PurposeTo study the pharmacokinetic characteristics of omeprazole in Chinese extensive and poor metabolizers.Methods The pharmacokinetics of omeprazole was studied in eighteen healthy volunteers. After a single oral dose of omeprazole capsule(40 mg), the plasma concentrations of omeprazole and its two metabolites, 5-hydroxyomeprazole and omeprazole sulfone, were determined with reversed HPLC method. The plasma concentration-time data were analyzed to estimate the pharmacokinetic parameters. Results Both plasma omeprazole concentration and the pharmacokinetic parameters exhibited marked interindividual variation. The metabolic ratio (MR= plasma omeprazole/5-hydroxyomeprazole) obtained 3.5 h after medication was used to distinguish between extensive and pcr)r metabolizers (EMs, PMs). The variances of AUC(0-12) caused by the two metabolizer phenotypes accounted for 75.4 % of the total interindividual variances. AUC(0-12) of omeprazole was (1 971.78 ±1 221.78)ng·h/ml in EMs( n=12) and (8 587.18±2 855.48) ng·h/ml in PMs (n = 6),respectively (P<0.01),and CL in EMs and PMs was estimated as (16.00±9.71) and (4.79±1.32) L/h (P<0.01). Accordingly,significantly lower level of plasma 5-hyclroxyomeprazole was found in PMs, revealing a slower hydroxylation rate compared with EMs. Conclusions The results suggest that individualized dose regimen of omeprazole, based on identification of metabolizer phenotype, can be of great benefit from the viewpoint of pharmacoeconomics.

Intrahepatic cholangiocellular carcinoma (ICC) is a primary tumor originating from the epithelial cells of bile duct. In recent years, incidence of ICC in the world is on the rise, and it has become the second common malignant tumors of the liver, with its incidence being next only to hepatocellular carcinoma (HCC). The onset of ICC is insidious, its clinical manifestations are lack of specificity, most of the patients are already in the advanced stage when the diagnosis is confirmed, thus, affecting the treatment and prognosis. Therefore, early diagnosis and treatment is essential. The radical treatment plan is mainly surgical excision, and other treatment options include systemic chemotherapy, local ablation, transcatheter arterial chemoembolization (TACE), selective intraarterial radiotherapy with yttrium-90 microspheres (SIRT-90Y), 125I seed implantation, etc. This article aims to make a comprehensive introduction about the recent advances in the diagnosis and treatment of ICC. (J Intervent Radiol, 2018, 27:285-289)

The oral direct-acting antiviral drug (DAA) offers tremendous opportunities to eliminate hepatitis C. We analyzed the market trends, price trends and global treatment progress of DAA drugs by reviewing the guidelines recommended by the World Health Organization for the treatment of hepatitis C, and discusses the current accessibility of DAA treatment and its influencing factors. The results show that WHO recommends the use of DAA for treatment of hepatitis C, but the price of DAA is expensive. Although some countries have taken measures to lower prices and improve accessibility, the advancement of DAA treatment has been unsatisfactory and coverage is still not high. In addition to price, factors such as strategy, health system, accessibility and service provision need to be considered, and public health methods should be adopted to promote DAA treatment to achieve the elimination of hepatitis C.

The oral direct-acting antiviral drug (DAA) offers tremendous opportunities to eliminate hepatitis C. We analyzed the market trends, price trends and global treatment progress of DAA drugs by reviewing the guidelines recommended by the World Health Organization for the treatment of hepatitis C, and discusses the current accessibility of DAA treatment and its influencing factors. The results show that WHO recommends the use of DAA for treatment of hepatitis C, but the price of DAA is expensive. Although some countries have taken measures to lower prices and improve accessibility, the advancement of DAA treatment has been unsatisfactory and coverage is still not high. In addition to price, factors such as strategy, health system, accessibility and service provision need to be considered, and public health methods should be adopted to promote DAA treatment to achieve the elimination of hepatitis C.

Objective To compare the prognostic ability of Hong Kong Liver Cancer (HKLC) staging system with that of Barcelona Clinic Liver Cancer (BCLC) staging system for Chinese patients with hepatocellular carcinoma (HCC) after receiving transarterial chemoembolization (TACE).Methods The clinical data of 180 Chinese patients with primary HCC,who were treated with TACE during the period from August 2008 to December 2015,were retrospectively analyzed.HCC staging of each patient was scored by two staging methods separately.Kaplan-Meier analysis was adopted to separately calculate the median survival time of each stage that was judged by the two staging methods.The likelihood ratio (LR) x2 values,the Akaike information criterion (AIC) value and Harrell's C value of the two staging methods were calculated.Results Statistically significant differences in the survival time of each period existed between the two staging systems.AIC value,LRx2 value and Harrell's C value of HKLC staging system were 1360,66.6,and 0.813 respectively,while those of BCLC staging system were 1365,61.8,and 0.772 respectively.Conclusion Compared with BCLC staging,HKLC staging is more suitable for predicting the survival time of Chinese patients with primary liver cancer treated with TACE.

