Uniaxial Compression Properties and Compression Fatigue Performance of Selective Laser Melted Ti–6Al–4V Cellular Structure

Ming‑Wei Wu,Jhewn‑Kuang Chen,Mo‑Kai Tsai,Pei Wang,Tien‑Lin Cheng,Bo‑Huan Lin,Po‑Hsing Chiang,Annadurai Dhinakar 대한금속·재료학회 2022 METALS AND MATERIALS International Vol.28 No.1

The selective laser melted (SLM) Ti–6Al–4V cellular solid is a promising material in biomedical and other applications. The mechanical properties of the SLM Ti–6Al–4V cellular material are predominantly controlled by the design of the cellular structure. The objective of this study was to investigate the uniaxial compressive properties and compressive fatigueperformance of the SLM Ti–6Al–4V cellular solid with a new cuboctahedron unit cell reinforced by four diagonal strutsand two horizontal struts along the X and Y axes. The infuences of hot isostatic pressing (HIP) on the various mechanicalproperties were also examined. The results showed a smoother stress–strain curve and fewer stress oscillations in the HIPspecimen than in the SLM specimen. The HIP process slightly decreased the yield strength of the SLM sample from 55 to52 MPa. Under uniaxial compressive stress, the SLM and HIP specimens exhibited layer-by-layer fracture and diagonalshear fracture, respectively. Furthermore, the HIP treatment signifcantly increased the fatigue performance and improved thefatigue endurance ratio at 106cycles from 0.15 to 0.35. The HIP treatment contributed to several positive efects, includingphase transformation from brittle α′ to α + β, the elimination of strut porosity and residual stress, an increase in lath size,and a better combination of strength and ductility, thereby improving the fatigue performance. The efects of stress mode onthe fracture mechanism were also clarifed using in situ observation in combination with digital image correlation.

Galangin Prevents Acute Hepatorenal Toxicity in Novel Propacetamol-Induced Acetaminophen-Overdosed Mice

Ming-Shiun Tsai,Chia-Chih Chien,Ting-Hui Lin,Chia-Chi Liu,Rosa Huang Liu,Hong-Lin Su,Yung-Tsung Chiu,Sue-Hong Wang 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.11

Acetaminophen (APAP) overdose causes severe liver and kidney damage. APAP-induced liver injury (AILI) represents the most frequent cause of drug-induced liver failure. APAP is relatively insoluble and can only be taken orally; however, its prodrug, propacetamol, is water soluble and usually injected directly. In this study, we examined the timedependent effects of AILI after propacetamol injection in mice. After analyses of alanine aminotransferase and aspartate aminotransferase activities and liver histopathology, we demonstrated that a novel AILI mouse model can be established by single propacetamol injection. Furthermore, we compared the protective and therapeutic effects of galangin with a known liver protective extract, silymarin, and the only clinical agent for treating APAP toxicity, N-acetylcysteine (NAC), at the same dose in the model mice. We observed that galangin and silymarin were more effective than NAC for protecting against AILI. However, only NAC greatly improved both the survival time and rate consequent to a lethal dose of propacetamol. To decipher the hepatic protective mechanism(s) of galangin, galangin pretreatment significantly decreased the hepatic oxidative stress, increased hepatic glutathione level, and decreased hepatic microsomal CYP2E1 levels induced by propacetamol injection. In addition, propacetamol injection also reproduced the probability of APAP-induced kidney injury (AIKI), appearing similar to a clinical APAP overdose. Only galangin pretreatment showed the protective effect of AIKI. Thus, we have established a novel mouse model for AILI and AIKI using a single propacetamol injection. We also demonstrated that galangin provides significant protection against AILI and AIKI in this mouse model.

Original Article : The Risk of Cellulitis in Cirrhotic Patients: A Nationwide Population-Based Study in Taiwan

( Ming Nan Lin ),( Chen Chi Tsai ),( Tsung Hsing Hung ),( Chih Chun Tsai ) The Editorial Office of Gut and Liver 2012 Gut and Liver Vol.6 No.4

Background/Aims: Cellulitis is a common infectious disease. However, the risk of cellulitis in cirrhotic patients is not well established, and whether liver cirrhosis is a risk factor for cellulitis remains unknown. This study evaluated the relationship between cellulitis and liver cirrhosis. Methods: The National Health Insurance Database, which was derived from the Taiwan National Health Insurance program, was used to identify patients. The study group consisted of 39,966 patients with liver cirrhosis, and the comparison group consisted of 39,701 randomly selected age- and sex-matched patients. Results: During the 3-year follow-up period, 2,674 (6.7%) patients with liver cirrhosis developed cellulitis, and 1,587 (4.0%) patients without liver cirrhosis developed cellulitis (p<0.001). Following a Cox`s regression analysis adjusted for age, sex, and underlying medical disorders, the cirrhotic patients demonstrated a greater risk for the occurrence of cellulitis than the non-cirrhotic patients during the 3-year period (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.55 to 1.77; p<0.001). Additionally, cirrhotic patients with complications also had a greater risk for the occurrence of cellulitis than those patients without complications (HR, 1.23; 95% CI, 1.14 to 1.33; p<0.001). Conclusions: We conclude that cirrhotic patients have a greater risk of cellulitis than non-cirrhotic patients. (Gut Liver 2012;6:482-485)

