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1.
BMC Musculoskelet Disord ; 21(1): 309, 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32416723

RESUMO

BACKGROUND: Postoperative pulmonary complications (PPCs) seems to be high in patients undergoing pelvic and sacrum tumor resection assisted by abdominal aortic balloon occlusion. We hypothesized that the accumulative occlusion time (AOT) of the abdominal aortic balloon may be predictive of PPCs. The objective of the study was to identify the influence of AOT on PPCs. METHODS: Retrospectively analyzed perioperative factors of 584 patients who underwent pelvic and sacrum tumor resection assisted by abdominal aortic balloon occlusion in our hospital from January 1, 2016 to December 31, 2018. PPCs including suspected pulmonary infection, atelectasis, pulmonary edema, pleural effusion, respiratory failure were clinically diagnosed. Perioperative parameters among patients with and without PPCs were compared. A receiver operating characteristic (ROC) analysis was conducted to evaluate the discriminative power of AOT with regard to PPCs. A multivariate logistic-regression model was finally established to identify independent risk factors for PPCs. RESULTS: The incidence of PPCs was 15.6% (91 patients). The median AOT in PPCs group was significantly higher than that in non-PPCs group (P <  0.001). The hospital stay was significantly prolonged in PPCs group (P <  0.001). The ROC analysis showed an AOT of 119 min as the threshold value at which the joint sensitivity (88.60%) and specificity (31.87%) was maximal. Finally, AOT ≥ 119 min (P = 0.046; odds ratio (OR) = 2.074), age (P < 0.001; OR = 1.032), ASA grade III (P = 0.015; OR = 3.264), and estimated blood loss (P = 0.022; OR = 1.235) were independent risk factors of PPCs by multivariate logistic regression analysis. CONCLUSION: The incidence of PPCs in patients undergoing the pelvic and sacrum tumor surgery assisted by abdominal aortic balloon occlusion was 15.6%. AOT ≥ 119 min was an independent predictor for PPCs. Surgeons should strive to minimize the AOT within 2 h.

2.
Fish Shellfish Immunol ; 101: 88-98, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32229294

RESUMO

Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) are a family of crucial signaling molecules that mediate the signal transduction of various immune signaling pathways. Extensive studies have demonstrated that TRAFs play vital roles in regulating cellular immune responses. However, the biological functions and expression profiling of TRAFs in Chinese soft-shelled turtle (Pelodiscus sinensis) remain unclear. In this study, the genes of the PsTRAF family at the genome-wide level were identified in P. sinensis, revealing six PsTRAF members that contained the conserved TRAF domain in the C-terminal regions. Molecular evolutionary analysis showed that PsTRAFs shared close evolutionary relationships and similar protein crystal structures with the TRAF homologs from other turtles, indicating the evolutionary conservation of PsTRAFs. Further expression analysis revealed the tissue-specific expression of PsTRAF genes. Obvious variations in the expression of PsTRAF genes were observed in the spleen in response to Aeromonas hydrophila infection. Three PsTRAF genes, PsTRAF2, PsTRAF3, and PsTRAF6, were significantly upregulated at the mRNA and protein levels post-infection, indicating their potential function in the immune response. Moreover, the protein-protein associations of PsTRAFs with several signaling receptors were predicted in P. sinensis. These results provide a basis for the investigation of the functional roles of PsTRAFs in immune defense against bacterial infection.

