Association between red blood cell distribution width and all-cause mortality in unselected critically ill patients: Analysis of the MIMIC-III database

BackgroundAlthough red cell distribution width (RDW) is widely observed in clinical practice, only a few studies have looked at all-cause mortality in unselected critically ill patients, and there are even fewer studies on long-term mortality. The goal of our study was to explore the prediction and inference of mortality in unselected critically ill patients by assessing RDW levels.MethodsWe obtained demographic information, laboratory results, prevalence data, and vital signs from the unselected critically ill patients using the publicly available MIMIC-III database. We then used this information to analyze the association between baseline RDW levels and unselected critically ill patients using Cox proportional risk analysis, smoothed curve fitting, subgroup analysis, and Kaplan–Meier survival curves for short, intermediate, and long-term all-cause mortality in unselected critically ill patients.ResultsA total of 26,818 patients were included in our study for the final data analysis after screening in accordance with acceptable conditions. Our study investigated the relationship between RDW levels and all-cause mortality in a non-selected population by a smoothed curve fit plots and COX proportional risk regression models integrating cubic spline functions reported results about a non-linear relationship. In the fully adjusted model, we found that RDW values were positively associated with 30-day, 90-day, 365-day, and 4-year all-cause mortality in 26,818 non-selected adult patients with HRs of 1.10 95%CIs (1.08, 1.12); 1.11 95%CIs (1.10, 1.13); 1.13 95%CIs (1.12, 1.14); 1.13 95%CIs (1.12, 1.14).ConclusionIn unselected critically ill patients, RDW levels were positively associated with all-cause mortality, with elevated RDW levels increasing all-cause mortality

Adjuvant therapy for T3N0 rectal cancer in the total mesorectal excision era- identification of the high risk patients

<p>Abstract</p> <p>Background</p> <p>Adjuvant therapy for T3N0 rectal cancer was controversial with respect to both radiation and the use of a combined regimen of chemotherapy. We evaluated both clinical features and biomarkers and sought to determine risk factors for those patients retrospectively.</p> <p>Methods</p> <p>A total of 122 patients with T3N0 rectal cancer were analyzed in this study from January 2000 to December 2005. Clinicopathologic and biomarkers were used to predict local recurrence (LR), disease-free survival (DFS), and overall survival (OS).</p> <p>Results</p> <p>The median follow-up interval was 45.4 months. Five-year LR, DFS, and OS rates were 10.4%, 68.3%, and 88.7%. Having a lower tumor location and showing low P21 and high CD44v6 expression were identified as risk factors for LR: patients with two or three of these risk factors had a higher 5-year LR rate (19.3%) than did patients with none or one of these risk factors (6.8%) (p = 0.05). A poorer DFS was related to low P21 nor high CD44v6 expression but not to tumor location: the 5-year DFS rates were 79.3% for those with neither, 65.9% for those with either one or the other, and 16.9% for those with both (p = 0.00).</p> <p>Conclusions</p> <p>The prognostic model including tumor location, P21 and CD44v6 expressions could help to distinguish these patients with high risk T3N0 patients and determine whether adjuvant therapy was beneficial.</p

Effects of guanidinoacetic acid supplementation on liver and breast muscle fat deposition, lipid levels, and lipid metabolism-related gene expression in ducks

