Absorption, tissue distribution, and excretion of glycycoumarin, a major bioactive coumarin from Chinese licorice (Glycyrrhiza uralensis Fisch).

Licorice (Glycyrrhiza uralensis Fisch) is a natural plant resource widely used as a food and herbal medication in China. Glycycoumarin (GCM) is a major coumarin in licorice that possesses several biological activities. However, little is known about its pharmacokinetic profile. The present study aimed to describe the oral absorption, tissue distribution, and excretion of GCM in rats. Free (parent drug) and/or total (parent drug plus the glucuronidated metabolite) GCM in biological samples was quantified before and after the hydrolysis reaction with ß-glucuronidase using a reliable LC-MS/MS method. The results indicated that GCM was rapidly absorbed and transformed into its conjugated metabolites after administration. Free GCM plasma concentrations after i. v. (10 mg/kg) administration quickly decreased with an average t1/2,λz of 0.71 h, whereas the total GCM concentration reduced slowly with a t1/2, λz of 2.46 h. The area under the curve of glucuronidated metabolites was approximately four-times higher than that of free GCM. Presumably, because of hepatic and/or intestinal tract first-pass metabolism, GCM exhibited a poor bioavailability of 9.22%, as estimated from its total plasma concentration. Additionally, GCM was distributed rapidly and widely in various tissues except the brain. The liver had the highest concentration; further, GCM was promptly eliminated from test tissues after intraperitoneal (20 mg/kg) administration, but only a small amount of GCM was excreted via bile and urine. Overall, GCM is absorbed and rapidly transformed into its conjugated metabolites with low bioavailability; further, it is distributed in various tissues, except the brain. These pharmacokinetic results are helpful for better understanding the characteristics and pharmacological effects of GCM.

Pharmacokinetic and pharmacodynamic analysis of cefoperazone/sulbactam for the treatment of pediatric sepsis by Monte Carlo simulation.

Pediatric sepsis syndrome is one of the most common reasons for pediatric intensive care unit hospitalization (PICU). Cefoperazone/sulbactam is a time-dependent beta-lactamase inhibitor combination which has been widely used in the treatment of sepsis. But the pharmacokinetic (PK) and pharmacodynamic (PD) data of cefoperazone/sulbactam are unknown in children with sepsis. The present work aimed to determine whether the usual dosing regimens of cefoperazone/sulbactam (1 hour infusion, 50 mg kg-1, every 12 hours) were suitable for these patients in PICU. A total of fourteen patients were enrolled and the PK parameters were estimated by non-compartmental analysis using WinNonlin software. The t1/2 and AUC0-12 of cefoperazone and sulbactam were 3.60 and 1.77 h, and 900.97 and 67.68 h µg mL-1, respectively. The Vd and CL of cefoperazone and sulbactam were 1.65 L and 5.16 L, and 17.41 mL min-1 and 122.62 mL min-1, respectively. The probability of target attainments (PTAs) of cefoperazone at different minimum inhibitory concentrations (MICs) based on the percentage time that concentrations exceed the minimum inhibitory concentration (% T > MIC) value were performed by Monte Carlo simulation and PTA was >90% at MICs ≤16 µg mL-1. The PK/PD profile of dosing regimens tested will assist in selecting the appropriate cefoperazone/sulbactam regimens for these patients. At a target of 80% T > MIC, the usual dosing regimens can provide good coverage for pathogens with MICs of ≤32 µg mL-1. The ratio between cefoperazone and sulbactam at 1 : 1 may be more suitable in pediatric sepsis. Individual dose and therapeutic drug monitoring in clinical practice will help achieve the best therapeutic effect while minimizing toxicity.

Analysis of Chest CT Results of Coronavirus Disease 2019 (COVID-19) Patients at First Follow-Up.

