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)

Phase II trial of VEGFR2 inhibitor apatinib for metastatic sarcoma: focus on efficacy and safety

Zhichao Liao,Feng Li,Chao Zhang,Lei Zhu,Yehui Shi,Gang Zhao,Xu Bai,Shafat Hassan,Xinyue Liu,Ting Li,Peipei Xing,Jun Zhao,Jin Zhang,Ruwei Xing,Sheng Teng,Yun Yang,Kexin Chen,Jilong Yang 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Apatinib (YN968D1) is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR- 2). We conducted a single-arm, nonrandomized phase II study (NCT03121846) to assess the efficacy and safety of apatinib in patients with stage IV sarcoma. We recruited 64 patients with stage IV sarcoma who had failed chemotherapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were progression-free survival rate (PFR), objective response rate (ORR), and disease control rate (DCR) at week 12. Treatment-related adverse effects (AEs) were evaluated. Fifty-nine patients were assessed for efficacy and 64 patients for AEs. The median PFS was 7.93 months. At 12 weeks, the PFR was 74%, the ORR was 16.95% (10/59), and the DCR was 86.44% (51/59). The final ORR was 15.25% (9/59) and the DCR was 57.63% (34/59). Notably, 22 patients (34.38%) who developed hypertension, hand-foot-skin reaction, or proteinuria had significantly longer OS than those without these AEs (18.20 vs. 10.73 months; P = 0.002). We conclude that apatinib is effective and well tolerated in patients with advanced sarcoma. The development of hypertension, hand-foot-skin reaction, or proteinuria may indicate a favorable prognosis, representing a novel finding in sarcoma patients.

A New 3D Statistical Parameter for Determining Roughness of Joint Surfaces Considering Shear Direction and Asperity Features

Juan Liu,Feng Gao,Yan Xing,Wenqi Zheng,Yun Bai 대한토목학회 2023 KSCE Journal of Civil Engineering Vol.27 No.11

The engineering rock mass is a multi-fracture body crisscrossed by geologic structure planes, and its safety is affected by the rock joints' mechanical properties and morphological features. The joint roughness coefficient (JRC) is a vital characterization method to describe joint surface roughness. Its precise quantization is a crucial factor in predicting shear strength. However, JRCin recent research did not reflect the directional effect of the joint morphology. A new 3D roughness parameter WAD (weighted apparent dip) was proposed to estimate JRC based on the apparent dip angle of the contact unit. The proposed parameter comprehensively reflects the contribution of shear direction and asperity features to the roughness. Based on the ten standard roughness profiles, we investigated the directionality of the WAD and studied the influence of the sampling interval (Sai) on WAD and their correlation with JRC. And the practicability of WAD in evaluating JRC was well verified by the comparison between the indoor test and calculated results with different roughness and shear directions, and the results showed that WAD could accurately estimate the shear strength of the joint rock.

An Iterative Calculation Method for Internal Forces and Deformation of Curved Tunnel Lining

Lu-yuan Wu,Meng Li,Hai-bo Bai,Yong-feng Yun,Hui Li,Yi Feng 대한토목학회 2024 KSCE Journal of Civil Engineering Vol.28 No.4

The accurate prediction of lining forces and deformations is crucial for the design of arched tunnel lining. However, in traditional tunnel structural mechanics methods, the distribution shape of the surrounding rock elastic resistance (SRER), as well as the zero point and maximal point locations of SRER, are not clearly defined. In this paper, an iterative calculation method is proposed based on the gradual convergence of the unitized values of SRER and total displacement (TD) of the lining, and the one-to-one functional relationship between the two in the stability process of the surrounding rock and lining. In this method involves using the initial displacement caused by the pressure of the surrounding rock pressure is used to initiate the iterative process, and iterative calculation is carried out until the errors between the unitized value of SRER and the unitized value of TD of the lining structure meet the error requirements. This enables precise determination of the SRER and TD. In order to verify the effectiveness of the proposed method, a case study is conducted on the tunnel of Lianghe Expressway tunnel in Yunnan province, China . The results showed that when the semi-lining structure is divided into unit blocks and the average error of consistency is required to be less than 1e-3, it takes about 20 iterations are needed to meet the error requirement. Furthermore, the accuracy of the calculated results is verified through site-measuring experiments. This method provides an effective tool for failure analysis of arched tunnel lining structures.

Prognostic value of preoperative neutrophil-to-lymphocyte ratio in histological variants of non-muscle-invasive bladder cancer

Deng-xiong Li,Xiao-ming Wang,Yin Tang,Yu-bo Yang,Dechao Feng,Ao Li,Fa-cai Zhang,Yun-jin Bai,Ping Han 대한비뇨의학회 2021 Investigative and Clinical Urology Vol.62 No.6

