Oxygen-loaded microbubble-mediated sonoperfusion and oxygenation for neuroprotection after ischemic stroke reperfusion

Yi‑Ju Ho,Hsiang‑Lung Cheng,Lun‑De Liao,Yu‑Chun Lin,Hong‑Chieh Tsai,Chih‑Kuang Yeh 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background Ischemic stroke-reperfusion (S/R) injury is a crucial issue in the protection of brain function after thrombolysis. The vasodilation induced by ultrasound (US)-stimulated microbubble cavitation has been applied to reduce S/R injury through sonoperfusion. The present study uses oxygen-loaded microbubbles (OMBs) with US stimulation to provide sonoperfusion and local oxygen therapy for the reduction of brain infarct size and neuroprotection after S/R. Methods The murine S/R model was established by photodynamic thrombosis and thrombolysis at the remote branch of the anterior cerebral artery. In vivo blood flow, partial oxygen pressure ( pO2), and brain infarct staining were examined to analyze the validity of the animal model and OMB treatment results. The animal behaviors and measurement of the brain infarct area were used to evaluate long-term recovery of brain function. Results The percentage of blood flow was 45 ± 3%, 70 ± 3%, and 86 ± 2% after 60 min stroke, 20 min reperfusion, and 10 min OMB treatment, respectively, demonstrating sonoperfusion, and the corresponding pO2 level was 60 ± 1%, 76 ± 2%, and 79 ± 4%, showing reoxygenation. After 14 days of treatment, a 87 ± 3% reduction in brain infarction and recovery of limb coordination were observed in S/R mice. The expression of NF-κB, HIF-1α, IL-1β, and MMP-9 was inhibited and that of eNOS, BDNF, Bcl2, and IL-10 was enhanced, indicating activation of anti-inflammatory and anti-apoptosis responses and neuroprotection. Our study demonstrated that OMB treatment combines the beneficial effects of sonoperfusion and local oxygen therapy to reduce brain infarction and activate neuroprotection to prevent S/R injury.

The effect of diabetes and prediabetes on the prevalence, complications and mortality in nonalcoholic fatty liver disease

Cheng Han Ng,Kai En Chan,Yip Han Chin,Rebecca Wenling Zeng,Pei Chen Tsai,Wen Hui Lim,Darren Jun Hao Tan,Chin Meng Khoo,Lay Hoon Goh,Zheng Jye Ling,Anand Kulkarni,Lung-Yi Loey Mak,Daniel Q Huang,Mark C 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.3

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is closely associated with diabetes. The cumulative impact of both diseases synergistically increases risk of adverse events. However, present population analysis is predominantly conducted with reference to non-NAFLD individuals and has not yet examined the impact of prediabetes. Hence, we sought to conduct a retrospective analysis on the impact of diabetic status in NAFLD patients, referencing non-diabetic NAFLD individuals. Methods: Data from the National Health and Nutrition Examination Survey 1999–2018 was used. Hepatic steatosis was defined with United States Fatty Liver Index (US-FLI) and FLI at a cut-off of 30 and 60 respectively, in absence of substantial alcohol use. A multivariate generalized linear model was used for risk ratios of binary outcomes while survival analysis was conducted with Cox regression and Fine Gray model for competing risk. Results: Of 32,234 patients, 28.92% were identified to have NAFLD. 36.04%, 38.32% and 25.63% were non-diabetic, prediabetic and diabetic respectively. Diabetic NAFLD significantly increased risk of cardiovascular disease (CVD), stroke, chronic kidney disease, all-cause and CVD mortality compared to non-diabetic NAFLD. However, prediabetic NAFLD only significantly increased the risk of CVD and did not result in a higher risk of mortality. Conclusions: Given the increased risk of adverse outcomes, this study highlights the importance of regular diabetes screening in NAFLD and adoption of prompt lifestyle modifications to reduce disease progression. Facing high cardiovascular burden, prediabetic and diabetic NAFLD individuals can benefit from early cardiovascular referrals to reduce risk of CVD events and mortality.

