Πέμπτη 26 Νοεμβρίου 2020

The Role of Oxymatrine in Amelioration of Acute Lung Injury Subjected to Myocardial I/R by Inhibiting Endoplasmic Reticulum Stress in Diabetic Rats

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Background. Oxymatrine (OMT) is the primary pharmacological component of Sophora flavescens Aiton., which has been shown to possess potent antifibrotic, antioxidant, and anti-inflammatory activities. The aim of the present study was to clarify the protective mechanism of OMT on acute lung injury (ALI) subjected to myocardial ischemia/reperfusion (I/R). Methods. A myocardial I/R-induced ALI model was achieved in diabetic rats by occluding the left anterior descending coronary artery for 1 h, followed by reperfusion for 1 h. The levels of inflammatory factors (tumor necrosis factor-α, interleukin- (IL-) 6, and IL-17) in bronchoalveolar lavage fluid were assessed using commercially available kits. The index of myocardial injury, including the detection of cardiac troponin I (cTnI), cardiac troponin T (cT nT), lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB), was also determined using commercially available kits. Hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to identify histological changes. The expression levels of endoplasmic reticulum chaperone BiP (GRP78), DNA damage-inducible transcript 3 protein (CHOP), eukaryotic translation initiation factor 2-alpha kinase 3 (PERK), inositol dependent enzyme 1α (IRE1α), ATF6, caspase-3, -9, and-12, Bcl-2, and Bax were determined by Western blotting. The mRNA expression levels of GRP78 and CHOP were detected by reverse transcription-quantitative PCR. Results. Myocardial I/R increased the levels of cTnI, cTnT, LDH, and CK-MB in diabetic rats. Damaged and irregularly arranged myocardial cells were also observed, as well as more serious ALI with higher lung injury scores and WET/DRY ratios and lower PaO2. Moreover, the expression of key proteins of endoplasmic retic ulum stress (ERS) was increased by I/R injury, including phosphorylated- (p-) PERK, p-IRE1ɑ, and ATF6, as well as decreased levels of apoptosis. These effects were all significantly reversed by OMT treatment. Conclusions. OMT protects against ALI subjected to myocardial I/R by inhibiting ERS in diabetic rats.
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The Development of Three-DNA Methylation Signature as a Novel Prognostic Biomarker in Patients with Colorectal Cancer

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Aims. The prognosis of colorectal cancer (CRC) remains poor. This study aimed to develop and validate DNA methylation-based signature model to predict overall survival of CRC patients. Methods. The methylation array data of CRC patients were retrieved from The Cancer Genome Atlas (TCGA) database. These patients were divided into training and validation datasets. A risk score model was established based on Kaplan-Meier and multivariate Cox regression analysis of training cohort and tested in validation cohort. Results. Among total 14,626 DNA methylation candidate markers, we found that a three-DNA methylation signature (NR1H2, SCRIB, and UACA) was significantly associated with overall survival of CRC patients. Subgroup analysis indicated that this signature could predict overall survival of CRC patients reg ardless of age and gender. Conclusions. We established a prognostic model consisted of 3-DNA methylation sites, which could be used as potential biomarker to evaluate the prognosis of CRC patients.
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The Nrf2/PGC1α Pathway Regulates Antioxidant and Proteasomal Activity to Alter Cisplatin Sensitivity in Ovarian Cancer

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Drug resistance remains a barrier in the clinical treatment of ovarian cancer. Proteasomal and antioxidant activities play important roles in tumor drug resistance, and increasing evidence suggests the existence of an interaction between antioxidant and proteasomal activities. However, the mechanism of the synergistic effects of proteasomal activity and antioxidation on tumor drug resistance is not completely clear. In this study, we compared two ovarian cancer cells, A2780 and SKOV3 cells. Among them, SKOV3 cell is a human clear cell carcinoma cell line that is resistant to platinum. We found that compared with the findings in A2780 cells, SKOV3 cells were less sensitive to both proteasomal inhibitor and cisplatin. Proteasomal inhibition enhanced the sensitivity of A2780 cells, but not SKOV3 cells, to cis platin. Notably, the Nrf2-mediated antioxidant pathway was identified as a resistance mechanism in proteasome inhibitor-resistant cells, but this was not the only factor identified in our research. In SKOV3 cells, PGC1α regulated the antioxidant activity of Nrf2 by increasing the phosphorylation of GSK3β, and in turn, Nrf2 regulated the transcriptional activity of PGC1α. Thus, Nrf2 and PGC1α synergistically participate in the regulation of proteasomal activity. Furthermore, the Nrf2/PGC1α pathway participated in the regulation of mitochondrial function and homeostasis, further regulating proteasomal activity in SKOV3 cells. Therefore, exploring the roles of PGC1α and Nrf2 in the regulation of proteasomal activity by antioxidant and mitochondrial functions may provide new avenues for reversing drug resistance in ovarian cancer.
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Neural Model Stealing Attack to Smart Mobile Device on Intelligent Medical Platform

