Dual Antiplatelet Therapy vs Alteplase for Patients With Minor Nondisabling Acute Ischemic Stroke

Importance Intravenous thrombolysis is increasingly used in patients with minor stroke, but its benefit in patients with minor nondisabling stroke is unknown. Objective To investigate whether dual antiplatelet therapy (DAPT) is noninferior to intravenous thrombolysis among patients with minor nondisabling acute ischemic stroke. Design, Setting, and Participants This multicenter, open-label, blinded end point, noninferiority randomized clinical trial included 760 patients with acute minor nondisabling stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤5, with ≤1 point on the NIHSS in several key single-item scores; scale range, 0-42). The trial was conducted at 38 hospitals in China from October 2018 through April 2022. The final follow-up was on July 18, 2022. Interventions Eligible patients were randomized within 4.5 hours of symptom onset to the DAPT group (n = 393), who received 300 mg of clopidogrel on the first day followed by 75 mg daily for 12 (±2) days, 100 mg of aspirin on the first day followed by 100 mg daily for 12 (±2) days, and guideline-based antiplatelet treatment until 90 days, or the alteplase group (n = 367), who received intravenous alteplase (0.9 mg/kg; maximum dose, 90 mg) followed by guideline-based antiplatelet treatment beginning 24 hours after receipt of alteplase. Main Outcomes and Measures The primary end point was excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 (range, 0-6), at 90 days. The noninferiority of DAPT to alteplase was defined on the basis of a lower boundary of the 1-sided 97.5% CI of the risk difference greater than or equal to −4.5% (noninferiority margin) based on a full analysis set, which included all randomized participants with at least 1 efficacy evaluation, regardless of treatment group. The 90-day end points were assessed in a blinded manner. A safety end point was symptomatic intracerebral hemorrhage up to 90 days. Results Among 760 eligible randomized patients (median [IQR] age, 64 [57-71] years; 223 [31.0%] women; median [IQR] NIHSS score, 2 [1-3]), 719 (94.6%) completed the trial. At 90 days, 93.8% of patients (346/369) in the DAPT group and 91.4% (320/350) in the alteplase group had an excellent functional outcome (risk difference, 2.3% [95% CI, −1.5% to 6.2%]; crude relative risk, 1.38 [95% CI, 0.81-2.32]). The unadjusted lower limit of the 1-sided 97.5% CI was −1.5%, which is larger than the −4.5% noninferiority margin (P for noninferiority <.001). Symptomatic intracerebral hemorrhage at 90 days occurred in 1 of 371 participants (0.3%) in the DAPT group and 3 of 351 (0.9%) in the alteplase group. Conclusions and Relevance Among patients with minor nondisabling acute ischemic stroke presenting within 4.5 hours of symptom onset, DAPT was noninferior to intravenous alteplase with regard to excellent functional outcome at 90 days. Trial Registration ClinicalTrials.gov Identifier: NCT0366141

Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke

Importance Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking. Objective To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke. Design, Setting, and Participants This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome. Interventions Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio. Main Outcomes and Measures The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points. Results Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference −1.9%; 95% CI, −3.6 to −0.2; P = .03). Similar bleeding events were found between 2 groups. Conclusions and Relevance Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke.Trial RegistrationClinicalTrials.gov Identifier: NCT0286900

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

MicroRNA-506 is up-regulated in the development of pancreatic ductal adenocarcinoma and is associated with attenuated disease progression

Abstract Background MicroRNA-506 (miR-506) has been reported to function in several tumors as a tumor suppressor gene or oncogene. However, the expression and role of miR-506 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we aimed to evaluate the phenotype of miR-506 in PDAC. Methods Using miRNA in situ hybridization, we examined the expression of miR-506 in 113 PDACs and 87 paired normal pancreatic tissues. We evaluated miR-506 expression in PDAC cells, normal pancreatic ducts, and acinus/islands, and we analyzed the associations between miR-506 expression and the clinicopathologic characteristics of PDAC patients. Results miR-506 expression was higher in PDAC than in matched normal pancreatic ductal cells (P < 0.001). On the other hand, the combined group of well and moderately differentiated PDACs showed higher levels of miR-506 than the poorly differentiated ones (P = 0.023). Moreover, miR-506 expression was negatively associated with pathologic T category (P = 0.004) and lymph node metastasis (P = 0.033), suggesting that miR-506 might inhibit the progression of PDAC. Conclusions Our results suggest that miR-506 either plays a role as an oncogene in the tumorigenesis and a tumor suppressor in the progression or serves as a house-keeping, tumor-suppressing miRNA, whose expression can be activated by oncogenic signals in early development to hinder the progression of PDAC

Boosting the Photocatalytic Ability of TiO₂ Nanosheet Arrays for MicroRNA-155 Photoelectrochemical Biosensing by Titanium Carbide MXene Quantum Dots

The electrodes of two-dimensional (2D) titanium dioxide (TiO2) nanosheet arrays were successfully fabricated for microRNA-155 detection. The (001) highly active crystal face was exposed to catalyze signaling molecules ascorbic acid (AA). Zero-dimensional (0D) titanium carbide quantum dots (Ti3C2Tx QDs) were modified to the electrode as co-catalysts and reduced the recombination rate of the charge carriers. Spectroscopic methods were used to determine the band structure of TiO2 and Ti3C2Tx QDs, showing that a type Ⅱ heterojunction was built between TiO2 and Ti3C2Tx QDs. Benefiting the advantages of materials, the sensing platform achieved excellent detection performance with a wide liner range, from 0.1 pM to 10 nM, and a low limit of detection of 25 fM (S/N = 3)

