: The rGPV RC16 containing genetic maker and the progeny virus are infectious in GEFs. The 164 K, 165 K, and 167 K of VP1 are vital for the proliferation of rGPV RC16 in vitro.

11.
BMC Plant Biol ; 19(1): 511, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752697

RESUMO

BACKGROUND: Application of the CRISPR/Cas9 system or its derived base editors enables targeted genome modification, thereby providing a programmable tool to exploit gene functions and to improve crop traits. RESULTS: We report that PmCDA1 is much more efficient than rAPOBEC1 when fused to CRISPR/Cas9 nickase for the conversion of cytosine (C) to thymine (T) in rice. Three high-fidelity SpCas9 variants, eSpCas9(1.1), SpCas9-HF2 and HypaCas9, were engineered to serve with PmCDA1 (pBEs) as C-to-T base editors. These three high-fidelity editors had distinct multiplex-genome editing efficiencies. To substantially improve their base-editing efficiencies, a tandemly arrayed tRNA-modified single guide RNA (sgRNA) architecture was applied. The efficiency of eSpCas9(1.1)-pBE was enhanced up to 25.5-fold with an acceptable off-target effect. Moreover, two- to five-fold improvement was observed for knock-out mutation frequency by these high-fidelity Cas9s under the direction of the tRNA-modified sgRNA architecture. CONCLUSIONS: We have engineered a diverse toolkit for efficient and precise genome engineering in rice, thus making genome editing for plant research and crop improvement more flexible.

12.
Int J Mol Sci ; 20(22)2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31766280

RESUMO

The mechanisms regulating vascular smooth muscle cell (VSMC) phenotype switching and the critical signal modulation affecting the VSMCs remain controversial. Physical exercise acts as an effective drug in preventing elevated blood pressure and improving vascular function. This study was designed to explore the influence of aerobic exercise on the suppression of VSMC phenotype switching by balancing of the Akt, also known as PKB (protein kinase B) and mitogen-activated protein kinase (MAPK) signaling pathways. Spontaneously hypertensive rats (SHRs) and normotensive rats were subjected to exercise treatment before measuring the vascular morphological and structural performances. Exercise induced reverse expression of VSMC protein markers (α-SM-actin, calponin, and osteopontin (OPN)) in spontaneously hypertensive rats. It is noteworthy that the low expression of phosphorylated Akt significantly decreased the expression of VSMC contractile phenotype markers (α-SM-actin and calponin) and increased the expression of the VSMC synthetic phenotype marker (OPN). However, the MAPK signal pathway exerts an opposite effect. VSMCs and whole vessels were treated by inhibitors, namely the p-Akt inhibitor, p-ERK inhibitor, and p-p38 MAPK inhibitors. VSMC phenotype markers were reversed. It is important to note that a significant reverse regulatory relationship was observed between the expression levels of MAPK and the contractile markers in both normotensive and spontaneously hypertensive rats. We demonstrate that aerobic exercise regulates the VSMC phenotype switching by balancing the Akt and MAPK signaling pathways in SHRs.

13.
Am J Crit Care ; 28(6): 462-470, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31676521

RESUMO

BACKGROUND: Serum level of interleukin 6 (IL-6) is known to be associated with postoperative delirium. However, no consensus has emerged on the postoperative time point at which IL-6 level may predict postoperative delirium after coronary artery bypass graft surgery. OBJECTIVES: To compare trends in IL-6 levels in patients with and without postoperative delirium and to examine the relationship between IL-6 levels at different times and postoperative delirium after coronary artery bypass graft. METHODS: A prospective cohort study of patients who underwent their first elective isolated coronary artery bypass graft between November 2013 and August 2015 at a cardiac intensive care unit in Beijing, China. Concentrations of IL-6 were measured before the operation and at the 6th, 12th, and 18th postoperative hours. Participants were assessed for postoperative delirium twice daily for 5 days. Univariate and multivariate logistic regression analyses were done to determine associations between IL-6 levels at different time points, postoperative changes in IL-6 levels, and the occurrence of postoperative delirium. RESULTS: Postoperative delirium was diagnosed in 85 of 266 patients (32%). Levels of IL-6 were significantly higher in patients with postoperative delirium than in patients without it at the 6th, 12th, and 18th postoperative hours (P = .03, .004, and .001, respectively). Change in IL-6 level (odds ratio, 2.97; 95% CI, 1.20-7.31; P = .02) and IL-6 level of 583 pg/mL or higher at the 18th postoperative hour (odds ratio, 5.20; 95% CI, 1.84-14.70; P = .002) were associated with higher incidence of postoperative delirium. CONCLUSION: Interleukin 6 level (≥ 583 pg/mL) at the 18th postoperative hour may serve as a potent predictor of postoperative delirium in coronary artery bypass graft patients.

