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1.
Mol Oncol ; 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33932092

RESUMO

Hot spot gene mutations in splicing factor 3b subunit 1 (SF3B1) are observed in many types of cancer and create abundant aberrant mRNA splicing, which is profoundly implicated in tumorigenesis. Here, we identified that the SF3B1 K700E (SF3B1K700E ) mutation is strongly associated with tumor growth in pancreatic ductal adenocarcinoma (PDAC). Knockdown of SF3B1 significantly retarded cell proliferation and tumor growth in a cell line (Panc05.04) with the SF3B1K700E mutation. However, SF3B1 knockdown had no notable effect on cell proliferation in two cell lines (BxPC3 and AsPC1) carrying wild-type SF3B1. Ectopic expression of SF3B1K700E but not SF3B1WT in SF3B1-knockout Panc05.04 cells largely restored the inhibitory role induced by SF3B1 knockdown. Introduction of the SF3B1K700E mutation in BxPC3 and AsPC1 cells also boosted cell proliferation. Gene set enrichment analysis demonstrated a close correlation between SF3B1 mutation and aerobic glycolysis. Functional analyses showed that the SF3B1K700E mutation promoted tumor glycolysis, as evidenced by glucose consumption, lactate release, and extracellular acidification rate. Mechanistically, the SF3B1 mutation promoted the aberrant splicing of PPP2R5A and led to the activation of the glycolytic regulator c-Myc via post-translational regulation. Pharmacological activation of PP2A with FTY-720 markedly compromised the growth advantage induced by the SF3B1K700E mutation in vitro and in vivo. Taken together, our data suggest a novel function for SF3B1 mutation in the Warburg effect, and this finding may offer a potential therapeutic strategy against PDAC with the SF3B1K700E mutation.

2.
Drug Des Devel Ther ; 15: 1569-1576, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33883880

RESUMO

Background: The effect of different administration routes of omeprazole remains unclear on the recovery in patients with obesity after laparoscopic sleeve gastrectomy (LSG). Methods: We designed a randomized clinical trial enrolling 120 patients with a BMI≥32.5 kg/m2 after LSG. They were randomized into two groups to be administered with omeprazole by rapid intravenous injection (group A) or by continuous micropump infusion (group B). The plasma concentration of omeprazole was monitored upon initiating administration. Change in intragastric pH and gastrointestinal symptoms during follow-up served as indicators for therapeutic evaluation. Results: Patients in the two groups showed no difference in the AUC curves (P=0.25), but group A had significantly higher peak concentration (P<0.001), and shorter time to reach peak concentration after administration (P<0.001), compared to group B. Before and after the administration of omeprazole, the average change in intragastric pH was much lower in group A (0.031 ± 0.61) than in group B (0.48 ± 0.74) (P=0.004). The incidence of gastrointestinal symptoms was similar between the two groups (P=0.85); however, the average duration of remaining symptoms was longer in group A (3.97 months; 95% CI, 2.90-5.04) than in group B (2.82 months; 95% CI, 2.01-3.63) (P=0.04). Conclusion: Continuous micropump infusion of omeprazole may improve the outcomes in patients with obesity after LSG. Trial registration: China Clinical Trial Registration Center (ChiCTR), ChiCTR-IPR-17013365. Registered 13 November 2017. http://www.chictr.org.cn/showproj.aspx?proj=22892.

3.
Cell Adh Migr ; 15(1): 116-125, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33843453

RESUMO

Phenotypic switching is the main cause of the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). We previously showed that Daxx exerted negative regulatory effect on AngII-induced VSMC proliferation and migration. However, the function of Daxx in VSMC phenotype switching remained unknown. Nicotinate-curcumin (NC) is an esterification derivative of niacin and curcumin that can prevent the formation of atherosclerosis. We found that NC significantly decreased AngII-induced VSMC phenotype switching. Furthermore, NC significantly inhibited AngII-induced cell proliferation and migration. Moreover, NC upregulated Daxx expression and regulated the PTEN/Akt signaling pathway. We concluded that NC inhibited AngII-induced VSMC phenotype switching by regulating the PTEN/Akt pathway, and through a mechanism that might be associated with the upregulation of Daxx expression.

