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)

Acute Hepatitis Due to Agomelatine Use in Elderly Women with Depression: Case Series

Cheng-Chen Chang,Yen-Jen Chen,Yu-An Chen,Yi-Cheng Liao 대한정신약물학회 2021 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.19 No.4

Although agomelatine may be associated with an increased risk of hepatotoxicity, the incidence rate of acute hepatitis seemed divergent between clinical trials and daily practice. Whether aging or gender is a risk factor in developing hepatotoxicity due to agomelatine is not clear. We present 3 older female cases with acute hepatitis occurring due to highly probable idiosyncratic drug-induced liver injury caused by agomelatine. From these cases, regular surveillance on liver function in the older women taking antidepressants would be of benefits.

Cav3.2 T-Type Ca2+ Channel-Dependent Activation of ERK in Paraventricular Thalamus Modulates Acid-Induced Chronic Muscle Pain.

Chen, Wen-Kwei,Liu, Ingrid Y,Chang, Ya-Ting,Chen, Yong-Cyuan,Chen, Chih-Cheng,Yen, Chen-Tung,Shin, Hee-Sup,Chen, Chien-Chang The Society 2010 The Journal of neuroscience Vol.30 No.31

<P>Treatments for chronic musculoskeletal pain, such as lower back pain, fibromyalgia, and myofascial pain syndrome, remain inadequate because of our poor understanding of the mechanisms that underlie these conditions. Although T-type Ca(2+) channels (T-channels) have been implicated in peripheral and central pain sensory pathways, their role in chronic musculoskeletal pain is still unclear. Here, we show that acid-induced chronic mechanical hyperalgesia develops in Ca(v)3.1-deficient and wild-type but not in Ca(v)3.2-deficient male and female mice. We also show that T-channels are required for the initiation, but not maintenance, of acid-induced chronic muscle pain. Blocking T-channels using ethosuximide prevented chronic mechanical hyperalgesia in wild-type mice when administered intraperitoneally or intracerebroventricularly, but not intramuscularly or intrathecally. Furthermore, we found an acid-induced, Ca(v)3.2 T-channel-dependent activation of ERK (extracellular signal-regulated kinase) in the anterior nucleus of paraventricular thalamus (PVA), and prevention of the ERK activation abolished the chronic mechanical hyperalgesia. Our findings suggest that Ca(v)3.2 T-channel-dependent activation of ERK in PVA is required for the development of acid-induced chronic mechanical hyperalgesia.</P>

Graphite-based selectorless RRAM: improvable intrinsic nonlinearity for array applications

Chen, Ying-Chen,Hu, Szu-Tung,Lin, Chih-Yang,Fowler, Burt,Huang, Hui-Chun,Lin, Chao-Cheng,Kim, Sungjun,Chang, Yao-Feng,Lee, Jack C. The Royal Society of Chemistry 2018 Nanoscale Vol.10 No.33

<P>Selectorless graphite-based resistive random-access memory (RRAM) has been demonstrated by utilizing the intrinsic nonlinear resistive switching (RS) characteristics, without an additional selector or transistor for low-power RRAM array application. The low effective dielectric constant value (<I>k</I>) layer of graphite or graphite oxide is utilized, which is beneficial in suppressing sneak-path currents in the crossbar RRAM array. The tail-bits with low nonlinearity can be manipulated by the positive voltage pulse, which in turn can alleviate variability and reliability issues. Our results provide additional insights for built-in nonlinearity in 1<I>R</I>-only selectorless RRAMs, which are applicable to the low-power memory array, ultrahigh density storage, and in-memory neuromorphic computational configurations.</P>

Association between Thioridazine Use and Cancer Risk in Adult Patients with Schizophrenia-A Population-Based Study

Cheng-Chen Chang,Ming-Hong Hsieh,Jong-Yi Wang,Nan-Ying Chiu,Yu-Hsun Wang,Jeng-Yuan Chiou,Hsiang-Hsiung Huang,Po-Chung Ju 대한신경정신의학회 2018 PSYCHIATRY INVESTIGATION Vol.15 No.11

Objective Several cell line studies have demonstrated thioridazine’s anticancer, multidrug resistance-reversing and apoptosis-inducing properties in various tumors. We conducted this nationwide population-based study to investigate the association between thioridazine use and cancer risk among adult patients with schizophrenia. Methods Based on the Psychiatric Inpatient Medical Claim of the National Health Insurance Research Database of Taiwan, a total of 185,689 insured psychiatric patients during 2000 to 2005 were identified. After excluding patients with prior history of schizophrenia, only 42,273 newly diagnosed patients were included. Among them, 1,631 patients ever receiving thioridazine for more than 30 days within 6 months were selected and paired with 6,256 randomly selected non-thioridazine controls. These patients were traced till 2012/12/31 to see if they have any malignancy. Results The incidence rates of hypertension and cerebrovascular disease were higher among cases than among matched controls. The incidence of hyperlipidemia, coronary artery disease and chronic pulmonary disease did not differ between the two groups. By using Cox proportional hazard model for cancer incidence, the crude hazard ratio was significantly higher in age, hypertension, hyperlipidemia, cerebrovascular disease, coronary artery disease and chronic pulmornary disease. However, after adjusting for other covariates, only age and hypertension remained significant. Thioridazine use in adult patients with schizophrenia had no significant association with cancer. Conclusion Despite our finding that thioridazine use had no prevention in cancer in adult patients with schizophrenia. Based on the biological activity, thioridazine is a potential anticancer drug and further investigation in human with cancer is warranted.

