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Chih-Ying Wu,1– 3 Li-Wei Chou,4– 6 Shih-Wei Huang,7 Wen-Ling Liao,1,8 Shiaw-Meng Chang,9 Han-Chung Lee,10 Cheng-Di Chiu,3,11– 14 Chih-Hsin Tang,13,15– 18 Ching-Liang Hsieh16,19,20 1Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan; 2Department of Neurosurgery, China Medical University Hsinchu Hospital, China Medical University, Hsinchu, Taiwan; 3Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan; 4Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan; 5Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan; 6Department of Physical Medicine and Rehabilitation, Asia University Hospital, Asia University, Taichung, Taiwan; 7Department of Traditional Chinese Medicine, China Medical University Hsinchu Hospital, China Medical University, Hsinchu, Taiwan; 8Center for Personalized Medicine, China Medical University Hospital, Taichung, Taiwan; 9Department of Industrial Engineering and Engineering Management, National Tsing Hua University, Hsinchu, Taiwan; 10Neuroscience center, Everan Hospital, Taichung, Taiwan; 11Spine Center, China Medical University Hospital, Taichung, Taiwan; 12School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; 13Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan; 14Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; 15Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan; 16Chinese Medicine Research Center, China Medical University, Taichung, Taiwan; 17Department of Medical Laboratory Science and Biotechnology, College of Health Science, Asia University, Taichung, Taiwan; 18Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu, Taiwan; 19Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan; 20Graduate Institute of Acupuncture Science, China Medical University, Taichung, TaiwanCorrespondence: Chih-Hsin Tang, Graduate Institute of Biomedical Science, College of Medicine, China Medical University, Taichung, 40402, Taiwan, Email chtang@mail.cmu.edu.tw Ching-Liang Hsieh, Graduate Institute of Acupuncture Science, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan, Tel +886-4-22053366, Fax +886-4-22037690, Email clhsieh0826@gmail.comBackground: Fu’s subcutaneous needling (FSN) is a novel acupuncture technique for pain treatment. This study investigated the effects of postsurgical FSN on postoperative pain in patients receiving surgery for degenerative spinal disorders.Methods: This single-center, single-blind, randomized-controlled study involved patients undergoing surgery for degenerative spinal disorders. Participants were randomized into either an FSN group or a control group that received sham FSN. The primary outcomes were scores on the Brief Pain Inventory Taiwan version (BPI-T) and Oswestry Disability Index before and at 1, 24, and 48 hours after surgery. Secondary outcomes were muscle hardness, pethidine use, and inflammatory biomarker presence.Results: Initially, 51 patients met the inclusion criteria and were allocated (26 in the FSN group and 25 in the control group). Two patients were lost to follow-up, and finally, 49 patients (25 in the FSN group and 24 in the control group) who completed the study were analyzed. The FSN group had significantly lower pain intensity measured on the BPI-T compared with the control group at 1, 24, 48, and 72 hours after surgical treatment (all p < 0.001). Additionally, pain interference as measured on the BPI-T was lower in the FSN group than in the control group 1 hour (p = 0.001), 24 hours (p = 0.018), 48 hours (p = 0.001), and 72 hours (p = 0.017) after surgical treatment. Finally, the FSN group exhibited less muscle hardness in the latissimus dorsi and gluteus maximus 24, 48, and 72 hours (all p < 0.05) after surgery compared with the control group; patients in the FSN group also exhibited less muscle hardness in the L3 paraspinal muscle 48 hours (p = 0.001) and 72 hours (p < 0.001) after surgery compared with the control group. There were no significant differences in serum CRP, IL-1β, IL-2, IL-6, and TNF-α levels between the FSN and control groups at 24 hours, 72 hours, and 1-month post-surgery (all p > 0.05).Conclusion: FSN treatment can reduce postoperative pain in patients receiving surgery for degenerative spinal disorders. However, larger sample sizes and multicenter clinical trials are required to verify these findings.Keywords: Fu’s subcutaneous needling, degenerative spinal disorders, postoperative pain, surgical treatment, clinical trial