4.
Europace ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33693595

RESUMO

AIMS: To characterize the association of phasic left atrial (LA) transport function and LA fibrosis guided by multimodality imaging containing cardiac magnetic resonance imaging (CMR) feature tracking and bipolar voltage mapping. METHODS AND RESULTS: Consecutive patients presenting for first-time ablation of atrial fibrillation (AF) were prospectively enrolled. Each patient underwent CMR prior to the ablation procedure. LA phasic indexed volumes (LA-Vi) and emptying fractions (LA-EF) were calculated and CMR feature tracking guided LA wall motion analysis was performed. LA bipolar voltage mapping was carried out in sinus rhythm to find areas of low voltage as a surrogate for fibrosis and arrhythmogenesis. One hundred and sixty-eight patients were enrolled. Low-voltage areas (LVAs) were present in 70 patients (42%). Contrary to LA volume, CMR based LA-EF [odds ratio (OR) 0.88, 95% confidence interval (CI) 0.80-0.96, P = 0.005] and LA booster pump strain rate (SR) (OR 0.98, 95% CI 0.97-0.99, P = 0.001) significantly predicted presence and extent of LVA in multivariate logistic regression analysis for patients scanned in SR. In receiver operating characteristic analysis, LA-EF <40% carried a sensitivity of 83% and specificity of 76% (area under the curve 0.8; 95% CI 0.71-0.89) to predict presence of LVA. For patients scanned in AF only minimal LA-Vi on CMR (OR: 1.06; 95% CI: 1.02-1.10; P = 0.002) predicted presence of LVA. CONCLUSION: For patients scanned in SR LA-EF and LA booster pump SR are closely linked to the presence and extent of LA LVA.

5.
Cancer Lett ; 508: 47-58, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-33766751

RESUMO

Perineural invasion (PNI) is a common feature of pancreatic ductal adenocarcinoma (PDAC) and is one of the important causes of local recurrence in resected pancreatic cancer, but the molecular mechanism remains largely unexplored. Here, we used immunohistochemistry staining to determine the expression of CD74. Then the in vivo PNI model, in vitro neuroplasticity assay, cell proliferation assay, wound healing and Transwell-based invasion assay were performed to examine the function of CD74 in pancreatic cancer cell lines. ChIP assay and Luciferase reporter assay were used to illustrate the mechanism underlying CD74 induced GDNF expression. We confirmed that the expression level of CD74 was an independent predictor of PNI and poor prognosis for PDAC. Moreover, we found that upregulation of CD74 on PDAC enhanced its migration and invasive capabilities and potentiated the secretion of neurotrophic factor GDNF to promote the neuroplasticity. Mechanistically, CD74 promoted GDNF production via the AKT/EGR-1/GDNF axis in PDAC. Taken together, our findings suggest a supportive role of CD74 in the PNI of PDAC, and deepen our understanding of how cancer cells promote neuroplasticity in the microenvironment of PDAC.

6.
Math Biosci Eng ; 18(2): 1864-1878, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33757215

RESUMO

In this paper, a crystal image analysis method is presented to measure and predict crystal sizes, based on cooling crystallization of ß-form L-glutamic acid (LGA) by using an in-situ non-invasive imaging system. The proposed method consists of image restoration, image segmentation, crystal size measurement, and size prediction. To cope with the effects of noise pollution, uneven illumination and movement blurring, the image processing method is conducted for segmenting crystal images captured from the stirring reactor. Thus, the crystal size distribution for crystal population is obtained by using a probability density function. In addition, a short-term prediction method is given for crystal sizes. An experimental study on the cooling crystallization process of ß-form LGA is shown to demonstrate the effectiveness of the proposed method.

