Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis

( Chen-hua Liu ),( Chi-yi Chen ),( Wei-wen Su ),( Chun-jen Liu ),( Ching-chu Lo ),( Ke-jhang Huang ),( Jyh-jou Chen ),( Kuo-chih Tseng ),( Chi-yang Chang ),( Cheng-yuan Peng ),( Yu-lueng Shih ),( Chia 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.4

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR₁₂) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. The safety profiles were reported. Results: The SVR₁₂ rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5-94.2%), 94.1% (95% CI, 87.8-97.3%), and 100% (95% CI, 96.2-100%). Number of patients who failed to achieve SVR₁₂ were attributed to virologic failures. The SVR₁₂ rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR₁₂, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16-14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 ㎡/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 ㎡/month; P<0.001). Conclusions: SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis. (Clin Mol Hepatol 2021;27:575-588)

Relationship between mitochondria DNA deletion of cumulus cells and embryo development during IVF/ICSI

( Yu Ching Chen ),( Horng Der Tsai ),( Jia Ni Hsieh ),( Chuan Mu Chen ),( Chin San Liu ) 대한산부인과학회 2007 대한산부인과학회 학술대회 Vol.93 No.-

Effectiveness of Virtual Reality Interactive Play for Children During Intravenous Placement: A Randomized Controlled Trial

Hsu Mei-Feng,Whu Yew-Wha,Lin I-Chen,Liu Chieh-Yu,Lai Fei-Chen,Liu Pei-Ching,Chen Chi-Wen 한국간호과학회 2022 Asian Nursing Research Vol.16 No.2

Purpose This study aimed to evaluate the effectiveness of an interactive virtual reality (VR) play intervention including instructional play and emotional catharsis play sessions in reducing children's pain and fear during intravenous placement. Methods A randomized controlled trial with parallel groups was conducted. The sample consisted of 134 hospitalized children aged 6–12 years (intervention group: n = 69; comparison group: n = 65). The intervention involved one immersive intravenous scene in VR before the actual intravenous placement and one emotional catharsis VR play after injection. The comparison group received an educational photo book about intravenous placement before receiving intravenous placement. The children and their caregivers rated their pain and fear by using the Wong–Baker FACES Pain Rating Scale and the Children's Fear Scale. The time required for successful intravenous insertion was also compared between the two groups. Results Children's pain (p = .028) and fear scores (p = .004) were significantly lower in the intervention group than in the comparison group. Their caregivers' pain and fear scores (both p < .001) were significantly lower in the intervention group. The time required for successful intravenous insertion did not differ significantly between the intervention and comparison groups. Conclusions The interactive play intervention with VR effectively reduced children's levels of pain and fear during the intravenous placement procedure. The results of this study can serve as a reference for the implementation of a feasible, child-friendly care practice for clinical intravenous placement in school-aged children.

Platelet-Derived Growth Factor Receptor-α Subunit Targeting Suppresses Metastasis in Advanced Thyroid Cancer In Vitro and In Vivo

( Ching-ling Lin ),( Ming-lin Tsai ),( Yu-hsin Chen ),( Wei-ni Liu ),( Chun-yu Lin ),( Kai-wen Hsu ),( Chien-yu Huang ),( Yu-jia Chang ),( Po-li Wei ),( Shu-huey Chen ),( Li-chi Huang ),( Chia-hwa Lee 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.5

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

Abstract title: Using 2-phase Image Learning to Improve the Competency of First-aid Management for Nurses

Wan-Ching Huang,Tzu-Ping Liu,Wan-Chen Li,Chia-Lun Lee 한국간호과학회 2019 한국간호과학회 학술대회 Vol.2019 No.10

Slide Session : OS-CAD-06 ; Cardiology : Erythrocytosis Increased One-Year Mortality in Patients with St-Segment Elevation Myocardial Infarction Un-dergoing Primary Percutaneous Coronary Intervention

