BACKGROUND:Although microRNAs (miRNAs) play essential roles in spermatogenesis, little is known about seminal plasma miRNAs in infertile men. We investigated the profile of seminal plasma miRNAs in infertile men to identify miRNAs that are altered in infertility; we then evaluated their diagnostic value.
1 In many cancer patients, 5-fluorouracil (5-FUra) treatment is toxic and even causes death. Nevertheless, all patients are subjected to a standard therapy regimen because there is no reliable way to identify beforehand those patients who are predisposed to 5-FUra-induced toxicity. In this study, we identified the dihydrouracil/uracil (UH2/Ura) ratio in plasma or urine as a potential biomarker reflecting the activity of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in 5-FUra metabolism. 2 UH2/Ura ratios were measured by high-performance liquid chromatography tandem triple quadrupole mass spectrometry (HPLC-MS/MS) in both healthy subjects (n ¼ 55) and in patients (n ¼ 20) diagnosed with grade I/II gestational trophoblastic tumours. In addition, rats (n ¼ 18) were used as an animal model to verify a correlation between UH2/Ura ratios and DPD levels in the liver. 3 A significant circadian rhythm was observed in UH2/Ura ratios in healthy subjects, whereas a disrupted rhythm occurred in cancer patients who were continuously infused with a high dose of 5-FUra. In rats, UH2/Ura ratios, liver DPD levels and PBMC DPD levels showed a definite circadian rhythm. Significant linear correlations with liver DPD levels were demonstrated for plasma UH2/Ura ratios (r ¼ 0.883, Po0.01), urine UH2/Ura ratios (r ¼ 0.832, Po0.01) and PBMC DPD levels (r ¼ 0.859, Po0.01). 4 The UH2/Ura ratio in biological fluid was significantly correlated with liver DPD levels; hence, this ratio could be a potential biomarker to identify patients with a deficiency in DPD.
These findings demonstrate the acquisition of H. pylori infection during early childhood in a population at high risk of stomach cancer, in a manner consistent with a person-to-person mode of transmission between parents and children.
AC0010 had a well-tolerated safety profile and promising antitumor activity in patients with NSCLC with acquired resistance to a first-generation EGFR TKI, supporting its continued development.
Aim: To investigate the pharmacokinetics, pharmacodynamics, and safety of higenamine, an active ingredient of Aconite root, in healthy Chinese volunteers. Methods: Ten subjects received continuous, intravenous infusion of higenamine at gradually escalating doses from 0.5 to 4.0, each dose was given for 3 min. Blood and urine samples were collected at designated time points to measure the concentrations of higenamine. Pharmacodynamics was assessed by measuring the subject's heart rate. A nonlinear mixed-effect modeling approach, using the software Phoenix NLME, was used to model the plasma concentration-time profiles and heart rate. .3% (range, 4.6%-12.4%) of higenamine was recovered in the urine. The pharmacokinetics of higenamine was successfully described using a two-compartment model with nonlinear clearance. In the pharmacodynamic model, heart rates were related to the plasma drug concentrations using a simple direct effect model with baseline. The E 0 , E max , and EC 50 were 68 bpm, 73 bpm and 8.1 μg/L, respectively. Conclusion: Higenamine has desirable pharmacokinetic and pharmacodynamic characteristics. The results provide important information for future clinical studies on higenamine.
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