3.
Ther Adv Respir Dis ; 14: 1753466620914220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32345137

RESUMO

BACKGROUND: Non-invasive ventilation (NIV) was one of the first-line ventilation supports for hematopoietic stem-cell transplantation (HSCT) patients with acute respiratory distress syndrome (ARDS). Successful NIV may avoid need for intubation. However, the influence NIV failure had on patients' outcome and its risk factors were hardly known. METHODS: In this retrospective observational study, we reported risk factors and incidence of NIV failure in HSCT patients who were admitted to the Intensive Care Unit (ICU) with a diagnosis of ARDS and supported with mechanical ventilation, in a 5-year period. Patient outcomes, such as ventilator-free days, ICU-free days, and ICU mortality were also reported. RESULTS: Of all the 94 patients included, 70 patients were initially supported with NIV. NIV failure occurred in 44 (63%) patients. Male sex, elevated serum galactomannan (GM) test, (1-3)-ß-D-glucan (BG) assay, or elevated serum creatinine level were risk factors for NIV failure. When compared with the NIV success group, failure of NIV was associated with much fewer ICU-free days (22 versus 0, p < 0.001, Cohen's d = 0.62) and higher ICU mortality (9.5% versus 75.5%, p < 0.001, Pearson's r = 0.75). There was no difference in ICU-free days, ventilator-free days and ICU mortality between NIV failure and initial invasive mechanical ventilation (IMV) groups. Patients who failed in NIV support had a higher ICU mortality (75.5%) than those who succeeded (9.5%). CONCLUSION: In a small cohort of HSCT patients with mainly moderate severity of ARDS, male patients with elevated serum GM/BG test or serum creatinine level had a higher risk of NIV failure. Both NIV failure and initial IMV groups were characterized by high mortality rate and extremely low ICU-free days and ventilator-free days; failure of NIV support may further aggravate patient prognosis. The reviews of this paper are available via the supplemental material section.

4.
Am J Physiol Lung Cell Mol Physiol ; 318(4): L787-L800, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32129084

RESUMO

Clinical studies have established that the capacity of removing excess fluid from alveoli is impaired in most patients with acute respiratory distress syndrome. Impaired alveolar fluid clearance (AFC) correlates with poor outcomes. Adenosine A2B receptor (A2BAR) has the lowest affinity with adenosine among four adenosine receptors. It is documented that A2BAR can activate adenylyl cyclase (AC) resulting in elevated cAMP. Based on the understanding that cAMP is a key regulator of epithelial sodium channel (ENaC), which is the limited step in sodium transport, we hypothesized that A2BAR signaling may affect AFC in acute lung injury (ALI) through regulating ENaC via cAMP, thus attenuating pulmonary edema. To address this, we utilized pharmacological approaches to determine the role of A2BAR in AFC in rats with endotoxin-induced lung injury and further focused on the mechanisms in vitro. We observed elevated pulmonary A2BAR level in rats with ALI and the similar upregulation in alveolar epithelial cells exposed to LPS. A2BAR stimulation significantly attenuated pulmonary edema during ALI, an effect that was associated with enhanced AFC and increased ENaC expression. The regulatory effects of A2BAR on ENaC-α expression were further verified in cultured alveolar epithelial type II (ATII) cells. More importantly, activation of A2BAR dramatically increased amiloride-sensitive Na+ currents in ATII cells. Moreover, we observed that A2BAR activation stimulated cAMP accumulation, whereas the cAMP inhibitor abolished the regulatory effect of A2BAR on ENaC-α expression, suggesting that A2BAR activation regulates ENaC-α expression via cAMP-dependent mechanism. Together, these findings suggest that signaling through alveolar epithelial A2BAR promotes alveolar fluid balance during endotoxin-induced ALI by regulating ENaC via cAMP pathway, raising the hopes for treatment of pulmonary edema due to ALI.

5.
Neurosci Bull ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32096115

RESUMO

Social defeat stress (SDS) plays a major role in the pathogenesis of psychiatric disorders like anxiety and depression. Sleep is generally considered to involve recovery of the brain from prior experience during wakefulness and is altered after acute SDS. However, the effect of acute SDS on sleep/wake behavior in mice varies between studies. In addition, whether sleep changes in response to stress contribute to anxiety is not well established. Here, we first investigated the effects of acute SDS on sleep/wake states in the active period in mice. Our results showed that total sleep time (time in rapid eye-movement [REM] and non-REM [NREM] sleep) increased in the active period after acute SDS. NREM sleep increased mainly during the first 3 h after SDS, while REM sleep increased at a later time. Then, we demonstrated that the increased NREM sleep had an anxiolytic benefit in acute SDS. Mice deprived of sleep for 1 h or 3 h after acute SDS remained in a highly anxious state, while in mice with ad libitum sleep the anxiety rapidly faded away. Altogether, our findings suggest an anxiolytic effect of NREM sleep, and indicate a potential therapeutic strategy for anxiety.

