Causes, Features, and Outcomes of Drug-Induced Liver Injury in 69 Children from China

( Yun Zhu ),( Yong Gang Li ),( Jia Bo Wang ),( Shu Hong Liu ),( Li Fu Wang ),( Yan Ling Zhao ),( Yun Feng Bai ),( Zhong Xia Wang ),( Jian Yu Li ),( Xiao He Xiao ) 대한소화기학회 2015 Gut and Liver Vol.9 No.4

Background/Aims: Drug-induced liver injury (DILI) is a frequent cause of pediatric liver disease; however, the data on DILI are remarkably limited. Methods: All 69 children hospitalized with DILI between January 2009 and December 2011 were retrospectively studied. Results: A total of 37.7% of the children had medical histories of respiratory infection. The clinical injury patterns were as follows: hepatocellular 89.9%, cholestatic 2.9%, and mixed 7.2%. Liver biopsies from 55 children most frequently demonstrated chronic (47.3%) and acute (27.3%) hepatitis. Hypersensitivity features, namely, fever (31.9%), rash (21.7%), and eosinophilia (1.4%), were found. Twenty-four children (34.8%) developed chronic DILI. Antibiotics (26.1%) were the most common Western medicines (WMs) causing DILI, and the major implicated herbs were Ephedra sinica and Polygonum multiflorum. Compared with WM, the children whose injuries were caused by Chinese herbal medicine (CHM) showed a higher level of total bilirubin (1.4 mg/dL vs 16.6 mg/dL, p=0.004) and a longer prothrombin time (11.8 seconds vs 17.3 seconds, p=0.012), but they exhibited less chronic DILI (2/15 vs 18/39, p=0.031). Conclusions: Most cases of DILI in children are caused by antibiotics or CHM used to treat respiratory infection and present with hepatocellular injury. Compared with WM, CHM is more likely to cause severe liver injury, but liver injury caused by CHM is curable. (Gut Liver 2015;9:525-533)

The Efficacy of Aspirin in Preventing the Recurrence of Colorectal Adenoma: a Renewed Meta-Analysis of Randomized Trials

Zhao, Tai-Yun,Tu, Jing,Wang, Yin,Cheng, Da-Wei,Gao, Xian-Kui,Luo, Hao,Yan, Bi-Chun,Xu, Xiao-Li,Zhang, Hong-Ling,Lu, Xing-Jun,Wang, Yao-Jun Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.5

Background: Through search the possible randomized control trials, we make a renewed meta-analysis in order to assess the impact of aspirin in preventing the recurrence of colorectal adenoma. Materials and Methods: The Medicine/PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese biomedical literature service system (SinoMed) databases were searched for the related randomized controlled trials until to the April 2016. Three different authors respectively evaluated the quality of studies and extracted data, and we used the STATA software to analyze, investigate heterogeneity between the data, using the fixed-effects model to calculate and merge data. Results: 7 papers were included the renewed meta-analysis, among these studies, two pairs were identified as representing the same study population, with the only difference being the duration of follow-up. Thus there were only five papers included our meta-analysis, and one Chinese paper were also included the work. Results were categorized by the length of follow-up, different kinds of people, varied dose of oral aspirin. The relative of adenoma in patients taking aspirin vs placebo were 0.73 (95% CI 0.55-0.98, P=0.039) with 1 year follow up; 0.84 (95% CI 0.72-0.98, P=0.484) with greater than 1 year follow up; for the advanced adenoma, the RR 0.68 (95% CI 0.49-0.94, P=0.582),for one year; RR=0.75 (95% CI 0.52-1.07, P=0.552) for greater one year. Furthermore the white population could divided into two subgroups according to the different length of follow-up time. When the length of follow-up time less than 3-year, The RR of two subgroups respective were RR=0.86 (95% CI 0.76-0.98, P=0.332), $I^2=0%$, RR=0.68 (95% CI 0.47-0.98, P=0.552), $I^2=64.6%$, But with the extension of follow-up time greater than 2-year, with the white, oral aspirin without considering dose had no efficacy on preventing the recurrence of any adenoma, the RR was 0.86 (95% CI 0.71-1.05, P=0.302), $I^2=16.4%$. Conclusions: This meta-analysis indicated that oral aspirin is associated with a remarkable decrease in the recurrence of any adenoma and advanced adenomas in patients follow-up for 1 year without concerning the dose of aspirin, but with the extension of follow-up time for greater than 1 year, oral aspirin can be effective on preventing the recurrence of any adenoma, but for the advanced adenoma, the result indicated that oral aspirin had no efficacy, According to the inclusion of ethnic groups, we also divided relevant papers into two subgroups as the yellow and white group. Then the follow-up time was less than 3 years, oral aspirin without considering the dose, had an significant efficacy on preventing the recurrence of any adenoma. But with the follow-up greater than 2 years, oral aspirin had no effect in the white.