Comparative proteomic analysis of seminal plasma exosomes in buffalo with high and low sperm motility

Abstract Background Exosomes are nanosized membranous vesicles secreted by various types of cells, which facilitate intercellular communication by transporting bioactive compounds. Exosomes are abundant in biological fluids including semen, and their protein composition and the potential of seminal plasma exosomes (SPEs) as fertility biomarkers were elucidated in humans, however, little information is available regarding buffalo (Bubalus bubalis). Here, we examined protein correlation between spermatozoa, seminal plasma (SP), and SPEs, and we compared and analyzed protein differences between high-motility (H-motility) and low-motility (L-motility) SPEs in buffalo. Results SPEs were concentrated and purified by ultracentrifugation combined with sucrose density gradient centrifugation, followed by verification using western blotting, nanoparticle tracking analysis, and transmission electron microscopy. Protein composition in spermatozoa, SP and SPEs, and protein difference in H- and L-motility SPEs were identified by LC-MS/MS proteomic analysis and were functionally analyzed through comprehensive bioinformatics. Many SPEs proteins originated from spermatozoa and SP, and nearly one third were also present in spermatozoa and SP. A series of proteins associated with reproductive processes including sperm capacitation, spermatid differentiation, fertilization, sperm-egg recognition, membrane fusion, and acrosome reaction were integrated in a functional network. Comparative proteomic analyses showed 119 down-regulated and 41 up-regulated proteins in L-motility SPEs, compared with H-motility SPEs. Gene Ontology (GO) enrichment of differentially expressed proteins (DEPs) showed that most differential proteins were located in sperm and vesicles, with activities of hydrolase and metalloproteinase, and were involved in sperm-egg recognition, fertilization, single fertilization, and sperm-zona pellucida binding processes, etc. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differential proteins were mainly involved in the PPRP signaling pathway, calcium signaling pathway, and cAMP signaling pathway, among others. Furthermore, 6 proteins associated with reproduction were validated by parallel reaction monitoring analysis. Conclusion This study provides a comprehensive description of the seminal plasma exosome proteome and may be of use for further screening of biomarkers associated with male infertility

Establishment and Validation of a Transdermal Drug Delivery System for the Anti-Depressant Drug Citalopram Hydrobromide

To enhance the bioavailability and antihypertensive effect of the anti-depressant drug citalopram hydrobromide (CTH) we developed a sustained-release transdermal delivery system containing CTH. A transdermal diffusion meter was first used to determine the optimal formulation of the CTH transdermal drug delivery system (TDDS). Then, based on the determined formulation, a sustained-release patch was prepared; its physical characteristics, including quality, stickiness, and appearance, were evaluated, and its pharmacokinetics and irritation to the skin were evaluated by applying it to rabbits and rats. The optimal formulation of the CTH TDDS was 49.2% hydroxypropyl methyl cellulose K100M, 32.8% polyvinylpyrrolidone K30, 16% oleic acid-azone, and 2% polyacrylic acid resin II. The system continuously released an effective dose of CTH for 24 h and significantly enhanced its bioavailability, with a higher area under the curve, good stability, and no skin irritation. The developed CTH TDDS possessed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it has the potential for clinical application as an antidepressant

Survival Analysis of Hepatocellular Carcinoma: A Comparison Between Young Patients and Aged Patients

Background: To compare the clinicopathological features and prognosis between younger and aged patients with hepatocellular carcinoma (HCC). Methods: We analyzed the outcome of 451 HCC patients underwent liver resection, transcatheter arterial chemoembolization and radiofrequency ablation, respectively. Then risk factors for aged and younger patients′ survival were evaluated by multivariate analysis, respectively. Results: The patients who were older than 55 years old were defined as the older group. The overall survival for aged patients was significantly worse than those younger patients. The younger patients had similar liver functional reserve but more aggressive tumor factors than aged patients. Cox regression analysis showed that the elevated levels of aspartate aminotransferase (AST) (Wald χ2 = 3.963, P = 0.047, hazard ratio [HR] =1.453, 95% confidence interval [CI]: 1.006-2.098), lower albumin (Wald χ2 = 12.213, P < 0.001, HR = 1.982, 95% CI: 1.351-2.910), tumor size (Wald χ2 = 8.179, P = 0.004, HR = 1.841, 95% CI: 1.212-2.797), and higher alpha-fetoprotein level (Wald χ2 = 4.044, P = 0.044, HR = 1.465, 95% CI: 1.010-2.126) were independent prognostic factors for aged patients, while only elevated levels of AST (Wald χ2 = 14.491, P < 0.001, HR = 2.285, 95% CI: 1.493-3.496) and tumor size (Wald χ2 = 21.662, P < 0.001, HR = 2.928, 95% CI: 1.863-4.604) were independent prognostic factors for younger patients. Conclusions: Age is a risk factor to determine the prognosis of patients with HCC. Aged patients who have good liver functional reserve are still encouraged to receive curative therapy