Ye Rim Kim,1,2,&ast; Sung Won Chung,1,2,&ast; Min-Ju Kim,3 Won-Mook Choi,1,2 Jonggi Choi,1,2 Danbi Lee,1,2 Han Chu Lee,1,2 Ju Hyun Shim1,2,4 1Division of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 2Liver Cancer Center, Asan Cancer Institute, Asan Medical Center, Seoul, Republic of Korea; 3Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Digestive Diseases Research Center, University of Ulsan College of Medicine, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Ju Hyun Shim, Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea, Tel +82-02-3010-3190, Fax +82-02-485-5782, Email s5854@amc.seoul.krIntroduction: We aimed to evaluate the generalizability of retrospective single-center cohort studies on prognosis of hepatocellular carcinoma (HCC) by comparing overall survival (OS) after various treatments between a nationwide multicenter cohort and a single-center cohort of HCC patients.Methods: Patients newly diagnosed with HCC between January 2008 and December 2018 were analyzed using data from the Korean Primary Liver Cancer Registry (multicenter cohort, n=16,443), and the Asan Medical Center HCC registry (single-center cohort, n=15,655). The primary outcome, OS after initial treatment, was compared between the two cohorts for both the entire population and for subcohorts with Child-Pugh A liver function (n=2797 and n=5151, respectively) treated according to the Barcelona-Clinic-Liver-Cancer (BCLC) strategy, using Log rank test and Cox proportional hazard models.Results: Patients of BCLC stages 0 and A (59.3% vs 35.2%) and patients who received curative treatment (42.1% vs 32.1%) were more frequently observed in the single-center cohort (Ps< 0.001). Multivariable analysis revealed significant differences between the two cohorts in OS according to type of treatment: the multicenter cohort was associated with higher risk of mortality among patients who received curative (adjusted hazard ratio [95% confidence interval], 1.48 [1.39– 1.59]) and non-curative (1.22 [1.17– 1.27]) treatments, whereas the risk was lower in patients treated with systemic therapy (0.83 [0.74– 0.92]) and best supportive care (0.85 [0.79– 0.91]). Subcohort analysis also demonstrated significantly different OS between the two cohorts, with a higher risk of mortality in multicenter cohort patients who received chemoembolization (1.72 [1.48– 2.00]) and ablation (1.44 [1.08– 1.92]).Conclusion: Comparisons of single-center and multicenter cohorts of HCC patients revealed significant differences in OS according to treatment modality after adjustment for prognostic variables. Therefore, the results of retrospective single-center cohort studies of HCC treatments may not be generalizable to real-world practice.Keywords: BCLC, UICC, liver cancer, retrospective cohort, external validation

Ming-Chuan Lee,1 Yu-Tsang Wang,2 Yu-Ju Li,1 Ching-Yi Tsai,1 Su-Te Chen,1 Wun-Jyun Jhuang,1,3 Meng-Chi Chang,1 Mei-Yu Chien,1 Hsiang-Chun Lee1,3– 5 1Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; 2Division of Medical Statistics and Bioinformatics, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; 3Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; 4Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; 5Institute/Center of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, 804, TaiwanCorrespondence: Hsiang-Chun Lee, Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, 100 Tzyou 1st Road, Kaohsiung, 807, Taiwan, Tel +886-7-3121101#2293, Fax +886-7-3234845, Email hclee@kmu.edu.twPurpose: Manifestations of metabolic syndrome (MetS) carry risks for atrial fibrillation (AF). The study determined whether any electrocardiographic parameter can reflect increased AF risk in individuals with MetS.Patients and Methods: From our University Hospital database, we examined the presence of AF and its correlation with MetS manifestations, renal function, lipid profiles, and electrocardiographic parameters (P wave duration, PR interval, QRS width, and QTc intervals). Between January 2008 and December 2015, data from 4479 adults (women 41.6% vs men 58.4%) were identified.Results: The overall prevalence of AF was 12.4%, without sex differences (women, 12.8% vs men, 12.1%). Patients with AF were older (age 73.9 ± 11.8 vs non-AF 67 ± 13.5 years), with lower lipid levels (TG, total cholesterol, and LDL-cholesterol, all p < 0.0001), and at lower eGFR level (64.1 ± 30.9 vs non-AF 68.8 ± 41.4 mL/min/1.73m2, p < 0.0001). Besides, sex differences were present in all electrocardiographic parameters (all p < 0.05). Hypertension had the highest odds ratio (1.33; p = 0.026) for AF. Comparing AF to non-AF, the QTc of quartiles was significantly different (p < 0.0089). The shortest and longest QTc quartiles had an increased incidence of AF.Conclusion: AF risk in patients with MetS phenotypes can be reflected by QTc quartiles.Keywords: atrial fibrillation, electrocardiography, metabolic syndrome, lipid, QTc interval

