A CRISPR-Cas12a-based electrochemical biosensor for the detection of microphthalmia-associated transcription factor.

A novel electrochemical biosensor that combines the CRISPR-Cas12a system with a gold electrode is reported for the rapid and sensitive detection of microphthalmia-associated transcription factor (MITF). The biosensor consists of a gold electrode modified with DNA1, which contains the target sequence of MITF and is labeled with ferrocene, an electroactive molecule. The biosensor also includes hairpin DNA, which has a binding site for MITF and can hybridize with helper DNA to form a double-stranded complex that activates CRISPR-Cas12a. When MITF is present, it binds to hairpin DNA and prevents its hybridization with helper DNA, thus inhibiting CRISPR-Cas12a activity and preserving the DPV signal of ferrocene. When MITF is absent, hairpin DNA hybridizes with helper DNA and activates CRISPR-Cas12a, which cleaves DNA1 and releases ferrocene, thus reducing the DPV signal. The biosensor can detect MITF with high sensitivity (with an LOD of 8.14 fM), specificity, and accuracy in various samples, such as cell nuclear extracts and human serum. The biosensor can also diagnose and monitor melanocyte-related diseases and melanin production. This work provides a simple, fast, sensitive, and cost-effective biosensor for MITF detection and a valuable tool for applications in genetic testing, disease diagnosis, and drug screening.

Targeting erythrocyte-mediated hypoxia to alleviate lung injury induced by pyrrolizidine alkaloids.

Pyrrolizidine alkaloids (PAs) are widely distributed natural toxins and have been extensively studied for their hepatotoxicity. However, PA-induced pulmonary toxicity remains less studied regarding the initiating mechanism and treatment approaches. Our previous study demonstrated the formation of pyrrole-hemoglobin adducts after PA exposure in vivo, which is suspected to affect the oxygen-carrying capacity of erythrocytes [red blood cells (RBCs)] consequently. The present study aimed to investigate the effects of PAs on the oxygen-carrying capacity of RBCs and the potential of targeting RBC-mediated hypoxia to alleviate PA-induced lung injury. First, rats were treated with retrorsine (RTS) or monocrotaline (MCT) intravenously at 0.2 mmol/kg. The results of Raman spectrometry analysis on blood samples revealed both RTS and MCT significantly reduced the oxygen-carrying capacity of RBCs. Further, MCT (0.2 mmol/kg) was orally given to the rats with or without pretreatment with two doses of erythropoietin (Epo, 500 IU/kg/dose every other day), an RBC-stimulating agent. Biochemical and histological results showed pretreatment with Epo effectively reduced the cardiopulmonary toxicity induced by MCT. These findings provide the first evidence that adduction on hemoglobin, and the resulting RBC damage and impaired oxygen-carrying capacity, are the major initiating mechanism underlying PA-induced pulmonary arterial hypertension (PAH), while targeting the RBC damage is a potential therapeutic approach for PA-induced lung injury.

Influential factors and transcriptome analyses of immature diploid embryo anthocyanin accumulation in maize.

BACKGROUND: Anthocyanins are widely applied as a marker for haploid identification after haploid induction in maize. However, the factors affecting anthocyanin biosynthesis in immature embryos and the genes regulating this process remain unclear. RESULTS: In this study, we analyzed the influence of genetic background of the male and female parents, embryo age and light exposure on anthocyanin accumulation in embryos. The results showed that light exposure was the most crucial factor enhancing the pigmentation of immature embryos. The identification accuracy of haploid embryos reached 96.4% after light exposure, but was only 11.0% following dark treatment. The total anthocyanin content was 7-fold higher in immature embryos cultured for 24 h under light conditions compared to embryos cultured in the dark. Transcriptome analysis revealed that the differentially expressed genes between immature embryos cultured for 24 h in dark and light chambers were significantly enriched in the pathways of flavonoid, flavone, flavonol and anthocyanin biosynthesis. Among the genes involved in anthocyanin biosynthesis, five up-regulated genes were identified: F3H, DFR, ANS, F3'H and the MYB transcription factor-encoding gene C1. The expression patterns of 14 selected genes were confirmed using quantitative reverse transcription-polymerase chain reaction. CONCLUSION: Light is the most important factor facilitating anthocyanin accumulation in immature embryos. After 24 h of exposure to light, the expression levels of the structural genes F3H, DFR, ANS, F3'H and transcription factor gene C1 were significantly up-regulated. This study provides new insight into the factors and key genes regulating anthocyanin biosynthesis in immature embryos, and supports improved efficiency of immature haploid embryo selection during doubled haploid breeding of maize.

