Infusion of Human Mesenchymal Stem Cells Improves Regenerative Niche in Thioacetamide-Injured Mouse Liver

Kao Ying-Hsien,Lin Yu-Chun,Lee Po-Huang,Lin Chia-Wei,Chen Po-Han,Tai Tzong-Shyuan,Chang Yo-Chen,Chou Ming-Huei,Chang Chih-Yang,Sun Cheuk-Kwan 한국조직공학과 재생의학회 2020 조직공학과 재생의학 Vol.17 No.5

Background: This study investigated whether xenotransplantation of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) reduces thioacetamide (TAA)-induced mouse liver fibrosis and the underlying molecular mechanism. Methods: Recipient NOD/SCID mice were injected intraperitoneally with TAA twice weekly for 6 weeks before initial administration of WJ-MSCs. Expression of regenerative and pro-fibrogenic markers in mouse fibrotic livers were monitored post cytotherapy. A hepatic stallate cell line HSC-T6 and isolated WJ-MSCs were used for in vitro adhesion, migration and mechanistic studies. Results: WJ-MSCs were isolated from human umbilical cords by an explant method and characterized by flow cytometry. A single infusion of WJ-MSCs to TAA-treated mice significantly reduced collagen deposition and ameliorated liver fibrosis after 2-week therapy. In addition to enhanced expression of hepatic regenerative factor, hepatocyte growth factor, and PCNA proliferative marker, WJ-MSC therapy significantly blunted pro-fibrogenic signals, including Smad2, RhoA, ERK. Intriguingly, reduction of plasma fibronectin (pFN) in fibrotic livers was noted in MSC-treated mice. In vitro studies further demonstrated that suspending MSCs triggered pFN degradation, soluble pFN conversely retarded adhesion of suspending MSCs onto type I collagen-coated surface, whereas pFN coating enhanced WJ-MSC migration across mimicked wound bed. Moreover, pretreatment with soluble pFN and conditioned medium from MSCs with pFN strikingly attenuated the response of HSC-T6 cells to TGF-β1-stimulation in Smad2 phosphorylation and RhoA upregulation. Conclusion: These findings suggest that cytotherapy using WJ-MSCs may modulate hepatic pFN deposition for a better regenerative niche in the fibrotic livers and may constitute a useful anti-fibrogenic intervention in chronic liver diseases.

Linking an Anxiety-Related Personality Trait to Cardiac Autonomic Regulation in Well-Defined Healthy Adults: Harm Avoidance and Resting Heart Rate Variability

Lien-Cheng Kao,Yu-Wen Liu,Nian-Sheng Tzeng,Terry B. J. Kuo,San-Yuan Huang,Chuan-Chia Chang,Hsin-An Chang 대한신경정신의학회 2016 PSYCHIATRY INVESTIGATION Vol.13 No.4

ObjectiveaaAnxiety trait, anxiety and depression states have all been reported to increase risks for cardiovascular disease (CVD), possibly through altering cardiac autonomic regulation. Our aim was to investigate whether the relationship between harm avoidance (HA, an anxiety-related personality trait) and cardiac autonomic regulation is independent of anxiety and depression states in healthy adults. MethodsaaWe recruited 535 physically and mentally healthy volunteers. Participants completed the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Tri-dimensional Personality Questionnaire. Participants were divided into high or low HA groups as discriminated by the quartile value. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV). We obtained the time and frequency-domain indices of HRV including variance (total HRV), the low-frequency power (LF; 0.05–0.15 Hz), which may reflect baroreflex function, the high-frequency power (HF; 0.15–0.40 Hz), which reflects cardiac parasympathetic activity, as well as the LF/HF ratio. ResultsaaThe BDI and HA scores showed associations with HRV parameters. After adjustment for the BDI scores and other control variables, HA is still associated with reduced variance, LF and HF power. Compared with the participants with low HA, those with high HA displayed significant reductions in variance, LF and HF power and a significant increase in their LF/HF ratio. ConclusionaaThis study highlights the independent role of HA in contributing to decreased autonomic cardiac regulation in healthy adults and provides a potential underlying mechanism for anxiety trait to confer increased risk for CVD.