This study aimed to investigate the technical feasibility of a percutaneous endoscopic limited-dorsal laminectomy (PELDL) and to evaluate if the decompression and examination of the lumbosacral vertebral canals could be achieved using an endoscope in small dogs. A total of eight fresh canine cadavers were used for the study. Following the injection of a barium and agarose mixture (BA-gel), which simulates intervertebral disc herniation, a PELDL was performed over L7-S1 in these animals. Computed tomography (CT) scans were obtained pre- and postoperatively to evaluate the surgical outcomes. All the procedures were completed with a clear visualisation of the spinal cord and removal of the BA-gel. The mean surgery time for the PELDL was 30.00 ± 12.01 minutes. In two dogs, iatrogenic nerve root injuries were caused by the surgical instruments during the operation. The CT scans showed that the amount of BA-gel removed was sufficient for a spinal-cord decompression. A PELDL could be used for the BA-gel removal to decompress the spinal cord and provide a clear view of the spinal canal. Therefore, it could be used as an alternative surgical option to treat lumbosacral disc disease in dogs.

An-Hsun Chou,1–3 Chia-Chih Liao,1,2 Hung-Chen Lee,1,4 Jiin-Tarng Liou,1,2 Fu-Chao Liu1,2 1Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Anesthesiology, Xiamen Chang Gung Hospital, Taoyuan, Taiwan; 4Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, TaiwanCorrespondence: Fu-Chao LiuDepartment of Anesthesiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 5, Fusing Street, Gueishan District, Taoyuan City 33305, TaiwanTel +886-3-3281200 (ext. 3624)Fax +886-3-3281200 (ext. 2787)Email ana5189@cgmh.org.twPurpose: Dexmedetomidine [DEX; (S)-4-[1-(2,3-dimethylphenyl)ethyl]-3H-imidazole] is a selective α2-adrenergic receptor (α2-AR) agonist that attenuates the liver damage associated with local or systemic inflammation. However, it remains unclear whether DEX has protective effects against acetaminophen (Paracetamol, PARA)-induced liver toxicity (PILT).Methods: PILT mice were established by intraperitoneal administration of a hepatotoxic dose of acetaminophen (300 mg/kg). Thirty minutes later, the mice were treated with DEX at a concentration of 0, 5, 25, or 50 μg/kg. Blood and liver samples were obtained for further analysis.Results: DEX treatment significantly attenuated PILT in mice, with the strongest beneficial effects at a dose of 25 μg/kg. The levels of hepatic cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), in addition to myeloperoxidase (MPO) activity, were significantly decreased following DEX treatment. Moreover, DEX treatment reduced macrophage recruitment around the area of hepatotoxicity and the expression levels of hepatic phosphorylated mitogen-activated protein kinase kinase 4 (MAP2K4), c-jun N-terminal kinase (JNK), and c-Jun expression induced by acetaminophen overdose.Conclusion: The data suggest that DEX likely downregulates the JNK signaling pathway and its downstream effectors to promote its hepatoprotective effect, providing a clinical application of DEX for the attenuation of PILT.Keywords: dexmedetomidine, acetaminophen-induced liver toxicity, MAP2K4/JNK/c-Jun