A newly characterized allele of ZmR1 increases anthocyanin content in whole maize plant and the regulation mechanism of different ZmR1 alleles.

KEY MESSAGE: The novel ZmR1CQ01 allele for maize anthocyanin synthesis was identified, and the biological function and regulatory molecular mechanisms of three ZmR1 alleles were unveiled. Anthocyanins in maize are valuable to human health. The R1 gene family is one of the important regulatory genes for the tissue-specific distribution of anthocyanins. R1 gene allelic variations are abundant and its biological function and regulatory molecular mechanisms are not fully understood. By exploiting genetic mapping and transgenic verification, we found that anthocyanin pigmentation in maize leaf midrib was controlled by ZmR1 on chromosome 10. Allelism test of maize zmr1 EMS mutants confirmed that anthocyanin pigmentation in leaf sheath was also controlled by ZmR1. ZmR1CQ01 was a novel ZmR1 allelic variation obtained from purple maize. Its overexpression caused the whole maize plant to turn purple. ZmR1B73 allele confers anthocyanin accumulation in near ground leaf sheath rather than in leaf midribs. The mRNA expression level of ZmR1B73 was low in leaf midribs, resulting in no anthocyanin accumulation. ZmR1B73 overexpression promoted anthocyanin accumulation in leaf midribs. Loss of exon 5 resulted in ZmR1ZN3 allele function destruction and no anthocyanin accumulation in leaf midrib and leaf sheath. DNA affinity purification sequencing revealed 1010 genes targeted by ZmR1CQ01, including the bz2 in anthocyanin synthesis pathway. RNA-seq analysis showed 55 genes targeted by ZmR1CQ01 changed the expression level significantly, and the expression of genes encoding key enzymes in flavonoid and phenylpropanoid biosynthesis pathways were significantly up-regulated. ZmR1 functional molecular marker was developed. These results revealed the effects of transcriptional regulation and sequence variation on ZmR1 function and identified the genes targeted by ZmR1CQ01 at the genome-wide level.

Fasting augments pyrrolizidine alkaloid-induced hepatotoxicity.

Pyrrolizidine alkaloids (PAs) are phytotoxins widely present in various natural products and foodstuffs. The present study aims to investigate the effects of fasting on PA-induced hepatotoxicity and the underlying biochemical mechanisms. The results of hepatotoxic study showed that 15-h overnight fasting significantly exacerbated the hepatotoxicity of retrorsine (RTS, a representative toxic PA) in fasted rats compared to fed rats, as indicated by remarkably elevated plasma ALT and bilirubin levels and obvious liver histological changes. Further toxicokinetic studies revealed that fasting significantly enhanced cytochromes P450 enzymes (CYPs)-mediated metabolic activation of RTS leading to increased formation of pyrrole-protein adducts and thus decreased the in vivo exposure and excretion of both parent RTS and its N-oxide metabolite. Metabolic studies demonstrated that fasting induced enzyme activities of CYP1A2, CYP2B6 and CYP2E1 that participated in catalyzing RTS to its reactive pyrrolic metabolites. Moreover, fasting also dramatically decreased hepatic glutathione (GSH) content, which restricted the detoxification of GSH by neutralizing the reactive pyrrolic metabolite of RTS, further contributing to the enhanced hepatotoxicity. The present findings may have an impact on future PA toxicity tests with different dietary styles and/or risk assessment of metabolite-mediated toxins by considering the profound effects of fasting.

