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Horng-Chyuan Lin,1– 3 Meng-heng Hsieh,1,2 Yu-Lun Lo,1,2 Hung-Yu Huang,1,2 Shih-Wei Huang,1,2 Chien-Da Huang,1,2 Po-Jui Chang,1,2 Chun-Yu Lo,1,2 Ting-Yu Lin,1,2 Yueh-Fu Fang,1,2 Shu-Min Lin,1,2 Chun-Yu Lin,1,2,* Ying-Huang Tsai1,2,4,* 1Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Respiratory Therapy, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 4Department of Pulmonary and Critical Care Medicine, Xiamen Chang Gung Hospital, Xiamen, 361028, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chun-Yu Lin, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Kweishan, Taoyuan, 33305, Taiwan, Tel +886-3-3281200 ext. 8467, Fax +886-3-3282474, Email pitiful1984@gmail.com Ying-Huang Tsai, Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung Medical Foundation and Department of Respiratory Therapy, College of Medicine, Chang Gung University, 5 Fu-Hsing Street, Kweishan, Taoyuan, 33305, Taiwan, Tel +886-3-3281200 ext. 8470, Fax +886-3-3282474, Email chestmed@cgmh.org.twBackground: Non-cystic fibrosis bronchiectasis is associated with airway pathogen colonization. We planned to investigate the inflammatory markers in patients with different airway pathogens and their correlation with disease severity.Methods: We enrolled patients aged between 20 and 75 from October 2021 to August 2022. All patients had sputum evaluation for bacterial and fungal cultures before enrollment, and were classified into four groups according to the culture results.Results: Forty-four patients with non-CF bronchiectasis and six controls were enrolled and categorized as follows: Group 1, no pathogens identified in sputum cultures (n = 14); Group 2, positive fungal culture results (n = 18); Group 3, positive P. aeruginosa culture results (n = 7); and Group 4, positive culture results for both fungi and P. aeruginosa (n = 5). Group 4 had significantly higher serum defensin α 1, IL-6 and tissue inhibitors of MMP (TIMP)-1 levels than group 1 patients. The serum levels of IL-6 and TIMP-1 were positively correlated with the FACED score and negatively correlated with distance-saturation product.Conclusion: Significantly higher levels of serum IL-6 and TIMP-1 were found in the patients who had concomitant fungal and P. aeruginosa colonization, and were closely related to clinical severity and may have important roles in disease monitoring.Keywords: TIMP-1, non-cystic fibrosis bronchiectasis, clinical severity

Ting-Yu Lin, Hao-Chien Cheng, Hung-Wen Liu, Tsung-Min Hung Department of Physical Education and Sport Sciences, National Taiwan Normal University, Taipei, TaiwanCorrespondence: Tsung-Min Hung, Institute for Research Excellence in Learning Sciences, National Taiwan Normal University, 162, Section 1, Heping E. Road, Taipei City, 106, Taiwan, Tel/Fax +886-2-7749-1111, Email ernesthungkimo@yahoo.com.twObjective: Given the recognized benefits of resistance exercise on both physical and cognitive domains, elucidating how to maximize its benefit is pivotal. This study aims to evaluate these effects in terms of their timing and intensity on cognitive performance.Methods: This was a four-arm, crossover randomized controlled trial. Healthy college-aged male adults with recreational resistance training experience participated in this study. Participants completed three separate sessions of circuit barbell resistance exercises, including back squat, press, and deadlift. Each session corresponded to a different intensity level: 65% 1RM, 72% 1RM, and 78% 1RM. Each session consisted of 5 repetitions across 3 sets, with a 3-minute rest between exercises and sets. For the control condition, participants engaged in a reading activity for the same duration. The subjective exercise intensity was measured using the rating of perceived exertion and repetitions in reserve immediately after each set. The primary outcome was the temporal effect of acute resistance exercise on inhibition, measured by the Stroop color-word task. The secondary outcome was the effect of different intensities.Results: 30 out of 31 recruited participants were randomized, with 28 completing all experiment sessions. Using repeated measures correlation (rrm), a linear temporal effect was observed on accuracy-adjusted congruent reaction time: rrm = 0.114, p = 0.045, 95% CI [0.002, 0.223]. Participants responded 19.1 ms faster than the control condition approximately 10 minutes post-intervention. This advantage, however, gradually declined at a rate of 4.3 ms every 15 minutes between 10– 55 minutes post-intervention. In contrast, no significant effects were detected for incongruent trials or the Stroop effect. When examining the linear relationship across exercise intensities, no significant correlations emerged for congruent trials.Conclusion: Resistance exercise demonstrates a temporal effect on cognitive performance, particularly in reaction speed for congruent trials, without significant changes in incongruent trials or the overall Stroop effect. The findings highlight the importance of timing in leveraging the cognitive benefits of acute resistance exercise, suggesting a window of enhanced cognitive performance following exercise. However, this study has a limitation regarding Type I error inflation, due to multiple measurements of cognitive performance being undertaken, suggesting caution in interpreting the observed temporal effects. Practically, scheduling crucial, cognitively demanding tasks within 10– 60 minutes post-exercise may maximize benefits, as positive effects diminish after this period.Keywords: executive function, physical exercise, resistance training, cognition, RCT