Do Young Kim,1 Ju Hyun Kim,2 Won Young Tak,3 Jong Eun Yeon,4 Joon Hyeok Lee,5 Jung Hwan Yoon,6 Youn Jae Lee,7 Byung Seok Lee,8 Byung Hoon Han,9 Han Chu Lee10 1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, 2Department of Gastroenterology, Gachon University Gil Medical Center, Incheon, 3Department of Internal Medicine, Kyungpook National University Hospital, Daegu, 4Department of Internal Medicine, Korea University Guro Hospital, Seoul, 5Department of Gastroenterology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 6Department of Internal Medicine, Seoul National University Hospital, Seoul, 7Department of Gastroenterology, Inje University Busan Paik Hospital, Busan, 8Department of Gastroenterology, Chungnam National University Hospital, Daejeon, 9Department of Gastroenterology, Kosin University Gospel Hospital, Busan, 10Department of Internal Medicine, Asan Medical Center, Ulsan University, Seoul, Republic of Korea Background and objective: Entecavir (ETV) is a standard of care for chronic hepatitis B (CHB). In a bioequivalence study, ETV from Dong-A ST (Baracle®) was found to have a pharmacokinetic profile equivalent to ETV from Bristol-Myers Squibb (BMS) (Baraclude®). The present study was conducted to evaluate the antiviral activity and safety of ETV from Dong-A ST in comparison to ETV from BMS in patients with CHB. Methods: In this multicenter, double-blind, active-controlled, stratified-randomized, parallel group, comparative trial, 118 treatment-naïve patients with CHB were randomly assigned to receive either 0.5 mg of ETV from Dong-A ST or ETV from BMS once daily for 48 weeks. The primary efficacy endpoint was virologic improvement (a mean reduction from baseline in serum HBV DNA levels) at 24 weeks. Secondary efficacy endpoints included a mean reduction in serum HBV DNA levels at 48 weeks, proportion of patients with undetectable levels of serum HBV DNA, rates of hepatitis B e antigen (HBeAg) loss and seroconversion, rates of HBsAg loss and seroconversion, and rates of normalization of alanine aminotransferase (ALT) levels. Results: From baseline to week 24, HBV DNA levels (log10) decreased by 4.81 and 4.63 with ETV from Dong-A ST and with ETV from BMS, respectively. The upper limit of two-sided 95% confidence intervals (CI) (equivalent to one-sided 97.5% CIs) for the difference between the treatment groups was 0.208, which was below the noninferiority margin of 1, thus supporting the noninferiority of ETV from Dong-A ST in comparison to ETV from BMS. No statistically significant differences were noted between the treatment groups in all secondary and tertiary efficacy endpoints. Safety profiles were also similar between the two groups. Conclusion: In patients with previously untreated HBeAg-positive or negative HBV infection, the efficacy of ETV from Dong-A ST was noninferior to that of ETV from BMS, and there were no significant differences in efficacy or safety between two groups. Keywords: chronic hepatitis B, generic, ETV from Dong-A ST (Baracle®)

Jui-Ming Liu,1–3,* Ren-Jun Hsu,3–5,* Fung-Wei Chang,6 Feng-Hsiang Chiu,7,8 Chia-Lun Yeh,1 Chun-Fa Huang,9,10 Shu-Ting Chang,11 Hung-Chang Lee,12 Hsin Chi,12,13 Chien-Yu Lin14,15 1Division of Urology, Department of Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, 2Department of Medicine, National Yang-Ming University, 3Graduate Institute of Life Sciences, 4Department of Pathology and Graduate Institute of Pathology and Parasitology, the Tri-Service General Hospital, National Defense Medical Center, 5Biobank Management Center of the Tri-Service General Hospital, 6Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, 7Department of Emergency Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 8Superintendent office, Lihuili Eastern Hospital, Ningbo, Zhejiang province, People’s Republic of China; 9School of Chinese Medicine, College of Chinese Medicine, China Medical University, 10Department of Nursing, College of Medical and Health Science, Asia University, Taichung City, 11Department of Gastroenterology, BinKun Women’s and Children’s Hospital, Taoyuan City, 12Department of Infectious Disease, MacKay Children’s Hospital, Taipei, 13Department of Medicine, MacKay Medical College, New Taipei city, 14Department of Pediatrics and Infectious Disease, Hsinchu MacKay Memorial Hospital, Hsinchu City, Taiwan; 15Division of Infection and Pathway Medicine, College of Medicine and Veterinary Medicine, The University of Edinburgh, Scotland, UK *These authors contributed equally to this work Objectives: Scabies is a common and annoying disorder. Pernicious anemia (PA) is a serious disease which, when untreated, leads to death. Mounting evidence suggests that immune-mediated inflammatory processes play a role in the pathophysiology of both diseases. The relationship between these two diseases has not been investigated. We conducted this study to explore the potential relationship between scabies and PA.Materials and methods: This nationwide, population-based study was conducted using the National Health Insurance Research Database of Taiwan. In total, 5,407 patients with scabies were identified as a study group and 20,089 matched patients were randomly selected as a control group. We tracked patients in both groups for a 7-year period to identify the incidence of PA. The demographic characteristics and comorbidities of the patients were analyzed, and Cox proportional hazards regression was used to calculate the hazard ratios for PA.Results: Of the 25,496 patients in this study, 183 (0.7%) patients with newly diagnosed PA were identified during the 7-year follow-up period; 71 of 5,407 (1.3%) from the scabies group and 112 of 20,089 (0.6%) from the control group. Patients with scabies had a higher risk of subsequent PA, with a crude hazard ratio of 2.368. After adjusting for covariates, the adjusted hazard ratio was 1.51 (95% confidence interval: 1.09–2.08).Conclusion: This study demonstrated an increased risk of PA (adjusted hazard ratio 1.51) among patients with scabies. Immune-mediated inflammatory processes may contribute to this association. Further studies are warranted to investigate the entire pathological mechanisms between these two diseases. Physicians should pay attention to patients with history of scabies presented with anemia. Further confirmative tests of PA may contribute to correct diagnosis and initiation of vitamin B12 supplement. Keywords: scabies, pernicious anemia, National Health Insurance Research Database, autoimmune gastritis, vitamin B12 deficiency, cobalamin