Determining the effective dose of esketamine for mitigating pain during propofol injection by Dixon's up-and-down method: a double-blind, prospective clinical study of drug dose response.

BACKGROUND: Propofol is an intravenous (IV) anesthetic medication widely used for procedural sedation, operative anesthesia, and in intensive care unit (ICU), but the incidence of pain during IV infusion can reach 28-90%. Ketamine can attenuate pain associated with IV propofol injection through local and central analgesic effects. Ketamine is gradually being transitioned to its S-enantiomer, esketamine, which has a similar mechanism of action. The purpose of our study is to determine the half effective dose (ED50), 95% effective dose (ED95), and 99% effective dose (ED99) of esketamine for attenuating propofol injection pain using Dixon's up-and-down method to provide a reference for optimal dose selection for surgeries and procedures. METHODS: Thirty gynecological patients undergoing hysteroscopic surgery were enrolled in a sequential method to determine the effective dose of esticketamine for analgesic propofol injection in order of operation. This study was based on the sequential allocation up-and-down rule designed by Dixon, and each patient was induced by esticketamine combined with propofol. During induction, the target dose of esketamine was first given via venous access in the left hand of the patient, and 30 s later, a fixed dose of 2 mg/kg (1 ml/s) of propofol was given. Patient perception of pain was scored with the verbal rating scale (VRS) every 5 s after the start of the propofol infusion, and the evaluation was stopped once the patient became unresponsive. The dosage of esketamine was increased or decreased up or down according to the patient's pain response. The initial dose of esketamine was 0.2 mg/kg, and the gradient of adjacent dose was 0.02 mg/kg. If the pain response assessment of the upper patient was positive (+), the dose of esselketamine in the next patient was increased by 0.02 mg/kg; if the pain response assessment of the upper patient was negative (-), the dose of esselketamine in the next patient was decreased by 0.02 mg/kg. The tests were carried out sequentially, with the pain response changing from positive to negative or from negative to positive, and the tests were stopped after at least 6 crossover points, and the effective dose of esticketamine was calculated using probit probability regression analysis. RESULTS: The ineffective group comprised patients with a positive pain response and the effective group comprised patients with a negative pain response. The 95% CI was set as the confidence interval of effective dose ED value，and we found esketamine's ED50 = 0.143 mg/kg (0.120, 0.162 mg/kg), ED95 = 0.176 mg/kg (0.159, 0.320 mg/kg), and ED99 = 0.189 mg/kg (0.167, 0.394 mg/kg). The esketamine dose and VRS score during propofol injection were significantly different between the two groups (P < 0.05), whereas surgical duration, emergence time, visual analogue scale (VAS) score of postoperative uterine contraction pain, and Riker sedation/anxiety scale (SAS) score were not significantly different. Bradycardia occurred in only one patient during anesthesia induction, while hemodynamics was stable in the rest of the patients without obvious adverse reactions. CONCLUSION: Small doses of esketamine combined with propofol can be safely and effectively used for hysteroscopic surgery. We recommended a dose of 0.2 mg/kg IV esketamine before induction of anesthesia to reduce the pain of propofol injection. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100048951. Date of registration: July 19, 2021.

Effect of additional equipotent fentanyl or sufentanil administration on recovery profiles during propofol-remifentanil-based anaesthesia in patients undergoing gynaecologic laparoscopic surgery: a randomized clinical trial.