14.
Opt Express ; 27(19): 26924-26939, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31674563

RESUMO

High-performance GeSn multiple-quantum-well (MQW) photodiode is demonstrated on a 200 mm Ge-on-insulator (GeOI) photonics platform for the first time. Both GeSn MQW active layer stack and Ge layer (top Ge layer of GeOI after bonding) were grown using a single epitaxy step on a standard (001)-oriented Si substrate (donor wafer) using a reduced pressure chemical vapor deposition (RPCVD). Direct wafer bonding and layer transfer technique were then employed to transfer the GeSn MQW device layers and Ge layer to a 200 mm SiO2-terminated Si handle substrate. The surface illuminated GeSn MQW photodiode realized on this platform exhibits an ultra-low leakage current density of 25 mA/cm2 at room temperature and an enhanced photo sensitivity at 2 µm of 30 mA/W as compared to a GeSn MQW photodiode on Si at 2 µm. The underlying GeOI platform enables monolithic integration of a complete suite of photonics devices operating at 2 µm band, including GeOI strip waveguides, grating couplers, micro-ring modulators, Mach-Zehnder interferometer modulators, etc. In addition, Ge CMOS circuits can also be realized on this common platform using a "photonic-first and electronic-last" processing approach. In this work, as prototype demonstration, both Ge p- and n-channel fin field-effect transistors (FinFETs) were realized on GeOI simultaneously with decent static electrical characteristics. Subthreshold swings of 150 and 99 mV/decade at |VD| = 0.1 V and drive currents of 91 and 10.3 µA/µm at |VG-VTH| = 1 V and |VD| = 0.75 V were achieved for p- and n-FinFETs, respectively. This works illustrates the potential of integrating GeSn (as photo detection material) on GeOI platform for Ge-based optoelectronics integrated circuits (OEICs) targeting communication applications at 2 µm band.

15.
Sci Rep ; 9(1): 16783, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727985

RESUMO

Duck hepatitis A virus (DHAV) causes an infectious disease that mainly affects 1- to 4-week-old ducklings, resulting in considerable loss to the duck industry. Although there have been many studies on DHAV in recent years, the effects on host infection and pathogenesis of DHAV-1 remain largely unknown. This study investigated the effects of the DHAV-1 structural protein VP3 on DHAV-1 virus adsorption and apoptosis to explore the role of VP3 in the viral life cycle. The effects of DHAV-1 VP3 and an antibody against the protein on virion adsorption was analyzed by qRT-PCR. The results showed that the virus copy number for the rabbit anti-VP3 IgG-treated group was significantly lower than that for the negative control group but higher than that for the rabbit anti-DHAV-1 IgG-treated group. This result indicates that VP3 mediates DHAV-1 virus adsorption but that it is not the only protein that involved in this process. In addition, a eukaryotic recombinant plasmid, pCAGGS/VP3, was transfected into duck embryo fibroblasts (DEFs), and the apoptotic rate was determined by DAPI staining, the TUNEL assay and flow cytometry. DAPI staining showed nucleus fragmentation and nuclear edge shifting. TUNEL assay results revealed yellow nuclei, and flow cytometry indicated a significant increase in the apoptotic rate. In addition, qRT-PCR revealed increased in the transcriptional levels of the apoptotic caspase-3, -8 and -9, with the largest increase for caspase-3, followed by caspase-9 and caspase-8. Enzyme activity analysis confirmed these results. Furthermore, the VP3 protein decreased the mitochondrial membrane potential, and the transcriptional levels of the proapoptotic factors Bak, Cyt c and Apaf-1 in the mitochondrial apoptotic pathway were significantly upregulated. These data suggest that expression of VP3 in DEFs induces apoptosis and may primarily activate caspase-3-induced apoptosis through mitochondrion-mediated intrinsic pathways. The findings provide scientific data to clarify DHAV-1 infection and pathogenesis.