7.
Plant Mol Biol ; 106(1-2): 145-156, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33694047

RESUMO

KEY MESSAGE: TwPDR1, a PDR transporter from Tripterygium wilfordii Hook.f., was proved to efflux triptolide and its stability could be enhanced by A1033T mutation. Triptolide, an abietane-type diterpene in Tripterygium wilfordii Hook.f., possesses many pharmacological activities. However, triptolide is in short supply and very expensive because it is present at low amounts in natural plants and lack alternative production methods. Transporter engineering, which increases the extracellular secretion of secondary metabolites in in vitro culture systems, is an effective strategy in metabolic engineering but is rarely reported. In this study, TwPDR1, a pleiotropic drug resistance-type ATP binding cassette transporter, was identified as the best efflux pump candidate for diterpenoids through bioinformatics analysis. TwPDR1 was located in the plasma membrane, highly expressed in adventitious roots, and induced by methyl jasmonate. The triptolide efflux function of TwPDR1 was confirmed by transient expression in tobacco BY-2 cells and by downregulation via RNA interference in the native host. However, the overexpression of TwPDR1 had a limited effect on the secretion of triptolide. As shown by previous studies, a single amino acid mutation might increase the abundance of TwPDR1 by increasing protein stability. We identified the A1033 residue in TwPDR1 by sequence alignment and confirmed that A1033T mutation could increase the expression of TwPDR1 and result in the higher release ratio of triptolide (78.8%) of the mutants than that of control (60.1%). The identification and functional characterization of TwPDR1 will not only provide candidate gene material for the metabolic engineering of triptolide but also guide other transporter engineering researches in the future.


Assuntos
Diterpenos/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Fenantrenos/metabolismo , Proteínas de Plantas/metabolismo , Tripterygium/metabolismo , Sequência de Aminoácidos , Transporte Biológico , Linhagem Celular , Compostos de Epóxi/metabolismo , Proteínas de Membrana Transportadoras/química , Mutagênese/genética , Filogenia , Proteínas de Plantas/química , Plantas Geneticamente Modificadas , Estabilidade Proteica , Protoplastos/metabolismo , Tabaco/genética , Transcrição Genética , Tripterygium/genética
8.
Ann Palliat Med ; 10(1): 646-656, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33545793

RESUMO

BACKGROUND: The timely weaning of mechanical ventilation can shorten intensive care unit (ICU) stay times and reduce the complications related to mechanical ventilation. This study sought to investigate the predictive role of a weaning index (WI) on mechanical ventilation evacuation by measuring minute ventilation volume (MVV) across different ventilation modes. METHODS: Patients suffering from respiratory failure for a variety of reasons were included in the study if they received mechanical ventilation for more than 48 hours in the ICU. The patients were randomly allocated to either the assist/control (A/C) group or the pressure support ventilation (PSV) group according to the ventilator mode. The factors associated with weaning success and failure were analyzed. RESULTS: A total of 40 patients participated in this study. Of these, 25 weaning cases were successful and 15 were failures. There were 19 cases in the A/C group, yielding a success rate of 63%, and 21 cases in the PSV group, yielding a success rate of 62%. There were no significant differences between the two groups in terms of age, gender, ideal weight, Acute Physiology and Chronic Health Evaluation (APACHE) II score, ICU stay time and hospitalization time. There were significant differences in the mechanical ventilation duration between the two groups (P<0.05). When the WI was less than 50.44, the sensitivity and specificity of predicting weaning success were 72% and 98%. The area under the receiver operating characteristic (ROC) curve was 0.928±0.03. When the WI of the A/C group was less than 61.45, the sensitivity and specificity of predicting weaning success were 98% and 72%, respectively. The area under the ROC curve was 0.917±0.068. When the WI of the PSV group was less than 51.45, the sensitivity and specificity of predicting weaning success were 74.6% and 100%, respectively. The area under the ROC curve was 0.933±0.046. CONCLUSIONS: Compared with RSBI, WI shows a better value in predicting weaning, especially for mechanically ventilated patients in PSV mode, WI has greater value in predicting weaning.