Objective: To investigate the dissipation and outcomes of pulmonary lesions at the first follow-up of patients who recovered from moderate and severe cases of COVID-19. Methods: From January 21 to March 3, 2020, a total of 136 patients with COVID-19 were admitted to our hospital. According to inclusion and exclusion criteria, 52 patients who recovered from COVID-19 were included in this study, including 33 moderate cases and 19 severe cases. Three senior radiologists independently and retrospectively analyzed the chest CT imaging data of 52 patients at the last time of admission and the first follow-up after discharge, including primary manifestations, concomitant manifestations, and degree of residual lesion dissipation. Results: At the first follow-up after discharge, 16 patients with COVID-19 recovered to normal chest CT appearance, while 36 patients still had residual pulmonary lesions, mainly including 33 cases of ground-glass opacity, 5 cases of consolidation, and 19 cases of fibrous strip shadow. The proportion of residual pulmonary lesions in severe cases (17/19) was statistically higher than in moderate cases (19/33) (χ 2 = 5.759, P < 0.05). At the first follow-up, residual pulmonary lesions were dissipated to varying degrees in 47 cases, and lesions remained unchanged in 5 cases. There were no cases of increased numbers of lesions, enlargement of lesions, or appearance of new lesions. The dissipation of residual pulmonary lesions in moderate patients was statistically better than in severe patients (Z = -2.538, P < 0.05). Conclusion: Clinically cured patients with COVID-19 had faster dissipation of residual pulmonary lesions after discharge, while moderate patients had better dissipation than severe patients. However, at the first follow-up, most patients still had residual pulmonary lesions, which were primarily ground-glass opacity and fibrous strip shadow. The proportion of residual pulmonary lesions was higher in severe cases of COVID-19, which required further follow-up.

Machine Learning-Based Differentiation of Nontuberculous Mycobacteria Lung Disease and Pulmonary Tuberculosis Using CT Images.

An increasing number of patients infected with nontuberculous mycobacteria (NTM) are observed worldwide. However, it is challenging to identify NTM lung diseases from pulmonary tuberculosis (PTB) due to considerable overlap in classic manifestations and clinical and radiographic characteristics. This study quantifies both cavitary and bronchiectasis regions in CT images and explores a machine learning approach for the differentiation of NTM lung diseases and PTB. It involves 116 patients and 103 quantitative features. After the selection of informative features, a linear support vector machine performs disease classification, and simultaneously, discriminative features are recognized. Experimental results indicate that bronchiectasis is relatively more informative, and two features are figured out due to promising prediction performance (area under the curve, 0.84 ± 0.06; accuracy, 0.85 ± 0.06; sensitivity, 0.88 ± 0.07; and specificity, 0.80 ± 0.12). This study provides insight into machine learning-based identification of NTM lung diseases from PTB, and more importantly, it makes early and quick diagnosis of NTM lung diseases possible that can facilitate lung disease management and treatment planning.

Genetic variations in inflammation-related genes and their influence on the susceptibility of pediatric acute lung injury in a Chinese population.

Acute lung injury (ALI) is a serious clinical syndrome that can cause respiratory failure and threaten the life of the patients. A biomarker that can predict the syndrome can contribute to a better clinical management of the patients. In adults, genetic polymorphisms in inflammatory-response genes have been shown to be a promising biomarker. However, the pathogenesis of ALI in adult is known to be different from that in children and no previous study has investigated the association between inflammatory gene polymorphisms and pediatric ALI (PALI) risk. In this work, we examined the association between 12 polymorphisms in six inflammatory-response genes (TNF, IL6, IL10, IL18, NFKB1 and NFKBIA) and risk of PALI. A total of 1075 children with ALI and 1382 non-ALI controls were recruited. The polymorphisms were genotyped employing RFLP method. The risk association was estimated via logistic regression analysis, with P < 0.004 being statistically significant after Bonferroni correction. A statistically significant association was observed for IL10 rs1800896 (heterozygous, P < 0.0001; homozygous variant, P < 0.0001; allele, P < 0.0001) and TNF rs1800629 (heterozygous, P < 0.0001; homozygous variant, P = 0.0012; allele, P < 0.0001) polymorphisms. On the other hand, no significant association was found for IL6 rs1800795, rs1800796 and rs1800797 polymorphisms, IL10 rs3021097 polymorphism, NFKB1 rs28362491 polymorphism, NFKBIA rs2233406 and rs696 polymorphisms, IL18 rs1946518 and rs187238 polymorphisms, and TNF rs1799964 polymorphism. In conclusion, IL10 rs1800896 and TNF rs1800629 may serve as a risk biomarker for pediatric ALI among Chinese.

Association between inflammatory-response gene polymorphisms and risk of acute kidney injury in children.