Sofosbuvir/Ledipasvir in the Treatment of Chronic Hepatitis C - A Subgroup Analysis from A Nationwide Real-World HCV Registry Program (TACR) in Taiwan

( Ming-Lung Yu ),( Chi-Yi Chen ),( Kuo-Chih Tseng ),( Ching-Chu Lo ),( Pin-Nan Cheng ),( Cheng-Yuan Peng ),( Ming-Jong Bair ),( Chih-Lang Lin ),( Chi-Ming Tai ),( Chi-Chieh Yang ),( Chih-Wen Lin ),( C 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: TASL HCV Registry (TACR) is a nationwide registry program organized and supervised by Taiwan Association for the Study of the Liver (TASL), which aims to setup the database and biobank of patients with chronic hepatitis C (CHC) in Taiwan. The present study aimed to evaluate the treatment outcome of sofosbuvir (SOF)/ledipasvir (LDV) in Taiwanese CHC patients in TACR. Methods: By May 2020, 19 tertiary hospitals, 23 community hospitals and one primary care clinic join the TACR program. The baseline characteristics, prior liver and non-liver related medical history, DAA regimens, laboratory results, treatment course and outcome were recorded. The primary objective was sustained virological response, defined as undetectable HCV RNA 3 months after end-of-treatment (SVR12). Results: A total of 4742 SOF/LDV+ ribavirin treated CHC patients with available SVR12 data from 39 sites were enrolled in the current analysis. The mean age was 61.3 years, and female accounted for 54.8% of the population. The dominant viral genotypes were GT1b (52.6%) and GT2 (35.6%). 1354 (28.6%) patients had liver cirrhosis, including 156 (3.3%) with liver decompensation, 552 (11.6%) had preexisting hepatocellular carcinoma (HCC) before DAAs treatment and 413 (8.7%) had hepatitis B virus dual infections. The overall SVR12 rate was 98.5%, with 98.5%, 98.2%, 99.7% and 98.6% in treatment- naïve non-cirrhotics, treatment-naïve cirrhotics, treatment- experienced non-cirrhotics and treatment-experienced cirrhotics patients, respectively. While patients were stratified by HCV genotype, the SVR12 was 98.5%, 98.4% and 98.5% among those with GT1, GT2 and GT6 infection, respectively. The strongest factor independent associated with treatment failure was DAA adherence < 60% (odds ratio [OR]/95% confidence intervals [CI]: 125.4/25.7-612.4, P<0.0001), followed by active HCC (OR/CI: 6.20/2.57-14.97, P<0.0001), HIV co-infection (OR/CI: 3.01/1.14-7.92, P=0.026), and male gender (OR/ CI: 1.85/1.09-3.13, P=0.023). The eGFR decreased significantly at the end of treatment (EOT) (89.3 ml/min/1.73㎡ vs. 93.2 ml/min/1.73㎡, P< 0.001) and remained stable 3 months after EOT (89.3 ml/min/1.73㎡). However, the decreased eGFR was observed only in patients whose baseline eGFR > 90 ml/ min/1.73㎡. Instead, patients with chronic kidney diseases whose pretreatment eGFR < 60 ml/min/1.73㎡ had improved eGFR after SOF/LDV. Conclusions: SOF/LDV is highly effective in treating CHC patients in real-world setting of Taiwan. The satisfactory result could be explicitly generalized to patients with different viral genotypes and liver disease severities.

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.

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.

Which is more influential on teaching practice, classroom management efficacy or instruction efficacy? Evidence from TALIS 2018

Robin Jung-Cheng Chen,Hsin-Chih Lin,Yi-Lung Hsueh,Chuan-Chung Hsieh 서울대학교 교육연구소 2020 Asia Pacific Education Review Vol.21 No.4

This study aims to explore relationship between teacher self-efficacy and teacher teaching practice in junior high schools at Taiwan. TALIS (2018) survey database is adopted, and 3106 teachers were analyzed in this research. Through literature review and exploratory factor analysis (EFA), the research model is assumed to include two constructs (classroom management efficacy and instruction efficacy) in teacher self-efficacy, and three constructs (clarity of instruction practice, cognitive activation practice, and classroom management practice) in teacher teaching practice. Through the analysis of Structural Equation Modeling (SEM), the main findings are as follows. (1) For clarity of instruction practice, instruction efficacy has more positive influences than classroom management efficacy. (2) For classroom management practice, classroom management efficacy as more positive influences than instruction efficacy. (3) For cognitive activation practice, instruction efficacy has positive influences but classroom management efficacy has negative influences.