Ting-Yu Lin,1,2 Firdian Makrufardi,3,4 Nguyen Thanh Tung,3,5 Amja Manullang,3 Po-Jui Chang,1,2 Chun-Yu Lo,1,2 Tzu-Hsuan Chiu,1 Pi-Hung Tung,1 Chiung-Hung Lin,1 Horng-Chyuan Lin,1,2 Chun-Hua Wang,1,2 Shu-Min Lin1,2 1Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4Department of Child Health, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada – Dr. Sardjito Hospital, Yogyakarta, Indonesia; 5Otorhinolaryngology Department, Cho Ray Hospital, Ho Chi Minh City, VietnamCorrespondence: Shu-Min Lin, Department of Thoracic Medicine, Chang Gung Memorial Hospital, 199 Tun-Hwa N. Road, Taipei, Taiwan, Fax +886 33272474, Email smlin100@gmail.comBackground: Early-onset asthma (EOA) and late-onset asthma (LOA) are two distinct phenotypes. Air pollution has been associated with an increase in poorer asthma outcomes. The objective of this study was to examine the effects of traffic-related air pollution (TRAP) on asthma outcomes in EOA and LOA patients.Methods: A cross-sectional study was conducted on 675 asthma patients (LOA: 415) recruited from a major medical center in Taiwan. The land-use regression (LUR) model was used to estimate the level of exposure to PM10, PM2.5, NO2, and O3 on an individual level. We investigated the association between TRAP and asthma outcomes in EOA and LOA patients, stratified by allergic sensitization status, using a regression approach.Results: An increase in PM10 was associated with younger age of onset, increased asthma duration, and decreased lung function in EOA patients (p< 0.05). An increase in PM10 was associated with older age of onset, and decreased asthma duration, eosinophil count, and Asthma Control Test (ACT) score in LOA patients. An increase in PM2.5 was associated with younger age of onset, increased asthma duration, decreased eosinophil count, and lung function in EOA patients (p< 0.05). An increase in PM2.5 was associated with decreased lung function and ACT score in LOA patients. An increase in NO2 was associated with increased eosinophil count and decreased lung function in EOA patients (p< 0.05). An increase in O3 was associated with decreased lung function in LOA patients (p< 0.05). In addition, associations of TRAP with age of onset and eosinophil counts were mainly observed in both EOA and LOA patients with allergic sensitization, and an association with ACT was mainly observed in LOA patients without allergic sensitization.Conclusion: The impact of TRAP on age of onset, eosinophil count, and lung function in EOA patients, and ACT in LOA patients, was affected by the status of allergic sensitization.Keywords: air pollution, allergy, early-onset asthma, late-onset asthma, respiratory disease