16.
Minerva Pediatr ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31729207

RESUMO

BACKGROUND: This study investigated the clinical characteristics, cranial magnetic resonance imaging (MRI) features, MRI follow-up, and prognosis of children with acute lymphoblastic leukemia (ALL) who developed posterior reversible encephalopathy syndrome (PRES) during remission induction chemotherapy. METHODS: We analyzed the age, gender, PRES symptoms and signs, cranial MRI findings, therapeutic effect, and prognosis of children with ALL who developed PRES during chemotherapy from January 2010 to December 2013 at the Hematology Oncology Center of Beijing Children's Hospital. Changes in cranial MRI findings were analyzed, and intelligence (IQ) and cognitive function were evaluated using the Wechsler Scale and the Wisconsin Card Score Test after the children completed chemotherapy. RESULTS: There were 850 children with newly diagnosed ALL in this period; 13 (1.5%), 6 boys and 7 girls, developed PRES. All were diagnosed as B-cell ALL. The median age at PRES onset was 7 years (2-11 years). The median day of PRES onset was day 28 (day 17-34) of remission induction chemotherapy. Of the 13 children with PRES onset and seizures, 4 had visual disturbances and 2 had consciousness disturbances. Cranial MRI showed hyperintensity in the subcortical white matter on T2-weighted axial and fluid-attenuated inversion recovery (FLAIR) images. The lesion locations were as follows: occipital lobe, 12 (92.3%) patients; frontal lobe, 7 (53.8%) patients; temporal lobe, 5 (38.4%) patients; parietal lobe, 3 (23.1%) patients; and cerebellum, 1 (7.7%) patient. There were 8 (61.5%) patients with vasogenic edema and 5 (38.5%) with cytotoxic edema. After treatment, all children recovered within one month,when their PRES symtoms were relieved, they continued to receive chemotherapy. However, 1 child (1.07%) died of severecentral nervous system infection one year after PRES treatment, and 3 (25%) had recurrent seizures and were diagnosed with epilepsy after three months of PRES treatment. Their cranial MRIs showed cytotoxic edema, which was acute stage on day 15, with aggravated lesions on cranial MRI. The cranial MRI lesions returned to normal at one month in 3 (23.1%) patients, at three months in 6 (46.1%) patients, at one year in 8 (61.5%) patients, and at two years in 12 (92.3%) patients. The 12 surviving children all returned to school, and their full-scale, verbal, and performance IQs were normal, with no significant differences in intelligence or cognitive function compared with children with ALL without PRES during the same period. CONCLUSIONS: PRES can occur during remission induction chemotherapy treatment of children with ALL, but the incidence is low. Cranial MRI can be used for diagnosis and to characterize lesions. The children recover about a month after treatment, and cranial MRI lesions return to normal within two years. The time for complete resolution of MRI lesions differs, and children with cytotoxic edema have worse prognosis with sequelae, such as epilepsy, which requires close monitoring. PRES does not affect intelligence or cognitive development.

