In recent years, the functional interplay between drug-metabolizing enzymes (DMEs) and drug transporters (DTs) in drug absorption and disposition, as well as the complex drug interactions (DIs), has become an intriguing contention, which has also been termed the “transport–metabolism interplay”. The current mechanistic understanding for this interplay is first discussed. In the present article, studies investigating the interplay between cytochrome P450 enzymes (CYPs) and efflux transporters have been systematically reviewed in vitro, in situ, in silico, in animals and humans, followed by CYPs–uptake transporters, CYPs–uptake transporters-efflux transporters, and phase II metabolic enzymes–transporters interplay studies. Although several cellular, isolated organ and whole animal studies, in conjunction with simulation and modelling, have addressed the issue that DMEs and DTs can work cooperatively to affect the bioavailability of shared substrate drugs, convincing evidences in human studies are still lacking. Furthermore, the functional interplay between DMEs and DTs will be highly substrate- and dose- dependent. Additionally, we review recent studies to evaluate the influence of genetic variations in the interplay between DMEs and DTs, which might be helpful for the prediction of pharmacokinetics (PK) and possible DIs in human more correctly. There is strong evidence of coordinately regulated DEMs and DTs gene expression and protein activity (e.g. nuclear receptors). Taken together, further investigations and analysis are urgently needed to explore the functional interplay of DMEs and DTs and to delineate the underlying mechanisms.

The number of coronavirus disease 2019 (COVID-19) cases has exceeded 10 million. However, little is known about the epidemiology and clinical characteristics of COVID-19 infants. We collected medical information of 46 confirmed patients (<1 year old) and retrospectively analyzed epidemiological history, clinical symptoms, and laboratory test results. The median age was 5 (interquartile range, 2–7) months. Sixteen cases had fever and 27 cases had cough. Moderate disease was present in 40 cases and cardiac injury occurred in 38 cases, following by liver dysfunction in 20 cases and lymphopenia in no cases. Of all infant patients, 2 received invasive mechanical ventilation and 1 died with multiple organ dysfunction syndrome.

Background: Orthostatic hypotension (OH) is a common disease of the elderly. It is generally believed that the pathogenesis of OH is related to the impairment of autonomic nerve function and the decreased vascular capacity regulation. This study aims to explore the relationship between OH and heart rate variability (HRV) parameters, which reflects autonomic nerve function; ankle-brachial pressure index (ABI), which reflects the degree of vascular stenosis; pulse wave velocity (PWV) index, which reflects vascular stiffness; and frailty index (FI), which reflects the overall health status of the elderly.Methods: From January to September 2018, 24-h HOLTER monitoring, PWV, and ABI were performed in 108 elderly patients with OH and 64 elderly patients who underwent physical examination in our hospital. Analysis software was used to record the subject's standard deviation of the cardiac cycle (SDNN), the standard deviation of the 5-min average cardiac cycle (SDANN), the square root of the average square sum of consecutive n-interval differences (rMSSD), the percentage of the number of adjacent cardiac interval differences >50 ms (pNN50), low frequency (LF), high frequency (HF), very low frequency (VLF), and low frequency/high frequency ratio (LF/HF). Then, FI was evaluated qualitatively and quantitatively in the form of a scale.Results: There was no statistical difference between the two groups on the basis of age, sex, body mass index (BMI), low-density lipoprotein (LDL), resting heart rate, blood pressure, fasting blood glucose, long-term medication, etc. There were significant differences in PWV, SDNN, LF, VLF, and LF/HF between the two groups (P < 0.05). The risk factor of OH in the qualitative (P = 0.04) and quantitative (P = 0.007) index FI was higher in the OH group than in the control group. The risk factors of OH were PWV, SDNN, VLF, LF/HF, and FI, where FI was positively correlated and LF/HF was negatively correlated.Conclusions: The pathogenesis of OH is related to vascular stiffness, imbalance of autonomic nerve regulation, and its comprehensive health status in the elderly. However, arteriosclerosis has not been confirmed as an independent risk factor.Clinical Trial Registration: Retrospectively registered, http://www.chictr.org.cn.