6.
BMC Ophthalmol ; 20(1): 10, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906917

RESUMO

BACKGROUND: Developing objective and repeatable indicators to evaluate the efficacy of PVRL treatment is important. The quantification of vitreous cells is a traditional criterion; however slight changes are difficult to ascertain. Spectral domain optical coherence tomography (SD-OCT) is objective, repeatable, and easily explained. The purpose of this study is to provide a longitudinal observation of OCT in PVRL treated with intravitreal injections of methotrexate (MTX) and to evaluate the utility of OCT in monitoring responsiveness of PVRL to treatment. METHODS: The medical records of patients with biopsy-positive PVRL attending our hospital between January 2016 and September 2017 who received intravitreal injections of MTX were included in this study. Pre- and post-treatment OCT images were reviewed independently by two researchers. RESULTS: Of the 24 cases reviewed, 10 patients (18 eyes) were included. SD-OCT abnormalities at the initial visit included vitreous cells (18/18), OR (outer retina) fuzzy borders (12/18), PED (pigment epithelium detachments) (9/18), subretinal hyperreflective infiltration (3/18), intraretinal infiltration (8/18), and SRF (subretinal fluid) (4/18). Post induction treatment, SRF in cases with RD (retinal detachment) was absorbed, and subretinal fibrosis appeared. Other lesions were significantly reduced. Post consolidation treatment, OR fuzzy borders, PED and SRF disappeared in 2 eyes, intraretinal infiltration disappeared in 1 eye, and other abnormalities further improved. Additionally, retinal fibrosis was observed in 3 eyes. One month post maintenance treatment, all abnormalities observed at the first visit vanished. At the last visit, OCT showed subretinal fibrosis and in 3 eyes (16.7%), the disruption of outer retina in 9 eyes (50%) and thinning of the whole layer in 4 eyes (22.2%). CONCLUSIONS: Our observations reveal that characteristic OCT features in PVRL patients can reduce gradually and finally vanish with therapy. We propose that SD-OCT may be employed to monitor the responsiveness of PVRL to treatment, which may influence decision making in the management of this disease.

7.
Biosens Bioelectron ; 150: 111870, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31748192

RESUMO

Detection of cancer biomarkers is crucial for the diagnosis and monitoring of malignant tumors. However, the accuracy and sensitivity still require sufficient improvement for practically clinical application. In this work, a reliable and sensitive dual-mode immunosensing method is described for carcinoembryonic antigen (CEA) detection using a biofunctional ZnO@SiO2 nanocomposite as a resonance Raman scattering (RRS)-infrared (IR) absorption nanoprobe. The multiphonon RRS signal originating from the ZnO and the characteristic IR fingerprint signal of the transverse optical and longitudinal optical phonon modes of the asymmetric stretching of Si-O-Si bonds showed no interference with each other. A CEA antibodies-immobilized substrate was fabricated to capture the analyte/nanoprobe complexes. The RRS intensity at 569 cm‒1 and the IR absorption at 1061 cm‒1 were used for quantitative analysis. Accurate CEA detection was performed as a result of the strong resistance of the dual-mode nanoprobe to surrounding interference. The limit of detection was 98.0 fg mL‒1. The detection range was 500 ng mL‒1 - 50 fg mL‒1, which is wider than those of single-mode RRS or IR absorption immunosensings. High reproducibility, selectivity and specificity were achieved. The assay performance of human serum samples demonstrated the practicability of the method in clinical cancer diagnosis.