Ting-Yu Lin,1,2 Chun-Yu Lo,1,2 Po-Jui Chang,1,2 Yu-Lun Lo,1,2 Chung-Shu Lee,1– 3 Chih-Hao Chang,1– 3 Chih-Teng Yu,1,2 Jonathan Huai Yao,1 Shu-Min Lin1,2 1Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Pulmonary and Critical Care Medicine, New Taipei Municipal Tucheng Hospital, New Taipei City, TaiwanCorrespondence: Shu-Min Lin, Department of Thoracic Medicine, Chang Gung Memorial Hospital, 199 Tun-Hwa N. Road, Taipei, Taiwan, Fax + 886 33272474, Email smlin100@gmail.comBackground: The immunological features of eosinophils in early-onset asthma (EOA) differ from those in late-onset asthma (LOA). Clinical trials of anti-interleukin-5 (IL-5) treatment for severe eosinophilic asthma showed a better response for LOA patients than EOA patients. We wonder if the transcriptional activity of activated eosinophils was different in EOA and LOA.Methods: Eosinophils obtained from well-controlled EOA and LOA patients and normal subjects were compared in terms of the mRNA expression of activation-related genes and specific markers related to cell functions in eosinophils activated by IL-5 or IL-17. The correlation between mRNA expression and clinical features and lung function was further analyzed.Results: The transcriptional expression of most genes was higher in activated eosinophils from LOA patients than in those from EOA patients and normal subjects. After IL-17 stimulation, the expression of certain genes was higher in atopic EOA patients than in non-atopic EOA patients. Similar observation was noted in obese EOA patients. After IL-5 stimulation, the transcriptional expression of most genes in eosinophils from LOA patients was negatively correlated with indicators of lung function. These correlations were less pronounced in EOA patients: After IL-17 stimulation, some genes in EOA patients were negatively correlated with post-bronchodilator changes in lung function.Conclusion: This study describes differences in the transcriptional active patterns of eosinophils and their correlation to atopy and obesity by age of onset. High transcriptional activity in activated eosinophils and a negative correlation to lung function indicate the importance of eosinophils in the pathogenesis of LOA.Graphical Abstract: Keywords: late-onset asthma, early-onset asthma, eosinophils, messenger RNA

Sung Huang Laurent Tsai,1– 3 Chien-Hao Chen,1,2 Eric H Tischler,3,4 Shyam J Kurian,5 Tung-Yi Lin,1,2 Chun-Yi Su,1,2 Greg Michael Osgood,3,5 Amber Mehmood,6 Tsai-Sheng Fu2,7 1Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Keelung branch, Keelung, 204, Taiwan; 2School of medicine, Chang Gung University, Taoyuan, 333, Taiwan; 3Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 4Department of Orthopaedic Surgery and Rehabilitation Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY, USA; 5Department of Orthopaedic Surgery, Johns Hopkins Hospital, Baltimore, MD, USA; 6University of South Florida College of Public Health,Tampa, FL, USA; 7Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Linkou, TaiwanCorrespondence: Chien-Hao Chen, Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Keelung branch, Taoyuan, 20401, Taiwan, Tel +886-2231131 (ext. 3016), Email john1982@adm.cgmh.org.twIntroduction: Fat embolism syndrome (FES) is a rare life-threatening condition that can develop after traumatic orthopedic injuries. Controversy remains concerning the epidemiology in the elderly population. Therefore, this study aims to report FES related to in-hospital mortality stratified by age.Methods: A retrospective trauma cohort study was conducted using data from the National Trauma Data Bank (NTDB) from 2007 to 2014. All FES cases were included in the study with the diagnosis of FES (ICD9 958.1). Death on arrival cases were excluded. Patients were stratified by age cohort: less than 40 (G1), 40– 64 (G2), and greater than 65 (G3) years of age. The primary outcome evaluated was in-hospital mortality. Multivariable regression models were performed to adjust for potential confounders.Results: Between 2007 and 2014, 451 people from a total of 5,836,499 trauma patients in the NTDB met the inclusion criteria. The incidence rate was 8 out of 100,000. The inpatient mortality rate was 11.8% for all subjects with the highest mortality rate of 17.6% in patients over 65. Multivariable analyses demonstrated that age greater than 65 years was an independent predictor of mortality (aOR 24.16, 95% CI 3.73, 156.59, p=0.001), despite higher incidence and injury severity of FES among patients less than 40. No significant association with length of hospital stay, length of intensive unit care, or length of ventilation use was found between the groups. Subgroup analysis of the elderly population also showed a higher mortality rate for FES in femoral neck fracture patients (18%) than other femoral fractures (14%).Conclusion: In this retrospective cohort analysis, old age (≥ 65 years) was found to be an independent risk factor for in-hospital mortality among fat embolism syndrome patients. Elderly patients specifically with femoral neck fractures should be monitored for the development of FES.Keywords: fat embolism, trauma, database, mortality, age