BACKGROUND: In clinical practice, sufentanil has a stronger sedative effect on patients than fentanyl at equivalent doses. This study hypothesized that, at equivalent doses, patients undergoing gynaecologic laparoscopic surgery (GLS) receiving fentanyl would have an earlier emergence from anaesthesia (EA), a shorter time to extubation (TE), and a better degree of wakefulness. Therefore, this study evaluated the effects of equipotent doses of fentanyl and sufentanil on the quality of emergence in patients undergoing GLS. METHODS: One hundred seven patients scheduled for GLS under general anaesthesia were randomly divided into two groups and were induced with 0.35 µg/kg sufentanil (Group S; n = 55) or 3.5 µg/kg fentanyl (Group F; n = 52). When the GLS was almost over, the patient's abdominal cavity was flushed with warm saline, and 5 µg of sufentanil or 50 µg of fentanyl in a double-blind manner was intravenously injected into the patients. The primary outcomes of the study included EA, TE, the rate of leaving the surgical bed voluntarily and the incidence of endotracheal tube tolerance. The Ramsay Sedation Scale (RSS), and Verbal Rating Scale (VRS) scores at 15 and 30 min in the postanaesthesia care unit (PACU), as well as other adverse events, including nausea and vomiting, itching, delirium, dizziness, chills, and respiratory depression (SpO2 < 95%) in the PACU, were evaluated as secondary outcomes. RESULTS: There were no statistically significant dissimilarities between the two groups with respect to baseline characteristics. For recovery, the EA (9.0 ± 4.8 min vs. 8.9 ± 3.0 min; P = 0. 146), TE (9.5 ± 4.7 min vs. 9.0 ± 3.0 min; P = 0.135), rate of leaving the surgical bed voluntarily (31.18% vs. 38.46%; P = 0.976), and incidence of endotracheal tube tolerance (94.55% vs. 96.15%; P = 0.694) were not significantly different between the two groups. In the PACU, the 15-min RSS score (2.07 ± 0.38 vs. 2.15 ± 0.36; P = 0.125), the 30-min RSS score (2.02 ± 0.13 vs. 2.04 ± 0.19; P = 0.207), the 15-min VRS score (0.50 ± 0.57 vs. 0.67 ± 0.55; P = 0.295), and the 30-min VRS score (0.45 ± 0.50 vs. 0.75 ± 0.52; P = 0.102) were not significantly different between Groups S and F. No adverse events, such as nausea, vomiting, pruritus, delirium, and tremors, occurred in either group. The rates of respiratory depression (1.82% vs. 1.92%; P = 0.968) and dizziness (0.00% vs. 4.85%; P = 0.142) were not different between Groups S and F in the PACU. CONCLUSIONS: The majority of patients scheduled for GLS were able to rapidly and smoothly emerge from anaesthesia. After surgery, similar outcomes, including EA, TE, the incidence of endotracheal tube tolerance, the rate of leaving the surgical bed voluntarily, RSS scores, VRS scores, and adverse events in the PACU, were achieved for the patients between the two anaesthetic protocols.

Stroke risk with vegetarian, low-animal and high-animal diets: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Vegetarian and prudent diets are associated with several health benefits but their role in stroke epidemiology is not as clear. This study aimed to evaluate stroke risk with vegetarian, low-animal, and high-animal diets. METHODS AND STUDY DESIGN: Studies reporting stroke risk with high versus low use of vegetarian or low/high-animal diets were identified by conducting literature search in Ebsco, Ovid, PubMed, Science Direct, and Web of Science databases. Relative risks (RRs) of stroke between high and low use of vegetarian, low-animal, and high-animal were pooled to achieve overall estimates. Relationship between stroke risk and increasing quantiles of dietary patterns was sought by performing metaregression analyses. RESULTS: 17 studies (932545 individuals; follow-up 11.7 years [95% confidence interval (CI): 9.5, 13.9]) were included. Compared to low use, high use of vegetarian and low-animal diets was associated with lower risk of hemorrhagic stroke (RR: 0.71 [95% CI: 0.47, 0.96] and 0.82 [95% CI: 0.64, 0.99]), ischemic stroke (RR: 0.78 [95% CI: 0.66, 0.91] and 0.70 [95% CI: 0.45, 0.95]) and total stroke (RR: 0.84 [95% CI: 0.71, 0.96] and 0.72 [95% CI: 0.61, 0.83]) respectively. Dose-response analyses further supported these findings. High use of high-animal diet was associated with relatively higher risk of stroke [RR: 1.12 [95%CI: 0.94, 1.29]. In vegetarians, relative to high use of vegetables, high use of fruits posed lower risk of stroke. CONCLUSIONS: Stroke risk is lower with more use of a vegetarian or low-animal diet but relatively higher with more use of a high-animal diet.