Species-specific primers in multiplex PCR for Bactrocera minax identification using an internal transcribed spacer

Regmi Prakriti,Tsai Cheng-Lung,Lin Ming-Ying,Chuang Yi-Yuan,Yeh Wen-Bin 한국응용곤충학회 2023 Journal of Asia-Pacific Entomology Vol.26 No.4

Bactrocera minax (Enderlein), commonly known as the Chinese citrus fly, is a citrus pest native to China and nearby countries. B. minax can cause substantial losses in citrus orchards. B. minax can be spread to countries free from it by the global trade of citrus and by travelers carrying citrus. Timely, convenient, and accurate identi fication of B. minax is essential in preventing its spread. In the present study, the nuclear ribosomal internal transcribed spacer 2 (ITS2) amplicon was used to design species-specific primer pairs that enable B. minax to be distinguished from 11 other fruit fly species. Four forward and four reverse species-specific primers were designed, and out of all possible sets of species-specific primer pairs obtained after intermixing them, seven sets of species-specific primer pairs were able to accurately identify B. minax. For B. minax identification, specific fragments ranging from 83 to 431 base pairs in length were amplified. The validity of the specific band only in B. minax was determined by visually inspecting the gel profile of the PCR product. B. minax was correctly identified using the designed species-specific primer pairs, with no cross-amplification with the 11 other fruit fly species included in the experiments. In addition to saving DNA sequencing costs, the application of these speciesspecific primer pairs facilitates rapid identification of B. minax, with identification in border scenarios being completable within 2–3 h.

Correlation between crystallinity and resistive switching behavior of sputtered WO3 thin films

Thi Bang Tam Dao,Kim Ngoc Pham,Yi-Lung Cheng,김상섭,Bach Thang Phan 한국물리학회 2014 Current Applied Physics Vol.14 No.12

The as-depositedWO3 thin films were post-annealed at different temperatures (300 C and 600 C) in air to investigate a correlation between crystallinity and switching behavior of WO3 thin films. Associating the results of XRD, FTIR, XPS and FESEM measurements, the annealing-caused crystallinity change contributes to the variation of the switching behaviors of theWO3 thin films. The as-depositedWO3 films with low crystalline structure are preferred for random Ag conducting path, resulting in large switching ratio but fluctuating IeV hysteresis, whereas the annealedWO3 films with crystallized compact structure limits Ag conducting path, favoring the stable IeV hysteresis but small switching ratio. It is therefore concluded that electrochemical redox reaction-controlled resistance switching depends not only on electrode materials (inert and reactive electrodes) but also on crystallinity of host oxide.

Effects of post anneal for the INZO films prepared by ultrasonic spray pyrolysis

Lan, Wen-How,Li, Yue-Lin,Chung, Yu-Chieh,Yu, Cheng-Chang,Chou, Yi-Chun,Wu, Yi-Da,Huang, Kai-Feng,Chen, Lung-Chien Techno-Press 2014 Advances in nano research Vol.2 No.4

Indium-nitrogen co-doped zinc oxide thin films (INZO) were prepared on glass substrates in the atmosphere by ultrasonic spray pyrolysis. The aqueous solution of zinc acetate, ammonium acetate and different indium sources: indium (III) chloride and indium (III) nitrate were used as the precursors. After film deposition, different anneal temperature treatment as 350, 450, $550^{\circ}C$ were applied. Electrical properties as concentration and mobility were characterized by Hall measurement. The surface morphology and crystalline quality were characterized by SEM and XRD. With the activation energy analysis for both films, the concentration variation of the films at different heat treatment temperature was realized. Donors correspond to zinc related states dominate the conduction mechanism for these INZO films after $550^{\circ}C$ high temperature heat treatment process.