In the present study, we investigated the association of 12 polymorphisms in six inflammatory-response genes (TNF, IL6, IL10, IL18, NFKB1 and NFKBIA) with risk of acute kidney injury (AKI) in children. The polymorphisms were genotyped in 1138 children with AKI and 1382 non-AKI controls. Logistic regression analysis was performed to calculate the odds ratio for estimating the risk association. After accounting for Bonferroni correction and adjustment for potential confounders, significant association was observed for NFKB1 rs28362491, NFKBIA rs2233406 and NFKBIA rs696 polymorphisms (P < 0.004). All three polymorphisms were associated with a reduced risk of AKI. For rs28362491 polymorphism, the OR for ID vs. II comparison was 0.75 (95% CI = 0.58-0.83) while that for DD vs. II was 0.44 (95% CI = 0.30-0.67). For rs2233406 polymorphism, the CT vs. CC comparison showed an OR of 0.90 (95% CI = 0.39-0.99), while the TT vs. CC comparison showed an OR of 0.43 (95% CI = 0.33-0.80). For rs696 polymorphism, the OR for AG vs. AA comparison was 0.71 (95% CI = 0.43-0.89), while the GG vs. AA comparison showed an OR of 0.39 (95% CI = 0.21-0.71). In conclusion, NFKB1 rs28362491, NFKBIA rs2233406 and NFKBIA rs696 polymorphisms may serve as biomarkers for predicting risk of AKI in children.

Inhibitory effects of Danhong Injection and its major constituents on human cytochrome P450 enzymes in vitro.

Danhong Injection (DHI) as a Chinese patent medicine is mainly used to treat ischemic encephalopathy and coronary heart disease in combination with other chemotherapy. However, the information on DHI's potential drug interactions is limited. The goal of this work was to examine the potential P450-mediated metabolism drug interaction arising from DHI and its active components. The results showed that DHI inhibited CYP2C19, CYP2D6, CYP3A4, CYP2E1 and CYP2C9 with IC50 values of 1.26, 1.42, 1.63, 1.10 and 1.67% (v/v), respectively. Danshensu and rosmarinic acid inhibited CYP2E1 and CYP2C9 with IC50 values of 36.63 and 75.76 µm, and 34.42 and 76.89 µm, respectively. Salvianolic acid A and B inhibited CYP2D6, CYP2E1 and CYP2C9 with IC50 values of 33.79, 21.64 and 31.94 µm, and 45.47, 13.52 and 24.15 µm, respectively. The study provides some useful information for safe and effective use of DHI in clinical practice.

Thin-section computed tomography detects long-term pulmonary sequelae 3 years after novel influenza A virus-associated pneumonia.

BACKGROUND: The aim of this research was to evaluate long-term pulmonary sequelae on paired inspiration-expiration thin-section computed tomography (CT) scans 3 years after influenza A (H1N1) virus-associated pneumonia, and to analyze the affecting factors on pulmonary fibrosis. METHODS: Twenty-four patients hospitalized with H1N1 virus-associated pneumonia at our hospital between September 2009 and January 2010 were included. The patients underwent thin-section CT 3 years after recovery. Abnormal pulmonary lesion patterns (ground-glass opacity, consolidation, parenchymal bands, air trapping, and reticulation) and evidence of fibrosis (architectural distortion, traction bronchiectasis, or honeycombing) were evaluated on follow-up thin-section CT. Patients were assigned to Group 1 (with CT evidence of fibrosis) and Group 2 (without CT evidence of fibrosis). Demographics, rate of mechanical ventilation therapy, rate of intensive care unit admission, cumulative prednisolone-equivalent dose, laboratory tests results (maximum levels of alanine aminotransferase, aspartate transaminase [AST], lactate dehydrogenase [LDH], and creatine kinase [CK]), and peak radiographic opacification of 24 patients during the course of their illness in the hospital were compared between two groups. RESULTS: Parenchymal abnormality was present in 17 of 24 (70.8%) patients and fibrosis occurred in 10 of 24 (41.7%) patients. Patients in Group 1 (10/24; 41.7%) had a higher rate of mechanical ventilation therapy (Z = -2.340, P = 0.019), higher number of doses of cumulative prednisolone-equivalent (Z = -2.579, P = 0.010), higher maximum level of laboratory tests results (AST [Z = -2.140, P = 0.032], LDH [Z = -3.227, P = 0.001], and CK [Z = -3.345, P = 0.019]), and higher peak opacification on chest radiographs (Z = -2.743, P = 0.006) than patients in group 2 (14/24; 58.3%). CONCLUSIONS: H1N1 virus-associated pneumonia frequently is followed by long-term pulmonary sequelae, including fibrotic changes, in lung parenchyma. Patients who need more steroid therapy, need more mechanical ventilation therapy, had higher laboratory tests results (maximum levels of AST, LDH, and CK), and had higher peak opacification on chest radiographs during treatment are more likely to develop lung fibrosis.