Validation of a Palliative Prognostic Index to Predict Life Expectancy for Terminally Ill Cancer Patients in a Hospice Consultation Setting in Taiwan

Cheng, Wei-Hong,Kao, Chen-Yi,Hung, Yu-Shin,Su, Po-Jung,Hsieh, Chia-Hsun,Chen, Jen-Shi,Wang, Hung-Ming,Chou, Wen-Chi Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Background: The aim of our study was to assess the practical utility of the palliative prognostic index (PPI) as a prognostic tool used by nurse specialists in a hospice consultation setting in Taiwan. Methods: In total, 623 terminal cancer patients under hospice consultation care from one medical center in northern Taiwan were enrolled between January 1 and June 30, 2011. PPI was assessed by a nurse specialist at first hospice consultation and patients categorized into groups by prognosis (good, intermediate, poor). Patient survival was analyzed retrospectively to determine significance of between-group differences. Results: By PPI sum score, 37.2% of patients were in the good prognosis group, 18% in the intermediate prognosis group and 44.8% in the poor prognosis group. The death rates were 56%, 81.2% and 89.6% and median survivals were 76, 18 and 7 days, respectively. The hazard ratio was 0.19 (95% confidence interval [CI] 0.10-0.24, p<0.001) for the poor versus good prognosis group and 0.54 (95% CI 0.43-0.69, p<0.001) for the poor versus intermediate prognosis group. The sensitivity and specificity for the poor prognosis group was 66% and 71%; the positive predictive value and negative predictive value were 81% and 52%, respectively, to predict patient death within 21 days (area under the curve of the receiver operating characteristic was 0.68). Conclusions: Assessment by PPI can accurately predict survival of terminal cancer patients receiving hospice consultation care. PPI is a simple tool and can be administered by nurse members of hospice consultation teams.

Equal Z standard-setting method to estimate the minimum number of panelists for a medical school’s objective structured clinical examination in Taiwan: a simulation study

Ying-Ying Yang,Pin-Hsiang Huang,Ling-Yu Yang,Chia-Chang Huang,Chih-Wei Liu,Shiau-Shian Huang,Chen-Huan Chen,Fa-Yauh Lee,Shou-Yen Kao,Boaz Shulruf 한국보건의료인국가시험원 2022 보건의료교육평가 Vol.19 No.-

Purpose Undertaking a standard-setting exercise is a common method for setting pass/fail cut scores for high-stakes examinations. The recently introduced equal Z standard-setting method (EZ method) has been found to be a valid and effective alternative for the commonly used Angoff and Hofstee methods and their variants. The current study aims to estimate the minimum number of panelists required for obtaining acceptable and reliable cut scores using the EZ method. Methods The primary data were extracted from 31 panelists who used the EZ method for setting cut scores for a 12-station of medical school’s final objective structured clinical examination (OSCE) in Taiwan. For this study, a new data set composed of 1,000 random samples of different panel sizes, ranging from 5 to 25 panelists, was established and analyzed. Analysis of variance was performed to measure the differences in the cut scores set by the sampled groups, across all sizes within each station. Results On average, a panel of 10 experts or more yielded cut scores with confidence more than or equal to 90% and 15 experts yielded cut scores with confidence more than or equal to 95%. No significant differences in cut scores associated with panel size were identified for panels of 5 or more experts. Conclusion The EZ method was found to be valid and feasible. Less than an hour was required for 12 panelists to assess 12 OSCE stations. Calculating the cut scores required only basic statistical skills.

Real-World Sustained Virologic Response Rates (SVR12) with Interferon (IFN)-Free Direct Acting Antiviral (DAA) Therapy in East Asia- Results from REAL-C (Real-World Effectiveness from the Asia Liver Consortium for Chronic Hepatitis C)

( Mindie H. Nguyen ),( Norihiro Furusyo ),( Dae Won Jun ),( Ming-Lung Yu ),( Jia-Horng Kao ),( Masaru Enomoto ),( Eiichi Ogawa ),( Etsuko Ilio ),( Chen-Hua Liu ),( Akihiro Tamori ),( Chia-Yen Dai ),( 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Since their recent introduction in Asia, IFN-free DAAs have revolutionized treatment of chronic hepatitis C across all HCV genotypes. However, experience from large and diverse routine clinical practice is still limited. The aim of this study was to report real-world outcomes from a large multinational co hort of East Asian HCV patients treated with IFN-free DAAs. Methods: Data were obtained using a required case report form from the REAL-C registry of patients who were initiated on IFN-free DAA therapy in routine practice and represented 10 study centers inclusive of 30 clinical sites in Hong Kong, Japan, Korea, and Taiwan. Cirrhosis was determined by liver biopsy, noninvasive tests (elastography/fibroscan, fibrotest), or the presence of clinical, radiologic, endoscopic, laboratory evidence of cirrhosis and/or portal hypertension. Results: A total of 3702 patients have been registered. Table 1 displays the patient characteristics. The average age was 63.6±12.8; 17.7% had diabetes, 8.7% had chronic renal impairment, 26% had cirrhosis (5.1% decompensated cirrhosis), and 5.4% had HCC at baseline or prior to DAA treatment initiation. The majority of patients were HCV GT1 (68.7%), followed by HCV GT2 (30.4%). Ten different DAA regimens were used, with the majority receiving LDV/SOF (43.7%), followed by SOF+RBV (27.8%). One-third were treatment experienced (24.8% with prior PEG-IFN+RBV, 4.5% with prior DAA). SVR12 overall rate was 96.6%. Significant decreases noted in all major liver enzymes at week 12 and 24 post treatment. No increase in creatinine noted across treatments; 3.2% stopped treatment and 13.4% had an adverse event with fatigue (5.6% in patients treated with RBV vs. 6.4% in those treated without RBV, P=0.61) and anemia (5.6%) the most reported. Table 2 displays SVR12 rates by cirrhosis and prior treatment status for the most commonly used DAA treatments for GT1 and GT2 patients. SVR12 rates were excellent ranging from 97.1% (95%CI: 94.1-98.8%) to 99.7% (95%CI: 99.0-99.9%) for GT1 patients treated with LDV/SOF who did not have cirrhosis regardless of prior treatment history and who were treatment-naive with cirrhosis but lower in the cirrhotic treatment-experienced group (92.2%; 95%CI: 86.7-95.9%) (P<0.0001). Sub-analysis results for GT1b were similar, with SVR12 99.7% for non-cirrhotic treatment-naive, 99.5% for non-cirrhotic treatment-experienced, 97.4% for cirrhotic treatment-naive, and 93.0% for cirrhotic treatment-experienced, (P<0.0001). For GT2 patients, SVR12 was excellent for all groups (96.8-98.0%) except for cirrhotic treatment-experienced patients (n=66) who experienced an SVR12 of 87.9% (95%CI: 77.5-94.6%) (P=0.002). Conclusions: HCV cure rates were high overall in the REALC cohort-LDV/SOF GT1 98%; SOF+RBV GT2 96% except for cirrhotic, treatment-experienced patients especially in GT2, suggesting alternative therapy is needed.