Hung-Yuan Lin,1– 3 Ting-Yu Lin,4 Ya-Jung Chuang,5 Li-Ju Lai,6 Pi-Jung Lin7 1Department ofOpthalmology, Universal Eye Center, Zhong-Li, Taiwan, Republicof China; 2Department of Optometry, Central Taiwan University of Science and Technology, Taichung City, Taiwan, Republicof China; 3Department of Ophthalmology, Shanghai Ruidong Hospital, Shanghai, People’s Republic ofChina; 4Department of Chemistry, Barnard College, Columbia University New York, New York, NY, USA; 5Department of Ophthalmology, Universal Eye Center, Long-Tan, Taiwan, Republicof China; 6Department of Ophthalmology, Universal Eye Center, Chia-Yi, Taiwan, Republic ofChina; 7Department of Ophthalmology, Universal Eye Center, Taipei, Taiwan, Republic ofChinaCorrespondence: Ya-Jung Chuang Tel + 886-983308370Email rannyposh@gmail.comPurpose: The purpose of this study was to evaluate the efficacy of a novel double-docking technique, incorporating the use of femtosecond laser arcuate keratotomy (FSAK) in correcting low-degree astigmatism and Malyugin ring, in a patient with intraoperative floppy iris syndrome (IFIS).Methods: A case report of a 72-year-old man with grade 4 cataract, low-degree astigmatism (< 2D), and IFIS (pupil size < 4 mm, intraoperatively) is presented. The patient underwent cataract surgery using a femtosecond laser to treat low-degree astigmatism because the patient requested for the use of a multifocal intraocular lens (IOL). The first docking was performed to complete arcuate keratotomy, produce the mainparacentesis incisions, and create clear corneal incisions. Insertion of the Malyugin ring was performed after the first docking, whereas the second one was executed to complete continuous curvilinear capsulotomy and lens fragmentation. The patient’s uncorrected visual acuity (UCVA) was measured pre- and post-operatively. The complications were evaluated post-operatively and 3 months later during the follow-up visit.Results: The patient’s UCVA for distance improved from 0.3 (6/12 Snellen equivalent) to 0 (6/6 Snellen equivalent) logMAR post-operatively. During the follow-up visit, the patient’s uncorrected near visual acuity was at J2. His corneal astigmatism changed from − 1.0 Diopter @177° pre-operative to − 0.12 D @173° post-operative. No other intraoperative or post-operative complications were observed.Conclusion: The double-docking technique, with the use of FSAK, and Malyugin ring produced successful surgical outcomes for the patient. The benefits of this technique allow surgeons to avoid changing the shape of the patient’s cornea from the injection of the viscoelastic device into the anterior chamber, which could lower the femtosecond laser’s precision and docking location.Keywords: femtosecond laser arcuate keratotomy, Malyugin ring, low-degree, astigmatism, intraoperative floppy iris syndrome

Mei-Hing Ng,1,2 Vincent Chin-Hung Chen,3,4 Hua Ting,1,5 Tsang-Yaw Lin,2 Sheng-Huang Chang,2 Michael Gossop61Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 2Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nan-Tou County, Taiwan; 3Department of Psychiatry, Chang Gung Medical Foundation, Chiayi Chang Gung Memorial Hospital, Chiayi County, Taiwan; 4Department of Psychiatry, School of Medicine, Chang Gung University, Taoyuan City, Taiwan; 5Department of Physical Medicine and Rehabilitation, Chung-Shan Medical, University Hospital, Chung-Shan Medical University, Taichung, Taiwan; 6National Addiction Center, Institute of Psychiatry, King’s College London, London, UKPurpose: Few empirical studies have investigated hematological parameters among people with a heroin use disorder. This study explores the prevalence of macrocytosis and associated factors among patients with heroin use disorder who were entering methadone maintenance treatment (MMT) in Taiwan.Patients and methods: In this cross-sectional study, hematological parameters were measured and the prevalence of macrocytosis was assessed in a sample of 958 patients with a heroin use disorder entering the MMT program at Tsaotun Psychiatric Center in Taiwan. The demographic characteristics, heroin-related issues, other substance use history, and other clinical variables were analyzed. Univariate analysis was used to assess the association of all variables. Multivariable logistic regression was used to identify the relationship between the significant factors and macrocytosis.Results: The study found that nearly one-fifth (19.5%) of the participants had macrocytosis. Older age, longer duration of heroin use, and more days of alcohol use within the previous month were associated with macrocytosis.Conclusion: We found that concurrent use of alcohol was an important factor related to macrocytosis among people with a heroin use disorder. The prevalence of macrocytosis indicated that alcohol use is common among this population. It is suggested that policies and practices regarding alcohol use should be addressed within methadone maintenance programs.Keywords: addiction, opioid dependence, substitution treatment, megalocytes

