Efficacy of Tirofiban Administered at Different Time Points after Intravenous Thrombolytic Therapy with Alteplase in Patients with Acute Ischemic Stroke.

OBJECTIVE: To evaluate the efficacy of tirofiban administered at different time points within 24 hours of intravenous thrombolysis with alteplase in acute ischemic stroke. METHODS: Patients who underwent intravenous thrombolysis with alteplase and fulfilled other inclusion criteria were randomly divided into 4 groups according to the time points of tirofiban administration: Group A (2 h), Group B (2-12 h), Group C (12-24 h), and Group D (control). The changes in National Institutes of Health Stroke Scale score, modified Rankin Scale score, and adverse events were analyzed. RESULTS: At 7 ± 1 day, the efficacy in Group A was better than that in Group C (P = .006) and Group D (P = .001), but there was no significant difference in the efficacy between Groups A and B (P = .268). Similarly, at 14 ± 2 d, the efficacy in Group A was better than that in Group C (P = .026) and Group D (P = .001), but there was no significant difference in the efficacy between Groups A and B (P = .394). As evaluated by the modified Rankin Scale, the prognosis in Groups A, B, and C was better than that in Group D (P = .042, .008, .027, respectively), which was unrelated to the time points of tirofiban administration. There was no significant difference in the incidence of adverse events among the four groups. CONCLUSIONS: Tirofiban combined with alteplase is effective and safe, and particularly beneficial when administered at 2 hour and 2-12 hours after intravenous thrombolysis with alteplase in acute ischemic stroke.

Highly efficient synthesis of monodisperse poly(ethylene glycols) and derivatives through macrocyclization of oligo(ethylene glycols).

A macrocyclic sulfate (MCS)-based approach to monodisperse poly(ethylene glycols) (M-PEGs) and their monofunctionalized derivatives has been developed. Macrocyclization of oligo(ethylene glycols) (OEGs) provides MCS (up to a 62-membered macrocycle) as versatile precursors for a range of monofunctionalized M-PEGs. Through iterative nucleophilic ring-opening reactions of MCS without performing group protection and activation, a series of M-PEGs, including the unprecedented 64-mer (2850 Da), can be readily prepared. Synthetic simplicity coupled with versatility of this new strategy may pave the way for broader applications of M-PEGs.

KLRB1 is a novel prognostic biomarker in endometrial cancer and is associated with immune infiltration.

Background: Endometrial cancer (EC) has the characteristics of high mortality and poor prognosis in the advanced stage, which seriously threatens women's health. Killer cell lectin-like receptor B1 (KLRB1) is a promising immune checkpoint of which the expression level can regulate the killing effect on tumor cells of the immune system, thereby affecting the survival and prognosis of tumor patients. However, it is still unclear whether KLRB1 is associated with survival and prognosis in patients with EC. Therefore, our study focused on the relationship between KLRB1 and immune cells to explore the role of KLRB1 on the immune microenvironment, and to further explore its feasibility as a prognostic marker in EC. Methods: In this study, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze the messenger RNA (mRNA) expression level of KLRB1 in normal endometrial and EC tissues. The University of Alabama at Birmingham Cancer data analysis Portal (UALCAN) database was used to determine the correlation between KLRB1 mRNA expression and clinical features among the EC patients. KLRB1 expression levels were investigated in the Tumor IMmune Estimation Resource (TIMER) database to reveal its relationship with immune cell infiltration of EC. Finally, using the R package clusterProfiler, enrichment analysis was performed on KLRB1 to study its potential function. Results: The results suggested that KLRB1 expression varied in different tumor tissues, and the EC group had lower mRNA expression levels than did the control group. It was also found that patients with high expression of KLRB1 had a better prognosis. According to further enrichment and immune infiltration analyses, KLRB1 expression had a closed relationship with the level of infiltration of some immune cell types, such as B cells memory, eosinophils, and Tregs, among others. Conclusions: KLRB1 expression is associated with the infiltration of immune cells and can be used as a prognostic biomarker in EC.

Reliability and Validity of the Repeatable Battery for Assessment of Neuropsychological Status Scale in Evaluation of Vascular Cognitive Impairment in Elderly Han Population.

Introduction: Vascular cognitive impairment (VCI) and Alzheimer's disease are the most common cognitive impairment diseases in the elderly. This study aimed to apply the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) scale to evaluate VCI in elderly patients and analyze its reliability and validity. Methods: We enrolled 278 VCI patients admitted to our hospital, from June 2017 to June 2018. The basic clinical information of each patient was documented, and the Mini-Mental State Examination (MMSE) and the RBANS scales were suggested to complete. Results: We found significant correlations between the RBANS total score and age, diabetes, hypertension, coronary heart disease and years of education. The internal consistency of the RBANS scale Cronbach αsuggested a good agreement with the total score and the single score at two time points. Moreover, the RBANS total score and the score of each dimension in the RBANS scale were positively correlated with the MMSE immediate memory, calculation ability, delayed memory, commanding ability, reading comprehension ability, command execution, sentence making, and pattern duplicating ability. Conclusion: In conclusion, the RBANS has good reliability and validity for the assessment of cognitive dysfunction in elderly VCI patients. It can be used as a routine clinical and research tool, for the simplicity in operation and superior acceptance.