The feasibility of detecting endometrial and ovarian cancer using DNA methylation biomarkers in cervical scrapings

Cheng-Chang Chang,Hui-Chen Wang,Yu-Ping Liao,Yu-Chih Chen,Yu-Chun Weng,Mu-Hsien Yu,Hung-Cheng Lai 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.1

Objective: We hypothesized that DNA methylation of development-related genes may occur in endometrial cancer (EC)/ovarian cancer (OC) and may be detected in cervical scrapings. Methods: We tested methylation status by quantitative methylation-specific polymerase chain reaction for 14 genes in DNA pools of endometrial and OC tissues. Tissues of EC/normal endometrium, OC/normal ovary, were verified in training set using cervical scrapings of 10 EC/10 OC patients and 10 controls, and further validated in the testing set using independent cervical scrapings in 30 EC/30 OC patients and 30 controls. We generated cutoff values of methylation index (M-index) from cervical scrapings to distinguish between cancer patients and control. Sensitivity/specificity of DNA methylation biomarkers in detecting EC and OC was calculated. Results: Of 14 genes, 4 (PTGDR, HS3ST2, POU4F3, MAGI2) showed hypermethylation in EC and OC tissues, and were verified in training set. POU4F3 and MAGI2 exhibited hypermethylation in training set were validated in independent cases. The mean M-index of POU4F3 is 78.28 in EC and 20.36 in OC, which are higher than that in controls (6.59; p<0.001 and p=0.100, respectively), and that of MAGI2 is 246.0 in EC and 12.2 in OC, which is significantly higher that than in controls (2.85; p<0.001 and p=0.480, respectively). Sensitivity and specificity of POU4F3/MAGI2 were 83%–90% and 69%–75% for detection of EC, and 61% and 62%–69% for the detection of OC. Conclusion: The findings demonstrate the potential of EC/OC detection through testing for DNA methylation in cervical scrapings.

Predicting the surgical reparability of large-to-massive rotator cuff tears by B-mode ultrasonography: a cross-sectional study

Po-Cheng Chen,Kuan-Ting Wu,Yi-Cun Chen,Yu-Chi Huang,Ching-Di Chang,Wei-Che Lin,Wen-Yi Chou 대한초음파의학회 2022 ULTRASONOGRAPHY Vol.41 No.1

Purpose: This study aimed to compare the ability of B-mode ultrasonography and magnetic resonance imaging (MRI) to predict the repairability of large-to-massive rotator cuff tears (RCTs). Methods: This cross-sectional study included participants with large-to-massive RCTs who underwent arthroscopic repair. B-mode ultrasonography and MRI were conducted prior to arthroscopic repair. B-mode ultrasonography was used to evaluate the echogenicity of the rotator cuff muscle using the Heckmatt scale. Intra-rater and inter-rater reliabilities were examined for two independent physicians. MRI was used to evaluate the degrees of tendon retraction, fatty infiltration of rotator cuff muscles, and muscle atrophy. Finally, two experienced orthopedic surgeons performed surgery and decided whether the torn stump could be completely repaired intraoperatively. Results: Fifty participants were included, and 32 complete repairs and 18 partial repairs were performed. B-mode ultrasonography showed good intra-rater reliability and inter-rater reliability for assessment of the muscle echogenicity of the supraspinatus and infraspinatus muscles. The correlation coefficients between B-mode ultrasound findings and MRI findings showed medium to large effect sizes (r=0.4-0.8). The Goutallier classification of the infraspinatus muscles was the MRI predictor with the best discriminative power for surgical reparability (area under the curve [AUC], 0.89; 95% confidence interval [CI], 0.81 to 0.98), while the Heckmatt scale for infraspinatus muscles was the most accurate ultrasound predictor (AUC, 0.85; 95% CI, 0.74 to 0.96). No significant differences in AUCs among the MRI and ultrasound predictors were found. Conclusion: B-mode ultrasonography was a reliable examination tool and had a similar ability to predict surgical reparability to that of MRI among patients with large-to-massive RCTs. Purpose: This study aimed to compare the ability of B-mode ultrasonography and magnetic resonance imaging (MRI) to predict the repairability of large-to-massive rotator cuff tears (RCTs).Methods: This cross-sectional study included participants with large-to-massive RCTs who underwent arthroscopic repair. B-mode ultrasonography and MRI were conducted prior to arthroscopic repair. B-mode ultrasonography was used to evaluate the echogenicity of the rotator cuff muscle using the Heckmatt scale. Intra-rater and inter-rater reliabilities were examined for two independent physicians. MRI was used to evaluate the degrees of tendon retraction, fatty infiltration of rotator cuff muscles, and muscle atrophy. Finally, two experienced orthopedic surgeons performed surgery and decided whether the torn stump could be completely repaired intraoperatively.Results: Fifty participants were included, and 32 complete repairs and 18 partial repairs were performed. B-mode ultrasonography showed good intra-rater reliability and inter-rater reliability for assessment of the muscle echogenicity of the supraspinatus and infraspinatus muscles. The correlation coefficients between B-mode ultrasound findings and MRI findings showed medium to large effect sizes (r=0.4-0.8). The Goutallier classification of the infraspinatus muscles was the MRI predictor with the best discriminative power for surgical reparability (area under the curve [AUC], 0.89; 95% confidence interval [CI], 0.81 to 0.98), while the Heckmatt scale for infraspinatus muscles was the most accurate ultrasound predictor (AUC, 0.85; 95% CI, 0.74 to 0.96). No significant differences in AUCs among the MRI and ultrasound predictors were found.Conclusion: B-mode ultrasonography was a reliable examination tool and had a similar ability to predict surgical reparability to that of MRI among patients with large-to-massive RCTs.

