Significant down-regulation of growth hormone receptor expression revealed as a new unfavorable prognostic factor in hepatitis C virus-related hepatocellular carcinoma

( Ching-chih Lin ),( Ta-wei Liu ),( Ming-lun Yeh ),( Yi-shan Tsai ),( Pei-chien Tsai ),( Chung-feng Huang ),( Jee-fu Huang ),( Wan-long Chuang ),( Chia-yen Dai ),( Ming-lung Yu ) 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.2

Background/Aims: Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC. Methods: The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed. Results: GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II-IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C. Conclusions: Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC. (Clin Mol Hepatol 2021;27:313-328)

The Application of Creative Thinking Teaching in Nursing Education for Youth Children’s Nutrition

Ching-Chi Yeh,Ju-Chen Yen,Pei-Yu Lee 한국간호과학회 2023 한국간호과학회 학술대회 Vol.2023 No.11

Tenofovir Alafenamide for Chronic Hepatitis B Patients with Advanced Fibrosis and Partial Virologic Responses to Oral Nucleos(T)Ide Analogues- Interim Report

( Ming-lung Yu ),( Ming-lun Yeh ),( Chi-yi Chen ),( Pin-nan Cheng ),( Ming-jong Bair ),( Jyh-jou Chen ),( Ching-chu Lo ),( Chi-ming Tai ),( Ching-yang Tsai ),( Kuo-chih Tseng ),( Chien-hung Chen ),( C 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Insufficient data regarding the treatment strategy for partial response to nucleot(s)ide analogue (NUC) raised the aim of investigating tenofovir alafenamide (TAF) switching for chronic hepatitis B (CHB) patients with advanced fibrosis and partial response to other NUCs. Methods: CHB patients with advanced fibrosis (stage 3 or 4) and under NUC (except TAF) therapy with detectable hepatitis B virus (HBV) DNA for >52 weeks are enrolled to TAF 25 mg/day for 96 weeks. The objectives are viral suppression, alanine aminotransferase (ALT) normalization and safety. Results: From Feb. 2019, 34 patients, including 21 (61.8%) with entecavir, 10 (29.4%) TDF and 3 (8.8%) lamivudine or adefovir, were enrolled (15 [44.1%] male, median 53 years). The fibroscan demonstrated a mean of 10.5 kPa (7 [20.6%] cirrhotic). Sixteen (47.1%) patients were HBV e antigen positive, seven (20.6%) had YMDD mutation. The median HBV DNA level declined from 68.5 IU/mL at enrollment to 27.0 IU/mL at 4^th week, and undetectable at 12^th, 24^th, 36^th week, respectively, after TAF switching, with undetectable HBV DNA in 14/34 (41.2%), 17/33 (51.5%), 15/25 (60.0%), and 9/15 (60.0%) patients and rate of ALT normalization (≤40 U/L) of 85.3%, 85.3%, 84.8%, 92.0%, and 80.0%, respectively, after TAF switching. (figure 1) Two patients experienced transient virological breakthrough and another one developed at the final time follow up. Serum creatinine and eGFR levels were stable after TAF switching (figure 1). Two patients early terminated including one at 12^th week due to personal reason, and another one accidently died at 20^th week due to acute heart attack. Others suffered only mild degrees of adverse events which were considered unrelated to treatment. Conclusions: The preliminary results demonstrated the TAF switching is effective and safe in viral suppression for CHB patients with advanced fibrosis and partial virologic responses to other NUCs.