Eosinophil-to-monocyte ratio is a potential biomarker in the prediction of functional outcome among patients with acute ischemic stroke.

BACKGROUND: It has been shown that eosinophils are decreased and monocytes are elevated in patients with acute ischemic stroke (AIS), but the impact of eosinophil-to-monocyte ratio (EMR) on clinical outcomes among AIS patients remains unclear. We aimed to determine the relationship between EMR on admission and 3-month poor functional outcome in AIS patients. METHODS: A total of 521 consecutive patients admitted to our hospital within 24 h after onset of AIS were prospectively enrolled and categorized in terms of quartiles of EMR on admission between August 2016 and September 2018. The endpoint was the poor outcome defined as modified Rankin Scale score of 3 to 6 at month 3 after admission. RESULTS: As EMR decreased, the risk of poor outcome increased (p < 0.001). Logistic regression analysis revealed that EMR was independently associated with poor outcome after adjusting potential confounders (odds ratio, 0.09; 95% CI 0.03-0.34; p = 0.0003), which is consistent with the result of EMR (quartile) as a categorical variable (odds ratio, 0.23; 95% CI 0.10-0.52; ptrend < 0.0001). A non-linear relationship was detected between EMR and poor outcome, whose point was 0.28. Subgroup analyses further confirmed these associations. The addition of EMR to conventional risk factors improved the predictive power for poor outcome (net reclassification improvement: 2.61%, p = 0.382; integrated discrimination improvement: 2.41%, p < 0.001). CONCLUSIONS: EMR on admission was independently correlated with poor outcome in AIS patients, suggesting that EMR may be a potential prognostic biomarker for AIS.

Propofol regulates activated macrophages metabolism through inhibition of ROS-mediated GLUT1 expression.

OBJECTIVE: Activated macrophages undergo a metabolic shift from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, which plays a critical role in inflammation. Increasing evidence suggests the important role of propofol in the regulation of inflammatory response and metabolism, but the effect of propofol on the metabolic shift in macrophage, and the mechanisms involved remain unclear. METHODS: The effect of propofol on the metabolic switch was analyzed by extracellular acidification rate and oxygen consumption rate assays. The effect of propofol on glycolysis was analyzed by lactate and glucose uptake assay. The mRNA, protein, cell surface levels of glucose transporter 1 (GLUT1) and the silencing of GLUT1 were employed to understand the effects of GLUT1-mediated metabolism by propofol. Finally, to understand the antioxidation of propofol on the regulation of metabolism, the reactive oxygen species (ROS) production and NADPH activity were performed. RESULTS: We show that propofol can change the metabolic pathway switch from aerobic glycolysis to OXPHOS in LPS-activated macrophages. Moreover, propofol suppresses aerobic glycolysis via inhibited GLUT1-mediated glucose uptake. Furthermore, we show that propofol reduces ROS overproduction, which in turn inhibits GLUT1 expression. Finally, we find that propofol reduces ROS production via inhibits NADPH activity. CONCLUSION: These findings shed light on the function and mechanism of propofol in the metabolic switch and highlight the importance of targeting metabolism by propofol in the clinical medication of inflammatory diseases.

Tu-San-Qi (Gynura japonica): the culprit behind pyrrolizidine alkaloid-induced liver injury in China.