Tao-Yan Lin,1,* Yan Chen,1,* Jun-Shuang Jia,1,* Chen Zhou,2 Mei Lian,3 Yue-Ting Wen,1 Xiao-Yan Li,3 Heng-Wei Chen,3 Xiao-Lin Lin,1 Xiao-Ling Zhang,4 Sheng-Jun Xiao,2 Yan Sun,5 Dong Xiao1,31Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou 510515, People’s Republic of China; 2Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, Guilin 541199, People’s Republic of China; 3Institute of Comparative Medicine and Laboratory Animal Center, Southern Medical University, Guangzhou 510515, People’s Republic of China; 4Department of Physiology, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin 541004, People’s Republic of China; 5Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, People’s Republic of China*These authors contributed equally to this workPurpose: The correlation of cold-inducible RNA-binding protein (Cirbp) expression with clinicopathological features including patient prognosis in nasopharyngeal carcinoma (NPC) was investigated.Methods: The expression of Cirbp in NPC cell lines and tissue specimens was examined by qRT-PCR or immunohistochemistry (IHC).Results: Immunohistochemistry (IHC) results showed that high Cirbp expression was detected in 61 of 61 non-cancerous nasopharyngeal squamous epithelial biopsies, whereas the significantly reduced expression of Cirbp was observed in NPC specimens. In addition, IHC assay for Cirbp protein illustrated that the cells of 177 NPC samples and nasopharyngeal squamous epithlial cells displayed strong signals in nuclei and faint signals in cytoplasm, whereas Cirbp protein is mainly detected in the cell’s cytoplasm in many other cancers. More importantly, TNM classification displayed that the low expression of Cirbp was more frequently observed in T3-T4, N2-N3, M1 and III-IV NPC biopsies, and undifferentiated carcinoma (UDC) than T1-T2, N0-N1, M0 and I-II tumors, and differentiated nonkeratinizing carcinoma (DNKC), suggesting that Cirbp loss is a key molecular event in advanced cases of NPC. Kaplan–Meier survival analysis indicated that NPC patients showing lower Cirbp expression had a significantly shorter overall survival time than those with high Cirbp expression. Multivariate analysis suggested that the level of Cirbp expression was an independent prognostic indicator for NPC survival. Finally, we revealed a significant positive association between Cirbp expression and E-cadherin, and a notable negative correlation between Cirbp expression and Ki67 labeling index in NPC biopsies.Conclusion: Collectively, these findings demonstrate that loss of Cirbp expression is correlated with malignant progression and poor prognosis in NPC.Keywords: cirbp, nasopharyngeal carcinoma; NPC, TNM stage, prognosis, E-cadherin, Ki67

Tsai-Yu Wang,1 Yu-Lun Lo,1,2 Pai-Chien Chou,1 Fu-Tsai Chung,1 Shu-Min Lin,1 Ting-Yu Lin,1 Horng-Chyuan Lin,1 Chun-Hua Wang,1 Chih-Teng Yu,1 Han-Pin Kuo1 1Department of Thoracic Medicine, School of Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taipei, Taiwan; 2Healthcare Center, Chang Gung Memorial Hospital, Taipei, Taiwan Background: Osteoporosis is an important issue for patients with chronic obstructive pulmonary disease (COPD). Worse systemic inflammation and reduced exercise capacity have been reported in COPD patients with obstructive sleep apnea (OSA), implying that OSA may be an independent factor for osteoporosis in COPD patients. Methods: A total of 66 patients with bone mineral density (BMD) and polysomnography results from a previous COPD cohort (January 2008 to January 2013) were retrospectively enrolled. Clinical characteristics such as medication, pulmonary function, BMD, and results of polysomnography were analyzed. Results: The BMD in those with OSA was significantly lower than in those without OSA (-1.99±1.63 versus -1.27±1.14, P=0.045). In univariate analysis, body mass index, forced expiratory volume in 1 second, percentage of predicted value, incremental shuttle walk test, apnea–hypopnea index, and oxygen desaturation index (ODI) were significantly associated with BMD. After multivariate linear regression analysis, the ODI was still an independent factor for BMD. In addition, smaller total lung capacity is significantly associated with higher ODI and lower BMD, which implies that lower BMD might cause severer OSA via decreased total lung capacity. Conclusion: OSA may be an independent factor for BMD in patients with COPD, which implies a possible vicious cycle takes place in these patients. Keywords: chronic obstructive pulmonary disease, osteoporosis, total lung capacity

