Time-degenerative Factors and the Risk of Hepatocellular Carcinoma after Antiviral Therapy among HCV Patients: A Model for Prioritization of Treatment

( Ming-lung Yu ),( Chung-feng Huang ),( Ming-lun Yeh ),( Jee-fu Huang ),( Chia-yen Dai ),( Wan-long Chuang ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Age and hepatic fibrosis are the factors that increase the risk of hepatocellular carcinoma (HCC) over time. We aimed to explore their impac at the initiation of antiviral therapy on HCC among chronic hepatitis C (CHC) patients. Methods: A total of 1281 biopsy-proven CHC patients receiving interferon- based therapy were followed for a mean period of 5.5 years. Results: The 5-year cumulative incidence of HCC did not differ between non-SVR and SVR patients who were <40 years old (7.7 % vs. 0.5%, P=0.1), but was significantly higher in non-SVR patients between 40 and 55 years old (18.0% vs. 1.3%, P<0.001) and >55 years old (15.1% vs. 7.9%, P=0.03). Compared with SVR, non-SVR was independently predictive of HCC in patients 40-55 years old (hazard ratio [HR]/95% confidence intervals [CI]: 10.92/3.78-31.56, P<0.001) and >55 years old (HR/CI: 1.96/1.06-3.63, P=0.03) but not in patients <40 years old (HR/CI: 2.76/0.41-18.84, P=0.3). The 5-year cumulative incidence of HCC did not differ between non-SVR and SVR patients whose fibrosis stage was F0-1 (4.6% vs. 1.9%, P=0.25) but was higher in non-SVR patients with F2-3 (21.4% vs. 4.3%, P<0.001) or F4 (33.5% vs. 8.4%, P=0.002). Compared with SVR, non-SVR was independently predictive of HCC in patients with F2-3 (HR/CI: 4.36 /2.10-9.03, P<0.001) and F4 (HR/CI: 3.84/1.59-9.30, P=0.03) but not in those with F0-1 (HR/CI: 1.53/ 0.49-4.74, P=0.47). Conclusions: Delayed HCV clearance for patients with CHC > 40 years old or with a fibrosis stage > 2 increases the risk of HCC over time.

Synthesis and Characterization of Folic Acid Labeled Upconversion Fluorescent Nanoprobes for in vitro Cancer Cells Targeted Imaging

Ming Huang,Lijun Wang,Xiaojuan Zhang,Jin Zhou,Lihua Liu,Yuefang Pan,Bin Yu,ZHANGSEN YU 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2017 NANO Vol.12 No.5

Upconversion nanoparticles (UCNPs) are widely used in the field of biomedicine, such as biosensing, cell labeling and medical multimodal imaging because of their unique optical properties. In this paper, we demonstrated the synthesis of polyethylenimine-modified NaLuF4:Yb,Er (RE = Lu 0.78, Yb 0.18, Er 0.02) UCNPs in three different solvents, such as water, ethylene glycol and diethylene glycol. The as-prepared UCNPs were characterized and the experimental results showed that the UCNPs synthesized in ethylene glycol had excellent properties. The obtained UCNPs in ethylene glycol had the smallest particle size and uniform size distribution, and the pure cubic phase of crystallization and Dynamic light scattering and particle dispersion index (DLS/Pdi) were the smallest. What's more, the upconversion fluorescence intensity was 7 and 52 times greater than that of UCNPs synthesized in diethylene glycol and water, respectively. In addition, the factors of reaction solvent that had an impact on the particle size, morphology, crystalline phase, DLS and upconversion fluorescence intensity of the synthesized UCNPs were discussed. Moreover, in order to obtain the targeted nanoprobe, we used an EDC/NHS covalent coupling method to modify folic acid to the NaLuF4:Yb,Er/PEI UCNP surface. The NaLuF4:Yb, Er/PEI–FA upconversion fluorescent nanoprobes had low cytotoxicity and were suitable for the application in HeLa cells targeted fluorescent imaging.