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To date, the Medical Internet of Things (MIoT) technology has been recognized and widely applied due to its convenience and practicality. The MIoT enables the application of machine learning to predict diseases of various kinds automatically and accurately, assisting and facilitating effective and efficient medical treatment. However, the MIoT are vulnerable to cyberattacks which have been constantly advancing. In this paper, we establish a MIoT platform and demonstrate a scenario where a trained Convolutional Neural Network (CNN) model for predicting lung cancer complicated with pulmonary embolism can be attacked. First, we use CNN to build a model to predict lung cancer complicated with pulmonary embolism and obtain high detection accuracy. Then, we build a copycat model using only a small amount of data labeled by the target network, aiming to steal the established prediction model. Experimental results prove that the stolen model can also achieve a relatively high prediction outcome, revealing that the copycat network could successfully copy the prediction performance from the target network to a large extent. This also shows that such a prediction model deployed on MIoT devices can be stolen by attackers, and effective prevention strategies are open questions for researchers.
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Current and Potential Applications of Artificial Intelligence in Gastrointestinal Stromal Tumor Imaging

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The most common mesenchymal tumors are gastrointestinal stromal tumors (GISTs), which have malignant potential and can occur anywhere along the gastrointestinal system. Imaging methods are important and indispensable of GISTs in diagnosis, risk staging, therapy, and follow-up. The recommended imaging method for staging and follow-up is computed tomography (CT) according to current guidelines. Artificial intelligence (AI) applies and elaborates theses, procedures, modes, and utilization systems for simulating, enlarging, and stretching the intellectual capacity of humans. Recently, researchers have done a few studies to explore AI applications in GIST imaging. This article reviews the present AI studies in GISTs imaging, including preoperative diagnosis, risk stratification and prediction of prognosis, gene mutation, and targeted therapy response.
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Robot-assisted neurosurgery versus conventional treatment for intracerebral hemorrhage: A systematic review and meta-analysis

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Intracerebral hemorrhage (ICH) is bleeding within the brain caused by rupture of blood vessels. It is one of the subtypes of stoke which is second leading cause of death around the world [1]. According to AHA/ASA Guideline for the Management of Spontaneous Intracerebral Hemorrhage, commonly used treatments for ICH are medical treatment including hemostasis, coagulopathy, antiplatelets and deep vein thrombosis prophylaxis, blood-pressure-lowering treatment and surgery containing endoscopic treatment, craniotomy and minimally invasive surgical evacuation [2].
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The Effect of Laparoscopic Sleeve Gastrectomy on Gastroesophageal Reflux Disease

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Abstract

Background

The laparoscopic sleeve gastrectomy (LSG) has become one of the most popular surgical weight loss options. Since its inception as a procedure intended to promote durable weight loss, the association between LSG and gastroesophageal reflux disease (GERD) has been a point of debate. First and foremost, it is known that GERD occurs more frequently in the obese population. With the sleeve gastrectomy growing to be the predominant primary bariatric operation in the United States, it is imperative that we understand the impact of LSG on GERD.

Objective

To examine the effects of LSG on GERD symptoms.

Methods

One hundred and ninety-one bariatric surgery candidates completed a Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) questionnaire before and after undergoing elective LSG (mean follow-up time of 20.4 ± 2.7 months). Values were stratified by the presence or absence of preoperative GERD, GERD medications, age, gender, crural repair, patient satisfaction with present condition, and percent total weight loss (%TWL).