Tzu-yin Lin,1 Hongyong Zhang,1 Juntao Luo,2,5 Yuanpei Li,2 Tingjuan Gao,3 Primo N Lara Jr,1,4,6 Ralph de Vere White,4 Kit S Lam,1,2 Chong-Xian Pan,1,3,61Division of Hematology and Oncology, Department of Internal Medicine, 2Department of Biochemistry and Molecular Medicine, 3NSF Center for Biophotonics Science and Technology, School of Medicine, 4Department of Urology, University of California-Davis, Sacramento, CA, 5Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, 6VA Northern California Health Care System, Mather, CA, USABackground: We previously developed a bladder cancer-specific ligand (PLZ4) that can specifically bind to both human and dog bladder cancer cells in vitro and in vivo. We have also developed a micelle nanocarrier drug-delivery system. Here, we assessed whether the targeting micelles decorated with PLZ4 on the surface could specifically target dog bladder cancer cells.Materials and methods: Micelle-building monomers (ie, telodendrimers) were synthesized through conjugation of polyethylene glycol with a cholic acid cluster at one end and PLZ4 at the other, which then self-assembled in an aqueous solution to form micelles. Dog bladder cancer cell lines were used for in vitro and in vivo drug delivery studies.Results: Compared to nontargeting micelles, targeting PLZ4 micelles (23.2 ± 8.1 nm in diameter) loaded with the imaging agent DiD and the chemotherapeutic drug paclitaxel or daunorubicin were more efficient in targeted drug delivery and more effective in cell killing in vitro. PLZ4 facilitated the uptake of micelles together with the cargo load into the target cells. We also developed an orthotopic invasive dog bladder cancer xenograft model in mice. In vivo studies with this model showed the targeting micelles were more efficient in targeted drug delivery than the free dye (14.3×; P < 0.01) and nontargeting micelles (1.5×; P < 0.05).Conclusion: Targeting micelles decorated with PLZ4 can selectively target dog bladder cancer cells and potentially be developed as imaging and therapeutic agents in a clinical setting. Preclinical studies of targeting micelles can be performed in dogs with spontaneous bladder cancer before proceeding with studies using human patients.Keywords: bladder urothelial carcinoma, nanoparticle, bladder cancer-specific peptide, targeted therapy, diagnostic imaging

Abstract The energy relaxation of electrons in γ-In2Se3nanorods was investigated by the excitation-dependent photoluminescence (PL). From the high-energy tail of PL, we determine the electron temperature (T e) of the hot electrons. TheT evariation can be explained by a model in which the longitudinal optical (LO)-phonon emission is the dominant energy relaxation process. The high-quality γ-In2Se3nanorods may be a promising material for the photovoltaic devices.

Background - Oxidative stress activates endothelial innate immunity and disrupts endothelial functions, including endothelial nitric oxide synthase - derived nitric oxide bioavailability. Here, we postulated that oxidative stress induces sterol regulatory element - binding protein 2 (SREBP2) and microRNA-92a (miR-92a), which in turn activate endothelial innate immune response, leading to dysfunctional endothelium. Methods and Results - Using cultured endothelial cells challenged by diverse oxidative stresses, hypercholesterolemic zebrafish, and angiotensin II - infused or aged mice, we demonstrated that SREBP2 transactivation of microRNA-92a (miR-92a) is oxidative stress inducible. The SREBP2-induced miR-92a targets key molecules in endothelial homeostasis, including sirtuin 1, Krüppel-like factor 2, and Krüppel-like factor 4, leading to NOD-like receptor family pyrin domain-containing 3 inflammasome activation and endothelial nitric oxide synthase inhibition. In endothelial cell - specific SREBP2 transgenic mice, locked nucleic acid - modified antisense miR-92a attenuates inflammasome, improves vasodilation, and ameliorates angiotensin II - induced and aging-related atherogenesis. In patients with coronary artery disease, the level of circulating miR-92a is inversely correlated with endothelial cell - dependent, flow-mediated vasodilation and is positively correlated with serum level of interleukin-1β. Conclusions - Our findings suggest that SREBP2 - miR-92a - inflammasome exacerbates endothelial dysfunction during oxidative stress. Identification of this mechanism may help in the diagnosis or treatment of disorders associated with oxidative stress, innate immune activation, and endothelial dysfunction.