8.
J Chem Inf Model ; 60(1): 391-399, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31800243

RESUMO

Protein sequence profile prediction aims to generate multiple sequences from structural information to advance the protein design. Protein sequence profile can be computationally predicted by energy-based or fragment-based methods. By integrating these methods with neural networks, our previous method, SPIN2, has achieved a sequence recovery rate of 34%. However, SPIN2 employed only one-dimensional (1D) structural properties that are not sufficient to represent three-dimensional (3D) structures. In this study, we represented 3D structures by 2D maps of pairwise residue distances and developed a new method (SPROF) to predict protein sequence profiles based on an image captioning learning frame. To our best knowledge, this is the first method to employ a 2D distance map for predicting protein properties. SPROF achieved 39.8% in sequence recovery of residues on the independent test set, representing a 5.2% improvement over SPIN2. We also found the sequence recovery increased with the number of their neighbored residues in 3D structural space, indicating that our method can effectively learn long-range information from the 2D distance map. Thus, such network architecture using a 2D distance map is expected to be useful for other 3D structure-based applications, such as binding site prediction, protein function prediction, and protein interaction prediction. The online server and the source code is available at http://biomed.nscc-gz.cn and https://github.com/biomed-AI/SPROF , respectively.

9.
J Chem Inf Model ; 60(1): 400-409, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31833767

RESUMO

Motivation: Identification of ligand-binding proteins is an important issue for drug development. Most of the current computational approach is developed only utilizing ligand structure similarity. However, the ligand structure similarity has failed to reflect the binding quality between the ligand and the target protein, which limited the performance of current methods. Results: The present study integrated two-dimensional (2D) and three-dimensional (3D) ligand structure similarity between query ligand and template with known ligand-protein binding affinity (BA) to identify proteins binding with the query ligand. This method is named as DStruBTarget. The performance of DStruBTarget was evaluated by 10-fold cross-validation in a dataset containing 9197 ligands and 1111 ligand-binding proteins (DBD dataset). This dataset was constructed by excluding the ligands with similar structures and the proteins with high sequence identity. The DStruBTarget achieved a hit rate of 77% in top 1 prediction, which is 4.80 and 3.00% better than the methods only using 2D structure similarity, and the method integrating 2D and 3D structure similarity (2D + 3D), respectively. An independent test of DStruBTarget was performed in a publicly available dataset constructed by SwissTargetPrediction. In this dataset, the top 1 hit rate of DStruBTarget reached 44.02%, which was better than the SwissTargetPrediction, and also outstands other methods, such as 2D, 3D, 2D + 3D, 2D integrating binding affinity (2D + BA), and 3D integrating binding affinity (3D + BA). DStruBTarget was compared to another newly published method HitPickV2 and achieved 52.17% hit rate of the top 1 prediction, which was significantly better than the result of HitpickV2 (30.43%). Finally, DStruBTarget was integrated with protein BLAST to predict the ligand-binding proteins not limited in a certain database. DStruBTarget with BLAST was tested in the DBD dataset. Its top 1 hit rate was 51.15%, which is lower than DStruBTarget without BLAST. Further comparison was on the ligands that bind to multiple numbers of proteins, which illustrated that DStruBTarget with BLAST performed better than without BLAST when the number of binding proteins of the query ligands is larger than six. Meanwhile, the prediction power of the DStruBTarget with BLAST in top 1 prediction was found to be positively correlated with the number of proteins binding with the query ligands, while the top 1 prediction power of DStruBTarget without BLAST was negatively correlated with the number of binding proteins for query ligands. Thus, DStruBTarget with BLAST is a potentially useful approach for predicting novel proteins for ligands that bind to multiple proteins.

10.
J Comput Chem ; 41(8): 745-750, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31845383

RESUMO

Protein structure determination has long been one of the most challenging problems in molecular biology for the past 60 years. Here we present an ab initio protein tertiary-structure prediction method assisted by predicted contact maps from SPOT-Contact and predicted dihedral angles from SPIDER 3. These predicted properties were then fed to the crystallography and NMR system (CNS) for restrained structure modeling. The resulted structures are first evaluated by the potential energy calculated by CNS, followed by dDFIRE energy function for model selections. The method called SPOT-Fold has been tested on 241 CASP targets between 67 and 670 amino acid residues, 60 randomly selected globular proteins under 100 amino acids. The method has a comparable accuracy to other contact-map-based modeling techniques. © 2019 Wiley Periodicals, Inc.