The association between acupuncture therapy and the risk of reduced pressure ulcers in dementia patients: a retrospective matched cohort study

Huang Chia-Yu,Wu Mei-Yao,Huang Ming-Cheng,Yu Teng-Shun,Yen Hung-Rong 한국한의학연구원 2023 Integrative Medicine Research Vol.12 No.3

Background: The pressure ulcer is a complication from dementia. The aim of this study is to study the association between the developing of pressure ulcers and the use of acupuncture therapy in patients with dementia. Methods: We performed a retrospective 1:1 propensity score-matched cohort study to investigate the association between acupuncture therapy and the risk of pressure ulcers in patients with dementia. Results: A total of 8,994 patients were identified, 237 patients in the acupuncture cohort and 362 patients in the no-acupuncture cohort developed pressure ulcers. A reduced cumulative incidence of pressure ulcers was observed in the acupuncture cohort (P < .001). The association between acupuncture and reducing the incidence of pressure ulcers was not affected by sex, age, residence, income, or comorbidities. The variables of etiologies to cause dementia did not change the final result. In the subgroups analyses, the patients without medication for dementia controlling had significant lower rate of pressure ulcers development when they had accepted acupuncture therapy (log-rank test, P <.001). Conclusion: Our results revealed the association between acupuncture therapy and a reduced incidence of pressure ulcer development in patients with dementia. This finding offers important ideas for further research.

Serial Serum MHC Class I Chain-Related a Levels in Predicting Hepatocellular Carcinoma in Chronic Hepatitis C Patients with Curative Antiviral Treatment

( Ming Lung Yu ),( Chung-feng Huang ),( Chia-yen Dai ),( Jee-fu Huang ),( Wan-long Chuang ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: MHC class I chain-related A (MICA) genetic variants and its serum level (sMICA) were associated with hepatitis C virus (HCV) related hepatocellular carcinoma (HCC) in untreated cohorts. The dynamic changes of serial sMICA levels regarding anti-HCV treatment and consequent HCC development is elusive. Methods: Single nucleotide polymorphism rs2596542 of MICA and serial sMICA levels were tested in chronic hepatitis C (CHC) patients with sustained virological response after antiviral treatment. Forty-two patients who developed HCC and another 84 age-, sex- and cirrhosis-propensity score matched non-HCC controls were compared. Serial sMICA levels were measured at three-time points: within 6 months of pretreatment (pre-sMICA), 6 months after the end of treatment (post-sMICA) and last visit before HCC occurrence or not (last-sMICA). Results: Compared to patients without HCC occurrence, those with HCC had lower platelet counts, higher levels of post-sMICA (197.4+398.0 pg/mL vs. 57.6+89.6 pg/mL, P=0.03) and last-sMICA (320.4+508.4 pg/mL vs. 37.7+140.2 pg/mL, P<0.001). Cox regression analysis revealed that last-sMICA is the only factor predictive of HCC development (hazard ratio [HR]/ 95 % confidence intervals [CI.]: 2.27 (per 1 log pg/mL increase)/1.672-3.082, P<0.001). Patients without HCC had a significantly decreased trend of sMICA levels during follow-up (trend P=0.001). In contrast, HCC patients had an increased trend of sMICA levels (trend P=0.024). MICA rs2596542 GG genotype carriers without HCC had a significantly decreased trend of sMICA levels during follow-up (trend P<0.001). However, HCC patients who carried GG genotype had a substantially increased trend of sMICA levels (trend P=0.06). Nevertheless, both trends were not observed in A allele carriers with or without HCC development. t three-time points: within 6 months of pretreatment (pre-sMICA), 6 months after the end of treatment (post-sMICA) and last visit before HCC occurrence or not (last-sMICA). Conclusions: Serial sMICA levels could serve as a surrogate marker for HCC development in CHC patients with SVR. The clinical utility is restricted to MICA rs2596542 GG genotype carriers. CA (320.4+508.4 pg/mL vs. 37.7+140.2 pg/mL, P<0.001). Cox regression analysis revealed that last-sMICA is the only factor predictive of HCC development (hazard ratio [HR]/ 95 % confidence intervals [CI.]: 2.27 (per 1 log pg/mL increase)/1.672-3.082, P<0.001). Patients without HCC had a significantly decreased trend of sMICA levels during follow-up (trend P=0.001). In contrast, HCC patients had an increased trend of sMICA levels (trend P=0.024). MICA rs2596542 GG genotype carriers without HCC had a significantly decreased trend of sMICA levels during follow-up (trend P<0.001). However, HCC patients who carried GG genotype had a substantially increased trend of sMICA levels (trend P=0.06). Nevertheless, both trends were not observed in A allele carriers with or without HCC development. t three-time points: within 6 months of pretreatment (pre-sMICA), 6 months after the end of treatment (post-sMICA) and last visit before HCC occurrence or not (last-sMICA).