9.
Neuroreport ; 32(1): 44-51, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33165190

RESUMO

MicroRNAs (miRNAs) play important roles in drug tolerance and regulating pain. The purpose of the present study is to explore the regulatory mechanism of miR-124-3p on dezocine tolerance against pain in a rat model. The expression of miR-124-3p and TRAF6 in spinal cord of rats was detected by quantitative reverse-transcription PCR. The paw withdrawal latency (PWL) and maximal potential efficiency % of rats were detected by PWL assay. The levels of IL-1ß and TNF-α in spinal cord tissues of rats were measured by ELISA assay. The interaction between TRAF6 and miR-124-3p was predicted by TargetScan software (http://www.targetscan.org) and confirmed by the dual-luciferase reporter assay. The protein level of TRAF6 was determined by western blot. MiR-124-3p expression was highly downregulated in a dezocine-resistant model. MiR-124-3p overexpression could alleviate dezocine tolerance in rats. TRAF6 expression was significantly upregulated in a dezocine-resistant model. MiR-124-3p targeted TRAF6 and TRAF6 was negatively modulated by miR-124-3p. In addition, overexpression of TRAF6 could reverse the inhibitory effects of miR-124-3p on dezocine tolerance. Overexpression of miR-124-3p alleviates dezocine tolerance against pain via regulating TRAF6 in a rat model, providing a possible solution to address dezocine tolerance in clinical.

10.
Sci Signal ; 13(659)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33234690

RESUMO

Overuse of ß2-adrenoceptor agonist bronchodilators evokes receptor desensitization, decreased efficacy, and an increased risk of death in asthma patients. Bronchodilators that do not target ß2-adrenoceptors represent a critical unmet need for asthma management. Here, we characterize the utility of osthole, a coumarin derived from a traditional Chinese medicine, in preclinical models of asthma. In mouse precision-cut lung slices, osthole relaxed preconstricted airways, irrespective of ß2-adrenoceptor desensitization. Osthole administered in murine asthma models attenuated airway hyperresponsiveness, a hallmark of asthma. Osthole inhibited phosphodiesterase 4D (PDE4D) activity to amplify autocrine prostaglandin E2 signaling in airway smooth muscle cells that eventually triggered cAMP/PKA-dependent relaxation of airways. The crystal structure of the PDE4D complexed with osthole revealed that osthole bound to the catalytic site to prevent cAMP binding and hydrolysis. Together, our studies elucidate a specific molecular target and mechanism by which osthole induces airway relaxation. Identification of osthole binding sites on PDE4D will guide further development of bronchodilators that are not subject to tachyphylaxis and would thus avoid ß2-adrenoceptor agonist resistance.