Exogenous supplementation of guanidinoacetic acid can mechanistically regulate the energy distribution in muscle cells. This study aimed to investigate the effects of guanidinoacetic acid supplementation on liver and breast muscle fat deposition, lipid levels, and lipid metabolism-related gene expression in ducks. We randomly divided 480 42 days-old female Jiaji ducks into four groups with six replicates and 20 ducks for each replicate. The control group was fed the basal diet, and the experimental groups were fed the basal diet with 400, 600, and 800 mg/kg (GA400, GA600, and GA800) guanidinoacetic acid, respectively. Compared with the control group, (1) the total cholesterol (p = 0.0262), triglycerides (p = 0.0357), malondialdehyde (p = 0.0452) contents were lower in GA400, GA600 and GA800 in the liver; (2) the total cholesterol (p = 0.0365), triglycerides (p = 0.0459), and malondialdehyde (p = 0.0326) contents in breast muscle were decreased in GA400, GA600 and GA800; (3) the high density lipoprotein (p = 0.0356) and apolipoprotein-A1 (p = 0.0125) contents were increased in GA600 in the liver; (4) the apolipoprotein-A1 contents (p = 0.0489) in breast muscle were higher in GA600 and GA800; (5) the lipoprotein lipase contents (p = 0.0325) in the liver were higher in GA600 and GA800; (6) the malate dehydrogenase contents (p = 0.0269) in breast muscle were lower in GA400, GA600, and GA800; (7) the insulin induced gene 1 (p = 0.0326), fatty acid transport protein 1 (p = 0.0412), and lipoprotein lipase (p = 0.0235) relative expression were higher in GA400, GA600, and GA800 in the liver; (8) the insulin induced gene 1 (p = 0.0269), fatty acid transport protein 1 (p = 0.0234), and lipoprotein lipase (p = 0.0425) relative expression were increased in GA400, GA600, and GA800 in breast muscle. In this study, the optimum dosage of 600 mg/kg guanidinoacetic acid improved the liver and breast muscle fat deposition, lipid levels, and lipid metabolism-related gene expression in ducks

Perceptions of the benefits of the basic medical insurance system among the insured: a mixed methods research of a northern city in China

BackgroundThe perceptions of the benefits of the basic medical insurance system among the insured not only reflect the system's performance but also the public's basic medical insurance policy literacy, valuable information for countries that have entered the stage of deepening reform. This study aims to examine the factors that affect the perceptions of the benefits of the basic medical insurance system in China, diagnose the key problems, and propose corresponding measures for improvement.MethodsA mixed method design was used. Data for the quantitative study were obtained from a cross-sectional questionnaire survey (n = 1,045) of residents of Harbin who had enrolled for basic medical insurance system. A quota sampling method was further adopted. A multivariate logistic regression model was then employed to identify the factors influencing the perceptions of the benefits of the basic medical insurance system, followed by semi-structured interviews with 30 conveniently selected key informants. Interpretative phenomenological analysis was used to analyze the interview data.ResultsApproximately 44% of insured persons reported low perceptions of benefits. The logistic regression model showed that low perceptions of the benefits of the basic medical insurance system was positively correlated with the experience of daily drug purchases (OR = 1.967), perceptions of recognition with basic medical insurance system (OR = 1.948), perceptions of the financial burden of participation costs (OR = 1.887), perceptions of the convenience of using basic medical insurance for medical treatment (OR = 1.770), perceptions of the financial burden of daily drug purchases costs (OR = 1.721), perceptions of the financial burden of hospitalization costs (OR = 1.570), and type of basic medical insurance system (OR = 1.456). The results of the qualitative analysis showed that the key problem areas of perceptions of the benefits of the basic medical insurance system were: (I) system design of basic medical insurance; (II) intuitive cognition of the insured; (III) rational cognition of the insured; and (IV) the system environment.ConclusionsImproving the perceptions of the benefits of the basic medical insurance system of the insured requires joint efforts in improving system design and implementation, exploring effective publicity methods of basic medical insurance system information, supporting public policy literacy, and promoting the health system environment

TRH Analog, Taltirelin Protects Dopaminergic Neurons From Neurotoxicity of MPTP and Rotenone