Herbs and dietary supplement-induced liver injury (HILI) is the leading cause of drug-induced liver injury in China. Among different hepatotoxic herbs, the pyrrolizidine alkaloid (PA)-producing herb Gynura japonica contributes significantly to HILI by inducing hepatic sinusoidal obstruction syndrome (HSOS), a liver disorder characterized by hepatomegaly, hyperbilirubinemia, and ascites. In China, G. japonica has been used as one of the plant species for Tu-San-Qi and is often misused with non-PA-producing Tu-San-Qi (Sedum aizoon) or even San-Qi (Panax notoginseng) for self-medication. It has been reported that over 50% of HSOS cases are caused by the intake of PA-producing G. japonica. In this review, we provide comprehensive information to distinguish these Tu-San-Qi-related herbal plant species in terms of plant/medicinal part morphologies, medicinal indications, and chemical profiles. Approximately 2156 Tu-San-Qi-associated HSOS cases reported in China from 1980 to 2019 are systematically reviewed in terms of their clinical manifestation, diagnostic workups, therapeutic interventions, and outcomes. In addition, based on the application of our developed mechanism-based biomarker of PA exposure, our clinical findings on the definitive diagnosis of 58 PA-producing Tu-San-Qi-induced HSOS patients are also elaborated. Therefore, this review article provides the first comprehensive report on 2214 PA-producing Tu-San-Qi (G. japonica)-induced HSOS cases in China, and the information presented will improve public awareness of the significant incidence of PA-producing Tu-San-Qi (G. japonica)-induced HSOS and facilitate future prevention and better clinical management of this severe HILI.

Green preparation of carbon dots from Momordica charantia L. for rapid and effective sensing of p-aminoazobenzene in environmental samples.

p-Aminoazobenzene (pAAB) is a hazardous azo dye that causes considerable harm to human health and the environment. The development of novel and sensitive sensors for the rapid detection of pAAB is in high demand. In this study, a simple fluorescent sensor for pAAB detection is designed based on carbon dots (CDs) which are prepared using green carbon source of Momordica charantia L. via a facile hydrothermal approach. The fluorescence spectra of CDs exhibit considerable overlap with the absorption band of pAAB, and the fluorescence is specifically suppressed in the presence of pAAB ascribed to the inner filter effect. Good and wide linearity is observed in the pAAB concentration range of 0.01-12.5 µg mL-1 with a lower detection limit of 3.9 ng mL-1. The established method achieves good results with a rapid analysis of pAAB in different practical water and soil samples. The as-constructed fluorescent sensor provides a simple, rapid, economical and eco-friendly platform and possesses prospective applications for the effective, selective and sensitive detection of pAAB in the environmental field.

Clinical application of pyrrole-hemoglobin adducts as a biomarker of pyrrolizidine alkaloid exposure in humans.

Pyrrolizidine alkaloids (PAs) are naturally occurring hepatotoxins widely present in hundreds of plant species and also known to contaminate many foodstuffs, such as grain, honey, and tea. The formation of pyrrole-protein adducts via metabolic activation of PAs has been suggested as a primary trigger initiating hepatotoxicity. The present study for the first time tested the suitability of pyrrole-hemoglobin adducts as a novel and specific biomarker of PA exposure in humans. The level and elimination kinetics of pyrrole-hemoglobin adducts were systematically investigated in the blood samples of 43 PA-induced liver injury (PA-ILI) patients. The results revealed significantly higher concentrations (84.50 ± 78.38 nM) and longer persistence (~ 4 months) of pyrrole-hemoglobin adducts than that (concentration: 9.53 ± 10.72 nM; persistence: ~ 2 months) of pyrrole-plasma protein adducts, our previously developed PA exposure biomarker. Our findings confirmed that pyrrole-hemoglobin adducts with higher level and longer persistence should serve as a more applicable PA exposure biomarker for future clinical diagnosis of PA-ILI in drug/herb-induced liver injury patients.

Developing urinary pyrrole-amino acid adducts as non-invasive biomarkers for identifying pyrrolizidine alkaloids-induced liver injury in human.

