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The HCV-Associated Hepatocarcinogenesis in Intracellular Low Viral Load Cells
( Chia-yen Dai ),( Shu-chi Wang ),( Chung-feng Huang ),( Wang-long Chung ),( Ming-lung Yu ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: There are differential viral load distribution in HCV infected liver tissues. We conduct the present study aimed to dissect the different viral load cells to investigate the viral-host resistance on the HCV asssoicated hepatocarcinogenesis. Methods: The study was performed using a replicated in vitro HCV-fluorescence infection model to discuss HCV-high viral load (HVL) cells and the HCV-low viral load (LVL) cells by Flow sort system. The next generation RNA sequence and miRNA array were used to explore the gene profiles and miRNA expression on different HCV-viral load cell populations. Results: The ROS indicator shows that the ROS abundantly in low viral load cells. The RNA-Seq analysis showed that significant enrichment in Cancer (P=5.00E-02 - 2.76E-04; 40 molecules) and a network of the Cellular Movement, Immune Cell Trafficking, Inflammatory Response (Score: 18) by IPA analysis. Protein analysis results confirmed the GADD45A and iNOS overexpression in the LVL cells which verified the oxidative stress qPCR array data in LVL cells. We also found the up-regulated Src oncoprotein expression and down-regulated E-cadherin expression in LVL cells. The miRNA array showed that miR-194, miR-192/215 and miR-10a were preferentially expressed in low viral load cells. Conclusions: With our established cell sorting system, this study provided the gene network between viral and host cells resistance by different viral load cells. The findings show the activated oxidative stress related-gene expression in hepatocytes is associated with the HCV-infected epithelial-to-mesenchymal transition (EMT), providing an important link between HCV viral load and liver cancer. The miRNA-gene intergraded dada need further studies.
( Chia-yen Dai ),( Shu-chi Wang ),( Meng-hsuan Hsieh ),( Cheng-fu Yang ),( Ching-i Huang ),( Chung-feng Huang ),( Ming-lun Yeh ),( Jee-fu Huang ),( Wang-long Chung ),( Ming-lung Yu ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: The different hepatitis C virus (HCV) replication has been reported among individual hepatocytes in chronic HCV infection by identifying hepatocytes with different HCV RNA levels. We have previously established a fluorescence-activated cell sorting (FACS) protocol to study the effects of different intracellular viral loads in HCV-infected cells. The present study aimed to further study the gene expression on different hepatocellular carcinoma (HCC) cells with different HCV viral load. Methods: The JFH1-EYFP viral florescence intensity was used to sort the high and low viral load cells after 5 days infection in vitro which has been shown in our previous study that infected cells efficiently and accurately discriminated between high- and low-viral load cell populations. The next generation sequence-RNA sequence was used to clarify the mRNA and miRNA gene network between HCV-high and HCV-low infected cells of the HCC cell line. Venn diagram summarizing the probe sets that were differentially expressingbetween the Huh7.5.1 versus each differential viral load cell population and miRDB and miRTar databases were used to predict HVL and LVL/S2 unique miRNA target genes. Results: By analyzing the NGS dataset and miRNA microarray dataset, of the significant transcripts, three miRNA were unique for the LVL/S2 cells and nine miRNA unique for the HVL. Twenty-three miRNA were common for all 3 viral load groups. We verified them by q-PCR and data confirmed the array data expression level. We found that high viral loads were associated with cell inflammation- and cell death-associated pathway; and the low viral loads were associated many stress response- and cell adhesion molecular (CAMs)-related genes. Conclusions: With the established cell sorting protocol, we have demonstrated that different gene network between HCV-high and HCV-low infected cells in JFH1-EYFP infectious cells exists. Our results may provide a boarder gene regulation map between high and low viral load cell populations.