11.
Cell Biochem Funct ; 2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33164256

RESUMO

Many studies have shown that adiponectin is closely related to chronic obstructive pulmonary disease (COPD), but the specific role of adiponectin in COPD is still not well understood. Adiponectin and IL-6 expression in patients with acute exacerbation of COPD (AECOPD) was detected by ELISA. Human bronchial epithelial cells (HBECs) were stimulated with TNF-α, IL-6, apoptotic cells or LPS. Then, the expression of adiponectin was detected by qRT-PCR and western blotting, and pro- and anti-inflammatory factors were detected by ELISA. Adiponectin expression in AECOPD patients increased after treatment. TNF-α and apoptotic cells promoted adiponectin expression in HBECs in a dose-dependent manner, and apoptotic cells significantly promoted adiponectin secretion. IL-6 also promoted adiponectin expression, but it inhibited adiponectin expression at high doses and with long treatment times. LPS inhibited adiponectin expression, but when HBECs were pretreated with anti-TNF-α and then treated with LPS, the expression and secretion of adiponectin increased significantly with increasing anti-TNF-α concentrations. Adiponectin stimulated the secretion of pro-inflammatory factors in HBECs, but this effect was not concentration dependent. Adiponectin promoted the secretion of anti-inflammatory factors in a dose-dependent manner. Although LPS also stimulated HBECs to secrete pro-inflammatory and anti-inflammatory factors, adiponectin inhibited LPS-induced pro-inflammatory factor secretion and enhanced anti-inflammatory factor secretion. Many factors regulate the expression and secretion of adiponectin, and adiponectin regulates the balance of the inflammatory response and inhibits further expansion of inflammation. SIGNIFICANCE OF THE STUDY: Many studies have shown that adiponectin is closely related to chronic obstructive pulmonary disease (COPD), but the specific role of adiponectin in COPD is still not well understood. Adiponectin expression in AECOPD patients increased after treatment. TNF-α, IL-6 and apoptotic cells promoted adiponectin expression in HBECs. Adiponectin stimulated the secretion of pro-inflammatory factors in HBECs, but this effect was not concentration dependent. Adiponectin promoted the secretion of anti-inflammatory factors in a dose-dependent manner. Adiponectin inhibited LPS-induced pro-inflammatory factor secretion and enhanced anti-inflammatory factor secretion. Therefore, many factors regulate the expression and secretion of adiponectin, and adiponectin regulates the balance of the inflammatory response and inhibits further expansion of inflammation.

12.
Ther Adv Med Oncol ; 12: 1758835920966574, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33149770

RESUMO

Aims: Within the past few years, there has been tremendous growth in clinical trials of chimeric antigen receptor (CAR) T-cell therapies. Unlike those of many small-molecule pharmaceuticals, CAR T-cell therapy clinical trials are fraught with risks due to the use of live cell products. The aim of this study is to reach a consensus with experts on the most relevant set of risks that practically occur in CAR T-cell therapy clinical trials. Methods: A Delphi method of consensus development was used to identify the risks in CAR T-cell therapy clinical trials, comprising three survey rounds. The expert panel consisted of principal investigators, clinical research physicians, members of institutional ethics committees, and Good Clinical Practice managers. Results: Of the 24 experts invited to participate in this Delphi study, 20 participants completed Round 1, Round 2, and Round 3. Finally, consensus (defined as >80% agreement) was achieved for 54 risks relating to CAR T-cell clinical trials. Effective interventions related to these risks are needed to ensure the proper protection of subject health and safety. Conclusion: The Delphi method was successful in gaining a consensus on risks relevant to CAR T-cell clinical trials in a geographically diverse expert association. It is hoped that this work can benefit future risk-based quality management in clinical trials and can potentially promote the better development of CAR T-cell therapy products.

13.
Depress Anxiety ; 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33225514

RESUMO

There is consistent evidence that mood disorders often co-occur with anxiety disorders, however, the strength of the association of these two broad groups of disorders has been challenging to summarize across different studies. The aim was to conduct a meta-analysis of publications reporting on the pairwise comorbidity between mood and anxiety disorders after sorting into comparable study types. We searched MEDLINE, Embase, CINAHL, Web of Science, and the grey literature for publications between 1980 and 2017 regardless of geographical locations and languages. We meta-analyzed estimates from original articles after sorting by: (a) broad or narrow diagnostic criteria, (b) study time-frame, and (c) estimates with or without covariate adjustments. Over 43 000 unique studies were identified through electronic searches, of which 391 were selected for full-text review. Finally, 171 studies were eligible for inclusion, including 53 articles from additional snowball searching. In general, regardless of variations in diagnosis type, study time-frame, temporal order, or use of adjustments, there was substantial comorbidity between mood and anxiety disorders. Based on the entire 90 separate meta-analyses, the median OR was 6.1 (range 1.5-18.7). Of these estimates, all 90 were above 1, and 87 were significantly greater than 1 (i.e., the 95% confidence intervals did not include 1). Fourteen of the 90 pooled estimates had ORs that were greater than 10. This systematic review found robust and consistent evidence of comorbidity between broadly defined mood and anxiety disorders. Clinicians should be vigilant for the prompt identification and treatment of this common type of comorbidity.