Clinical efficacy and imaging evaluation of recombinant tissue plasminogen activator thrombolytic therapy in patients with wake up stroke: A randomized controlled trial.

INTRODUCTION: Wake up stroke starts in sleep and is a more common form of ischemic stroke. At present, it is still controversial whether wake up stroke can be treated with thrombolytic therapy. Therefore, this study will combine imaging techniques to assess the onset time of wake up stroke patients, and to analyze the imaging characteristics of wake up stroke patients and patients suitable for thrombolytic therapy within the time window. METHODS/DESIGN: This study will be a single-blinded, randomized controlled trial with 2 parallel groups. It will be conducted at North China University of science and technology affiliated hospital. DISCUSSION: There is no consistent conclusion about the pathogenesis of wake up stroke. Wake up stroke is more likely to manifest as small vessel disease. The incidence of wake up stroke patients is relatively high, and the effectiveness and safety of intravenous thrombolysis under the guidance of multimode imaging therapy in wake up stroke need to be further explored by prospective, large-scale studies. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000034402, Registered on 05 July 2020.

Synthesis and biological evaluation of 20-epi-amino-20-deoxysalinomycin derivatives.

To improve the druggability of salinomycin, a 20-epi-amino-20-deoxysalinomycin derivatives library was synthesized with high efficacy from which a few salinomycin derivatives with high potency and selectivity were identified through comprehensive cytotoxicity assay, including a fluorine-19 magnetic resonance sensitive tool molecule. Using a K-ras cellular model, salinomycin and its derivatives showed different molecular mode of action from literature reports. These results would be valuable for developing salinomycin-based cancer therapy.

Prevalence of Abnormal Glucose Regulation according to Different Diagnostic Criteria in Ischaemic Stroke without a History of Diabetes.

We aimed to investigate the prevalence and distribution of abnormal glucose regulation, including prediabetes and newly diagnosed diabetes, according to different criteria in ischaemic stroke patients without a history of diabetes. Data were derived from a representative cohort across China. Prediabetes was defined as fasting plasma glucose (FPG) 5.6-6.9 mmol/L or 2-hour oral glucose tolerance test (OGTT) 7.8-11.0 mmol/L or haemoglobin A1c (HbA1c) 5.7-6.4%. Newly diagnosed diabetes was defined as FPG ≥ 7.0 mmol/L, 2 h OGTT ≥ 11.1 mmol/L or HbA1c ≥ 6.5%. Among 1251 ischaemic stroke patients, 471 (37.5%) were detected as prediabetes and 539 (43.1%) were detected as newly diagnosed diabetes. Prediabetes was present in 118 (9.4%), 290 (23.2%) and 314 (25.1%) stroke patients, and newly diagnosed diabetes was present in 138 (11.0%), 370 (29.6%), and 365 (29.2%) stroke patients, based on FPG, 2 h OGTT, and HbA1c criteria, respectively. Dependency on FPG alone would have missed 74.9% of patients in the prediabetes range and 74.4% of patients in the diabetes range. Our study demonstrated a high prevalence of prediabetes and diabetes in ischaemic stroke patients without a history of diabetes. OGTT and HbA1c helped detect the majority of prediabetes and newly diagnosed diabetes in ischaemic stroke patients.

Effects of dietary lipids on the hepatopancreas transcriptome of Chinese mitten crab (Eriocheir sinensis).

Fish oil supplies worldwide have declined sharply over the years. To reduce the use of fish oil in aquaculture, many studies have explored the effects of fish oil substitutions on aquatic animals. To illustrate the effects of dietary lipids on Chinese mitten crab and to improve the use of vegetable oils in the diet of the crabs, 60 male juvenile Chinese mitten crabs were fed one of five diets for 116 days: fish oil (FO), soybean oil (SO), linseed oil (LO), FO + SO (1:1, FSO), and FO + LO (1:1, FLO). Changes in the crab hepatopancreas transcriptome were analyzed using RNA sequencing. There were a total 55,167 unigenes obtained from the transcriptome, of which the expression of 3030 was significantly altered in the FLO vs. FO groups, but the expression of only 412 unigenes was altered in the FSO vs. FO groups. The diets significantly altered the expression of many enzymes involved in lipid metabolism, such as pancreatic lipase, long-chain acyl-CoA synthetases, carnitine palmitoyltransferase I, acetyl-CoA carboxylase, fatty acid synthase, and fatty acyl Δ9-desaturase. The dietary lipids also affected the Toll-like receptor and Janus activated kinase-signal transducers and activators of transcription signaling pathways. Our results indicate that substituting fish oil with vegetable oils in the diet of Chinese mitten crabs might decrease the digestion and absorption of dietary lipids, fatty acids biosynthesis, and immunologic viral defense, and increase ß-oxidation by altering the expression of the relevant genes. Our results lay the foundation for further understanding of lipid nutrition in Chinese mitten crab.