Background: Microsporum canis is a zoonotic disease that can cause dermatophytosis in animals and humans. Objectives: In clinical practice, ketoconazole (KTZ) and other imidazole drugs are commonly used to treat M. canis infection, but its molecular mechanism is not completely understood.The antifungal mechanism of KTZ needs to be studied in detail. Methods: In this study, one strain of fungi was isolated from a canine suffering with clinical dermatosis and confirmed as M. canis by morphological observation and sequencing analysis.The clinically isolated M. canis was treated with KTZ and transcriptome sequencing was performed to identify differentially expressed genes in M. canis exposed to KTZ compared with those unexposed thereto. Results: At half-inhibitory concentration (½MIC), compared with the control group, 453 genes were significantly up-regulated and 326 genes were significantly down-regulated (p < 0.05). Quantitative reverse transcription polymerase chain reaction analysis verified the transcriptome results of RNA sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the 3 pathways of RNA polymerase, steroid biosynthesis, and ribosome biogenesis in eukaryotes are closely related to the antifungal mechanism of KTZ. Conclusions The results indicated that KTZ may change cell membrane permeability, destroy the cell wall, and inhibit mitosis and transcriptional regulation through CYP51, SQL, ERG6, ATM, ABCB1, SC, KER33, RPA1, and RNP genes in the 3 pathways. This study provides a new theoretical basis for the effective control of M. canis infection and the effect of KTZ on fungi.

Objective To explore the clinical efficacy and safety of transarterial chemoembolization(TACE)combined with immune checkpoint inhibitor(ICI)and molecular targeted therapy for Child-Pugh grade B hepatocellular carcinoma(HCC).Methods The patients with Child-Pugh grade B HCC,who received TACE combined with ICI and molecular targeted therapy(combination group)or TACE monotherapy(monotherapy group)at the three medical centers including the Affiliated Zhongda Hospital of Southeast University of China between January 2018 and May 2021,were enrolled in this study.The primary outcome was overall survival(OS),and the secondary outcomes included progression-free survival(PFS),objective response rate(ORR),and clinical safety.Results A total of 126 patients were enrolled in this study,including 64 patients in the combination group and 62 patients in the monotherapy group.No statistically significant difference in median OS existed between the combination group and the monotherapy group[17.7 months(95％CI:11.9-29.9 months)vs.13.2 months(95％CI:7.8-19.9 months);P=0.160].In the combination group,the patients having a Child-Pugh score of 7 points obtained a significantly better OS[19.0months(95％CI:13.6-NR)vs.13.2 months(95％CI:8.0-NR),P=0.024].The differences in the median PFS and ORR between the two groups were not statistically significant(P=0.720 and P=0.960 respectively).Grade Ⅲ/Ⅳ adverse events occurred in 19 patients(14.1％)of the combination group and in 6 patients(9.7％)of the monotherapy group.Conclusion In treating patients with Child-Pugh grade B HCC,TACE combined with ICI and molecular targeted therapy does not show a better prognosis than TACE monotherapy,however,the patients having a Child-Pugh score of 7 points in the combination group can have a much better OS.