Purpose: Many studies identified that the preoperative neutrophil-to-lymphocyte ratio (PNLR) was associated with patient prognosis in non-muscle-invasive bladder cancer (NMIBC). We hypothesized that PNLR could be prognostic in patients with histological variants of NMIBC (VH-NMIBC). Materials and Methods: This retrospective study included patients with VH-NMIBC admitted at our center between January 2009 and May 2019. The best cut-off value of NLR was measured by the receiver operating characteristic curve and Youden index. The Kaplan-Meier method and Cox proportional hazard regression models were employed to evaluate the association between PNLR and disease prognosis, including recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Results: A total of 243 patients with VH-NMIBC were enrolled in our study. According to the Kaplan-Meier method results, patients with PNLR ≥2.2 were associated with poor RFS (p<0.001), PFS (p<0.001), CSS (p<0.001), and OS (p<0.001). Multivariable analyses indicated that PNLR ≥ 2.2 was an independent prognostic factor of RFS (hazard ratio [HR], 2.11; 95% confidence interval [CI, 1.57–1.83; p<0.001), PFS (HR, 2.34; 95% CI, 1.70–3.21; p<0.001), CCS (HR, 2.87; 95% CI, 1.96–4.18; p< 0.001), and OS (HR, 2.83; 95% CI, 1.96–4.07; p<0.001). Conclusions: This study identified that PNLR ≥2.2 was usually associated with a poor prognosis for patients with VH-NMIBC.

Anti-viral activity of compounds from <i>Agrimonia pilosa</i> and <i>Galla rhois</i> extract mixture

Kwon, Jeong Eun,Lee, Yeong-Geun,Kang, Ji-Hun,Bai, Yun-Feng,Jeong, Yong Joon,Baek, Nam-In,Seo, Young-Jin,Kang, Se Chan Academic Press 2019 Bioorganic chemistry Vol.93 No.-

<P><B>Abstract</B></P> <P>Hepatitis C virus (HCV) infection is a significant health problem, with a worldwide prevalence of about 170 million. Recently, the development of direct acting antiviral (DAA) as a therapeutic agent for HCV has been rapidly increasing. However, DAA has a side effect and is costly. Therefore, it is still necessary to develop a therapeutic agent to treat HCV infection using products.</P> <P> <I>Agrimonia pilosa</I> (AP) and <I>Galla rhois</I> (RG) are traditional medicines and are known to display therapeutic activity on various diseases. Notably, they have been reported to have an anti-viral effect on HBV and influenza virus infections. It is expected that anti-viral activity will increase when two extracts are mixed.</P> <P>To investigate their anti-viral activity, the expression level of HCV Core 1b and NS5A was measured. Remarkably, AP, RG, and their mixed compound (APRG64) strongly inhibited the expression of viral proteins, which led us to identify their metabolites. A total of 14 metabolites were identified using liquid chromatography mass spectrometry (LC-MS). These metabolites were evaluated for their anti-HCV activity to identify active ingredients.</P> <P>In conclusion, our results unveiled that anti-HCV activity of <I>Agrimonia pilosa</I> and <I>Galla rhois</I> extract mixture could lead to the development of a novel therapy for HCV infection.</P> <P><B>Highlights</B></P> <P> <UL> <LI> HCV is a significant liver health problem in worldwide. </LI> <LI> <I>Agrimonia pilosa</I> and <I>Galla rhois</I> observed anti-viral effects. </LI> <LI> 14 secondary metabolites of APRG64 were identified through HPLC-QTof/MS. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

DEPTOR Expression Negatively Correlates with mTORC1 Activity and Tumor Progression in Colorectal Cancer

Lai, Er-Yong,Chen, Zhen-Guo,Zhou, Xuan,Fan, Xiao-Rong,Wang, Hua,Lai, Ping-Lin,Su, Yong-Chun,Zhang, Bai-Yu,Bai, Xiao-Chun,Li, Yun-Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers, including colorectal cancer (CRC). DEPTOR is an mTOR inhibitor whose expression is negatively regulated by mTOR. However, the role of DEPTOR in the development of CRC is not known. The aim of this study was to investigate the expression of DEPTOR and mTORC1 activity (P-S6) in a subset of CRC patients and determine their relation to tumor differentiation, invasion, nodal metastasis and disease-free survival. Here, Immunohistochemical expression of P-S6 (S235/236) and DEPTOR were evaluated in 1.5 mm tumor cores from 90 CRC patients and in 90 samples of adjacent normal mucosa by tissue microarray. The expression of P-S6 (S235/236) was upregulated in CRC, with the positive rate of P-S6 (S235/236) in CRC (63.3%) significantly higher than that in control tissues (36.7%, 30%) (p<0.05). P-S6 (S235/236) also correlated with high tumor histologic grade (p=0.002), and positive nodal metastasis (p=0.002). In contrast, the expression level of DEPTOR was correlated with low tumor histological grade (p=0.006), and negative nodal metastasis (p=0.001). Interestingly, P-S6 (S235/236) expression showed a significant negative association with the expression of DEPTOR in CRC (p=0.011, R= -0.279). However, upregulation of P-S6 (S235/236) (p=0.693) and downregulation of DEPTOR (p=0.331) in CRC were not significantly associated with overall survival. Thus, we conclude that expression of DEPTOR negatively correlates with mTORC1 activity and tumor progression in CRC. DEPTOR is a potential marker for prognostic evaluation and a target for the treatment of CRC.