Efficacy and Safety of 12 Weeks of Daclatasvir, Asunaprevir Plus Ribavirin for the Treatment of HCV Genotype 1b Infection without Baseline NS5A Resistance-Associated Variants (DARING)-Interim Report

( Ming-lung Yu ),( Chao-hung Hung ),( Yi-hsiang Huang ),( Cheng-yuan Peng ),( Chun-yen Lin ),( Pin-nan Cheng ),( Rong-nan Chien ),( Shih-jer Hsu ),( Chen-hua Liu ),( Jee-fu Huang ),( Chung-feng Huang 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The current study aims to elucidate the treatment efficacy (defined as undetectable HCV RNA throughout 12 weeks of post-treatment follow-up, SVR12) and safety DCV/ASV plus ribavirin for 12 weeks in HCV-1b patients without NS5A RAS. Methods: This is a single-arm, open-label phase 2 study. Seventy directly acting antivirals (DAA)-naïve HCV-1b patients without L31/Y93 RAS are planned to receive daclatasvir (60 mg/ day) and asunaprevir (100 mg twice daily) plus weight-based ribavirin (1000-1200 mg/day) for 12 weeks. After treatment they were followed up for 12 weeks. Results: As of 31 Oct 2017, 58 eligible patients are allocated to treatment, with a mean age of 59.3 years and female predominance (67.2%, 39/58). The mean HCV RNA was 5.87+0.77 log10 IU/mL; 23 patients (39.7 %) had significant hepatic fibrosis (>F2). In the modified intention-to-treat analysis, the rate of undetectable HCV at week 1, week 2, week 4, week 8 and endof- treatment was 25 % (14/56), 84.8 % (39/46), 100 % (46/46), 100 % (38/38) and 100 % (27/27), respectively. Undetectable HCV RNA were observed in all of the patients with HCV RNA assessable 4 weeks (SVR4, 18/18) and 12 weeks (SVR12, 12/12) post treatment. None of the 18 patients who completed the 12-week treatment experienced relapse during post-treatment follow-up. The most common adverse event was fatigue (78.3 %), followed by pruritus (65.2 %) and dizziness (52.2 %), of which were considered as ribavirin related. None of the participating subjects withdrew treatment or follow-up throughout the trial peroid. Three serious adverse events were reported which included urosepsis, appendicitis and left ureteral stone. All were unrelated to the investigating drugs. Conclusions: 12 weeks of DCV/ASV plus ribavirin was highly effective and safe in HCV-1b patients without NS5A RAS in the interim analysis. The satisfactory results would be anticipated in the full patient set.