INVESTIGATING SATISFIED BUT DISLOYAL BUSINESS CUSTOMERS

Ming-Chih Tsai,Rico Merkert,Shiau-Chi Lin,Mei-Ting Tsai 글로벌지식마케팅경영학회 2018 Global Marketing Conference Vol.2018 No.07

Satisfaction paradox indicates customer satisfaction does not necessarily translate into customer repurchase. Competitor’s attractiveness and customer demographics are two main moderators for the paradoxical phenomenon. Competitor’s attractiveness exhibits customer switching effect, whereas customer demographics imply customers moored with their current service provider. Still, the cases were few investigated in B2B settings where customers are in general more complex than consumers as involving more intricate organizational network influences. In a business network, transactions may incur buyer/seller relational activities that mitigate paradoxical behavior. Nonetheless, the variable is yet identified and the interacting effects between the moderating variables are not clarified. Thus, this study aims to develop an operational model to classify satisfied customers into loyal, moored and paradoxical segments using three genres of moderators: competitor’s attractiveness, organizational and transactional variables in a B2B setting. In the model, the theoretical bases of switching behaviors are applied for four statistical analysis executed in a logic sequence, including a factor analysis to consolidate quality measurements, a quadrant analysis to locate the effect of competitor’s attractiveness, a clustering analysis to segment satisfied customers into four segments, and finally, nonparametric tests to validate the organizational and transactional segmentation variables. Empirically, we study Taiwanese manufacturers who engaged in global trade and have had experiences in choosing the global air express services that form an oligopolistic market and a strategic group so competitor’s attractiveness can be better calibrated. A total of 180 valid samples are collected and analyzed. The results contribute to the literatures of B2B service marketing.

Significant down-regulation of growth hormone receptor expression revealed as a new unfavorable prognostic factor in hepatitis C virus-related hepatocellular carcinoma

( Ching-chih Lin ),( Ta-wei Liu ),( Ming-lun Yeh ),( Yi-shan Tsai ),( Pei-chien Tsai ),( Chung-feng Huang ),( Jee-fu Huang ),( Wan-long Chuang ),( Chia-yen Dai ),( Ming-lung Yu ) 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.2

Background/Aims: Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC. Methods: The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed. Results: GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II-IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C. Conclusions: Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC. (Clin Mol Hepatol 2021;27:313-328)

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.

Transarterial Chemoembolization Using Gelatin Sponges or Microspheres Plus Lipiodol-Doxorubicin versus Doxorubicin-Loaded Beads for the Treatment of Hepatocellular Carcinoma

Yi-Sheng Liu,Ming-Ching Ou,Yi-Shan Tsai,Xi-Zhang Lin,Chien-Kuo Wang,Hong-Ming Tsai,Ming-Tsung Chuang 대한영상의학회 2015 Korean Journal of Radiology Vol.16 No.1

To retrospectively compare treatment of hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE) using gelatin sponges or microspheres plus lipiodol-doxorubicin vs. doxorubicin-loaded drug-eluting beads (DEB). A total of 158 patients with HCC received TACE from November 2010 to November 2011 were enrolled in this study, including 64 (40.5%) received TACE with lipiodol-doxorubicin and gelatin sponges (group A), 41 (25.9%) received TACE with lipiodol-doxorubicin and microspheres (group B), and 53 (33.5%) received TACE with doxorubicin-loaded DEB (group C). Tumor response and adverse events (AEs) were evaluated. No significant difference was found at baseline among the three groups. The doxorubicin dosage in group C wassignificantly (p < 0.001) higher compared to the dose used in groups A or B (median, 50 mg vs. 31 mg or 25 mg). Significantly (p < 0.001) more patients in group C achieved complete response compared to those in groups A or B (32.1% vs. 6.3% or 2.4%). Significantly (p < 0.001) less patients in group C had progressive disease compared to those in groups A or B (34.0% vs. 57.8% or 68.3%). Minor AEs were more common in groups A and B compared to group C, with rates of 54.7%, 34.1%, and 5.7%, respectively. In patients with HCC, TACE with DEB offers better safety and efficacy profiles compared to either TACE with gelatin sponges or TACE with microspheres.