11.
Mol Cancer ; 18(1): 160, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31722716

RESUMO

BACKGROUND: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn much attention in the pathogenesis of human cancers. However, the role of circRNAs in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we aimed to identify novel circRNAs that regulate ESCC progression and explored their regulatory mechanisms and clinical significance in ESCC. METHODS: Differentially expressed circRNAs between ESCC and paired adjacent normal tissues were identified using microarrays. The effects of a specific differentially expressed circRNA (circGSK3ß) on tumor progression were explored in vitro and in vivo. Plasma samples from patients with ESCC, benign lesions and healthy controls were subjected to droplet digital PCR (ddPCR) analyses for circGSK3ß, and the detection rates of plasma circGSK3ß for ESCC were investigated. RESULTS: We demonstrated that upregulated expression of circGSK3ß was positively associated with advanced clinical stage and poor outcome in patients with ESCC. We further revealed that circGSK3ß promoted ESCC cell migration and invasion via direct interaction with GSK3ß and inhibiting GSK3ß activity, providing a novel mechanism of circRNA in cancer progression. Importantly, we identified that circGSK3ß expression in plasma was a biomarker for detection of ESCC and early stage of ESCC with the area under curve (AUC) of 0.782 and 0.793, respectively. CONCLUSIONS: CircGSK3ß exerts critical roles in promoting ESCC metastasis and may serve as a novel therapeutic target for ESCC patients. The plasma level of circGSK3ß have potential to serve as a novel diagnostic and prognostic biomarker for ESCC detection.

12.
Mikrochim Acta ; 186(11): 701, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31620903

RESUMO

A colorimetric method is described for the determination of Cu(II). It is based on branched polyethylenimine (BPEI) droplet evaporation on a superhydrophilic-superhydrophobic polystyrene micropatterned surface. Exposure to Cu(II) leads to a color change from colorless to light blue and dark blue. The micropatterned surface was fabricated via combining electrospinning with oxygen plasma and served as a detection substrate. Analysis requires only a single drop of blood. The method has a linear response in the 5.0 µM to 2.5 mM Cu(II) concentration range which is within the physiological range (15.7 ∼ 23.6 µM). Compared to an assay in solution, the detection limit is decreased from 386 nM to 89 nM. Excellent selectivity over other metal ions and anions was achieved. Graphical abstract A rapid and sensitive colorimetric detection platform for Cu(II) was fabricated by using branched-polyethylenimine droplet evaporation on a superhydrophilic-superhydrophobic micropatterned surface. Only a single drop of blood was needed for the analysis. The sensitivity was improved about 4.3 times.

13.
Aging (Albany NY) ; 11(18): 7880-7898, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31548434

RESUMO

Liquid storage of spermatozoa is important for artificial insemination and herd genetic breeding. However, the extended time of storage inducing the rapid decline in spermatozoa quality limits the development of this technology. The molecular mechanisms underlying liquid storage of spermatozoa remain largely unexplored. In this study, the effects of liquid storage on functional quality of spermatozoa were assessed in goat (Capra hircus). The time-dependent decline in spermatozoa motility showed a strong correlation with the significant increase in apoptosis. Moreover, apoptosis-related ultrastructural changes were observed, especially the defects in mitochondria. A significant decrease in mitochondrial membrane potential and changes in the expression of mitochondrial apoptosis-related proteins indicated mitochondrial dysfunction and mitochondrial apoptotic pathway activation. Notably, the abnormally high level of reactive oxygen species (ROS) caused by liquid storage resulted in oxidative damage to mitochondria and accelerated mitochondria-dependent apoptosis, as demonstrated by the addition of ROS scavenger N-acetylcysteine. Furthermore, critical differentially expressed proteins involved in mitochondria-dependent apoptosis and antioxidant defense were identified and profiled by quantitative proteomic analysis, facilitating the understanding of molecular regulation of ROS-induced mitochondria-dependent apoptosis. These outcomes provide insights into the mechanisms underlying liquid storage of goat spermatozoa and enhance the progress of semen storage technology.