( Chia-yen Dai ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
The overall outcome of patients with chronic hepatitis C virus (HCV) infection may have the chance of improvement from the advancement in the treatment efficacy of antiviral therapies. With higher efficacy of the standard of care (pegylated interferon- alpha (PegIFN) plus ribavirin therapy and/or new all oral direct-acting antiviral agents (DAAs), the sustained virological response (SVR) has greatly improved the treatment efficacy. However, some special issues for some patient groups need to be noticed. For patients with hepatitis B virus (HBV)/HCV coinfection, hepatitis B reactivation associated with DAA therapy is emerging to be an important cause of morbidity and mortality. The positivity of HBsAg and HBV DNA are the major determinants of hepatitis B reactivation. With the previous reports by the IFN-based therapy, hepatitis B reactivation was observed about 40% during 5-year post-treatment follow-up with rare clinical hepatitis event. After treatment of DAAs for CHC, the hepatitis B reactivation seems different from the IFN-based therapy. Recent data suggest that in patients with positive HBsAg and HCV infection, reactivation of HBV can occur in up to 70% of the subjects during the DAA therapy and within one year after cessation of DAA therapy. Less than 20% of the subjects developed hepatitis flare accompanying HBV reactivation. The major guidelines have highlighted the needs of monitoring for HV reactivation or even initiating the prophylactic therapy with nucleos(t)ide analogues which may need further studies to clarify the predictive factors and the patient groups who will get the benefits. Another special consideration that should be discussed is related to hepatocellular carcinoma (HCC). The effect of the viral eradication on the development of HCC is an important issue which reflects the outcome of secondary and tertiary prevention in CHC patients with antiviral therapies. With the SVR achieved after the IFN-based therapy, it has been shown that successful antiviral therapy can reduce the risk of HCC development in HCV patients who were without HCC. For patients with HCC receiving HCC therapy, there were some reports revealing no benefit of eradication of HCV on the prevention of the recurrence of HCC. However, large cohort studies have shown that for patients after HCV-related HCC After curative therapy, IFN therapy has been shown to improve outcomes these patients. In the DAA era, with the very high cure rate of HCV, most of the reports show that DAAs therapy seems not to be associated with the occurrence of the HCC. There were some reports indicated the effect of secondary prevention of HCC in CHC patients. Nevertheless, the risk of HCC in patients after therapy for HCC, such as the curative therapy has been debated with DAA therapy. Some studies have shown the lack of preventing recurrence of the HCC in patients with DAAs therapy after treatment of the HCC. On the country, there is the raised concern of the surprisingly increased risk of recurrence of the HCC in these DAAs-treated patients after the curative therapies for HCC. There are more evidences recently reported that no observation about such an increasing of the recurrence of HCC. The efficacy of tertiary prevention needs further long-term studies and assessment.
Multiple dependent state repetitive sampling plans based on one-sided process capability indices
Yen, Ching-Ho,Chang, Chia-Hao,Aslam, Muhammad,Jun, Chi-Hyuck Informa UK (TaylorFrancis) 2018 Communications in Statistics Vol.47 No.6
<P>In this research, multiple dependent state and repetitive group sampling are used to design a variable sampling plan based on one-sided process capability indices, which consider the quality of the current lot as well as the quality of the preceding lots. The sample size and critical values of the proposed plan are determined by minimizing the average sample number while satisfying the producer's risk and consumer's risk at corresponding quality levels. In addition, comparisons are made with the existing sampling plans [Pearn and Wu (2006a), Yen etal. (2015)] in terms of average sample number and operating characteristic curve. Finally, an example is provided to illustrate the proposed plan.</P>
Measuring the Development of Knowledge-Based Economy in Taiwan
Yang, Chia Yen,Lin, Hsiu Ying 이화여자대학교 국제통상협력연구소 2001 Asian International Studies Review Vol.4 No.1/2
The progress of information and communication technology (ICT) has been regarded as one crucial factor bringing about the phenomenon of knowledge-based economy, while other factors such as human resource development, and related institutional settings have also played important roles behind the scene. Our measurement reflects Taiwan's potential knowledge-based economy (KBE) developments, which nevertheless indicates considerable room for improvement. Except for ICT investment, the other knowledge investment indicators supported the perspective of Taiwan's KBE development. However, the knowledge diffusion is perhaps the weakest part of Taiwan's KBE development; Taiwan needs much improvement in order to stay close to the developed countries, finally, as for the knowledge output and application, Taiwan's outstanding performance in research publication and patents is consistent with that in research and development (R&D) of human resources, but the obviously weak performance of knowledge-intensive service sector might have result from Taiwan's relative disadvantages indicated by the measurement of the knowledge diffusion. Given the above status of Taiwan's KBE development, Taiwan will inevitably encounter the following two major challenges; one is related to the difficulty in upgrading Taiwan's science and technology (S&T), and the other is related to the noted issues of digital divide and economic stability.
Molecular structure and developmental expression of zebrafish atp2a genes
Yen-Yu Lai,Chiung-Wen Pai,I-Ting Tsai,Chi-Yuan Chou,Chia-Ti Tsai,Yau-Hung Chen 한국유전학회 2011 Genes & Genomics Vol.33 No.5
We isolated two atp2a genes, atp2a1 and atp2a2a, from embryonic zebrafish. Amino acid sequences deduced from zebrafish atp2a genes are aligned with orthologue proteins from other species, the results showed that they share high percentage of identities (82%-94%) and acidic pIs (5.03-5.33). Whole mount in situ hybridization experiments showed that atp2a1and atp2a2a are maternal inherited genes which can be detected at 1-cell stage embryos and express in the entire animal pole from 6 hours post-fertilization (hpf) to 12 hpf. At the later stages (48-96 hpf), expression of atp2a1 was restricted in head and trunk muscles as well as in some neurons. In contrast to the strongly expression of atp2a1 in head muscle,expression of atp2a2a was detected in head muscle in a fainter manner. In addition, transcripts of atp2a2a were observed in the developing heart during early cardiogenesis. The present studies not only help us to comparatively analyze atp2a genes across species, but also provide useful information about expressions during early embryogenesis that will help in further investigations of functional studies of Atp2a in the future.
