Sepsis will induce stroke, new-onset atrial fibrillation (AF) increase ischemic stroke (IS) in in-hospitalization and long-term period after sepsis. Physicians must alert this condition and given ...suitable treatment.
The associated of IS and new-onset AF in septicemia survivors after discharge have to be evaluated.
The inpatient data was used of the Taiwan National Health Insurance Database (NHIRD) in 2010. We identified patients suffered their first occurrence of septicemia (International Classification of Disease, Ninth Revision, Clinical Modification ICD-9-CM is 038, 003.1, 036.1) and excluded less than 18 years old. Patients had AF (ICD-9-CM to 427.3×) during the same admission or after septicemia hospitalization discharged were defined as new-onset AF. The outcome was IS happened after septicemia discharge (ICD-9-CM as 433-437).
The factors related to IS after septicemia survival were established using multivariate logistic regression with forward stepwise selection.
There were 1286 new-onset AF and 1026 IS happened after septicemia discharge. The crude odds ratio (OR) were 3.88 (95% confidence interval C.I.: 1.69-8.89) and 1.62 (95% C.I.: 1.14-2.3) in middle-aged and elderly septicemia survivors with new-onset AF induced IS. The risk of IS after septicemia survivors was noticed adjusted OR 1.74 (95% C.I.: 1.26-2.41) for new-onset AF.
The middle-aged and elderly septicemia survivors suffered from new-onset AF had increased incidence of IS within three months. New-onset AF was a mediator factor of IS in septicemia survivors of Asian population.
Stathmin1 (STMN1) is a candidate oncoprotein and prognosis marker in several kinds of cancers. This study was aimed to analyze its expression and biological functions in gastric cancer. The ...expression of STMN1 was evaluated by qRT-PCR, western blot and immunohistochemistry. The biological function of STMN1 was determined by MTT proliferation assays, monolayer colony formation and cell invasion assays using small interference RNA technique in gastric cancer cell lines. We also explored the regulation of STMN1 expression by microRNA-223. STMN1 was upregulated in gastric cancer cell lines and primary gastric adenocarcinomas. STMN1-positive tumors were more likely to be found in old age group and associated with p53 nuclear expression. In diffuse type gastric adenocarcinomas, STMN1 expression was correlated with age (p = 0.043), T stage (p = 0.004) and lymph node metastasis (p = 0.046). Expression of STMN1 in diffuse type gastric adenocarcinoma was associated with poor disease specific survival by univariate analysis (p = 0.01). STMN1 knockdown in AGS and MKN7 cell lines suppressed proliferation (p<0.001), reduced monolayer colony formation (p<0.001), inhibited cell invasion and migration ability (p<0.001) and induced G1 phase arrest. siSTMN1 could also suppress cell growth in vivo (p<0. 01). We finally confirmed that STMN1 is a putative downstream target of miR-223 in gastric cancer. Our findings supported an oncogenic role of STMN1 in gastric cancer. STMN1 might serve as a prognostic marker and a potential therapeutic target for gastric cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Thioamides antithyroid‐drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD‐induced agranulocytosis is important for clinical management. ...We performed a genome‐wide association study (GWAS) involving 20 patients with ATD‐induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single‐nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD‐induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8–103.7; P = 1.3 × 10‐24) and replication (OR = 37; 95% CI = 3.7–367.4; P = 9.6 × 10‐7). HLA‐B*38:02:01 was in complete linkage disequilibrium with rs185386680. High‐resolution HLA typing confirmed that HLA‐B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)‐induced agranulocytosis (OR = 265.5; 95% CI = 27.9–2528.0; P = 2.5 × 10‐14), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA‐B*38:02:01 in predicting CMZ/MMI‐induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.
Obesity is a major risk factor for cancers including hepatocellular carcinoma (HCC) that develops from a background of non-alcoholic fatty liver disease (NAFLD). Hypercholesterolemia is a common ...comorbidity of obesity. Although cholesterol biosynthesis mainly occurs in the liver, its role in HCC development of obese people remains obscure. Using high-fat high-carbohydrate diet-associated orthotopic and spontaneous NAFLD-HCC mouse models, we found that hepatic cholesterol accumulation in obesity selectively suppressed natural killer T (NKT) cell-mediated antitumor immunosurveillance. Transcriptome analysis of human liver revealed aberrant cholesterol metabolism and NKT cell dysfunction in NAFLD patients. Notably, cholesterol-lowering rosuvastatin restored NKT expansion and cytotoxicity to prevent obesogenic diet-promoted HCC development. Moreover, suppression of hepatic cholesterol biosynthesis by a mammalian target of rapamycin (mTOR) inhibitor vistusertib preceded tumor regression, which was abolished by NKT inactivation but not CD8
T cell depletion. Mechanistically, sterol regulatory element-binding protein 2 (SREBP2)-driven excessive cholesterol production from hepatocytes induced lipid peroxide accumulation and deficient cytotoxicity in NKT cells, which were supported by findings in people with obesity, NAFLD and NAFLD-HCC. This study highlights mTORC1/SREBP2/cholesterol-mediated NKT dysfunction in the tumor-promoting NAFLD liver microenvironment, providing intervention strategies that invigorating NKT cells to control HCC in the obesity epidemic.
Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms ...involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol-∣miRNA-520h-∣PP2A/C-∣Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.