Nerve growth factor upregulates sirtuin 1 expression in cholestasis: a potential therapeutic target

Ming-Shian Tsai,Po-Huang Lee,Cheuk-Kwan Sun,Ting-Chia Chiu,Yu-Chun Lin,I-Wei Chang,Po-Han Chen,Ying-Hsien Kao 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression of NGF and its cognate receptors in human livers with hepatolithiasis and the effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile duct ligation (BDL) mouse model. Histopathological and molecular analyses showed that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis, compared with non-hepatolithiasis livers. In the BDL model without NGF therapy, p75NTR, but not TrkA antagonism, significantly deteriorated BDL-induced liver injury. By contrast, the hepatoprotective effect of NGF was abrogated only by TrkA and not by p75NTR antagonism in animals receiving NGF therapy. Intriguingly, a positive correlation between hepatic SIRT1 and NGF expression was found in human livers. In vitro studies demonstrated that NGF upregulated SIRT1 expression in mouse livers and human Huh-7 and rodent hepatocytes. Both NGF and proNGF induced protective effects against hydrogen peroxide-induced cytotoxicity in Huh-7 cells, whereas inhibition of TrkA and p75NTR activity prevented oxidative cell death. Mechanistically, NGF, but not proNGF, upregulated SIRT1 expression in human Huh-7 and rodent hepatocytes via nuclear factor (NF)-κB activity, whereas NGF-induced phosphoinositide-3 kinase/Akt, extracellular signal–regulated kinase and NF-κB signaling and SIRT1 activity were involved in its hepatoprotective effects against oxidative injury. These findings suggest that pharmacological manipulation of the NGF/SIRT1 axis might serve as a novel approach for the treatment of cholestatic disease.

Opportunities for 2-[18F] Fluoro-2-Deoxy-D-Glucose PET/CT in Cervical-Vaginal Neuroendocrine Carcinoma: Case Series and Literature Review

Yin Lin,Wan Y. Lin,Ji A. Liang,Yu Y. Lu,Hsin Y. Wang,Shih C. Tsai,Chia H. Kao 대한영상의학회 2012 Korean Journal of Radiology Vol.13 No.6

