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Background/aim The molecular mechanisms underlying the association between cell cycle and asthma are poorly understood, and cyclin D1 (CCND1) is found to be upregulated in asthma airway smooth muscle. We investigated whether the most frequently examined functional variants in CCND1 determine asthma susceptibility. Materials and methods We genotyped 651 participants for single-nucleotide polymorphisms (SNPs) at rs9344 and rs678653 on CCND1 and assessed the association of these SNPs with asthma risk. Results Significant differences were found in the distributions of genotypic (p=0.0064) and allelic (p=0.0021) frequencies of CCND1 rs9344. In addition, AG or GG carriers had 0.63- or 0.48-fold adjusted odds ratios for asthma risk (95%confidence intervals=0.48-0.92 and 0.22-0.78, respectively) than those who carried the AA wildtype. Conclusion Our results suggest that cell cycle regulation may play a role in asthma initiation and development, and the CCND1 rs9344 genotype may serve as an early detection marker for asthma.

Background Randomized controlled trials had demonstrated local therapy, such as radiotherapy, can improve outcomes of patients with lung cancer with oligometastatic disease (OMD). However, the definition of OMD is not uniform and the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) proposed a new classification in 2020 comprising nine subtypes. Therefore, we aimed to investigate the prognostic significance of this European classification for patients with lung OMD treated with definitive radical radiotherapy. Patients and methods We identified eligible patients via an in-house database. Patient, disease, and treatment characteristics, as well as outcomes, were obtained via chart review plus peer review. Overall and progression-free survival were estimated via the Kaplan-Meier method. Log-rank test was used in univariate analysis and Cox regression in multivariable analyses to investigate the prognostic significance of the subtypes of OMD. Results We identified 35 eligible patients with six different OMD subtypes treated from 2011 to 2019. After a median follow-up of 23 (range=2-88) months, the median progression-free and overall survival were 11 and 38 months, respectively. The prognosis for patients with the subtype 'induced oligoprogression' was statistically worse than for those without in both univariate (p=0.02) and multivariate (adjusted hazard ratio for death=4.8, 95% confidence interval=1.4-16.2, p=0.01) analyses. Conclusion We found the subtype with induced oligoprogression in the European classification to be associated with worse survival. Further studies are needed to confirm our finding.

Idiopathic pulmonary fibrosis (IPF) is characterized by fibrotic change in alveolar epithelial cells and leads to the irreversible deterioration of pulmonary function. Transforming growth factor-beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in type 2 lung epithelial cells contributes to excessive collagen deposition and plays an important role in IPF. Atractylodin (ATL) is a kind of herbal medicine that has been proven to protect intestinal inflammation and attenuate acute lung injury. Our study aimed to determine whether EMT played a crucial role in the pathogenesis of pulmonary fibrosis and whether EMT can be utilized as a therapeutic target by ATL treatment to mitigate IPF. To address this topic, we took two steps to investigate: 1. Utilization of anin vitro EMT model by treating alveolar epithelial cells (A549 cells) with TGF-β1 followed by ATL treatment for elucidating the underlying pathways, including Smad2/3 hyperphosphorylation, mitogen-activated protein kinase (MAPK) pathway overexpression, Snail and Slug upregulation, and loss of E-cadherin. Utilization of an in vivo lung injury model by treating bleomycin on mice followed by ATL treatment to demonstrate the therapeutic effectiveness, such as, less collagen deposition and lower E-cadherin expression. In conclusion, ATL attenuates TGF-β1-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in mice.

Cadmium oxide (CdO)-ZnO alloys (Cd

Background The study aims to evaluate the contribution of excision repair cross-complementing group 1 (ERCC1), which plays an important role in genome integrity maintenance, to lung cancer risk. Materials and methods ERCC1 rs11615 and rs3212986 genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism analysis and their association with lung cancer risk was examined among 358 lung cancer patients and 716 controls. Results The proportions of CC, CT and TT for the rs11615 genotype were 43.6%, 41.6% and 14.8% in the case group and 50.0%, 41.1% and 8.9% in the control group, respectively (p for trend=0.0082). Allelic analysis showed that ERCC1 rs11615 T-allele carriers have a 1.32-fold higher risk of lung cancer than wild-type C-allele carriers [95%confidence interval (CI)=1.09-1.60, p=0.0039]. In addition, a significant interaction between the rs11615 genotype and smoking status was observed. Conclusion The T allele of ERCC1 rs11615 jointly with smoking habits may contribute to a higher lung cancer risk in Taiwan.