Suture Repair in Endoscopic Surgery for Craniovertebral Junction

Mei-Yin Yeh,Wen-Cheng Huang,Jau-Ching Wu,Chao-Hung Kuo,Hsuan-Kan Chang,Tsung-Hsi Tu,Peng-Yuan Chang,Yu-Shu Yen,Henrich Cheng 대한척추신경외과학회 2019 Neurospine Vol.16 No.2

Objective: Endoscopic approaches to the craniovertebral junction (CVJ) have been established as viable and effective surgical treatments in the past decade. One of the major complications is leakage of the cerebrospinal fluid (CSF). This study aimed to investigate the efficacy and feasibility of suture closure at the nasopharyngeal mucosa upon durotomy. Methods: A series of consecutive patients who underwent different endoscopic approaches to the CVJ were retrospectively reviewed. The pathologies, surgical corridors, neurological and functional outcomes, radiological evaluations, and complications were analyzed. Different strategies of repair for the intraoperative CSF leakage were described and compared. Results: A total of 22 patients covering 13 years were analyzed. There were 12, 2, and 8 patients who underwent transnasal, transoral, and combined approaches, respectively. There were 8 patients (36.4%) who experienced intraoperative CSF leakage, and were grouped into 2: 4 in the nonsuture (NS) group and 4 in the suture-repaired (SR) group. The NS group had 3 (75%) persistent CSF leakages postoperation that caused 1 mortality, whereas patients of the SR group had only 1 minor CSF rhinorrhea that healed spontaneously within days. Conclusion: In this series of 22 patients who required anterior endoscopic resection of pathologies at the CVJ, there was 1 (4.5%) serious complication related to CSF leakage. For patients who had no durotomy, the mucosal incision at the nasopharynx usually healed rapidly and there were few procedure-related complications. For patients with intraoperative CSF leakage, suture closure was technically challenging but could significantly lower the risks of postoperative complications.

Eosinophilia in Pleural Effusions: a Speculative Negative Predictor for Malignancy

Chu, Fang-Yeh,Liou, Ching-Biau,Sun, Jen-Tang,Bei, Chia-Hao,Liou, Tse-Hsuan,Tan, N-Chi,Yu, Yun-Chieh,Chang, Chih-Chun,Yen, Tzung-Hai,Su, Ming-Jang Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3

Background: Eosinophilic pleural effusion (EPE) is an eosinophil count more than 10% on cytology of pleural samples. Recently, it was reported that malignancy had been the most prevalent cause inducing EPE. Therefore, we conducted an analysis on the prevalence and etiology of EPE and investigated the relationship between EPE and malignancy. Materials and Methods: Data for pleural cell differential count from patients receiving thoracentesis during the period from January 2008 to December 2013 were compared with clinical data and established diagnosis of patients obtained via electronic chart review. Results: A total of 6,801 requests of pleural cytology from 3,942 patients with pleural effusion who had received thoracentesis were available at Far Eastern Memorial Hospital from 2008 to 2013, and of these subjects, 115 (2.9%) were found to have EPE. The most frequent cause of EPE was malignancy (33.0%, n=38), followed by parapneumonic effusions (27.8%, n=32), tuberculosis pleuritis (13.9%, n=16), transudate effusions (12.2%, n=14) and the presence of blood or air in pleural space (10.4%, n=12). Additionally, an inverse relationship of eosinophilia in pleural fluid was identified in patients with malignancy and EPE. The cut-off eosinophil count in pleural fluid was 15% for the most accurate discrimination between malignancy and benign disorders in patients with EPE. At the cut-off level, the sensitivity and specificity were 65.8% and 67.5%, respectively. Conclusions: Pleural fluid eosinophilia was a speculative negative predictor for malignancy, despite the fact that cancers, including lung cancers and metastatic cancers to lung, were the most leading cause of pleural fluid eosinophilia. An inverse correlation was observed between the pleural eosinophil percentage and the likelihood of malignancy in patients with EPE.

