Barkervilladsen1662

Lung cancer is still a main cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC) accounts for the majority of lung cancers, and gefitinib is an effective targeted drug for NSCLC. It is important to explore the underlying molecular mechanisms of gefitinib resistance to provide new treatment strategies and to improve the prognosis of gefitinib-resistant NSCLC patients. This study aimed to examine the role of filamin A (FLNA) in acquired resistance to gefitinib in NSCLC, and identify ANXA2 (annexin A2), one of calcium-dependent phospholipid-binding proteins, as its corresponding regulatory factor. First, we established resistant cells via long-term exposure to gefitinib to analyse the association between FLNA and gefitinib resistance. Through quantitative real-time polymerase chain reaction (qRT-PCR), Cell Counting Kit-8 (CCK-8), western blotting (WB), and flow cytometry assays, we evaluated the role of FLNA. The effect of FLNA knockdown or overexpression was analysed not only in cell lines but also in mouse models. We verified the FLNA-interacting protein through coimmunoprecipitation (CoIP) experiments and found that the downstream signalling pathway was regulated by FLNA and its interacting protein. Finally, the upstream transcription factor was identified by chromatin immunoprecipitation (ChIP). Increased FLNA expression induced gefitinib resistance. Knockdown of FLNA restored gefitinib sensitivity and induced apoptosis in vivo and in vitro. FLNA and ANXA2 cooperatively led to the activation of the Wnt pathway, which was closely linked to gefitinib resistance. Subsequently, SP1 promoted transcriptional activation of FLNA to regulate gefitinib resistance. We determined that FLNA serves as a regulator of gefitinib resistance in NSCLC and found that FLNA and ANXA2 together induced gefitinib resistance by activating the Wnt pathway.

To investigate the effect of combined lipid-lowering therapy on low-density lipoprotein cholesterol (LDL-C) variability and cardiovascular adverse events in patients with acute coronary syndrome (ACS).

A total of 200 patients with acute coronary syndrome, admitted to the first Hospital of Hebei Medical University from January 2018 to June 2019, were randomly divided into the observation group (100 cases were treated with combined lipid-lowering drugs, including 10mg/day atorvastatin and 10mg/day ezetimibe) and the control group (100 cases were given an intensive statin regimen, including 40mg/day atorvastatin). The levels of blood lipids, creatine kinase (CK), alanine transaminase (ALT), matrix metalloproteinase-9 (MMP-9) and high-sensitivity C-reactive protein (hsCRP) were observed and compared between the two groups. Focus was laid on the concentration of the above-mentioned parameters and follow-up results including the drug safety and incidence of cardiovascular adverse events.

Before treatment, thened lipid-lowering drugs are considered valid and alternative approaches for wide clinical practice.

Combination therapy with atorvastatin and ezetimibe potentially provides remarkable effects in terms of treating acute coronary syndrome, controlling the variation of LDL-C, alleviating the inflammatory state and reducing the incidence of cardiovascular adverse events with a safe profile. Combined lipid-lowering drugs are considered valid and alternative approaches for wide clinical practice.

Levodopa/carbidopa intestinal gel (LCIG; carbidopa/levodopa enteral suspension) has been widely used and studied for the treatment of motor fluctuations in levodopa-responsive patients with advanced Parkinson's disease (PD) when other treatments have not given satisfactory results. Reduction in 'off'-time is a common primary endpoint in studies of LCIG, and it is important to assess the durability of this response. This systematic literature review was conducted to qualitatively summarise the data on the long-term effects of LCIG therapy on 'off'-time.

Studies were identified by searching PubMed, EMBASE and Ovid on 30 September 2019. Studies were included if they reported on patients with PD, had a sample size of ≥ 10, LCIG was an active intervention and 'off'-time was reported for ≥ 12months after initiation of LCIG treatment. Randomised clinical trials, retrospective and prospective observational studies, and other interventional studies were included for selection. Dansylcadaverine mouse Data were collected on 'off'-time (at to provide a durable effect in reducing 'off'-time.

Video Abstract.

Video Abstract.The occurrence of mycotoxins and mycotoxigenic fungi in palm dates has not been thoroughly documented. The aims of the present study were to identify the mycobiota present in commercial date samples (n = 19), to determine the ability of the isolated fungi to produce mycotoxins, and to determine and quantify the presence of OTA in date fruits. The majority of products originated from Tunisia (n = 14) and Algeria (n = 3). The dominant fungal species were Aspergillus niger, Aspergillus tubingensis and Aspergillus flavus which were most frequently found in premium quality and organic produce, produced without chemical preservatives. OTA was found in only one sample at a concentration of 0.75 µg/kg, as determined by HPLC with fluorescence detection. Although this preliminary study did not find elevated levels of OTA, its presence in one out of 19 samples indicates that palm dates for human consumption require continuous and stringent control, in order to prevent contaminated produce from entering the market.This meta-analysis of randomized clinical trials (RCT) aimed to compare peritoneal irrigation followed by suction with aspiration only during laparoscopic surgery for complicated appendicitis (LA). PRISMA guidelines with the random-effects model were adopted using Review Manager Version 5.3 for pooled estimates. We retained six eligible RCT published between 2012 and 2019. They involved a total of 1019 patients (541 patients in the aspiration group and 478 patients in the irrigation group). Aspiration only during LA is associated with shorter operative time (MD = 8.50 min, 95% CI [- 12.97 to - 4.02], p = 0.0002) and lower reoperation rate (OR = 0.37 95% CI [0.14-0.96], p = 0.04). There was no difference between aspiration group and irrigation group in terms of Intraperitoneal abscess (IPA) (OR = 0.99 95% CI [0.54-1.81], p = 0.95), morbidity rate (OR = 1.14 95% CI [0.44-2.98], p = 0.79), wound infection (OR = 0.94 95% CI [0.20-4.40], p = 0.94), and hospital stay (MD = 0.65 day, 95% CI [- 0.52 to 1.82], p = 0.27).