Background/aim A single study has shown positive association and genotype-phenotype correlation between metalloproteinase-9 (MMP-9) promoter genotypes and adult acute lymphocytic leukemia (ALL). However, there is no report about childhood ALL. Thus, this study aimed at examining the role of MMP-9 rs3918242 genotypes in childhood ALL risk. Patients and methods A total of 266 childhood ALL cases and 266 healthy controls in Taiwan were examined for their MMP-9 rs3918242 genotypes via polymerase chain reaction-restriction fragment length polymorphism methodology. Results The MMP-9 rs3918242 CT or TT genotype carriers only had a slightly increased risk compared with CC carriers (p=0.6386 and 0.6005, respectively). The allelic frequency analysis also supported the idea that the variant T allele at MMP-9 rs3918242 is not differentially distributed between the case and control groups (p=0.4834). Conclusion MMP-9 rs3918242 genotypes may indirectly influence the risk of childhood ALL. Further validations in other populations and analysis of the detail mechanisms are needed.

Aim The aim of this study was to evaluate the contribution of human mouse double minute 2 (MDM2) gene polymorphisms to the risk of Taiwan lung cancer. Materials and methods In this case-control study, the association of MDM2 rs2279744 genotypes with lung cancer risk was investigated among 358 lung cancer patients and 716 age-, gender- and smoking status-matched controls in Taiwan. Results The percentages of MDM2 rs2279744 GT and GG genotypes were 50.0% and 27.4% in lung cancer group and 50.0% and 26.5% in control group, respectively [odds ratio (OR)=1.03 and 1.07, 95% confidence interval (CI)=0.75-1.43 and 0.75-1.53, respectively]. The analysis about allelic frequency showed that G allele at MDM2 rs2279744 conferred a non-significant increased cancer risk (OR=1.03, 95%CI=0.86-1.24). Conclusion Polymorphisms of MDM2 rs2279744 may play a role in lung carcinogenesis. However, the studied genotypes were not shown as predictors of lung cancer susceptibility.

// Wen-Yen Huang 1, 2 , Chia-Hsiang Li 3 , Cheng-Li Lin 4, 5 , Ji-An Liang 6, 7 1 Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 2 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan 3 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan 4 Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan 5 College of Medicine, China Medical University, Taichung, Taiwan 6 Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan 7 Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan Correspondence to: Ji-An Liang, email: d4615@mail.cmuh.org.tw Keywords: lung cancer, statin, population-based case-control study Received: March 15, 2016 Accepted: May 20, 2016 Published: June 07, 2016 ABSTRACT Background: Clinical studies have obtained inconsistent results of statin use on cancer outcomes. This study investigated the association between statin use and lung cancer mortality. Results: The use of statin decreased mortality (hazard ratio = 0.91; 95% confidence interval: 0.86–0.96; P < .01). The patients with a high cumulative defined daily dose of statin use before lung cancer diagnosis exhibited a low risk of mortality. Materials and Methods: We conducted a population-based case-control study of patients with dyslipidemia. Among them, 6270 had used statins for at least 3 months before lung cancer diagnosis, and 6270 had never used statins. Conclusions: We found that statin use can reduce lung cancer mortality. A further prospective study is necessary to confirm these findings.

Study objectives Previous literature lacks the analysis of non-apnea sleep disorder (NASD) and peripheral arterial disease (PAD). The aim of this study was to evaluate the association between NASD and risk of developing PAD using retrospective data from a national database in Taiwan. Design, setting, and participants We identified 46,064 patients with NASD using the catastrophic illness registry of the Taiwan National Health Insurance Research Database (NHIRD) from 1996 to 2010. We also selected a comparison cohort of 92,128 subjects who were randomly frequency-matched by age, sex, and entry year of the NASD cohort from the same database. Interventions non-apnea sleep disorders. Main outcome and measurements The study followed up all subjects from their entry date to the occurrence of PAD. We evaluated the risks of PAD using Cox proportional hazards regression models. The survival function for PAD was assessed using the Kaplan–Meier method. Results The risk of PAD was 1.49-fold in patients with NASD compared with patients without NASD after adjusting for age, sex, and comorbidities. Patients with NASD and diabetes or with NASD and hyperlipidemia had an increased risk of PAD compared to those without NASD and diabetes or hyperlipidemia. Conclusions We demonstrated the significantly increased risk of PAD in NASD patients through a nationwide population-based retrospective cohort study.