Results

For the entire group, mean weight loss, %TWL, and reduction in BMI were 79 pounds, 28.1%, and 12.7 kg/m2 respectively. Within the overall cohort, there was no significant change in GERD symptoms from before to after surgery (mean GERD-HRQL scores were 6.1 before and after surgery, p = 0.981). However, in a subgroup analysis, patients without GERD preoperatively demonstrated a worsening in mean GERD-HRQL scores after surgery (from 2.4 to 4.5, p = 0.0020). The percentage of change in the usage of medications to treat GERD was not statistically significant (from 37 to 32%, p = 0.233). The percent of patients satisfied with their condition postoperatively was significantly increased in those with preoperative GERD, older age, crural repair intraoperatively, and in those with the highest %TWL.

Conclusion

These results suggest that while overall LSG does not significantly affect GERD symptoms, patients without GERD preoperatively may be at risk for developing new or worsening GERD symptoms after surgery. It is important to remark that this is a review of the patient's clinical symptoms of GERD, not related to any endoscopic, pathological, or manometry studies. Such studies are necessary to fully establish the effect of LSG on esophageal health.

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[News] Carcinogenicity of acrolein, crotonaldehyde, and arecoline

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In October–November, 2020, a Working Group of 20 scientists from ten countries met remotely at the invitation of the International Agency for Research on Cancer (IARC) to finalise their evaluations of the carcinogenicity of acrolein, crotonaldehyde, and arecoline. Acrolein was classified as "probably carcinogenic to humans" (Group 2A) on the basis of "sufficient" evidence of carcinogenicity in experimental animals and "strong" mechanistic evidence. Crotonaldehyde and arecoline were classified as "possibly carcinogenic to humans" (Group 2B) on the basis of "strong" mechanistic evidence.
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[Articles] Global burden of acute lower respiratory infection associated with human metapneumovirus in children under 5 years in 2018: a systematic review and modelling study

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Infants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries.
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[Comment] The place for remdesivir in COVID-19 treatment

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Finding antivirals that reduce mortality from severe respiratory viral infections has proven challenging. Phase 3 trials of baloxavir and pimodivir for severe influenza were unsuccessful (NCT03684044 and NCT03376321). Lopinavir–ritonavir and hydroxychloroquine are not efficacious in treating COVID-19.1,2 Interim results from the WHO-led, open-label, randomised SOLIDARITY trial3 of patients with COVID-19 report that 301 (11·0%) of 2743 patients analysed who received remdesivir and 303 (11·2%) of 2708 patients analysed who received standard care died by day 28 (Kaplan-Meier rate ratio [RR] 0·95, 95% CI 0·81–1·11; p=0·50).
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Economic Evaluation of Suture Versus Clip Anastomosis in Arteriovenous Fistula Creation

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Techniques like the use of nonpenetrating vascular clips for arteriovenous fistula (AVF) anastomotic creation have been developed in an effort to reduce fistula-related complications. However, the outcome data for the use of clips remains equivocal, while cost evaluations to support their use have been largely theoretical. Therefore, this study aimed to determine both the clinical and cost outcomes of AVFs created with nonpenetrating vascular clips compared to continuous suture technique over a 10-year period at a single institution.
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Professionals guidance about palliative medicine in chronic heart failure: a mixed-method study

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Introduction

Healthcare professionals (HCPs) experience difficulties in timely recognising and directing palliative care (PC) needs of their patients with chronic heart failure (CHF). The aim of this study was to develop a comprehensive tool to enable HCPs in timely recognising and directing PC needs in CHF.

Methods

A four-stage mixed-method study was performed. Stage 1: identification of needs and questions of patients and families; stage 2: prioritisation and refinement of the needs and questions; stage 3a: t esting and online feedback on V.1; stage 3b: selecting and refining care recommendations; stage 4: testing and review of V.2. Iterative reviews followed each step in the development process to ensure a wide range of stakeholder input. In total, 16 patients, 12 family members and 54 HCPs participated.

Results

A comprehensive set of 13 PC needs was identified, redefined and tested. The resulting tool, called Identification of patients with HeARt failure with PC needs (I-HARP), contains an introduction prompt with open questions to start the conversation, 13 closed screening questions with additional in-depth questions, and recommendations on actions for identified needs.

Conclusion

I-HARP contains an evidence-based set of questions and palliative CHF care suggestions for HCPs in the Netherlands. The resulting tool, approved by HCPs, patients and family members, is a promising guidance for HCP to timely recognise and direct PC needs in CHF.

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