Wai-Tao Chan,1–3 Cheng-Che Liu,4 Jen-Shiu Chiang Chiau,5 Shang-Ting Tsai,6 Chih-Kai Liang,6 Mei-Lien Cheng,5 Hung-Chang Lee,7,8 Chun-Yun Yeung,1,3,9 Shao-Yi Hou2,6 1Department of Pediatric Gastroenterology, Hepatology and Nutrition, MacKay Children’s Hospital, 2Graduate Institute of Engineering Technology, National Taipei University of Technology, 3Mackay Medicine, Nursing, and Management College, 4Institute of Preventive Medicine, National Defense Medical Center, Taipei, 5Department of Medical Research, MacKay Memorial Hospital, Hsinchu, 6Graduate Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei, 7Department of Pediatrics, MacKay Memorial Hospital, Hsinchu, 8Department of Pediatrics, Taipei Medical University, Taipei, 9Department of Medicine, Mackay Medical College, New Taipei, Taiwan, Republic of China Abstract: Silica nanoparticles (SiNPs) are being studied and used for medical purposes. As nanotechnology grows rapidly, its biosafety and toxicity have frequently raised concerns. However, diverse results have been reported about the safety of SiNPs; several studies reported that smaller particles might exhibit toxic effects to some cell lines, and larger particles of 100 nm were reported to be genotoxic to the cocultured cells. Here, we investigated the in vivo toxicity of SiNPs of 150 nm in various dosages via intravenous administration in mice. The mice were observed for 14 days before blood examination and histopathological assay. All the mice survived and behaved normally after the administration of nanoparticles. No significant weight change was noted. Blood examinations showed no definite systemic dysfunction of organ systems. Histopathological studies of vital organs confirmed no SiNP-related adverse effects. We concluded that 150 nm SiNPs were biocompatible and safe for in vivo use in mice. Keywords: in vivo, mice, silica nanoparticle, nanotoxicity

Nan-Chang Chiu,1,2,* Chien-Yu Lin,3,* Hsin Chi,1 Chun-Yan Yeung,1,2 Wei-Hsin Ting,1 Wai-Tao Chan,1 Chuen-Bin Jiang,1 Sung-Tse Li,3,4 Chao-Hsu Lin,3 Hung-Chang Lee1,2 1Department of Pediatrics, MacKay Children’s Hospital, 2Department of Medicine, MacKay Junior College of Medicine, Nursing and Management, Taipei, 3Department of Pediatrics, Hsinchu MacKay Memorial Hospital, Hsinchu City, 4Department of Statistics and Information Science, Fu Jen Catholic University, New Taipei, Taiwan *These authors contributed equally to this work Purpose: The long-term impact of Helicobacter pylori infection is complex, and concerns about the need for eradication exist. We conducted this case control study to investigate the association between H. pylori infection and failure to thrive (FTT).Patients and methods: From January 2009 to December 2011, 53 children with FTT group and matched children with the same sex and age and similar socioeconomic status without FTT (control group) were enrolled. A questionnaire was administered to the parents/guardian, and a 13C-urea breath test was performed to detect H. pylori infection.Results: We found that the total prevalence of H. pylori infection was 29.2% and that there was no association between FTT and H. pylori infection (FTT group: 32%; control group: 26.4%; P=0.67). Short stature was more common in the FTT group and abdominal pain in the control group (FTT group: 37.7%; control group: 11.3%; P=0.003). In a comparison between the H. pylori-positive and -negative groups, abdominal pain (87.1% vs 64%; P=0.032) and the frequency of endoscopy (74.2% vs 32%; P