Current Sensing Methods for Standby Power Control of Digital-Controlled DC/DC Converter
Yen-Shin Lai,Zih-Jie Su,Chia-An Yeh,Fumikazu Takahashi,Masahiro Hamaogi 전력전자학회 2011 ICPE(ISPE)논문집 Vol.2011 No.5
The main theme of this paper is to study the current sensing methods for standby power reduction control of digital-controlled DC/DC converter. These methods include using transformer of full-bridge converter, coupling inductor and ORing MOSFET. The most suitable sensing method was verified with a digital-controlled 500W class DC/DC converter (input/output voltage: 400V/12V). Experimental results derived from digital-controlled DC/DC converter using the TI DSP (TMS320F2812) as the control platform show that current sensed by voltage across ORing MOSFET method provides superb solution. This method offers linear relationship between output voltage of sensing circuit and load current while not causing response delay under standby conditions and thereby truly reflecting accurate standby conditions.
Effect of Intra-layer Vs Fluctuation on Linear Seismic Site Response
Yen-Hsiang Chang,Chi-Chin Tsai,Chien-Chia Huang,박두희 대한토목학회 2021 KSCE JOURNAL OF CIVIL ENGINEERING Vol.25 No.10
Soil properties vary in space even within a soil layer. Nevertheless, site response analyses are typically conducted using a best-characterized shear wave velocity (Vs) profile without considering its fluctuation. In this study, the random field theory is adopted to model heterogeneous Vs profiles for a range of coefficient of variations (COVs) and correlation lengths (CLs). Linear 1D site responses are analyzed with the randomized profiles to quantify the influence of spatial Vs variation on the propagated ground motions. Results reveal that a higher COV of randomized Vs profiles leads to a lower mean ground response compared with a homogeneous Vs profile. The variation of CL does not significantly affect the surface response and peak ground acceleration profile, but is shown to influence the degree of fluctuation of the maximum shear strain profiles. For idealized profiles, the effect of heterogeneous Vs on ground response can be approximately predicted by using reduced Vs and enlarged small strain damping that are dependent on COV.
Yen-Hsiang Huang,Kuo-Hsuan Hsu,Jeng-Sen Tseng,Kun-Chieh Chen,Chia-Hung Hsu,Kang-Yi Su,Jeremy J. W. Chen,Huei-Wen Chen,Sung-Liang Yu,Tsung-Ying Yang,Gee-Chen Chang 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4
Purpose The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)mutant lung adenocarcinoma patients with acquired resistance after firstline EGFRtyrosine kinase inhibitor (TKI) treatment. Materials and Methods We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFRmutation status. Results A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression- free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). Conclusion PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746- A750 mutation are associated with the frequency of T790M mutation.
Delay of Surgery for Spinal Metastasis due to the COVID-19 Outbreak Affected Patient Outcomes
Chia-Jung Hsieh,Chun-Yu Wu,Yen-Heng Lin,Yu-Cheng Huang,Wen-Chi Yang,Tom Wei-Wu Chen,Wei-Li Ma,Wei-Hsin Lin,Feng-Ming Hsu,Furen Xiao,Shih-Hung Yang,Dar-Ming Lai,Chang-Mu Chen,Shin-Yi Chao,Fon-Yih Tsuan 대한척추신경외과학회 2023 Neurospine Vol.20 No.4
Objective: The present study is to analyze the effects of the coronavirus disease 2019 (COVID 2019) outbreak and the subsequent lockdown on the outcomes of spinal metastasis patients. Methods: The study was a retrospective analysis of data from a prospective cohort study. All patients underwent surgical intervention for spinal metastases between January 2019 and December 2021 and had at least 3 months of postoperative follow-up. The primary outcome was overall mortality during the 4 different stages (pre-COVID-19 era, COVID-19 pandemic except in Taiwan, national lockdown, lifting of the lockdown). The secondary outcomes were the oncological severity scores, medical/surgical accessibility, and patient functional outcome during the 4 periods as well as survival/mortality. Results: A total of 233 patients were included. The overall mortality rate was 41.20%. During the Taiwan lockdown, more patients received palliative surgery than other surgical methods, and no total en bloc spondylectomy was performed. The time from surgeon visit to operation was approximately doubled after the COVID-19 outbreak in Taiwan (75.97, 86.63, 168.79, and 166.91 hours in the 4 periods, respectively). The estimated survival probability was highest after the national lockdown was lifted and lowest during the lockdown. In the multivariate analysis, increased risk of mortality was observed with delay of surgery, with emergency surgery having a higher risk with delays above 33 hours, urgent surgery (below 59 and above 111 hours), and elective surgery (above 332 hours). Conclusion: The COVID-19 pandemic and related policies have altered daily clinical practice and negatively impacted the survival of patients with spinal metastases.