( Cheng Wei Liu ),( Yi Ching Lin ),( Chung Ming Tu ),( Pen Chih Liao ),( Kuan Change Chen ),( Yen Wen Wu ) 대한내과학회 2014 대한내과학회 추계학술발표논문집 Vol.2014 No.1

Background: Anemia is associated with poor prognosis in patients with ST-segment elevation myocardial infarction(STEMI). However, it is unclear that erythrocytosis has protective effect in these populations. Hence, we conducted a retrospective cohort study to examine the relationship between erythrocytosis and mortality in patients with STEMI undergoing primary percutaneous coronary intervention (PCI ). Materials and Methods: We screened 1,156 consecutive patients with STEMI undergoing primary PCI in a single center during Feb 2007 and January 2012. There were 201 missing data for door-to-balloon time and 4 missing data for hemoglobin. Of 951 analyzable patients, they were divided into anemia (Hemoglobin<13.0mg/dl in men or <12.0mg/dl in women), normal hemoglobin, and erythrocytosis (hemoglobin =16.0mg/dl in men or =15.0mg/dl in women) groups. The study end point was one-year mortality. Results: There were 148, 535, and 268 patients in anemia, normal hemoglobin, and erythrocytosis groups, respectively. Patients in the anemia group were older and had lower body mass index than other two groups. There was more female, smokers, hypertension, and diabetes in the anemia group. One-year mortality rates were 16.2%, 6.5%, 2.6% (P<0.001) respectively. In univariate proportional hazards regression analysis, age, hemoglobin, total cholesterol, statin use, glycoprotein llb/llla inhibitor use, and TIMI risk score were associated with 1-year mortality in three groups. After adjustment for potential confounders, hemoglobin levels remained an independent predictor of one-year mortality in both anemia (hazard ratio 0.697, 95% CI 0.528-0.960) and erythrocytosis group (hazard ratio 3.129, 95% CI 1.1.474-6.642). Conclusions: Patients with STEMI and anemia had the worst outcomes than normal hemoglobin and erythrocytosis groups. Expectedly, hemoglobin had the protective effect on prognosis in anemia group. However, a hemoglobin level was an independent risk factor of one-year mortality in those with erythrocytosis.

The role of the genomic mutation signature and tumor mutation burden on relapse risk prediction in head and neck squamous cell carcinoma after concurrent chemoradiotherapy

Wang Hui-Ching,Moi Sin-Hua,Chan Leong-Perng,Wu Chun-Chieh,Du Jeng-Shiun,Liu Pei-Lin,Chou Meng-Chun,Wu Che-Wei,Huang Chih-Jen,Hsiao Hui-Hua,Pan Mei-Ren,Chen Li-Tzong 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Personalized genetic profiling has focused on improving treatment efficacy and predicting risk stratification by identifying mutated genes and selecting targeted agents according to genetic testing. Therefore, we evaluated the role of genetic profiling and tumor mutation burden (TMB) using next-generation sequencing in patients with head and neck squamous cell carcinoma (HNSC). The relapse mutation signature (RMS) and chromatin remodeling mutation signature (CRMS) were explored to predict the risk of relapse in patients with HNSC treated with concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy. Patients in the high RMS and CRMS groups showed significantly shorter relapse-free survival than those in the low RMS and CRMS groups, respectively (p < 0.001 and p = 0.006). Multivariate Cox regression analysis showed that extranodal extension, CCRT response, and three somatic mutation profiles (TMB, RMS, and CRMS) were independent risk predictors for HNSC relapse. The predictive nomogram showed satisfactory performance in predicting relapse-free survival in patients with HNSC treated with CCRT.