14.
Am J Physiol Endocrinol Metab ; 317(5): E911-E924, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31526292

RESUMO

In the context of hepatic insulin resistance, hepatic gluconeogenesis is abnormally increased, which results in increased hepatic glucose production and hyperglycemia, but the underlying mechanisms remain to be fully elucidated. Micro-RNAs (miRNAs) have been identified as critical regulators of diabetes and other metabolic disorders. In this study, we found that the expressions of miRNA-27 family members miRNA-27a and miRNA-27b (miR-27a/b) decreased significantly in the livers of diabetic mice. Moreover, the levels of miR-27a/b increased in the serum of patients with type 2 diabetes. Our present results showed that inhibition of miR-27a/b expression led to increased hepatic protein levels of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase and enhanced hepatic gluconeogenesis in vitro and in vivo. Overexpression of miR-27a/b suppressed hepatic glucose output and alleviated hyperglycemia in diabetic mice. Further study revealed that forkhead box O1 (FOXO1) is a downstream target of miR-27a/b. Taken together, we found novel evidence suggesting that miR-27a/b contributes to hepatic gluconeogenesis through targeting FOXO1 and provided novel mechanistic insight into the pathophysiology of insulin resistance.

15.
J Cheminform ; 11(1): 52, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31392430

RESUMO

Performance of structure-based molecular docking largely depends on the accuracy of scoring functions. One important type of scoring functions are knowledge-based potentials derived from known three-dimensional structures of proteins and/or protein-ligand complex structures. This study seeks to improve a knowledge-based protein-ligand potential based on a distance-scale finite ideal-gas reference (DFIRE) state (DLIGAND) by expanding the representation of protein atoms from 13 mol2 atom types to 167 residue-specific atom types, and employing a recently updated dataset containing 12,450 monomer protein chains for training. We found that the updated version DLIGAND2 has a consistent improvement over DLIGAND in predicting binding affinities for either native complex structures or docking-generated poses. More importantly, DLIGAND2 has a 52% increase over DLIGAND in enrichment factors in top 1% predictions based on the DUD-E decoy set, and consistently improves over Autodock Vina and other statistical energy functions in all three benchmark tests. We further found that DLIGAND2 outperforms empirical and machine-learning methods compared for virtual screening on new targets that are not homologous to the DUD-E training set. Given the best performance as a parameter-free statistical potential and among the best in all performance measures, DLIGAND2 should be useful for re-assessing the poses generated by docking software, or acting as one term in other scoring functions. The program is available at https://github.com/sysu-yanglab/DLIGAND2 .

16.
J Crit Care ; 54: 136-144, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31446231

RESUMO

PURPOSE: To identify the impact of non-opioid analgesics as adjuvants to opioid on opioid consumption and its side effects, as well as the analgesic effectiveness in adult patients in the ICU. METHODS: Only randomized clinical trials using non-opioid analgesics for analgesia in the ICU were included. Pooled analyses with 95% CI were determined. RESULTS: Twelve studies (mainly surgical and Guillain-Barre syndrome patients) were included. Non-opioid analgesics as adjuvants to opioid were associated with a significant reduction in the consumption of opioids when compared with opioid use alone at Day 1 (MD -15.40; 95% CI -22.41 to -8.39; P < .001) and Day 2 (MD -22.93; 95% CI -27.70 to -18.16; P < .001). Non-opioid analgesics as adjuvants to opioid were associated with a significantly lower incidence of nausea and vomiting when compared with opioid use alone (RR 0.46; 95% CI 0.30 to 0.68; P < .001). Non-opioid analgesics as adjuvants to opioid significantly decreased the pain score at Day 1 (MD -0.68; 95% CI -1.28 to -0.08; P = .03) and Day 2 (MD -1.36; 95% CI -2.47 to -0.24; P = .02). CONCLUSIONS: Non-opioid analgesics as adjuvants to opioid reduced the consumption and the side effects of opioids in adult surgical and Guillain-Barre syndrome patients in the ICU. TRIAL REVIEW REGISTRATION: PROSPERO international prospective register of systematic reviews on January 23, 2017, registration number CRD42017055768.