We investigated 68 respiratory specimens from 35 coronavirus disease patients in Hong Kong, of whom 32 had mild disease. We found that severe acute respiratory syndrome coronavirus 2 and subgenomic ...RNA were rarely detectable beyond 8 days after onset of illness. However, virus RNA was detectable for many weeks by reverse transcription PCR.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gastric cancer is a heterogeneous disease with multiple environmental etiologies and alternative pathways of carcinogenesis. Beyond mutations in TP53, alterations in other genes or pathways account ...for only small subsets of the disease. We performed exome sequencing of 22 gastric cancer samples and identified previously unreported mutated genes and pathway alterations; in particular, we found genes involved in chromatin modification to be commonly mutated. A downstream validation study confirmed frequent inactivating mutations or protein deficiency of ARID1A, which encodes a member of the SWI-SNF chromatin remodeling family, in 83% of gastric cancers with microsatellite instability (MSI), 73% of those with Epstein-Barr virus (EBV) infection and 11% of those that were not infected with EBV and microsatellite stable (MSS). The mutation spectrum for ARID1A differs between molecular subtypes of gastric cancer, and mutation prevalence is negatively associated with mutations in TP53. Clinically, ARID1A alterations were associated with better prognosis in a stage-independent manner. These results reveal the genomic landscape, and highlight the importance of chromatin remodeling, in the molecular taxonomy of gastric cancer.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The explosive growth of phytoplankton under favorable conditions in subtropical coastal waters can lead to water discolouration and massive fish kills. Traditional water quality monitoring relies on ...manual field sampling and laboratory analysis of chlorophyll-a (Chl-a) concentration, which is resources intensive and time consuming. The cloudy weather of Hong Kong also precludes using satellite images for algal blooms monitoring. This study for the first time demonstrates the use of an Unmanned Aerial Vehicle (UAVs) to quantitatively map surface water Chl-a distribution in coastal waters from a low altitude. An estimation model for Chl-a concentration from visible images taken by a digital camera on a UAV has been developed and validated against one-year field data. The cost-effective and robust technology is able to map the spatial and temporal variations of Chl-a concentration during an algal bloom. The proposed method offers a useful complement to traditional field monitoring for fisheries management.
Display omitted
•First time used a drone to quantitatively map surface chlorophyll-a concentration•Camera spectral response analysed as a function of chlorophyll-a concentrations•Chlorophyll-a estimation model successfully validated against one-year field data•Success in mapping spatial and temporal variation of Chl-a for an algal bloom
Summary
Current bibliometric analyses of the evolving trends in research scope category across different time periods using the H‐classics method in implantology are considerably limited. The purpose ...of this study was to identify the classic articles in implantology to analyse bibliometric characteristics and associated factors in implantology for the past four decades. H‐Classics in implantology were identified within four time periods between 1977 and 2016, based on the h‐index from the Scopus® database. For each article, the principal bibliometric parameters of authorship, geographic origin, country origin, and institute origin, collaboration, centralisation, article type, scope of study and other associated factors were analysed in four time periods. A significant increase in mean numbers of authors per H‐Classics was found across time. Both Europe and North America were the most productive region/country and steadily dominated this field in each time period. Collaborations of author, internationally and inter‐institutionally had significantly increased across time. A significant decentralisation in authorships, institutes and journals was noted in past four decades. The journal of Clinical Oral Implant Researches has raised its importance for almost 30 years (1987‐2016). Research on Complications, peri‐implant infection/pathology/therapy had been increasing in production throughout each period. This is the first study to evaluate research trends in implantology in the past 40 years using the H‐classics method, which through analysing via principle bibliometric characteristics reflected a historical perspective on evolutionary mainstream in the field. Prominence of research regarding complications may forecast innovative advancements in future.
Background and Purpose
Hypoxia‐mediated neovascularization plays an important role in age‐related macular degeneration (AMD). There are few animal models or effective treatments for AMD. Here, we ...investigated the effects of the flavonoid silibinin on hypoxia‐induced angiogenesis in a rat AMD model.
Experimental Approach
Retinal pigmented epithelial (RPE) cells were subjected to hypoxia in vitro and the effects of silibinin on activation of key hypoxia‐induced pathways were examined by elucidating the hypoxia‐inducible factor‐1 alpha (HIF‐1α) protein level by Western blot. A rat model of AMD was developed by intravitreal injection of VEGF in Brown Norway rats, with or without concomitant exposure of animals to hypoxia. Animals were treated with oral silibinin starting at day 7 post‐VEGF injection and AMD changes were followed by fluorescein angiography on days 14 and 28 post‐injection.
Key Results
Silibinin pretreatment of RPE cells increased proline hydroxylase‐2 expression, inhibited HIF‐1α subunit accumulation, and inhibited VEGF secretion. Silibinin‐induced HIF‐1α and VEGF down‐regulation required suppression of hypoxia‐induced phosphatidylinositol 3‐kinase/Akt/mammalian target of rapamycin (mTOR) pathway. In the rat model of AMD, silibinin administration prevented VEGF‐ and VEGF plus hypoxia‐induced retinal oedema and neovascularization.
Conclusion and Implications
The effects of silibinin, both in vitro and in vivo, support its potential as a therapeutic for the prevention of neovascular AMD.