Sang Joon Lee,1,* Young-Il Jeong,2,* Hyung-Kyu Park,3 Dae Hwan Kang,2,4 Jong-Suk Oh,3 Sam-Gyu Lee,5 Hyun Chul Lee31Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 2Biomedical Research Institute, Pusan National University Hospital, Busan, 3Department of Microbiology, Chonnam National University Medical School, Gwangju, 4Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Gyeongnam, 5Department of Physical and Rehabilitation Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea*These authors contributed equally to this workBackground: Since cancer cells are normally over-expressed cathepsin B, we synthesized dendrimer-methoxy poly(ethylene glycol) (MPEG)-doxorubicin (DOX) conjugates using a cathepsin B-cleavable peptide for anticancer drug targeting.Methods: Gly-Phe-Leu-Gly peptide was conjugated with the carboxylic acid end groups of a dendrimer, which was then conjugated with MPEG amine and doxorubicin by aid of carbodiimide chemistry (abbreviated as DendGDP). Dendrimer-MPEG-DOX conjugates without Gly-Phe-Leu-Gly peptide linkage was also synthesized for comparison (DendDP). Nanoparticles were then prepared using a dialysis procedure.Results: The synthesized DendGDP was confirmed with 1H nuclear magnetic resonance spectroscopy. The DendDP and DendGDP nanoparticles had a small particle size of less than 200 nm and had a spherical morphology. DendGDP had cathepsin B-sensitive drug release properties while DendDP did not show cathepsin B sensitivity. Further, DendGDP had improved anticancer activity when compared with doxorubicin or DendDP in an in vivo CT26 tumor xenograft model, ie, the volume of the CT26 tumor xenograft was significantly inhibited when compared with xenografts treated with doxorubicin or DendDP nanoparticles. The DendGDP nanoparticles were found to be relatively concentrated in the tumor tissue and revealed stronger fluorescence intensity than at other body sites while doxorubicin and DendDP nanoparticles showed strong fluorescence intensity in the various organs, indicating that DendGDP has cathepsin B sensitivity.Conclusion: DendGDP is sensitive to cathepsin B in tumor cells and can be used as a cathepsin B-responsive drug targeting strategy. We suggest that DendGDP is a promising vehicle for cancer cell targeting.Keywords: cathepsin B, CT26 cell, enzyme-sensitive dendrimer, tumor targeting, tetra peptide

Hsin-chung Lee,1,2 Qing-Dong Ling,1,3 Wan-Chun Yu,4 Chunh-Ming Hung,4 Ta-Chun Kao,4 Yi-Wei Huang,4 Akon Higuchi3–51Graduate Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taoyuan, 2Department of Surgery, Cathay General Hospital, Da'an District, Taipei, 3Cathay Medical Research Institute, Cathay General Hospital, Hsi-Chi City, Taipei, 4Department of Chemical and Materials Engineering, National Central University, Jhongli, Taoyuan, Taiwan; 5Department of Reproduction, National Research Institute for Child Health and Development, Okura, Tokyo, JapanPurpose: We evaluated the higher levels of carcinoembryonic antigen (CEA) secreted by the LoVo human colon carcinoma cells in a medium containing anticancer drugs. Drug-resistant LoVo cells were analyzed by subcutaneously xenotransplanting them into mice. The aim of this study was to evaluate whether the drug-resistant cells isolated in this study were cancer-initiating cells, known also as cancer stem cells (CSCs).Methods: The production of CEA was investigated in LoVo cells that were cultured with 0–10 mM of anticancer drugs, and we evaluated the increase in CEA production by the LoVo cells that were stimulated by anticancer drug treatment. The expression of several CSC markers in LoVo cells treated with anticancer drugs was also evaluated. Following anticancer drug treatment, LoVo cells were injected subcutaneously into the flanks of severe combined immunodeficiency mice in order to evaluate the CSC fraction.Results: Production of CEA by LoVo cells was stimulated by the addition of anticancer drugs. Drug-resistant LoVo cells expressed lower levels of CSC markers, and LoVo cells treated with any of the anticancer drugs tested did not generate tumors within 8 weeks from when the cells were injected subcutaneously into severe combined immunodeficiency mice. These results suggest that the drug-resistant LoVo cells have a smaller population of CSCs than the untreated LoVo cells.Conclusion: Production of CEA by LoVo cells can be stimulated by the addition of anticancer drugs. The drug-resistant subpopulation of LoVo colon cancer cells could stimulate the production of CEA, but these cells did not act as CSCs in in vivo tumor generation experiments.Keywords: drug treatment, colon cancer cell, 5-fluorouracil, stem cell, CD133