17.
Ecol Evol ; 9(12): 6968-6985, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31467669

RESUMO

Heat-shock proteins 70/110 (Hsp70/110) are vital molecular chaperones and stress proteins whose expression and production are generally induced by extreme temperatures or external stresses. The Hsp70/110 family is largely conserved in diverse animals. Although many reports have studied and elaborated on the characteristics of Hsp70/110 in various species, the systematic identification and analysis of Hsp70/110 are still poor in turtles. In this study, a genomewide search was performed, and 18 candidate PsHSP70/110 family genes were identified in Chinese soft-shelled turtle, Pelodiscus sinensis. These PsHSP70/110 proteins contained the conserved "heat shock protein 70" domain. Phylogenetic analysis of PsHSP70/110 and their homologs revealed evolutionary conservation of Hsp70/110 across different species. Tissue-specific expression analysis showed that these PsHSP70/110 genes were differentially expressed in different tissues of P. sinensis. Furthermore, to examine the putative biological functions of PsHSP70/110, the dynamic expression of PsHSP70/110 genes was analyzed in the testis of P. sinensis during seasonal spermatogenesis following germ cell apoptosis. Notably, genes such as PsHSPA1B-L, PsHSPA2, and PsHSPA8 were significantly upregulated in P. sinensis testes along with a seasonal decrease in apoptosis. Protein interaction prediction revealed that PsHSPA1B-L, PsHSPA2, and PsHSPA8 may interact with each other and participate in the MAPK signaling pathway. Moreover, immunohistochemical analysis showed that PsHSPA1B-L, PsHSPA2, and PsHSPA8 protein expression was associated with seasonal temperature variation. The expression profiling and interaction relationships of the PsHSPA1B-L, PsHSPA2, and PsHSPA8 proteins implied their potential roles in inhibiting the apoptosis of germ cells in P. sinensis. These results provide insights into PsHSP70/110 functions and will serve as a rich resource for further investigation of HSP70/110 family genes in P. sinensis and other turtles.

18.
Fish Shellfish Immunol ; 92: 821-832, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31299462

RESUMO

Interferon regulatory factors (IRFs) were originally identified as transcriptional regulators of type I interferon (IFN) expression. Recent studies have widely identified the roles of IRFs as central mediators in immune defence against pathogen infection. However, the functional roles and expression profiles of IRFs are still unclear in Chinese soft-shelled turtle (Pelodiscus sinensis). In this study, eight members of the PsIRF family were identified in P. sinensis through a genome-wide search. These PsIRF genes contained the conserved domains of this group of proteins, including the N-terminal DNA-binding domain and C-terminal IRF-associated domain. Phylogenetic analyses among IRF homologs showed that the PsIRFs shared the closest phylogenetic relationships with IRFs of other turtle species. Further molecular evolutionary analyses revealed evolutionary conservation of the PsIRF genes. Moreover, expression profiling demonstrated that eight PsIRF genes exhibited constitutive expression in different tissues of P. sinensis. Several genes, such as PsIRF1, PsIRF2 and PsIRF4, showed predominant expression in the spleen and were significantly upregulated upon Aeromonas hydrophila infection. Remarkably, PsIRF1, PsIRF2 and PsIRF4 exhibited rapid increases in their protein expression levels post-infection and were mainly expressed in the splenic red pulp according to immunohistochemistry analysis. These results provide rich resources for further exploration of the roles of PsIRFs in immune regulation in P. sinensis and other turtles.