A brain somatic RHEB doublet mutation causes focal cortical dysplasia type II

Shanshan Zhao,Zhenghui Li,Muxian Zhang,Lingliang Zhang,Honghua Zheng,Jinhuan Ning,Yanyan Wang,Feng-Peng Wang,Xiaobin Zhang,Hexia Gan,Yuanqing Wang,Xian Zhang,Hong Luo,Guojun Bu,Huaxi Xu,Yi Yao,Yun-wu 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Focal cortical dysplasia type II (FCDII) is a cerebral cortex malformation characterized by local cortical structure disorganization, neuronal dysmorphology, and refractory epilepsy. Brain somatic mutations in several genes involved in the PI3K/AKT/mTOR pathway are associated with FCDII, but they are only found in a proportion of patients with FCDII. The genetic causes underlying the development FCDII in other patients remain unclear. Here, we carried out whole exome sequencing and targeted sequencing in paired brain–blood DNA from patients with FCDII and identified a brain somatic doublet mutation c.(A104T, C105A) in the Ras homolog, mTORC1 binding (RHEB) gene, which led to the RHEB p.Y35L mutation in one patient with FCDII. This RHEB mutation carrier had a dramatic increase of ribosomal protein S6 phosphorylation, indicating mTOR activation in the region of the brain lesion. The RHEB p.Y35L mutant protein had increased GTPλS-binding activity compared with wild-type RHEB. Overexpression of the RHEB p. Y35L variant in cultured cells also resulted in elevated S6 phosphorylation compared to wild-type RHEB. Importantly, in utero electroporation of the RHEB p.Y35L variant in mice induced S6 phosphorylation, cytomegalic neurons, dysregulated neuron migration, abnormal electroencephalogram, and seizures, all of which are found in patients with FCDII. Rapamycin treatment rescued abnormal electroencephalograms and alleviated seizures in these mice. These results demonstrate that brain somatic mutations in RHEB are also responsible for the pathogenesis of FCDII, indicating that aberrant activation of mTOR signaling is a primary driver and potential drug target for FCDII.

Effectiveness and Safety of Dabrafenib in the Treatment of 20 Chinese Children with BRAFV600E-Mutated Langerhans Cell Histiocytosis

Ying Yang,Dong Wang,Lei Cui,Hong-Hao Ma,Li Zhang,Hong-Yun Lian,Qing Zhang,Xiao-Xi Zhao,Li-Ping Zhang,Yun-Ze Zhao,Na Li,Tian-You Wang,Zhi-Gang Li,Rui Zhang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.1

Purpose We sought to investigate the effectiveness and safety of dabrafenib in children with BRAFV600E-mutated Langerhans cell histiocytosis (LCH). Materials and Methods A retrospective analysis was performed on 20 children with BRAFV600E-mutated LCH who were treated with dabrafenib. Results The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)+ group and six patients (30%) in the RO– group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAFV600E (cfBRAFV600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients. Conclusion Some children with BRAFV600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.