Clinical Features of Patients with Esophageal and Second Primary Cancers

Tsai, Huang-Wen,Chang, Chih-Chun,Sun, Jen-Tang,Liou, Ching-Biau,Lin, Hsiu-Chen,Lin, I-Hsin,Yu, Yun-Chieh,Weng, Wei-Ling,Leong, Ka-I,Yen, Tzung-Hai,Wu, Jiann-Ming Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Background: The prevalence of esophageal cancer (EC) with second primary cancers (SPC) is increasing worldwide. This study was aimed to understand the clinical features of EC patients with SPC in the Taiwanese population. Materials and Methods: Clinical and laboratory data for 180 EC patients with or without SPC were collected between January 2009 and December 2013. Information on treatment approaches, location of SPCs and ABO blood type were also collected and stratified. Results: The most common SPC in EC patients was hypopharyngeal cancer, followed by laryngeal cancer and hepatocellular carcinoma in our study. Malignancies of colon, prostate and lung were also found. There was a significant higher portion of blood type A in the EC patients with SPC compared with those without (42.4% vs 19.5%, P=0.006). Conclusions: The frequency and SPC site distribution and blood type A should be considered in clinical evaluation of EC patients with a high risk of developing SPC in the Taiwanese population.

Mesenchymal Stem Cell Secreted-Extracellular Vesicles are Involved in Chondrocyte Production and Reduce Adipogenesis during Stem Cell Differentiation

Tsai Yu-Chen,Cheng Tai-Shan,Liao Hsiu-Jung,Chuang Ming-Hsi,Chen Hui-Ting,Chen Chun-Hung,Zhang Kai-Ling,Chang Chih-Hung,Lin Po-Cheng,Huang Chi-Ying F. 한국조직공학과 재생의학회 2022 조직공학과 재생의학 Vol.19 No.6

BACKGROUND: Extracellular vesicles (EVs) are derived from internal cellular compartments, and have potential as a diagnostic and therapeutic tool in degenerative disease associated with aging. Mesenchymal stem cells (MSCs) have become a promising tool for functional EVs production. This study investigated the efficacy of EVs and its effect on differentiation capacity. METHODS: The characteristics of MSCs were evaluated by flow cytometry and stem cell differentiation analysis, and a production mode of functional EVs was scaled from MSCs. The concentration and size of EVs were quantitated by Nanoparticle Tracking Analysis (NTA). Western blot analysis was used to assess the protein expression of exosomespecific markers. The effects of MSC-derived EVs were assessed by chondrogenic and adipogenic differentiation analyses and histological observation. RESULTS: The range of the particle size of adipose-derived stem cells (ADSCs)- and Wharton’s jelly -MSCs-derived EVs were from 130 to 150 nm as measured by NTA, which showed positive expression of exosomal markers. The chondrogenic induction ability was weakened in the absence of EVs in vitro. Interestingly, after EV administration, type II collagen, a major component in the cartilage extracellular matrix, was upregulated compared to the EV-free condition. Moreover, EVs decreased the lipid accumulation rate during adipogenic induction. CONCLUSION: The results indicated that the production model could facilitate production of effective EVs and further demonstrated the role of MSC-derived EVs in cell differentiation. MSC-derived EVs could be successfully used in cell-free therapy to guide chondrogenic differentiation of ADSC for future clinical applications in cartilage regeneration.

Traditional Chinese medicine attenuates hospitalization and mortality risks in diabetic patients with carcinoma in situ in Taiwan

Tsai Li-Jen,Chung Chi-Hsiang,Lin Chien-Jung,Su Sheng-Chiang,Kuo Feng-Chih,Liu Jhih-Syuan,Chen Kuan-Chan,Ho Li-Ju,Kuo Chih-Chun,Chang Chun-Yung,Lin Ming-Hsun,Chu Nain-Feng,Lee Chien-Hsing,Hsieh Chang-H 한국한의학연구원 2022 Integrative Medicine Research Vol.11 No.2

Background: Diabetic patients are at high risk of developing cancer. Traditional Chinese medicine (TCM) has become increasingly popular as an adjuvant treatment for patients with chronic diseases, and some studies have identified its beneficial effect in diabetic patients with cancer. The purpoes of this study was to outline the potential of TCM to attenuate hospitalization and mortality rates in diabetic patients with carcinoma in situ (CIS). Methods: A total of 6,987 diabetic subjects with CIS under TCM therapy were selected from the National Health Insurance Research Database of Taiwan, along with 38,800 of 1:1 sex-, age-, and index year-matched controls without TCM therapy. Cox proportional hazard analysis was conducted to compare hospitalization and mortality rates during an average of 15 years of follow-up. Results: A total of 3,999/1,393 enrolled-subjects (28.62%/9.97%) had hospitalization/mortality, including 1,777/661 in the TCM group (25.43%/9.46%) and 2,222/732 in the control group (31.80%/10.48%). Cox proportional hazard regression analysis showed a lower rate of hospitalization and mortality for subjects in the TCM group (adjusted HR=0.536; 95% CI=0.367–0.780, P<0.001; adjusted HR=0.783; 95% CI=0.574– 0.974, P = 0.022). Kaplan-Meier analysis showed that the cumulative risk of hospitalization and mortality in the case and control groups was significantly different (log rank, P<0.001 and P = 0.011, respectively). Conclusions: Diabetic patients with CIS under TCM therapy were associated with lower hospitalization and mortality rates compared to those without TCM therapy. Thus, TCM application may reduce the burden of national medical resources.