Doxorubicin Promotes Migration and Invasion of Breast Cancer Cells through the Upregulation of the RhoA/MLC Pathway

Chien-Liang Liu,Ming-Jen Chen,Jiunn-Chang Lin,Chi-Hsin Lin,Wen-Chien Huang,Shih-Ping Cheng,Shan-Na Chen,Yuan-Ching Chang 한국유방암학회 2019 Journal of breast cancer Vol.22 No.2

Purpose: Cancer cells develop acquired resistance induced by chemotherapeutic drugs. In this study, we investigated the effects of brief treatment with cytotoxic drugs on the phenotype of breast cancer cells. Methods: Breast cancer cells MCF7 and BT-474 were briefly treated with paclitaxel or doxorubicin. Clonogenic, migration, and invasion assays were performed on the treated cells. Western blot analysis and RhoA activity assay were also performed. Results: Breast cancer cells when briefly treated with paclitaxel or doxorubicin showed reduced clonogenic ability. Doxorubicin, but not paclitaxel, augmented cell migration and invasion. The invasion-promoting effects of doxorubicin were lost when the two drugs were sequentially used in combination. Myosin light chain (MLC) 2 phosphorylation and RhoA activity were upregulated by doxorubicin and downregulated by paclitaxel. Pretreatment with RhoA inhibitors abolished the migration- and invasion-promoting effects of doxorubicin. Conclusion: Doxorubicin activates the RhoA/MLC pathway and enhances breast cancer cell migration and invasion. Therefore, this pathway might be explored as a therapeutic target to suppress anthracycline-enhanced tumor progression.

GROUND OBSERVATIONS OF SPRITES AND OTHER TLES IN TAIWAN

WANG YUN-CHING,HSU RUE-RON,SU HAN-TZONG,CHEN ALFRED BING-CHIH,LEE YI-JEN,KUO CHENG-LING,TSAY WEAN-SHUN,CHANG CHAN-KAO,WANG SHI-CHUN,LEE LOU-CHUANG,LIU TIE-YUE The Korean Astronomical Society 2005 Journal of The Korean Astronomical Society Vol.38 No.2

Sprites, elves and blue jets are collectively denominated as the upper atmospheric transient luminous events (TLEs). They are recently discovered optical flashes between active thunderstorms and the ionosphere. In this report, a brief introduction to the most important characteristics of TLEs is given. Since 2001, scientists from the National Cheng Kung University have been performing yearly summer campaigns from various locations in Taiwan. The main achievements of their yearly campaign are presented.

Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

Wheeler, Eleanor,Leong, Aaron,Liu, Ching-Ti,Hivert, Marie-France,Strawbridge, Rona J.,Podmore, Clara,Li, Man,Yao, Jie,Sim, Xueling,Hong, Jaeyoung,Chu, Audrey Y.,Zhang, Weihua,Wang, Xu,Chen, Peng,Marut Public Library of Science 2017 PLoS medicine Vol.14 No.9

<▼1><P><B>Background</B></P><P>Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.</P><P><B>Methods & findings</B></P><P>Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (<I>N</I> = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04–1.06, per HbA1c-raising allele, <I>p</I> = 3 × 10<SUP>−29</SUP>); whereas GS-E was not (OR = 1.00, 95% CI 0.99–1.01, <I>p</I> = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked <I>G6PD</I> G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66–0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38–0.97) in homozygous women. The <I>G6PD</I> variant may cause approximately 2% (<I>N</I> = 0.65 million, 95% CI 0.55–0.74) of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.</P><P><B>Conclusions</B></P><P>As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the <I>G6PD</I> genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where <I>G6PD</I> deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.</P></▼1><▼2><P>Ines Barroso and colleagues identify a genetic variant that leads to reduced levels of HbA1c in African American adults; 2% of this population are at risk of missed diagnosis for diabetes.</P></▼2><▼3><P><B>Author summary</B></P><P><B>Why was this study done?</B></P><P>Blood glucose binds in an irreversible manner to circulating hemoglobin in red blood cells (RBCs), generating “glycated hemoglobin,” called HbA1c. HbA1c is used to diagnose and monitor diabetes.</P><P>Previous large-scale human genetic studies have demonstrated that HbA1c is influenced by genetic variants. Some vari