Microstructures and Mechanical Properties of In-Situ Al3Ti/2024 Aluminum Matrix Composites Fabricated by Ultrasonic Treatment and Subsequent Squeeze Casting

Gang Chen,Xusheng Chang,Jingxuan Zhang,Yu Jin,Cheng Sun,Qiang Chen,Zude Zhao 대한금속·재료학회 2020 METALS AND MATERIALS International Vol.26 No.10

Squeeze casting is a near net shaping technology which is advantageous to refining the microstructures and improving themechanical properties. In the present work, in-situ Al3Ti/2024 Aluminum matrix composites with different amount of Al3Tireinforcements were successfully fabricated by ultrasonic treatment and subsequent squeeze casting. The effects of specificpressure and the amount of reinforcements on microstructures and mechanical properties were studied. The results show thatwhen the specific pressure is increased from 0 to 150 MPa, the average grain sizes of α-Al matrix are decreased by 39.8%, andthe yield strength and compressive strength are increased by 16.8% and 22.9%, respectively. However, severe segregationsof eutectic structures were generated under an excessive specific pressure of 200 MPa, which also results in deterioration inthe mechanical strength. The mass fraction of Al3Tiphases has significant influence on morphology of eutectic structures. When the mass fraction of Al3Tiphases is increased from 4 to 16 wt%, the eutectic structures was changed from continuousnetwork to dispersed structures gradually. The compressive strength was increased from 611.2 to 712.0 MPa (increasedby 16.5%), as the Al3Ticontent increasing from 0 to 16 wt%. However, as the mass fraction of Al3Tiphases increased, thevariation in the yield strength is not monotonically increasing.

Novel application of Influenza A virus-inoculated chorioallantoic membrane to characterize a NP-specific monoclonal antibody for immunohistochemistry assaying

Yang-Chang Tu,Kuang-Yu Chen,Chung-Kung Chen,Ming-Chu Cheng,Shu-Hwae Lee,Ivan-Chen Cheng 대한수의학회 2019 Journal of Veterinary Science Vol.20 No.1

Monoclonal antibodies (MAbs) are widely applied in disease diagnoses. Herein, we report a MAb, WF-4, against Influenza A virus nucleoprotein (NP), its broad response with Influenza A virus, and its application in an immunohistochemistry (IHC) assay. WF-4 was screened by immunofluorescence assay (IFA). The results showed that its reactivity with baculovirus-expressed full-length recombinant NP (rNP) in Western blot (WB), indicating its IHC applicability. Fifteen Influenza A virus (reference subtypes H1 to H15) infected chicken embryonated chorioallantoic membranes (CAM), fixed by formalin, were all detectable in the WF-4-based IHC assay. Also, the reactivity of the IHC test with NP from experimentally inoculated H6N1 and from all recent outbreaks of H5 subtype avian Influenza A virus (AIV) field cases in Taiwan showed positive results. Our data indicate that CAM, a by-product of Influenza A virus preparation, is helpful for Influenza A virus-specific MAb characterization, and that the WF-4 MAb recognizes conserved and linear epitopes of Influenza A virus NP. Therefore, WF-4 is capable of detecting NP antigens via IHC and may be suitable for developing various tests for diagnosis of Influenza A virus and, especially, AIV infection.

Resonant-Frequency-Dependent Flux Noise of a High-TC rf SQUID Coupled to a Substrate Resonator

Ji-Cheng Chen,Hong-Chang Yang,Chiu-Hsien Wu,Herng-Er Horng,Jen-Tzong Jeng,Kuen-Lin Chen 한국물리학회 2006 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.48 No.5I

In the recent development of a high-TC rf SQUID magnetometer, Zhang et al. used a SrTiO3 substrate resonator with a YBCO thin film flux concentrator on it. The effective area was improved by a flux concentrator. However, there was no study of the resonant frequency of the substrate resonator. In this work, the frequency-dependent flux noise of a high-TC rf SQUID coupled to a substrate resonator was investigated. The results were analyzed with the noise theory. The optimization of the SQUID with a substrate resonator and its flux noise are discussed.