17.
Int J Nurs Stud ; 102: 103451, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31734218

RESUMO

BACKGROUND: As the majority of out-of-hospital cardiac arrest occur at patients' homes, implementing high-quality cardiopulmonary resuscitation by family members is critical in improving patient outcomes. However, the survival rate remains low due to low bystander cardiopulmonary resuscitation rate and rapid skill deterioration in individuals who complete the training. OBJECTIVES: To evaluate the effectiveness of audio-visual review model and audio-visual-practice review model on cardiopulmonary resuscitation skill retention 12 months after training. DESIGN: A randomized, double-blind, placebo controlled, and three-arm parallel study. PARTICIPANTS: A total of 641 family members of patients at high risk of out-of-hospital cardiac arrest enrolled in the study and 448 participants completed the follow-up. METHODS: Family members from Beijing, China were recruited. All families underwent initial cardiopulmonary resuscitation training. Their cardiopulmonary resuscitation skill and knowledge were assessed immediately after training. Trainees who were rated "adequate skill and knowledge" were assigned randomly into one of three groups. The control group was given a cardiopulmonary resuscitation instruction booklet and a placebo-DVD without any reminders. Both audio-visual and audio-visual-practice groups were reinforced by a telephone reminder every 3 months. The audio-visual-practice group was also asked to simultaneously practice the skills while watching the instructional-DVD. The trainees' cardiopulmonary resuscitation skills and knowledge were re-assessed 12 months after training. RESULTS: The retention rates of cardiopulmonary resuscitation skills in both audio-visual-practice (N = 177) and audio-visual (N = 157) groups were higher than that in control group (N = 114) 12 months after training (all P-values  < 0.001). The cardiopulmonary resuscitation skill retention rate in audio-visual-practice group was higher than that in audio-visual group (49.7% vs 36.9%, P = 0.019), but no difference was found in intention-to-treat analysis (32.1% vs 27.1%, P = 0.230). Both audio-visual-practice and audio-visual groups had higher correct rates on all skill elements than that in control group (all P-values < 0.05). The cardiopulmonary resuscitation knowledge scores in both audio-visual-practice and audio-visual groups were higher than that in control group (all P-values < 0.001). However, no significant difference was found between audio-visual-practice and audio-visual groups (P = 0.243). CONCLUSIONS: Both audio-visual-practice and audio-visual review models demonstrated better long-term retention of cardiopulmonary resuscitation skills for families of people at higher risk of out-of-hospital cardiac arrest. (Registration number: chiCTR-TRC-12002149).

18.
World J Surg Oncol ; 17(1): 177, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31677642

RESUMO

BACKGROUND: Inflammation plays a critical role in the development and progression of cancers. The advanced lung cancer inflammation index (ALI) is thought to be able to reflect systemic inflammation better than current biomarkers. However, the prognostic significance of the ALI in various types of cancer remains unclear. Our meta-analysis aimed to comprehensively investigate the relationship between the ALI and oncologic outcomes to help physicians better assess the prognosis of cancer patients. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched for relevant studies. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated and pooled from the included studies. Furthermore, a sensitivity analysis was performed to evaluate the reliability of the articles. Finally, Begg's test, Egger's test, and the funnel plot were applied to assess the significance of publication bias. RESULTS: In total, 1736 patients from nine studies were included in our meta-analysis. The median cutoff value for the ALI was 23.2 (range, 15.5-37.66) in the analyzed studies. The meta-analysis showed that there was a statistically significant relationship between a low ALI and worse overall survival (OS) in various types of cancer (HR = 1.70, 95% CI = 1.41-1.99, P < 0.001). Moreover, results from subgroup meta-analysis showed that the ALI had a significant prognostic value in non-small cell lung cancer, small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma, and diffuse large B cell lymphoma (P < 0.05 for all). CONCLUSIONS: These results showed that a low ALI was associated with poor OS in various types of cancer, and the ALI could act as an effective prognostic biomarker in cancer patients.

20.
J Med Chem ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769665

RESUMO

Antiviral drug resistance in influenza infections has been a major threat to public health. In order to develop a broad-spectrum inhibitor of influenza to combat the problem of drug resistance, we previously identified the highly conserved E339…R416 salt bridge of the nucleoprotein trimer as a target, and compound 1 as an inhibitor disrupting the salt bridge with an EC50 = 2.7 µM against influenza A (A/WSN/1933). We have further modified this compound via a structure-based approach and performed an antiviral activity screen to identify compounds 29 and 30 with EC50 values of 110 and 120 nM respectively and without measurable host cell cytotoxicity. Compared to the clinically used neuraminidase inhibitors, these two compounds showed better activity profiles against drug-resistant influenza A strains, as well as influenza B, and improved survival of influenza-infected mice.

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