Pyrrolizidine alkaloids (PAs) have been found in over 6000 plants worldwide and represent the most common hepatotoxic phytotoxins. Currently, a definitive diagnostic method for PA-induced liver injury (PA-ILI) is lacking. In the present study, using a newly developed analytical method, we identified four pyrrole-amino acid adducts (PAAAs), namely pyrrole-7-cysteine, pyrrole-9-cysteine, pyrrole-9-histidine, and pyrrole-7-acetylcysteine, which are generated from reactive pyrrolic metabolites of PAs, in the urine of PA-treated male Sprague Dawley rats and PA-ILI patients. The elimination profiles, abundance, and persistence of PAAAs were systematically investigated first in PA-treated rat models via oral administration of retrorsine at a single dose of 40 mg/kg and multiple doses of 5 mg/kg/day for 14 consecutive days, confirming that these urinary excreted PAAAs were derived specifically from PA exposure. Moreover, we determined that these PAAAs were detected in ~ 82% (129/158) of urine samples collected from ~ 91% (58/64) of PA-ILI patients with pyrrole-7-cysteine and pyrrole-9-histidine detectable in urine samples collected at 3 months or longer times after hospital admission, indicating adequate persistence time for use as a clinical test. As direct evidence of PA exposure, we propose that PAAAs can be used as a biomarker of PA exposure and the measurement of urinary PAAAs could be used as a non-invasive test assisting the definitive diagnosis of PA-ILI in patients.

Resting Heart Rate and In-Hospital Mortality in Acute Ischemic Stroke Patients With and Without Atrial Fibrillation.

BACKGROUND: The prognostic role of resting heart rate (RHR) on mortality in acute ischemic stroke (AIS) patients including atrial fibrillation (AF) is unclear. This study evaluated the relationship between RHR and in-hospital mortality among all AIS patients with and without AF.Methods and Results:The study enrolled 3,447 AIS patients from December 2013 to May 2014 across 22 hospitals in Suzhou City. Patients were divided into 2 groups based on median baseline RHR (<76 and ≥76 beats/min). Cox proportional hazard regression models were used to estimate the effects of RHR on all-cause in-hospital mortality. During hospitalization, 124 patients (3.6%) died from all causes. A multivariable model adjusted for potential covariates showed that higher RHR (≥76 beats/min) was associated with an increase in the risk of in-hospital mortality among AIS patients (hazard ratio [HR] 1.63; 95% confidence interval [CI] 1.09-2.45; P=0.018). This relationship was consistent in a subgroup analysis of patients without AF (HR 2.39; 95% CI 1.29-4.45; P=0.006). However, there was no significant association between higher RHR and in-hospital mortality among patients with AF (P=0.654). Similar findings were confirmed in analyses with heart rate as a continuous variable. CONCLUSIONS: Higher RHR at admission was independently associated with in-hospital mortality in AIS patients without AF.

Prognostic Significance of Plasma CLEC-2 (C-Type Lectin-Like Receptor 2) in Patients With Acute Ischemic Stroke.

Background and Purpose- CLEC-2 (C-type lectin-like receptor 2) is a C-type lectin receptor highly expressed on platelets with the prominent involvement in platelet activation, which was increased in coronary heart disease. Given the role of platelet activation in ischemic stroke and the connections between coronary heart disease and ischemic stroke, CLEC-2 might be a candidate marker of ischemic stroke. Here, we aimed to examine the prognostic significance of CLEC-2 in patients with acute ischemic stroke (AIS). Methods- Three hundred fifty-two patients with AIS within 7 days and 112 healthy controls were prospectively studied. Plasma CLEC-2 (pCLEC-2) and some conventional risk factors of stroke were examined. Stroke progression was defined as any new neurological symptoms/signs or any neurological worsening within 7 days after stroke onset, and poor prognosis was defined as modified Rankin Scale scores >2 at 90 days. The association between pCLEC-2 and stroke progression/prognosis was evaluated using regression models. Results- Patients with AIS had a significantly higher level of pCLEC-2 than that of healthy controls (P<0.05). Patients with AIS with progressive stroke or poor prognosis had a much higher level of pCLEC-2 compared with those with stable stroke or good prognosis (all P<0.05). Increasing pCLEC-2 was significantly associated with an increased risk of stroke progression (odds ratio, 1.97; 95% CI, 1.11-3.50; P=0.021) and poor prognosis (odds ratio, 1.70; 95% CI, 1.17-2.48; P=0.006). Patients with the highest pCLEC-2 level were 7- to 8-fold more likely to have stroke progression compared with the lowest quartile (odds ratio, 7.69; 95% CI, 1.43-41.41). Patients with the highest pCLEC-2 level were also more likely to have poor prognosis at 90 days (odds ratio, 5.58; 95% CI, 1.76-17.68). The optimal cutoff points of pCLEC-2 for predicting stroke progression and poor prognosis were 235.48 and 207.08 pg/mL, respectively. Conclusions- Increased pCLEC-2 was associated with stroke progression and poor prognosis at 90 days significantly, which indicates the prognostic role of pCLEC-2 in AIS. However, it needs to be confirmed in large-scale studies.