14.
Mol Nutr Food Res ; 64(22): e2000353, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33002297

RESUMO

SCOPE: Huangjinya is a light-sensitive tea mutant containing low levels of tea polyphenols. Currently, most studies focused on characteristics formation, free amino acid metabolism and phytochemical purification. The biological activity of Huangjinya black tea (HJBT) on metabolic syndrome regarding fecal metabolome modulation is unavailable and is studied herein. METHODS AND RESULTS: High-fat diet (HFD)-fed mice are treated with HJBT for 9 weeks, various metabolic biomarkers and fecal metabolites are determined. HJBT reduces adipogenic and lipogenic gene expression, enhances lipolytic gene expression, decreases adipocyte expansion, and prevents the development of obesity. HJBT reduces lipogenic gene expression, increases fatty acid oxidation-related genes expression, which alleviates liver steatosis. HJBT enhances glucose/insulin tolerance, increases insulin/Akt signaling, attenuates hyperlipidemia and hyperglycemia, prevents the onset of insulin resistance. HJBT modulates bile acid metabolism, promotes secondary/primary bile acid ratio; increases short-chain fatty acids production, promotes saturated and polyunsaturated fatty acids content; reduces carnitines and phosphocholines, but increases myo-inositol content; decreases branched-chain and aromatic amino acids content; increases the metabolite content related to pentose phosphate pathway. CONCLUSION: This study reported the association between fecal metabolome modulation and metabolism improvement due to HJBT administration, proposes HJBT as a dietary intervention for preventing obesity and metabolic disorders.

15.
Front Aging Neurosci ; 12: 532386, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061904

RESUMO

Acetylcholinesterase inhibitors (AChEIs) including donepezil (DNP) are considered to be the most promising therapeutic possibilities of Alzheimer's disease (AD). The response to DNP in AD patients varies and it is valuable to identify the potential markers that can predict the efficacy. Moreover, DNP has been found to affect bone function, but the exact mechanism is still unclear. Lipids and adipokine may link to AD and DNP directly or indirectly and might be potential biomarkers or therapeutic drug targets. The goal of this study was to investigate the relationships among adiponectin (APN), lipids levels, and the response to DNP, and to identify whether the effect of DNP in AD treatment is related to its effect on the level of APN in systemic circulation. The study recruited 85 AD patients with DNP treatment, of whom 47 were DNP responders and 38 were DNP nonresponders. The Mini-Mental State Examination was performed to evaluate the memory impairment. Plasma APN was measured with ELISA. The genotypes of single nucleotide polymorphisms rs1501299 and rs22417661 in APN for each patient were identified. Plasma lipids were quantified with gas chromatography coupled with mass spectrometry. Correlations among APN, lipid metabolomics, and DNP responded were evaluated. APN was significantly decreased in DNP responders. Methyl stearate and glycerol-3-phosphate, used for characterizing adipogenic differentiation, were significantly decreased in DNP responders compared to DNP nonresponders. APN and small-molecule lipids can be used as potential biomarkers to evaluate the efficacy of DNP. The results of metabolomics indicated that there was no change in the metabolic pathway of fatty acid metabolism and glucose metabolism in DNP responders, suggesting that APN-related biological function did not decrease in DNP responders. Our result suggests that more attention should be pay to the sources and biological functions of APN in AD with DNP treatment.