Objective Approximately 10%–15% patients with epidermal growth factor receptor (EGFR) mutations harbor non-classical mutations. However, the effects of EGFR-tyrosine kinases (TKIs), particularly second-generation EGFR-TKI (afatinib) compared to first-generation EGFR-TKIs (gefitinib/erlotinib), in patients with non-classical EGFR mutations remain unknown. Methods We conducted this retrospective study at the China Medical University Hospital (Taichung, Taiwan) from June 2011 to July 2016. Specimens from 1632 patients were tested for EGFR mutations. We surveyed the effectiveness of afatinib and gefitinib/erlotinib in stage IIIb-IV lung adenocarcinoma patients with non-classical EGFR mutations. Results Fifty-six patients with advanced-stage (stage IIIB-IV) lung adenocarcinoma with non-classical mutations and receiving EGFR-TKI treatment had completed follow-up and were further analyzed. Afatinib versus gefitinib/erlotinib showed that the objective response rates were 62.5% versus 50.0% (p = 0.35). Median progression-free survival (PFS) of 11.0 versus 3.6 months (p = 0.03), respectively, was observed for the 51 non-classical EGFR mutated (excluding 5 patients with exon 20 insertions) lung adenocarcinomas. Subset analysis showed that PFS curves of afatinib were more easily distinguished in non-classical EGFR mutations lacking a combination with a classical mutation (non-classical with classical complex mutations group: median PFS, 11.0 versus 8.2 months, p = 0.19; non-classical mutation alone or in combination with other non-classical mutations group: median PFS, 18.3 versus 2.8 months, p = 0.07). Conclusions Afatinib may be a first-choice EGFR-TKI for patients with advanced-stage lung adenocarcinomas harboring non-classical mutations.

The studies on the risk of tuberculosis (TB) in patients with type 1 diabetes mellitus (T1DM) alone are limited. We examined this relationship using a population-based retrospective cohort study. From claims data of the National Health Insurance system of Taiwan, we identified 5195 patients with T1DM newly diagnosed from 2002 to 2011 and 20,780 randomly selected controls without T1DM, frequency matched by age, sex, and year of diagnosis. Both cohorts were followed up until the end of 2011 to evaluate the risk of TB. The overall incidence of TB was 4.07-fold higher in the T1DM cohort than in the control cohort (1.18 vs 0.29 per 1000 person-years, P

Objective: Previous research has shown that patients with chronic obstructive pulmonary disease (COPD) tend to have a higher risk for cognitive impairment and dementia, a neurodegenerative disorder. The goal of this study was to examine what relationship, if any, exists between COPD and Parkinson’s disease (PD), which is also a neurodegenerative disorder. Method: Our study analyzed medical data from the population of Taiwan from 1998 to 2008, with a follow-up period extending to the end of 2010. We identified patients with COPD by the Taiwan National Health Insurance Research Database (NHIRD). We selected a comparison cohort from the general population that was random frequency-matched by age (in 5-year increments), sex and index year, and further analyzed the risk of PD using Cox’s regression model, including sex, age and comorbidities. Results: The study enrolled 20 728 COPD patients (71.1% male, mean age = 68.2 years) and 41 147 controls. The risk of developing PD was 1.37 times greater in patients with COPD compared with patients without COPD after adjusting for age, sex and comorbidities. A significantly increased risk of PD was also found in patients with COPD who had any comorbidity other than diabetes. Conclusion: This nationwide retrospective cohort study demonstrates that PD risk is significantly increased in patients with COPD compared with those of the general population.