AT1 Receptor Modulator Attenuates the Hypercholesterolemia-Induced Impairment of the Myocardial Ischemic Post-Conditioning Benefits

Yun-Wei Li,Yan-Ming Li,Yan Hon,Qi-Lin Wan,Rui-Li He,Zhi-Zhong Wang,Cui-Hua Zhao 대한심장학회 2017 Korean Circulation Journal Vol.47 No.2

Background and Objectives: Ischemic post-conditioning (PostC) has been demonstrated as a novel strategy to harness nature’s protection against myocardial ischemia-reperfusion (I/R). Hypercholesterolemia (HC) has been reported to block the effect of PostC on the heart. Angiotensin II type-1 (AT1) modulators have shown benefits in myocardial ischemia. The present study investigates the effect of a novel inhibitor of AT1, azilsartan in PostC of the heart of normocholesterolemic (NC) and HC rats. Materials and Methods: HC was induced by the administration of high-fat diet to the animals for eight weeks. Isolated Langendorff’s perfused NC and HC rat hearts were exposed to global ischemia for 30 min and reperfusion for 120 min. I/R-injury had been assessed by cardiac hemodynamic parameters, myocardial infarct size, release of tumor necrosis factor-alpha troponin I, lactate dehydrogenase, creatine kinase, nitrite in coronary effluent, thiobarbituric acid reactive species, a reduced form of glutathione, superoxide anion, and left ventricle collagen content in normal and HC rat hearts. Results: Azilsartan post-treatment and six episodes of PostC (10 sec each) afforded cardioprotection against I/R-injury in normal rat hearts. PostC protection against I/R-injury was abolished in HC rat hearts. Azilsartan prevented the HC-mediated impairment of the beneficial effects of PostC in I/R-induced myocardial injury, which was inhibited by L-N5-(1-Iminoethyl)ornithinehydrochloride, a potent inhibitor of endothelial nitric oxide synthase (eNOS). Conclusion: Azilsartan treatment has attenuated the HC-induced impairment of beneficial effects of PostC in I/R-injury of rat hearts, by specifically modulating eNOS. Azilsartan may be explored further in I/R-myocardial injury, both in NC and HC conditions, with or without PostC.

Sublethal effects of buprofezin on development, reproduction, and chitin synthase 1 gene (SfCHS1) expression in the white-backed planthopper, Sogatella furcifera (Hemiptera: Delphacidae)

Zhao Wang,Cao Zhou,Gui-yun Long,Hong Yang,Dao-chao Jin 한국응용곤충학회 2018 Journal of Asia-Pacific Entomology Vol.21 No.2

The white-backed planthopper, Sogatella furcifera (Horváth) (Hemiptera: Delphacidae), is a major rice pest in some Asia-Pacific countries. Buprofezin is an insect growth regulator with relatively low mammalian toxicity but high efficacy to many rice pests. In this study, we estimated the toxicity of buprofezin against 3rd-instar nymphs of S. furcifera using the rice-stem dipping method. The results showed that the LC50 of buprofezin to 3rd-instar nymphs were 0.89 mg/L. When 3rd-instar nymphs were exposed to the LC10 and LC25 (0.10 and 0.28 mg/L) of buprofezin, the duration of juvenile development was significantly prolonged in the F0 and F1 generations. The fecundity (eggs per female) of the F1 females was reduced by 5.29% and 12.34%, respectively, in addition to the survival rate, emergence rate, copulation rate, and hatchability were decreased by treatment with buprofezin at LC10 and LC25, compared with the control group. The relative fitness of S. furcifera in LC10 and LC25 treatments was reduced by 47% and 63%, respectively. Furthermore, real-time quantitative PCR analyses revealed increased the expressions of SfCHS1 and its two variants following the exposure of nymphs to buprofezin. Increased these genes mRNA levels associated with reduced chitin biosynthesis may result from the inhibition of chitin synthase activity, and thereby leading to a higher mortality of S. furcifera. Overall, sublethal concentrations of buprofezin suppressed the population growth of S. furcifera.