Dopaminergic neurons loss is one of the main pathological characters of Parkinson’s disease (PD), while no suitable neuroprotective agents have been in clinical use. Thyrotropin-releasing hormone (TRH) and its analogs protect neurons from ischemia and various cytotoxins, but whether the effect also applies in PD models remain unclear. Here, we showed that Taltirelin, a long-acting TRH analog, exhibited the neuroprotective effect in both cellular and animal models of PD. The in vitro study demonstrated that Taltirelin (5 μM) reduced the generation of reactive oxygen species (ROS) induced by MPP+ or rotenone, alleviated apoptosis and rescued the viability of SH-SY5Y cells and rat primary midbrain neurons. Interestingly, SH-SY5Y cells treated with Taltirelin also displayed lower level of p-tau (S396) and asparagine endopeptidase (AEP) cleavage products, tau N368 and α-synuclein N103 fragments, accompanied by a lower intracellular monoamine oxidase-B (MAO-B) activity. In the subacute MPTP-induced and chronic rotenone-induced PD mice models, we found Taltirelin (1 mg/kg) significantly improved the locomotor function and preserved dopaminergic neurons in the substantia nigra (SN). In accordance with the in vitro study, Taltirelin down-regulated the levels of p-tau (S396), p-α-synuclein (S129) tau N368 and α-synuclein N103 fragments in SN and striatum. Together, this study demonstrates that Taltirelin may exert neuroprotective effect via inhibiting MAO-B and reducing the oxidative stress and apoptosis, preventing AEP activation and its subsequent pathological cleavage of tau and α-synuclein, thus provides evidence for Taltirelin in protective treatment of PD

TRH Analog, Taltirelin Improves Motor Function of Hemi-PD Rats Without Inducing Dyskinesia via Sustained Dopamine Stimulating Effect

Thyrotropin-releasing hormone (TRH) and its analogs are able to stimulate the release of the endogenic dopamine (DA) in the central nervous system. However, this effect has not been tested in the Parkinson’s disease (PD), which is characterized by the DA deficiency due to the dopaminergic neurons loss in the substantia nigra. Here, we investigated the therapeutic effect of Taltirelin, a long-acting TRH analog on 6-hydroxydopamine-lesioned hemi-Parkinsonian rat model. 1–10 mg/kg Taltirelin i.p. administration significantly improved the locomotor function and halted the electrophysiological abnormities of PD animals without inducing dyskinesia even with high-dose for 7 days treatment. Microdialysis showed that Taltirelin gently and persistently promoted DA release in the cortex and striatum, while L-DOPA induced a sharp rise of DA especially in the cortex. The DA-releasing effect of Taltirelin was alleviated by reserpine, vanoxerine (GBR12909) or AMPT, indicating a mechanism involving vesicular monoamine transporter-2 (VMAT-2), dopamine transporter (DAT) and tyrosine hydroxylase (TH). The in vivo and in vitro experiments further supported that Taltirelin affected the regulation of TH expression in striatal neurons, which was mediated by p-ERK1/2. Together, this study demonstrated that Taltirelin improved motor function of hemi-PD rats without inducing dyskinesia, thus supporting a further exploration of Taltirelin for PD treatment

Construction of a cross-species cell landscape at single-cell level.

Individual cells are basic units of life. Despite extensive efforts to characterize the cellular heterogeneity of different organisms, cross-species comparisons of landscape dynamics have not been achieved. Here, we applied single-cell RNA sequencing (scRNA-seq) to map organism-level cell landscapes at multiple life stages for mice, zebrafish and Drosophila. By integrating the comprehensive dataset of > 2.6 million single cells, we constructed a cross-species cell landscape and identified signatures and common pathways that changed throughout the life span. We identified structural inflammation and mitochondrial dysfunction as the most common hallmarks of organism aging, and found that pharmacological activation of mitochondrial metabolism alleviated aging phenotypes in mice. The cross-species cell landscape with other published datasets were stored in an integrated online portal-Cell Landscape. Our work provides a valuable resource for studying lineage development, maturation and aging

Potent Neutralization of Influenza A Virus by a Single-Domain Antibody Blocking M2 Ion Channel Protein

Influenza A virus poses serious health threat to humans. Neutralizing antibodies against the highly conserved M2 ion channel is thought to offer broad protection against influenza A viruses. Here, we screened synthetic Camel single-domain antibody (VHH) libraries against native M2 ion channel protein. One of the isolated VHHs, M2-7A, specifically bound to M2-expressed cell membrane as well as influenza A virion, inhibited replication of both amantadine-sensitive and resistant influenza A viruses in vitro, and protected mice from a lethal influenza virus challenge. Moreover, M2-7A showed blocking activity for proton influx through M2 ion channel. These pieces of evidence collectively demonstrate for the first time that a neutralizing antibody against M2 with broad specificity is achievable, and M2-7A may have potential for cross protection against a number of variants and subtypes of influenza A viruses