Rationale: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of myeloid cells that suppress T-cell immunity in tumor-bearing hosts. Their clinical relevance remains unclear.Objectives: To identify subtypes of myeloid-derived suppressor cells in patients with non-small cell lung cancer (NSCLC) and their clinical relevance.Methods: CD11b(+)CD14(-) and CD11b(+)CD14(+) cells, determined and phenotyped by fluorescence-activated cell sorter analysis, in the peripheral blood mononuclear cells (PBMCs) of treatment-naive patients with advanced NSCLC were correlated with clinical data. T-cell activation in response to CD3/CD28 costimulation was determined by carboxy-fluorescein diacetate succinimidyl ester (CFSE) staining and ELISA analysis of IFN-γ. The percentage of CD11b(+)CD14(+)S100A9(+) cells in PBMCs was correlated with and tested as a predictor for treatment response in a cohort of patients prospectively receiving first-line cisplatin-based chemotherapy.Measurements and Main Results: Patients with NSCLC had a significantly higher ratio of CD11b(+)CD14(+) cells than healthy subjects, which was correlated with poor performance status and poor response to chemotherapy. The depletion of these cells in the PBMC reversed the suppression of CD8(+) and CD4(+) T cells. Isolated CD11b(+)CD14(+) cells suppressed CD8(+) T-cell proliferation and IFN-γ production, and the former effect was attenuated by the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine hydrochloride, arginase inhibitor N-hydroxy-nor-l-arginine (nor-NOHA), and blocking antibodies for IL-4Rα(+) and IL-10. CD11b(+)CD14(+) cells were monocyte-like, expressing CD33(+), CD15(-/low), IL-4Rα(+), and S100A9(+) and producing iNOS, arginase, and several cytokines. The ratio of S100A9(+) cells positively correlated with the suppressive ability of the CD11b(+)CD14(+) cells, was associated with poor response to chemotherapy, and predicted shorter progression-free survival.Conclusions: CD14(+)S100A9(+) inflammatory monocytes in patients with NSCLC are a distinct subset of MDSCs, which suppress T cells by arginase, iNOS, and the IL-13/IL-4Rα axis. The amount of these inflammatory monocytes is associated with poor response to chemotherapy. Clinical trial registered with www.clinicaltrials.gov (NCT 01204307). [ABSTRACT FROM AUTHOR]

Objective: To evaluate the implications of a newly defined severity scoring of empyema in children for the prediction of surgical management and to compare the length of hospitalization as an outcome measure of patients treated using medical therapy, salvage video-assisted thoracoscopic surgery (VATS) vs early elective VATS.Methods: A retrospective chart review of parapneumonic empyema of patients below 18 years of age admitted to a tertiary children's hospital in northern Taiwan from April 1993 to December 2002 was performed. Patients were categorized into a medical group who received antibiotic therapy, needle aspirations with/without tube thoracostomy; a salvage VATS group when the patients required surgery for the relief of persistent fever > 38 degrees C, chest pains or dyspneic respirations despite initial medical therapy; an early VATS group when the patients received elective surgery early after admission. The demographic data, clinical features, laboratory findings, and duration of hospitalization were compared using a severity score of empyema (SSE).Results: Streptococcus pneumoniae was the most common infecting organism, followed by Staphylococcus aureus, Pseudomonas aeruginosa. No organisms were recovered in 39% of patients. A pleural pH < 7.1 increases the odds of requiring surgical intervention by 6 times among this cohort. Children who required decortication of empyema had a higher severity score (mean 4.8 vs 3.0, p < 0.005). The duration of hospitalization for patients having early VATS showed a shortening stay (mean 18 vs 28 days) as compared to salvage VATS.Conclusion: A pleural pH < 7.1 and a newly designed clinical severity score of empyema 4 are two predictors of surgical intervention for fibrinopurulent empyema in the present study. Early elective VATS may be adopted not later than 7 days after failure of appropriate antibiotic therapy and adequate drainage of empyema to decrease the length of stay and minimize morbidity. [ABSTRACT FROM AUTHOR]