Effect of Simple Exercise Training in Nursing Staffs with Muscle Endurance

Szu-Tine Fang,Chia-Ching Yu,Hsiang-Yin Yeh 한국간호과학회 2009 한국간호과학회 학술대회 Vol.2009 No.10

Comedications and potential drug-drug interactions with direct-acting antivirals in hepatitis C patients on hemodialysis

( Po-yao Hsu ),( Yu-ju Wei ),( Jia-jung Lee ),( Sheng-wen Niu ),( Jiun-chi Huang ),( Cheng-ting Hsu ),( Tyng-yuan Jang ),( Ming-lun Yeh ),( Ching-i Huang ),( Po-cheng Liang ),( Yi-hung Lin ),( Ming-ye 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.1

Background/Aims: Direct-acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). Conclusions: HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs. (Clin Mol Hepatol 2021;27:186-196)

A study on behavior of steel joints that combine high-strength bolts and fillet welds

Heui-Yung Chang,Ching-Yu Yeh 국제구조공학회 2019 Steel and Composite Structures, An International J Vol.31 No.4

In recent years, considerable attention has been paid to the research and development of high-strength steel plates, with particular emphasis on the enhancement of the seismic resistance of buildings and bridges. Many efforts have also been undertaken to improve the properties of high-strength bolts and weld materials. However, there are still different opinions on steel joints that combine high-strength bolts and fillet welds. Therefore, it is necessary to verify the design specifications and guidelines, especially for newly developed 1,400-MPa high-strength bolts, 570-MPa steel plates, and weld materials. This paper presents the results of literature reviews and experimental investigations. Test parameters include bolt strengths, weld orientations, and their combinations. The results show that advances in steel materials have increased the plastic deformation capacities of steel welds. That allows combination joints to gain their maximum strength before the welds have fracture failures. When in combination with longitudinal welds, high-strength bolts slip, come in contact with cover plates, and develop greater bearing strength before the joints reach their maximum strength. However, in the case of combinations with transverse welds, changes in crack angles cause the welds to provide additional strength. The combination joints can therefore develop strength greater than estimated by adding the strength of bolted joints in proportion to those of welded joints. Consequently, using the slip resistance as the available strength of high-strength bolts is recommended. That ensures a margin of safety in the strength design of combination joints.

The Different Expression of Gene Profiles on Hepatocellular Carcinoma Cells with Different Intracellular Hepatitis C Viral Load

( 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.

Decellularized Human Umbilical Artery Exhibits Adequate Endothelialization in Xenogenic Transplantation

Kai Hsia,Tien-Shiang Wang,Chin-Su Liu,Chih-Kuan Su,Chien-Chin Chen,Chang-Ching Yeh,Hsinyu Lee,Chao-Ling Yao,Tsung-Yu Tseng,Shih-Hwa Chiou,Hsu Ma,Chih-Hsun Lin,Jen-Her Lu 한국생물공학회 2023 Biotechnology and Bioprocess Engineering Vol.28 No.3

Decellularized human umbilical arteries (dHUA) is an off-the-shelf graft that can potentially serve as vascular scaffolds in tissue engineering of small-diameter vascular grafts. This research aimed to investigate that dHUA could exhibit adequate endothelialization for a long term in xenogenic transplantation. 13 dHUAs were implanted in rat abdominal aortas up to 90 days. Rats were divided into three groups in terms of survival period: Group 1, one to seven days (n = 6); Group 2, 14 to 30 days (n = 4) and Group 3, 90 days (n = 3). The explants were analyzed by histological, immunohistochemistry and magnetic resonance angiography (MRA) examination. Allograft implantation of 12 decellularized rat abdominal aortas` were processed the same way as the rat in order to make a comparison for survival rates (Group 1, n = 5; Group 2, n = 4; Group 3, n = 3). The results demonstrated that the survival rates of xenograft and allograft implantation were estimated to be 59.2% vs. 58.3% in Group 1, 50.7% vs. 58.3% in Group 2 and 3. Grafts harvested from Group 2 were showed CD31, endothelial nitric oxide synthase expression at intima, and α-smooth muscle actin, CD45, CD68 and CD168 expression at the tunica externa. A layer structure with obvious endothelialization and fiber regeneration/orientation could be inspected from the explants of Group 3. MRA demonstrated the patency of dHUA on day 30 and 90. In conclusion, more than 50% dHUA maintained patency in the xenogenic model till 90 days after surgery. A mature vessel-like functional structure with intact endothelial layer was observed then. This warrants further study in the reinforcement of decellularized vascular scaffolds.