Objective:To explore the effect of oxidative stress on cognitive function following chest blast injury in mice.Methods:Sixty male C57BL/6 mice were divided into control group ( n=15) and chest blast group ( n=45) according to a random number table. The chest blast group was subgrouped at 1, 3, 7 days after injury for subsequent experiments. A self-developed blast injury device was used to prepare the mouse model of chest blast injury. Toklu score was used to evaluate the behavior changes in mice. Morris water maze test was used to evaluate the changes in spatial memory. HE staining was used to observe the pathological changes in the frontal cortex and hippocampus. Tissue reactive oxygen species (ROS) assay kit was used to detect ROS expression in the frontal cortex and hippocampus. Western blotting was used to assess changes of malondialdehyde (MDA) and cyclooxygenase-2 (COX2) in the frontal cortex and hippocampus. Results:The Toklu score of the chest blast group at 1 day after injury was (6.7±2.1)points, significantly higher than that of the control group [(2.0±0.0)points], as well as those of the chest blast group at 3 and 7 days after injury [(2.7±1.2)points and (2.0±0.0)points] (all P<0.01). There was no significant difference in the Toklu score between the control group and the chest blast group at 3 and 7 days after injury (all P>0.05). The Morris water maze test showed that the latency periods at 1 and 3 days after injury were 60.1(60.1, 60.1)seconds and 60.1(56.3, 60.1)seconds, significantly longer than that of the control group [10.1(3.9, 18.3)seconds] (all P<0.01). The latency period of the chest blast group at 7 days after injury was 60.1(30.5, 60.1)seconds, with no difference from the control group ( P>0.05). No significant differences were found in the latency periods of the chest blast group at 1, 3 and 7 days after injury (all P>0.05). In the control group, the pyramidal cells in the frontal cortex and hippocampus were regular in shape, with intensely-stained and clearly visible nuclei as well as uniform cytoplasm. In the chest blast group, diflerent degree of necrosis of pyramidal cells in the frontal cortex and strong cytoplasmic eosinophilia in the hippocampus were observed at different time points after injury. The levels of ROS in the frontal cortex of the chest blast group were (10.43±0.36)RFU/mg and (2.91±0.35)RFU/mg at 3 and 7 days after injury, which were significantly higher than that of the control group [(0.70±0.01)RFU/mg] ( P<0.05 or 0.01). The level of ROS in the frontal cortex of the chest blast group at 3 days after injury was significantly higher than that at 1 day [(2.13±0.65)RFU/mg] and that at 7 days after injury (all P<0.01). There were no statistical differences in the levels of ROS in the frontal cortex of the chest blast group at 1 and 7 days after injury ( P>0.05). The levels of ROS in the hippocampus of the chest blast group were (5.39±0.79)RFU/mg and (5.65±1.17)RFU/mg at 3 and 7 days after injury, which were significantly higher than those of the control group and of the chest blast group at 1 day after injury [ (0.73±0.06)RFU/mg and (2.33±0.02)RFU/mg] (all P<0.01). No significant differences were found between the levels of ROS in the hippocampus of the chest blast group at 3 and 7 days after injury and between the ROS levels of the control group and of the chest blast group at 1 day after injury (all P>0.05). The levels of ROS in the frontal cortex and hippocampus showed significant differences between the chest blast group at 3 and 7 days after injury (all P<0.01) but no significant differences between the control group and the chest blast group at 1 day after injury (all P>0.05). Western blotting showed that the levels of MDA in the frontal cortex of the chest blast group were 0.73±0.04, 0.83±0.04 and 0.99±0.06 at 1, 3 and 7 days after injury, which were significantly higher than that of the control group (0.56±0.04) ( P<0.05 or 0.01). The level of MDA in the frontal cortex of the chest blast group was significantly higher at 7 days after injury compared with that at 1 and 3 days after injury ( P<0.05 or 0.01), but there was no statistical difference between 1 day and 3 days after injury ( P>0.05). The levels of COX2 in the frontal cortex of the chest blast group were 2.93±0.02, 4.82±0.15 and 4.76±0.06 at 1, 3 and 7 days after injury, which were significantly higher than that of the control group (1.93±0.06) (all P<0.01). There were statistical differences in the levels of COX2 in the frontal cortex of the chest blast group at 3 and 7 days after injury compared with that at 1 day after injury (all P<0.01), but no statistical significance was found between 3 and 7 days after injury ( P>0.05). The levels of MDA in the hippocampus of the chest blast group were 0.92±0.11, 0.83±0.03 and 0.68±0.03 at 1, 3 and 7 days after injury, which were significantly higher than that of the control group (0.49±0.03) (all P<0.01). There was a significant difference in the level of MDA in the hippocampus of the chest blast group at 7 days after injury compared with those at 1 and 3 days after injury ( P<0.05 or 0.01), but the difference was not statistically significant among other groups (all P>0.05). The levels of COX2 in the hippocampus of the chest blast group were 0.88±0.06, 0.87±0.06 and 0.80±0.06 at 1, 3 and 7 days after injury, which were significantly higher than that of the control group (0.37±0.04) (all P<0.01). There were significant differences in the levels of COX2 of the chest blast group among 1, 3 and 7 days after injury (all P>0.05). Statistically significant differences were found between the levels of MDA in the frontal cortex and hippocampus of the chest blast group at 1 and 7 days after injury (all P<0.01), but no statistical significant difference between the control group and the chest blast group at 1 day after injury ( P>0.05). The levels of COX2 in the frontal cortex and hippocampus were significantly different among all groups (all P<0.01). Conclusions:In the short term after chest blast injury, there will be cognitive dysfunction in mice. Oxidative stress is one of the important contributing factors, and the cognitive damage in the frontal cortex is more serious than that in the hippocampus.