Predictors of Remission of Early-Onset Poststroke Depression and the Interaction Between Depression and Cognition During Follow-Up

Objectives: This study aimed to examine the rate of remission in individuals experiencing early-onset poststroke depression (PSD) in China and to identify predictors of remission during a 3-month follow-up. This study also explored the interaction between cognitive impairment and depression.Methods: A total of 820 patients with PSD from a massive multicenter prospective cohort project in China (PRIOD) were included in the present study. Depressive symptoms were measured with the Hamilton Depression Rating Scale (17 Items, HDRS-17) at 2 weeks and the endpoint of the 3-month follow-up. The cut-off score of HDRS-17 (< 8) was used to define remission of depression at the endpoint. The Mini-Mental State Exam (MMSE) was used to evaluate the cognitive impairment of the patients (at the 2-week follow-up and 3-month endpoint). The National Institutes of Health Stroke Scale (NIHSS) was used to measure the severity of stroke.Results: (1) Six hundred and forty-two patients completed the 3-month follow-up, and 332 (51.7%) patients remitted by the end of the study. Univariate analyses indicated that there was a higher proportion of patients who had hypertension, frontal lobe lesion, basal ganglia lesion, poor outcome at 2 weeks, high scores on the NIHSS at 2 weeks, major life events within 3 months, and major medical diseases within 3 months in the nonremission group. In stepwise multiple logistic regression analyses, remission was significantly predicted by lower NIHSS scores at 2 weeks (p = 0.001, OR = 1.086, 95% CI 1.035–1.139), fewer major life events (p = 0.036, OR = 5.195, 95% CI 1.111–27.283), fewer major medical comorbidities (p = 0.015, OR = 2.434, 95% CI 1.190–4.979), and fewer frontal lobe lesions (p = 0.042, OR = 1.717, 95% CI 1.019–2.891). (2) After controlling for confounding variables, repeated measures analysis of variance revealed a significant interaction between time (2 weeks vs. 3 months) and group (remitters vs. nonremitters) on MMSE scores [F(1, 532) = 20.2, p < 0.001].Conclusions: Early-onset PSD patients with milder neurological impairment, fewer major life events, fewer major medical comorbidities and no frontal lobe lesion at baseline were more likely to achieve remission 3 months after stroke. Only remitters of PSD improved significantly in cognitive impairment after stroke.The PRIOD trial is registered at http://www.isrctn.com/, number ISRCTN62169508

An Application of 24Model to Analyse Capsizing of the Eastern Star Ferry

In the present study, the Eastern Star ferry accident was analyzed via 24Model. 24Model, as an accident causation model based on system thinking, holds that all causations of the accident are hazards and all hazards in the system need to be identified and comprehensively controlled in accident prevention. The result showed that five factors were the main causes of the accident. First, the direct causes: bad weather, the bad condition of the hull and the unsafe acts of the captain. Second, the indirect cause: the lack of safety awareness and safety knowledge of both the captain and the company’s senior management. Third, there were loopholes in safety management system, including the training, supervision and execution of the company. Forth, the root cause: the company didn’t establish a good safety culture. Last, the external causes: the severe market pressure, excessive regulatory authorities with puzzled relations and responsibilities-seriously hindered effective supervision. In order to prevent this kind of accident and to secure shipping system, the shipping companies and the relevant regulatory units should draw lessons from the five factors mentioned above, and take measures to identify and control those hazards

Polymer Optical Waveguide Grating-Based Biosensor to Detect Effective Drug Concentrations of Ginkgolide A for Inhibition of PMVEC Apoptosis

In this work, we successfully developed a fluorinated cross-linked polymer Bragg waveguide grating-based optical biosensor to detect effective drug concentrations of ginkgolide A for the inhibition of pulmonary microvascular endothelial cell (PMVEC) apoptosis. Fluorinated photosensitive polymer SU-8 (FSU-8) as the sensing core layer and polymethyl methacrylate (PMMA) as the sensing window cladding were synthesized. The effective drug concentration range (5–10 µg/mL) of ginkgolide A for inhibition of PMVEC apoptosis was analyzed and obtained by pharmacological studies. The structure of the device was optimized to be designed and fabricated by direct UV writing technology. The properties of the biosensor were simulated with various refractive indices of different drug concentrations. The actual sensitivity of the biosensor was measured as 1606.2 nm/RIU. The resolution and detection limit were characterized as 0.05 nm and 3 × 10−5 RIU, respectively. The technique is suitable for safe and accurate detection of effective organic drug dosages of Chinese herbal ingredients

Echinococcus granulosus cyst fluid inhibits inflammatory responses through inducing histone demethylase KDM5B in macrophages