Objective: Neuroendocrine cervical carcinoma is a rare subtype of cervical cancer. These tumors exhibit an aggressive behavior with early regional lymph node and distant metastases. The purpose of our study was to describe five cases of neuroendocrine cervical-vaginal carcinoma and to discuss the potential of the 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan for the detection of this rare malignancy. Materials and Methods: Five cases of cervical-vaginal neuroendocrine tumor were retrospectively collected, during a two year (from September 2009 to August 2011) period in our hospital. The clinical staging distributions were International Federation of Gynecology and Obstetrics (FIGO) stage IB2 (1 of 5), stage IIA (3 of 5) and stage IVA (1 of 5). Results: Two cases (cases 1 and 4) were restaged after 18F-FDG PET/CT scan in the initial staging process. Post-treatment 18F-FDG PET/CT scans, in three patients, revealed positive findings for tumor recurrence or lymph node metastases. Two patients (cases 2 and 3) died of tumor within two years. Conclusion: 18F-FDG PET/CT scan is a useful tool in cervical-vaginal neuroendocrine tumor. In its initial staging, the 18F-FDG PET/CT scan may help assess the possible nodal involvement or early hematogeneous spreading. We can also use the 18F-FDG PET/CT to detect local recurrence and to evaluate the treatment response after clinical manipulation. Objective: Neuroendocrine cervical carcinoma is a rare subtype of cervical cancer. These tumors exhibit an aggressive behavior with early regional lymph node and distant metastases. The purpose of our study was to describe five cases of neuroendocrine cervical-vaginal carcinoma and to discuss the potential of the 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan for the detection of this rare malignancy. Materials and Methods: Five cases of cervical-vaginal neuroendocrine tumor were retrospectively collected, during a two year (from September 2009 to August 2011) period in our hospital. The clinical staging distributions were International Federation of Gynecology and Obstetrics (FIGO) stage IB2 (1 of 5), stage IIA (3 of 5) and stage IVA (1 of 5). Results: Two cases (cases 1 and 4) were restaged after 18F-FDG PET/CT scan in the initial staging process. Post-treatment 18F-FDG PET/CT scans, in three patients, revealed positive findings for tumor recurrence or lymph node metastases. Two patients (cases 2 and 3) died of tumor within two years. Conclusion: 18F-FDG PET/CT scan is a useful tool in cervical-vaginal neuroendocrine tumor. In its initial staging, the 18F-FDG PET/CT scan may help assess the possible nodal involvement or early hematogeneous spreading. We can also use the 18F-FDG PET/CT to detect local recurrence and to evaluate the treatment response after clinical manipulation.

Response to DAA in HCV Patients with HCC from East Asia: A REAL-C Study with Propensity Score Matching (PSM)

( Mindie H. Nguyen ),( Norihiro Furusyo ),( Dae Won Jun ),( Ming-Lung Yu ),( Jia-Horng Kao ),( Masaru Enomoto ),( Eiichi Ogawa ),( Etsuko Ilio ),( Chen-Hua Liu ),( Akihiro Tamori ),( Chia-Yen Dai ),( 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Reports suggest HCV-HCC patients do not respond as well to the IFN-free DAAs, but background risks and confounders for treatment failures may not have been adequately controlled. Our goal was to compare SVR12 of DAAs in East Asian patients with HCV-HCC to those without HCC using PSM to balance the HCC and non-HCC groups. Methods: Data were from 10 study centers comprising of 30 clinical sites in Hong Kong, Japan, Korea, and Taiwan representing the Real-World Evidence from the Asia Liver Consortium for Chronic Hepatitis C (REAL-C) - a registry of patients treated with IFN-free DAAs in routine practice (n=3702). 1:1 PSM matching on cirrhosis, prior treatment, baseline platelet, age, sex, baseline HCV RNA, treatment regimen, baseline ALT, HCV genotype, and BMI was used to balance the groups at baseline. Results: In our cohort, there were 195 patients with HCC at baseline or prior to DAA initiation and 3507 patients who did not have HCC at baseline. Prior to PSM, HCC patients were significantly older, more likely male, more likely to have renal insufficiency, cirrhosis, and decompensation (all P< 0.004). After PSM, there were 171 HCC and N=171 non-HCC patients for analysis. As shown in Table 1, there were no significant differences in the baseline characteristics between the matched HCC and non-HCC cohorts. The majority (51-55%) of both groups received LDV/SOF; eight (three HCC, five non-HCC) stopped treatment before completion while ~10-12% had an adverse reaction (most common: anemia [ >~5-6%] and fatigue [~3-5%]). There were seven deaths: five in the HCC group (four were liver-related) and two in the non-HCC group (both were non-liver-related). Overall, SVR12 rate was >96% for both groups with no significant differences. (Table 2) Conclusions: This PSM study compared treatment for HCV patients with/without HCC, finding no difference in treatment tolerability, completion, and cure rates.

EVOLUTION OF THE TIMES WHEN THE TRADITIONAL MATERIALS ENCOUNTER INTERACTIVE TECHNOLOGY

Chen-Wei Chiang,Min-Shiue Wu,Meng-Te Hsieh,Chia-Yu Kao,Chun-Yan Liu 한국디자인학회 2015 한국디자인학회 학술발표대회 논문집 Vol.2015 No.10

The Reflection of Bamboo combines traditional materials with interactive technology, analyzing what the characteristics of the old and new materials are, as well as how to apply technology to the integration of these materials. Through this installation, we reconsider the possibility of integrating traditional materials with modern technology. Adopting bamboo as the main material, this installation raises the spirit of traditional techniques in a unique way and employs bamboo’s special tenacity. Viewers can interact with this installation and experience the strength, esthetics and variation in the demonstrated shadow.