State-of-charge Estimation for Lithium-ion Batteries Using a Multi-state Closed-loop Observer

Zhao, Yulan,Yun, Haitao,Liu, Shude,Jiao, Huirong,Wang, Chengzhen The Korean Institute of Power Electronics 2014 JOURNAL OF POWER ELECTRONICS Vol.14 No.5

Lithium-ion batteries are widely used in hybrid and pure electric vehicles. State-of-charge (SOC) estimation is a fundamental issue in vehicle power train control and battery management systems. This study proposes a novel model-based SOC estimation method that applies closed-loop state observer theory and a comprehensive battery model. The state-space model of lithium-ion battery is developed based on a three-order resistor-capacitor equivalent circuit model. The least square algorithm is used to identify model parameters. A multi-state closed-loop state observer is designed to predict the open-circuit voltage (OCV) of a battery based on the battery state-space model. Battery SOC can then be estimated based on the corresponding relationship between battery OCV and SOC. Finally, practical driving tests that use two types of typical driving cycle are performed to verify the proposed SOC estimation method. Test results prove that the proposed estimation method is reasonably accurate and exhibits accuracy in estimating SOC within 2% under different driving cycles.

Explore China cold regions village residential green technology strategy

ZHAO Yun duo,Wang zi wen 국제온돌학회 2013 International Journal of Ondol Vol.2013 No.-

In 2013, the Chinese government formulated the Action Plan for Green Building , which focuses on the task clearly should actively promote the construction of rural housing. In this paper, for the question about how to promote the cold region of China rural house green, put forward to improve the quality of residential priority, to save energy resources as the most important,and to use pervasive technology-based applications as the main content,which is basic principles.The paper also proposed four technical strategies for a new house on the village is to use local natural resources, to optimize the design to improve the quality of living,to reduce shape coefficient to adjust the layout,to improve the insulation properties of architecture maintenance in structure increases.And with the above principles and technology strategies,I design a green rural house which reflect on the characteristics of cold region.

Screening of MicroRNA in Patients with Esophageal Cancer at Same Tumor Node Metastasis Stage with Different Prognoses

Zhao, Bao-Sheng,Liu, Shang-Guo,Wang, Tian-Yun,Ji, Ying-Hua,Qi, Bo,Tao, Yi-Peng,Li, Han-Chen,Wu, Xiang-Nan Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

Patients at the same pathological stage of esophageal cancer (EC) that received the same surgical therapy by the same surgeon may have distinct prognoses. The current study aimed to explore the possibility of differentially-expressed microRNAs (miRNAs) underlying this phenomenon. Samples were collected from EC patients at the same tumor node metastasis (TNM) stage but with different prognoses. Paracancerous normal tissues were taken as controls. The specimens were histopathologically analyzed. Differentially-expressed miRNAs were analyzed using real-time quantitative reverse transcription polymerase chain reaction. Compared with patients with poor prognosis, those with good prognosis exhibited 88 two-fold or more than two-fold increased miRNA fragments and 4 half-decreased miRNAs. The most noticeably up-regulated miRNAs included hsa-miR-31, hsa-miR-196b, hsa-miR-652, hsa-miR-125a-5p, hsa-miR-146b, hsa-miR-200c, hsa-miR-23b, hsa-miR-29a, hsa-miR-186, hsa-miR-205, hsa-miR-376a, hsa-miR-410, hsa-miR-532-3p, and hsa-miR-598, whereas the most significantly-downregulated miRNAs were hsa-let-7e, hsa-miR-130b, and hsa-miR-103. EC patients at same TNM stage but with different prognoses show differentially-expressed miRNAs.

Effects of Ohmic Area Etching on Buffer Breakdown Voltage of AlGaN/GaN HEMT

Wang, Chong,Wel, Xiao-Xiao,Zhao, Meng-Di,He, Yun-Long,Zheng, Xue-Feng,Mao, Wei,Ma, Xiao-Hua,Zhang, Jin-Cheng,Hao, Yue The Korean Institute of Electrical and Electronic 2017 Transactions on Electrical and Electronic Material Vol.18 No.3

This study is on how ohmic area etching affects the buffer breakdown voltage of AlGaN/GaN HEMT. The surface morphology of the ohmic metal can be improved by whole etching on the ohmic area. The buffer breakdown voltages of the samples with whole etching on the ohmic area were improved by the suppression of the metal spikes formed under the ohmic contact regions during high-temperature annealing. The samples with selective etching on the ohmic area were investigated for comparison. In addition, the buffer leakage currents were measured on the different radii of the wafer, and the uniformity of the buffer leakage currents on the wafer were investigated by PL mapping measurement.