ObjectiveThe objectives of this study are to use network analysis to describe the pattern of neonatal transfers in California, to compare empirical sub-networks with established referral regions and to determine factors associated with transport outside the originating sub-network.Study designThis cross-sectional database study included 6546 infants

Utilizing ambient pressure X-ray photoelectron spectroscopy (AP-XPS), the surface segregation and oxidation of Pt3Ni(1 1 1) alloys are investigated as a function of temperature and oxygen pressure. The in situ AP-XPS measurements of oxygen oxidation process show that the Pt "skin" surface is not stable under the exposure of oxygen pressure of 100 mTorr at room temperature. As the temperature and pressure are elevated, the formations of Ni2O3, NiOx, and NiO are observed on surface while Pt atom starts to reduce its adsorbed oxygen, which is a clear sign of surface segregation of Ni to surface. Upon the evacuation of oxygen gas, i.e. ultrahigh vacuum condition, both of NiOx and NiO oxide get reduced and Ni2O3 remains on the surface. The DFT calculation is employed to explain the formation of surface oxides under oxidation condition.

Utilizing ambient pressure X-ray photoelectron spectroscopy (AP-XPS), the surface segregation and oxidation of Pt3Ni(1 1 1) alloys are investigated as a function of temperature and oxygen pressure. The in situ AP-XPS measurements of oxygen oxidation process show that the Pt "skin" surface is not stable under the exposure of oxygen pressure of 100 mTorr at room temperature. As the temperature and pressure are elevated, the formations of Ni2O3, NiOx, and NiO are observed on surface while Pt atom starts to reduce its adsorbed oxygen, which is a clear sign of surface segregation of Ni to surface. Upon the evacuation of oxygen gas, i.e. ultrahigh vacuum condition, both of NiOx and NiO oxide get reduced and Ni2O3 remains on the surface. The DFT calculation is employed to explain the formation of surface oxides under oxidation condition.

ObjectiveSurvival of preterm and very low birth weight (VLBW) infants has steadily improved. However, the rates of mortality and morbidity among the very smallest infants are poorly characterized.Study designData from the California Perinatal Quality Care Collaborative for the years 2005 to 2012 were used to compare the mortality and morbidity of profoundly low birth weight (ProLBW, birth weight 300 to 500 g) and profoundly small for gestational age (ProSGA, 80% of AGA and VLBW infants. The largest increase in mortality in ProSGA and ProLBW infants occurred prior to 12 h of age, and most mortality happened in this time period. Survival of the ProLBW and ProSGA infants was positively associated with higher gestational age, receipt of antenatal steroids, cesarean section delivery and singleton birth.ConclusionSurvival of ProLBW and ProSGA infants is uncommon, and survival without substantial morbidity is rare. Survival is positively associated with receipt of antenatal steroids and cesarean delivery.

© 2014 Taylor & Francis Previous research has demonstrated a strong link between prosocial behavior – particularly autonomous prosocial behavior – and well-being. Little is known, however, about whether and how autonomy might be boosted in the context of everyday kindnesses. We tested the effect of supporting students’ autonomy on well-being gains from practicing acts of kindness in a six-week randomized experimental study in the United States and South Korea. As predicted, performing kind acts while receiving autonomy support led to greater improvements in well-being than performing kind acts without autonomy support or engaging in comparison activities (i.e. focusing on one’s academic work, with or without autonomy support). Notably, these well-being improvements were mediated by feelings of autonomy, competence, and relatedness. The current study is one of the first to demonstrate the causal effect of autonomous prosocial behavior on well-being, as well as the psychological mechanism (i.e. need satisfaction) explaining this effect.

Objective:To investigate the incidence and risk factors associated with uncomplicated maternal sepsis and progression to severe sepsis in a large population-based birth cohort.Methods:This retrospective cohort study used linked hospital discharge and vital