Efficient parallel video processing techniques on GPU: from framework to implementation.

Through reorganizing the execution order and optimizing the data structure, we proposed an efficient parallel framework for H.264/AVC encoder based on massively parallel architecture. We implemented the proposed framework by CUDA on NVIDIA's GPU. Not only the compute intensive components of the H.264 encoder are parallelized but also the control intensive components are realized effectively, such as CAVLC and deblocking filter. In addition, we proposed serial optimization methods, including the multiresolution multiwindow for motion estimation, multilevel parallel strategy to enhance the parallelism of intracoding as much as possible, component-based parallel CAVLC, and direction-priority deblocking filter. More than 96% of workload of H.264 encoder is offloaded to GPU. Experimental results show that the parallel implementation outperforms the serial program by 20 times of speedup ratio and satisfies the requirement of the real-time HD encoding of 30 fps. The loss of PSNR is from 0.14 dB to 0.77 dB, when keeping the same bitrate. Through the analysis to the kernels, we found that speedup ratios of the compute intensive algorithms are proportional with the computation power of the GPU. However, the performance of the control intensive parts (CAVLC) is much related to the memory bandwidth, which gives an insight for new architecture design.

[The role of THRIVE score in prediction of outcomes of acute ischemic stroke patients with atrial fibrillation].

OBJECTIVE: To study whether the totaled health risks in vascular events (THRIVE) score could predict the prognosis in the acute ischemic stroke patients with atrial fibrillation. METHODS: A total of 169 patients were enrolled in the study, with NIH Stroke Scale (NIHSS) score, THRIVE score and CHADS2 score given to each patients at admission and modified Rankin Scale (mRS) given at 3 months follow up. All patients were divided into the following 3 groups according to their THRIVE score: 1-3 score group, 4-5 score group and 6-9 score group. RESULTS: (1) There were 59 patients (34.9%) in the 1-3 score group, 71 patients (42.0%) in the 4-5 score group and 39 patients (23.1%) in the 6-9 score group. As the THRIVE score increased, significant difference was observed among the 3 groups in the mean age (F = 31.360, P = 0.000) and the level of fasting glucose (F = 12.410, P = 0.000). (2) As the THRIVE score increased in the 3 groups, the percentage of good prognosis in 3 months was significantly reduced (χ² = 48.259, P < 0.001), while the percentage of death and pulmonary infection were significantly increased (χ² = 36.754, P < 0.001; χ² = 16.590, P < 0.001, respectively). No significant difference was found in the percentage of intracerebral hemorrhage (ICH) among the 3 groups (χ² = 2.064, P = 0.356). (3) In the receiver operating characteristic (ROC) curve analysis, the THRIVE score was superior than the CHADS2 score in predicting poor prognosis (AUCROC = 0.797, P < 0.001 vs AUCROC = 0.579, P = 0.085) , death (AUCROC = 0.796, P < 0.001 vs AUCROC = 0.569, P = 0.198) and pulmonary infection (AUCROC = 0.708, P < 0.001 vs AUCROC = 0.573, P = 0.152). (4) Multifactor regression analysis suggested that the THRIVE score was an independent risk factor for good prognosis (OR = 0.406, P = 0.000) , death (OR = 2.083, P = 0.000) and pulmonary infection (OR = 2.168, P = 0.000). CONCLUSIONS: In the acute ischemic stroke patients with atrial fibrillation, the THRIVE score negatively correlates with good prognosis, while positively correlates with death and pulmonary infection. The THRIVE score could strongly predict the clinical outcomes in those patients.