Validation of the Chinese Version of Penn Alcohol Craving Scale for Patients With Alcohol Use Disorder

Yu-Yu Ko,Su-Chen Fang,Wei-Chien Huang,Ming-Chyi Huang,Hu-Ming Chang 대한신경정신의학회 2024 PSYCHIATRY INVESTIGATION Vol.21 No.2

Objective The Penn Alcohol Craving Scale (PACS) is a five-item, single-dimension questionnaire that is used to measure a patient’s alcohol craving. We sought to develop the Chinese version of the PACS (PACS-C) and assess its reliability and validity.Methods A total of 160 Taiwanese patients with alcohol use disorder were enrolled in this study. The internal consistency and concurrent validity of the PASC-C with the visual analogue scale (VAS) for craving, the Yale–Brown Obsessive Compulsive Scale for heavy drinking (YBOCS-hd), and the Severity of Alcohol Dependence Questionnaire (SADQ) were assessed. The test–retest reliability of the PASC-C was evaluated 1 day after the baseline measurements. Confirmatory factor analysis (CFA) was performed to examine the psychometric properties of the PACS-C.Results The PACS-C exhibited good internal consistency (Cronbach’s α=0.95) and test–retest reliability (r=0.97). This scale showed high correlations with the VAS (r=0.81) and YBOCS-hd (r=0.81 and 0.79 for the obsession and compulsion subscales, respectively), and moderate correlation with the SADQ-C (r=0.47). Furthermore, CFA results revealed that the PACS-C had good fit indices under various models.Conclusion The PACS-C appears to be a reliable and valid tool for assessing alcohol craving in patients with alcohol use disorder in Taiwan.

Transcriptome analysis of differentially expressed genes in rabbits’ ovaries by digital gene-expression profiling

Tao Huang,Ya‑dong Wang,Ming‑ming Xue,Xue Feng,Cai‑Xia Sun,An‑si Wang,Shu‑yu Xie,Meng Zhang,Gui‑Rong Sun,Ming Li 한국유전학회 2018 Genes & Genomics Vol.40 No.7

Reproduction is a complex physiological process that is regulated by multiple genes and pathways. Compared with studies of common livestock, fewer studies of genes related to the fertility of rabbits (Oryctolagus cuniculus) have been reported, and the molecular mechanism of their high productivity is still poorly understood. To identify candidate genes associated with development and prolificacy in rabbits, we analyzed gene expression differences among the ovaries of mature Californian rabbit (LC), and mature (HH) and immature Harbin white rabbit (IH) using digital gene expression technology. We detected 885 and 321 genes that were significantly differentially expressed in comparisons between HH/IH and HH/LC, respectively. The functions of the differentially expressed genes (DEGs) were determined by GO classification and KEGG pathway analysis. The results suggest that most of the DEGs between the mature and immature developmental stages were predominantly associated with DNA replication, cell cycle, and progesterone-mediated oocyte maturation, and most were up-regulated in the IH group compared with the HH group. The DEGs involved in disparate fecundities between HH and LC were associated with reproduction, fructose and mannose metabolism, steroid hormone biosynthesis, and pyruvate metabolism. Our results will contribute to a better understanding of changes in the regulatory network in ovary at different developmental stages and in different fertility of rabbit.

Management of Hyperacute Stroke during the Coronavirus Disease of 2019 Pandemic: The Modified Code Stroke in a Medical Center in Taiwan

Po-Yu Lin,Yu-Ming Chang,Chih-Yuan Huang,Chih-Hao Lin,Ming-Tsung Chuang,Po-Lin Chen,Pi-Shan Sung,Chih-Hung Chen 대한뇌졸중학회 2020 Journal of stroke Vol.22 No.2

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The tyrosine kinase inhibitor nintedanib activates SHP-1 and induces apoptosis in triple-negative breast cancer cells

Chun-Yu Liu,Tzu-Ting Huang,Pei-Yi Chu,Chun-Teng Huang,Chia-Han Lee,Wan-Lun Wang,Ka-Yi Lau,Wen-Chun Tsai,Tzu-I Chao,Jung-Chen Su,Ming-Huang Chen,Chung-Wai Shiau,Ling-Ming Tseng,Kuen-Feng Chen 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.

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.