16.
Ann Palliat Med ; 9(5): 3162-3169, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33065782

RESUMO

BACKGROUND: Evaluate the accuracy of IWI predicting weaning in patients with mechanical ventilation greater than 72 hours. METHODS: All patients were divided into two groups, according to FiO2 in the intensive care unit (ICU) with mechanically ventilated for more than 72 hours. Recorded Integrative weaning index (IWI) related indicators in all patients. Evaluate the accuracy of IWI predicting weaning success. RESULTS: Within these 50 patients, 32 of them were weaning successfully, and 18 of the patients failed. Using IWI >45.70 mL/cmH2O breaths/minute/liter as a threshold of predicting successful weaning, the sensitivity is 0.91, and the specificity is 0.83. The AUC of IWI was 0.91. In the group with FiO2 =0.40, 17 patients were successfully liberated from MV, while 8 patients failed. The sensitivity is 0.8235, and specificity is 0.88 using IWI >50.40 mL/cmH2O breath/minute/liter as a threshold for predicting the outcome of weaning. The AUC of IWI was 0.846±0.117. In the FiO2 =0.35 group, 15 patients were successfully liberated from MV, while 10 patients failed. Using IWI >39.33 mL/cmH2O breaths/minute/liter, as a threshold to predict successful weaning, results in a sensitivity of 0.93 and a specificity of 0.90. The AUC of IWI was 0.953±0.395. CONCLUSIONS: Results showed IWI has a significantly higher AUC value compared with other traditional weaning indexes. Hence, it can be a significant predictor for weaning outcomes.

17.
Sensors (Basel) ; 20(19)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977473

RESUMO

Due to complicated processing technology, the mass distribution of a hemispherical resonator made of fused silica is not uniform, which can affect the azimuth of the standing wave of a resonator under the linear vibration excitation. Therefore, the analysis of standing wave evolution of a resonator with mass imperfection under linear vibration excitation is of significance for the improvement of the output accuracy of a gyroscope. In this paper, it is assumed that the resonator containing the first-third harmonics of mass imperfection is excited by horizontal and vertical linear vibration, respectively; then, the equations of motion of an imperfect resonator under the second-order vibration mode are established by the elastic thin shell theory and Lagrange mechanics principle. Through error mechanism analysis, it is found that, when the frequency of linear vibration is equal to the natural frequency of resonator, the standing wave is bound in the azimuth of different harmonics of mass imperfection with the change in vibration excitation direction. In other words, there are parasitic components in the azimuth of the standing wave of a resonator under linear vibration excitation, which can cause distortion of the output signal of a gyroscope. On the other hand, according to the standing wave binding phenomenon, the azimuths of the first-third harmonics of mass imperfection of a resonator can also be identified under linear vibration excitation, which can provide a theoretical method for the mass balance of an imperfect resonator.

18.
Thorac Cancer ; 11(11): 3234-3242, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32989915

RESUMO

BACKGROUND: Circulating genetically abnormal cells (CACs) with specific chromosome variations have been confirmed to be present in non-small cell lung cancer (NSCLC). However, the diagnostic performance of CAC detection remains unclear. This study aimed to evaluate the potential clinical application of the CAC test for the early diagnosis of NSCLC. METHODS: In this prospective study, a total of 339 participants (261 lung cancer patients and 78 healthy volunteers) were enrolled. An antigen-independent fluorescence in situ hybridization was used to enumerate the number of CACs in peripheral blood. RESULTS: Patients with early-stage NSCLC were found to have a significantly higher number of CACs than those of healthy participants (1.34 vs. 0.19; P < 0.001). The CAC test displayed an area under the receiver operating characteristic (ROC) curve of 0.76139 for discriminating stage I NSCLC from healthy participants with 67.2% sensitivity and 80.8% specificity, respectively. Compared with serum tumor markers, the sensitivity of CAC assays for distinguishing early-stage NSCLC was higher (67.2% vs. 48.7%, P < 0.001), especially in NSCLC patients with small nodules (65.4% vs. 36.5%, P = 0.003) and ground-glass nodules (pure GGNs: 66.7% vs. 40.9%, P = 0.003; mixed GGNs: 73.0% vs. 43.2%, P < 0.001). CONCLUSIONS: CAC detection in early stage NSCLC was feasible. Our study showed that CACs could be used as a promising noninvasive biomarker for the early diagnosis of NSCLC. KEY POINTS: What this study adds: This study aimed to evaluate the potential clinical application of the CAC test for the early diagnosis of NSCLC. Significant findings of the study: CAC detection in early stage NSCLC was feasible. Our study showed that CACs could be used as a promising noninvasive biomarker for the early diagnosis of NSCLC.