Abstract Background Echinococcus granulosus cyst fluid (EgCF) weakens macrophage inflammatory responses, thereby enabling the parasite to evade the immune system. However, the role of histone modification in this process remains to be explored. Methods The levels of IL-6, TNF-α, IL-10, H3K4me3, and KDM5B were detected using quantitative real-time PCR, ELISA, and Western blotting. The enrichment of H3K4me3 and KDM5B at the promoter of inflammatory factors was detected by chromatin immunoprecipitation. Results Based on EgCF-stimulated macrophage models, we found that EgCF significantly inhibited mRNA expression and protein secretion of IL-6 and TNF-α and upregulated mRNA expression of IL-10 under the influence of TLR4. EgCF lowered the level of H3K4me3 and promoted the transcription and protein stability of histone demethylase KDM5B. Chromatin immunoprecipitation analysis revealed that EgCF suppressed the enrichment of H3K4me3 modification at the promoters of TNF-α and IL-6 and downregulated their expression in macrophages. Additionally, the inhibition of KDM5B activity by CPI-455 weakened the anti-inflammatory effect of EgCF. Conclusions Our findings demonstrate a novel mechanism through which EgCF promotes KDM5B expression and inhibits the enrichment of H3K4me3 at the promoters of inflammatory cytokines to suppress the inflammatory response. Graphical Abstrac

Ensuring sample quality for blood biomarker studies in clinical trials: a multicenter international study for plasma and serum sample preparation

Background Sample quality is critical for biomarker detection in oncology, and platelet degradation and contamination in plasma have a remarkable impact on the ability to accurately quantify many blood-based biomarkers. Platelet factor 4 (PF4) can be used as an indicator to monitor sample quality. This multicenter study aimed to determine the impact of critical components of the blood sample handling process on platelet degradation/contamination and to establish an optimal method for collecting platelet-poor plasma samples. Methods At each of six participating centers, blood samples were drawn from 12–13 healthy volunteers. Serum and plasma samples were prepared from whole blood samples using nine different methods that have been commonly used in ongoing multicenter trials. PF4 levels in the prepared samples were measured by enzyme-linked immunosorbent assay (ELISA). Paired t-tests were used for statistical analysis. Results Blood samples were collected from 74 subjects enrolled in six centers. PF4 levels were significantly higher in serum samples than in plasma samples (P<0.001), in plasma samples from blood that sat at room temperature for 5 minutes (P=0.021), in plasma samples prepared at an insufficient centrifugal force (P<0.001), and in plasma samples prepared from blood that sat for longer than 4 hours on ice (P=0.001). For each method, the PF4 levels did not differ significantly among the centers or between Chinese and American subjects. The methods that resulted in normal levels of PF4 involved keeping blood samples on ice for 30 minutes to <4 hours and centrifugation at 2,500–3,000 ×g for 30 min. Conclusions This multicenter study evaluated multiple blood sample handling conditions for minimizing platelet degradation during plasma serum preparation and determined an optimal method for preparing platelet-poor plasma. The findings of this study can be applied in future blood biomarker studies

Liver Transcriptome and miRNA Analysis of Silver Carp (Hypophthalmichthys molitrix) Intraperitoneally Injected With Microcystin-LR

Next-generation sequencing was used to analyze the effects of toxic microcystin-LR (MC-LR) on silver carp (Hypophthalmichthys molitrix). Silver carps were intraperitoneally injected with MC-LR, and RNA-seq and miRNA-seq in the liver were analyzed at 0.25, 0.5, and 1 h. The expression of glutathione S-transferase (GST), which acts as a marker gene for MC-LR, was tested to determine the earliest time point at which GST transcription was initiated in the liver tissues of the MC-LR-treated silver carps. Hepatic RNA-seq/miRNA-seq analysis and data integration analysis were conducted with reference to the identified time point. Quantitative PCR (qPCR) was performed to detect the expression of the following genes at the three time points: heme oxygenase 1 (HO-1), interleukin-10 receptor 1 (IL-10R1), apolipoprotein A-I (apoA-I), and heme binding protein 2 (HBP2). Results showed that the liver GST expression was remarkably decreased at 0.25 h (P &lt; 0.05). RNA-seq at this time point revealed that the liver tissue contained 97,505 unigenes, including 184 significantly different unigenes and 75 unknown genes. Gene Ontology (GO) term enrichment analysis suggested that 35 of the 145 enriched GO terms were significantly enriched and mainly related to the immune system regulation network. KEGG pathway enrichment analysis showed that 18 of the 189 pathways were significantly enriched, and the most significant was a ribosome pathway containing 77 differentially expressed genes. miRNA-seq analysis indicated that the longest miRNA had 22 nucleotides (nt), followed by 21 and 23 nt. A total of 286 known miRNAs, 332 known miRNA precursor sequences, and 438 new miRNAs were predicted. A total of 1,048,575 mRNA–miRNA interaction sites were obtained, and 21,252 and 21,241 target genes were respectively predicted in known and new miRNAs. qPCR revealed that HO-1, IL-10R1, apoA-I, and HBP2 were significantly differentially expressed and might play important roles in the toxicity and liver detoxification of MC-LR in fish. These results were consistent with those of high-throughput sequencing, thereby verifying the accuracy of our sequencing data. RNA-seq and miRNA-seq analyses of silver carp liver injected with MC-LR provided valuable and new insights into the toxic effects of MC-LR and the antitoxic mechanisms of MC-LR in fish.The RNA/miRNA data are available from the NCBI database Registration No. : SRP075165