Ligustrazine alleviates acute pancreatitis by accelerating acinar cell apoptosis at early phase via the suppression of p38 and Erk MAPK pathways.

OBJECTIVE: This study aimed to investigate the role of ligustrazine on apoptosis and inflammatory reaction in acute pancreatitis. METHODS: Rats and acinar cells were treated with caerulein to induce acute pancreatitis models. Cell models were treated with saline, p38 inhibitor, Erk inhibitor and ligustrazine. Then, the levels of TNF-α, IL-1ß and IL-6 were determined by ELISA assay, the protein levels of p38, Erk1/2, p53 and cleaved caspase3 were determined by western blotting, and apoptosis were measured by flow cytometry. Rat models were treated with saline and ligustrazine. Plasma amylase and pancreatic myeloperoxidase activity and the levels of TNF-α, IL-1ß and IL-6 in rats were determined. The protein levels of p38, Erk1/2, p53 and cleaved caspase3 in pancreas tissues were determined by western blotting, and pancreas tissues were also performed TUNEL staining to observe apoptosis status. RESULTS: Ligustrazine downregulated the levels of TNF-α, IL-1ß, IL-6. The protein levels of p38 and Erk were reduced by p38 inhibitor, Erk inhibitor and ligustrazine, while the levels of p53 and cleaved caspase 3 were upregulated. Apoptosis of AP acinar cells and cells in AP rat models was promoted after treated with ligustrazine. Plasma amylase and pancreatic myeloperoxidase activity in AP rat models were reduced by ligustrazine. CONCLUSION: Ligustrazine alleviates acute pancreatitis by accelerating acinar cell apoptosis at early phase via the suppression on p38 and Erk MAPK pathways. It is capable of attenuating the severity of acute pancreatitis and may have a therapeutic effect on patients with acute pancreatitis.

Discovery of a (19)F MRI sensitive salinomycin derivative with high cytotoxicity towards cancer cells.

Salinomycin is a promising anti-cancer agent which selectively targets cancer stem cells. To improve its potency and selectivity, an analog library of salinomycin was generated by site-specific modification and CuAAc derivatization. Through a cytotoxicity analysis of the library, a fluorinated analog with high potency, selectivity, and (19)F MRI sensitivity was discovered as a novel theranostic agent.

Correction: Discovery of a (19)F MRI sensitive salinomycin derivative with high cytotoxicity towards cancer cells.

Correction for 'Discovery of a (19)F MRI sensitive salinomycin derivative with high cytotoxicity towards cancer cells' by Qiuyan Shi et al., Chem. Commun., 2016, 52, 5136-5139.

The molecular mechanism underlying morphine-induced Akt activation: roles of protein phosphatases and reactive oxygen species.

Although Akt is reported to play a role in morphine's cardioprotection, little is known about the mechanism underlying morphine-induced Akt activation. This study aimed to define the molecular mechanism underlying morphine-induced Akt activation and to determine if the mechanism contributes to the protective effect of morphine on ischemia/reperfusion injury. In cardiac H9c2 cells, morphine increased Akt phosphorylation at Ser(473), indicating that morphine upregulates Akt activity. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a major regulator of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling, was not involved in the action of morphine on Akt activity. Morphine decreased the activity of PP2A, a major protein Ser/Thr phosphatase, and inhibition of PP2A with okadaic acid (OA) mimicked the effect of morphine on Akt activity. The effects of morphine on PP2A and Akt activities were inhibited by the reactive oxygen species (ROS) scavenger N-(2-mercaptopropionyl)glycine (MPG) and the mitochondrial K(ATP) channel closer 5-hydroxydecanoate (5HD). In support, morphine could produce ROS and this was reversed by 5HD. Finally, the cardioprotective effect of morphine on ischemia-reperfusion injury was mimicked by OA but was suppressed by 5HD or MPG, indicating that protein phosphatases and ROS are involved in morphine's protection. In conclusion, morphine upregulates Akt activity by inactivating protein Ser/Thr phosphatases via ROS, which may contribute to the cardioprotective effect of morphine.