19.
Food Chem Toxicol ; 145: 111744, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32918987

RESUMO

To explore the impact of Huangjinya on metabolic disorders and host endogenous metabolite profiles, high-fat diet (HFD)-fed mice were administrated with Huangjinya green tea extract (HGT) at the dose of 150 or 300 mg/kg for 9 weeks. Epigallocatechin gallate was the main catechin derivative, followed by epigallocatechin and catechin presented in HGT, which contained high levels of free amino acids (50.30 ± 0.60 mg/g). HGT significantly alleviated glucose and insulin intolerance, reduced hepatic lipid accumulation and liver steatosis, and prevented white adipose tissue expansion in HFD-fed mice. Untargeted mass spectrometry-based metabolomics analysis revealed that HGT reduced the abundance of fecal branched-chain amino acids, aromatic amino acids, sphingolipids, and most acyl cholines, modulated bile acid metabolism by increasing chenodeoxycholate and reducing cholic acid content, and increased unsaturated fatty acids content. Fatherly, HGT activated insulin/PI3K/Akt and AMPK signaling pathways in the liver, reduced adipogenic and lipogenic genes expression, and promoted the genes expression related to lipolysis and adipocyte browning in white adipose tissue, contributed to improving metabolic syndrome in HFD-fed mice. The current study reported the impact of HGT supplementation on endogenous metabolite profiles, and highlights the positive roles of HGT in preventing diet-induced obesity and the related metabolic disorders.

20.
J Steroid Biochem Mol Biol ; 204: 105754, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32946925

RESUMO

OBJECTIVES AND METHODS: A total of 41 GDM and 40 normal glucose tolerance subjects were recruited. Through detecting the level of Serum vitamin D with electrochemical luminescence and vitamin D receptor (VDR) with Enzyme-linked immunosorbent assay (ELISA) in maternal and cord blood, the expression leves of CYP24A1, CYP27B1, VDR protein and mRNA in placenta and umbilical cord with western blotting and RT-PCR, and the DNA methylation levels of CYP24A1 and CYP27B1 gene in placenta with methylation-specific PCR (MSP) and direct bisulfite sequencing (BSP) analysis to explore the potential role of the vitamin D and its related genes in gestational diabetes mellitus (GDM). RESULTS: Serum vitamin D concentrations were significantly higher in normal pregnant than women with GDM in maternal blood (P < 0.01) and cord blood (P = 0.014). Compared to the control group, the expression levels of CYP24A1 protein (P < 0.01) and mRNA (P = 0.021) and VDR protein (P = 0.026) and mRNA (P = 0.023) in the GDM group were significantly higher in placenta and umbilical cord tissues (P = 0.015, P < 0.01, P = 0.028, P < 0.01, respectively), while that of CYP27B1 protein (P < 0.01) and mRNA (P = 0.042) was significantly lower (P = 0.022, P = 0.032, respectively). Moreover, partial DNA methylation of CYP24A1 and CYP27B1 genes was observed in both GDM and control groups. CONCLUSIONS: Vitamin D deficiency participates in the pathogenesis of GDM, and changes in the expression of genes related to the vitamin D metabolic pathway are closely related to vitamin D levels in the pregnancy and fetus. However, DNA methylation of CYP24A1 and CYP27B1 might not be involved in the pathogenesis of GDM.

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