Assuntos
Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/imunologia , Tartarugas/genética , Tartarugas/imunologia , Aeromonas hydrophila/fisiologia , Animais , Perfilação da Expressão Gênica/veterinária , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Família Multigênica/imunologia , RNA Mensageiro/genética , Proteínas de Répteis/genética , Proteínas de Répteis/imunologia
19.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(6): 689-693, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31315724

RESUMO

OBJECTIVE: To investigate the characteristics and failure risk factors of sequential high-flow nasal cannula oxygen therapy (HFNC) after weaning from invasive ventilation. METHODS: The patients who received sequential HFNC after weaning from invasive ventilation admitted to surgical intensive care unit (ICU) of Peking University People's Hospital from June 1st 2016 to May 31st 2018 were retrospectively analyzed. Clinical variables, respiratory therapy parameters, respiratory variables, cardiac variables and outcomes were reviewed and analyzed. Treatment characteristics of HFNC after weaning was analyzed. Patients were divided into HFNC success group and HFNC failure group according to the failure of HFNC, and the differences between the two groups were compared. The independent risk factors of HFNC treatment failure were analyzed by Logistic regression analysis. The value of predictive treatment failure of risk factors and regression models were analyzed by receiver operating characteristic (ROC) curve. RESULTS: A total of 99 patients were included, 61 men, and the median age was 67.0 (57.0, 76.0) years old. The medianinitial HFNC flow was 50 (50, 60) L/min, and inspired oxygen concentration (FiO2) was 0.50 (0.40, 0.60). Eighteen patients experienced HFNC failure (18.2%). Compared with the HFNC success group, the sequential organ failure assessment (SOFA) score in the HFNC failure group was higher [4 (3, 5) vs. 2 (1, 3), P < 0.01], B type natriuretic peptide (BNP) before HFNC therapy were significant higher [ng/L: 647.2 (399.2, 1 331.3) vs. 127.2 (55.2, 369.5), P < 0.01], and respiratory frequency (RR) and heart rate (HR) were significant faster, mean arterial pressure (MAP) was significant higher, oxygen index (PaO2/FiO2) was significant lower after 30 minutes HFNC treatment [RR (times/min): 26 (22, 28) vs. 19 (17, 21), HR (bpm): 105 (97, 107) vs. 85 (77, 90), MAP (mmHg, 1 mmHg = 0.133 kPa): 104.3 (101.7, 110.7) vs. 92.3 (88.3, 97.7), PaO2/FiO2 (mmHg): 207.3 (185.8, 402.8) vs. 320.2 (226.2, 361.5), all P < 0.05]. It was shown by multiple Logistic regression analysis that the SOFA score [odds ratio (OR) = 2.818, P = 0.022, ß = 1.036], BNP before HFNC treatment (OR = 1.002, P = 0.033, ß = 0.002) and HR after HFNC treatment 30 minutes (OR = 1.140, P = 0.032, ß = 0.131) were independent risk factors for HFNC treatment failure. It was shown by ROC curve that the area under the ROC curve (AUC) for the prediction of HFNC failure was 0.840, 0.859, 0.860 and 0.962 for SOFA, BNP before HFNC treatment, HR after HFNC treatment 30 minutes, and regression model, all had good forecast values (all P < 0.01). CONCLUSIONS: HFNC is one of the commonly used oxygen therapy methods in the ICU, but not all patients who are treated as a sequential therapy after invasive mechanical ventilation weaning can benefit from it. SOFA score, BNP before HFNC treatment and HR after 30 minutes HFNC treatment were independent risk factors of HFNC failure. Each independent risk factor and regression model can predict the success of HFNC treatment.


Assuntos
Cânula , Oxigenoterapia/métodos , Desmame do Respirador , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Centro Cirúrgico Hospitalar , Falha de Tratamento
20.
Hum Mutat ; 40(9): 1215-1224, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31301154

RESUMO

Precision medicine and sequence-based clinical diagnostics seek to predict disease risk or to identify causative variants from sequencing data. The Critical Assessment of Genome Interpretation (CAGI) is a community experiment consisting of genotype-phenotype prediction challenges; participants build models, undergo assessment, and share key findings. In the past, few CAGI challenges have addressed the impact of sequence variants on splicing. In CAGI5, two challenges (Vex-seq and MaPSY) involved prediction of the effect of variants, primarily single-nucleotide changes, on splicing. Although there are significant differences between these two challenges, both involved prediction of results from high-throughput exon inclusion assays. Here, we discuss the methods used to predict the impact of these variants on splicing, their performance, strengths, and weaknesses, and prospects for predicting the impact of sequence variation on splicing and disease phenotypes.

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