Search

The objective of this research was to evaluate and compare the pharmacokinetic profiles and safety of lisinopril/hydrochlorothiazide (10 mg/12.5 mg) tablets in the test and reference formulations administered to participants in both fasting and postprandial states and to evaluate the bioequivalence of the 2 products in healthy Chinese volunteers. This study employed a single‐center, randomized, open‐label, single‐dose dosing trial involving a cumulative 96 healthy adult participants (60 in the fasting group and 36 in the postprandial group). Each group comprised 2 sequence sets, and a 2‐week washout period was implemented. There were no statistically significant differences in time to maximum concentration and terminal elimination half‐life between the test and control groups under fasting and postprandial conditions (P >.05), and the 90% CIs for area under the plasma concentration–time curve and maximum plasma concentration were within the bioequivalence range of 80%‐125%. Pharmacokinetic results indicate a large food effect for lisinopril, meaning that there is a loss of approximately 20%‐25% of systemic exposure from fasting to postprandial administration for both preparations. The study demonstrated that a single oral dose of generic lisinopril/hydrochlorothiazide is bioequivalent to the reference product and well tolerated, with no significant adverse events observed, and that both products are similarly safe in a cohort of healthy Chinese male and female participants, following administration under fasting and postprandial conditions. [ABSTRACT FROM AUTHOR]

Rapid identification of pathogens is critical for early and appropriate treatment of bloodstream infections. The various culture‐independent assays that have been developed often have long turnaround times, low sensitivity and narrow pathogen coverage. Here, we propose a new multiplex PCR assay, MeltArray, which uses intact microbial cells as the source of genomic DNA (gDNA). The successive steps of the MeltArray assay, including selective lysis of human cells, microbial cell sedimentation, microbial cellular DNA extraction, target‐specific pre‐amplification and multiplex PCR detection, allowed the detection of 35 major bloodstream infectious pathogens in whole blood within 5.5 h. The limits of detection varied depending on the pathogen and ranged from 1 to 5 CFU/mL. Of 443 blood culture samples, including 373 positive blood culture samples and 70 negative blood culture samples, the MeltArray assay showed a sensitivity of 93.8% (350/373, 95% confidence interval [CI] = 90.7%–96.0%), specificity of 98.6% (69/70, 95% CI = 91.2%–99.9%), positive predictive value of 99.7% (95% CI = 98.1%–99.9%), and negative predictive value of 75.0% (95% CI = 64.7%–83.2%). The MeltArray detection results of 16 samples differed from MALDI–TOF and were confirmed by Sanger sequencing. Further testing of 110 whole blood samples from patients with suspected bloodstream infections using blood culture results revealed that the MeltArray assay had a clinical sensitivity of 100% (9/9, 95% CI = 62.8%–100.0%), clinical specificity of 74.5% (70/94, 95% CI = 64.2%–82.7%), positive predictive value of 27.3% (95% CI = 13.9%–45.8%), and negative predictive value of 100.0% (95% CI = 93.5%–100.0%). Compared with metagenomic next‐generation sequencing, the MeltArray assay displayed a positive agreement of 85.7% (6/7, 95% CI = 42.0%–99.2%) and negative agreement of 100.0% (4/4, 95% CI = 39.6%–100.0%). We conclude that the MeltArray assay can be used as a rapid and reliable tool for direct identification of pathogens in bloodstream infections. [ABSTRACT FROM AUTHOR]

Potassium (K+) is an endogenous substance that is an essential dietary component. However, the interaction between dietary arrangements and specific effects of dietary K+ intake in bioequivalence studies remains unclear. To investigate the influence of dietary arrangement on the bioequivalence of potassium chloride (KCl) sustained‐release tablets in healthy Chinese volunteers, the pharmacokinetics of KCl were compared in two open‐label, single‐center, randomized, two‐period crossover studies with different dietary conditions. All volunteers received an oral dose of 6 g of KCl sustained‐release tablets under fasting conditions, with different dietary arrangements. Urine samples were collected on baseline days and 48 hours after tablet consumption. Inductively coupled plasma–optical emission spectrometry was used to measure the concentration of K+ in the urine samples. Pharmacokinetic parameters were analyzed using Phoenix WinNonlin software in a noncompartmental model. In either clinical trial, no significant differences were observed in the maximal rate of urinary excretion and cumulative urinary excretion from 0 to 24 hours of K+ between the reference and test drugs. The bioequivalence studies of both KCl sustained‐release tablet formulations were successfully conducted under different dietary conditions. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence has highlighted the correlation between microRNAs (miRNAs) and the progression of glioma. However, the role of miR cluster MC‐let‐7a‐1 ~ let‐7d in glioma remains elusive. Thus, the current study aimed to investigate the effect of miR cluster MC‐let‐7a‐1 ~ let‐7d on glioma progression. Methods and Results: Microarray data analysis provided data indicating the involvement of miR cluster MC‐let‐7a‐1 ~ let‐7d in glioma via STAT3. The expression of let‐7a‐1, let‐7d, let‐7f‐1, and miR cluster MC‐let‐7a‐1 ~ let‐7d was diminished in the glioma tissues and the cell lines. Additionally, our results revealed that STAT3 was a target gene of let‐7d, let‐7a‐1, and let‐7f‐1, which was further verified by the dual‐luciferase reporter gene assay. Moreover, STAT3 expression was negatively mediated by let‐7a‐1, let‐7d, and let‐7f‐1. Up‐regulated miR cluster MC‐let‐7a‐1 ~ let‐7d or silenced STAT3 suppressed cell proliferation but accelerated cell apoptosis and autophagy. Moreover, restrained tumor growth was identified in the nude mice treated with miR cluster MC‐let‐7a‐1 ~ let‐7d mimics or STAT3 siRNA. Conclusion: Taken together, the miR cluster MC‐let‐7a‐1 ~ let‐7d promotes glioma cell autophagy and apoptosis by repressing STAT3. The current study highlights the potential of the miR cluster MC‐let‐7a‐1 ~ let‐7d as biomarkers and promising treatment strategies for glioma. [ABSTRACT FROM AUTHOR]

To obtain different instant tea, three tea leaves (Pu'er tea, Gold Junmei tea and Tie Guanyin tea) were extrated by conventional (90 °C, 30 min) and pressurized (120 °C, 30 min) methods and dried in freezing and spraying condition. The amino acid composition and content were determined by the automatic amino acid analyzer, and the sensory evaluation was conducted. The yield and the content of free amino acids in instant tea powder was higher under the conditions of 120 °C pressurized hot extraction and freeze drying. The sensory evaluation showed freeze drying tea sample was more aromatic, better soluble, more mellow in taste, and it soup color was easier to accept than spray drying tea sample. [ABSTRACT FROM AUTHOR]