Although lymphoma and thymoma are common etiologies of anterior mediastinal masses (AMMs), smaller percentages and numbers of patients with these diseases have been enrolled in previous ultrasound-guided biopsy studies. To date, there has been no study of color Doppler sonographic features to support the differentiation of AMMs. For this retrospective cohort study, a search of the database of the China Medical University Hospital using the clinical coding "ultrasound-guided biopsy" was conducted for the period December 2003 to February 2013. We selected patients diagnosed with AMMs (not cysts) using radiographic records. This search yielded a list of 80 cases. Real-time ultrasound-guided core needle biopsy (CNB) was performed in all but 5 patients without a sufficient safety range. In 89% (67/75) of these ultrasound-guided CNB cases, the diagnostic accuracy achieved subclassification. Fine-needle aspiration cytology achieved subclassification in only 10% of cases. On color Doppler sonography, 71% of lymphomas were characterized as "rich vascular with central/crisscross collocations" and 29% as "avascular or localized/scattered peripheral vessels." However, decreased proportions of "rich vascular with central/crisscross collocations" were found in lung cancer (4% [1/23], odds ratio = 0.018, 95% confidence interval: 0.002-0.154, p0.001) and thymoma/thymic carcinoma (25% [4/16]; odds ratio = 0.133, 95% confidence interval: 0.035-0.514, p = 0.003) compared with the lymphoma group. We conclude that the vessels in lymphoma AMMs have specific patterns on color Doppler sonography. Ultrasound-guided CNB of AMMs had an accuracy of ≤ 89% in diagnosis and subclassification. Fine-needle aspiration cytology itself cannot aid in the diagnosis. Color Doppler sonographic evaluation of AMMs followed by real-time CNB is a more efficient method.

Summary Background: This study identifies the effects of gall stone on the risks of developing renal stone in a nationwide cohort study. Aim: Studies on the association between gall stone and renal stone are scarce. Methods: We identified patients with gallstones using the catastrophic illness registry of the Taiwan National Health Insurance Research Database (NHIRD). We selected a comparison cohort, random frequency-matched by age, sex and index year, from the general population. We analyzed the risk of renal stones by using Cox proportional hazards regression models for sex, age and comorbidities. Results: Of the 23.74 million people in the database, we followed 25 258 gallstone patients (54.5% female) and 101 029 control patients. The risk of developing renal stones was 1.68-fold greater in gallstone patients, compared with patients without gallstones after adjusting for age, sex and comorbidities. The substantially increased risk of renal stones was also significant in gallstone patients regardless of comorbidities. In the follow-up period

A 17-year-old youth came to the Emergency Department (ED) with stridor in March, 2009. Commencing 6 months prior, he had developed bilateral progressive hearing loss along with frequent vertigo. Both auricles appeared erythematous and swollen over the prior 2 months. Intermittent dyspnoea with episodic stridor and easy choking had developed. The neck soft tissue X-ray study showed a narrowing of the airway (Fig. 1). The nasal fiberscopic examination revealed bilateral vocal paralysis with oedematous swelling of the arytenoids and false vocal cords. Left external ear destruction (Fig. 2a), right ear induration (Fig. 2b) and a saddle nose deformity (Fig. 2c) were noted. Because of the acute respiratory stress and stridor, the patient was immediately treated with endotracheal intubation in the ED. Due to soft tissue swelling, the intubation could only be performed with 6.5 French endotracheal tube. A computed tomography (CT scan) of the neck showed circumferential thickening of the tracheal wall along with tracheal lumen narrowing of the subglottic trachea (Fig. 3). The patient then underwent tracheostomy, and was successfully weaned from mechanical ventilation. The biopsy of the trachea showed acute and chronic inflammatory infiltrates surrounding the elastic cartilage with foci of perichondrial erosion and chondrocyte destruction. Biopsy of the ear revealed acutely inflamed granulation tissue with patchy organising microhemorrhage. A diagnosis of relapsing polychondritis was established by the combination of clinical typical findings (McAdam’s criteria) [1], imaging studies, and biopsies of the trachea and ear. Relapsing polychondritis is a rare multisystem inflammatory process that may potentially compromise the structural and function of all of the cartilage in the body, especially the ears, nose, eyes, joints, and respiratory tract. Auricular chondritis is the most common initial presentation [2], and the prevalence of airway involvement is about

The proposed approach is to design a feedforward controller for piezoelectric motion platform. A Prandtl-Ishlinskii(PI) hysteresis model is proposed for the hysteresis behavior of piezoelectric actuators. This model is more mathematically simple when compared to Preisach operator. The PI operator is more efficient phenomenological fit as it is a first order gradient, rather than a step change. The weights of main hysteresis loop are identified by using LMS(LeastMean-Square) algorithm. An inverse feedforward controller is to cascade the inverse PI operator with the actual hysteresis, which is to linearize the hysteresis response. The effectiveness of the proposed method is demonstrated through experimental.

A 50-year-old man with a history of type 2 diabetes mel-litus presented with a 40-day history of right chest tightness.He was afebrile. Physical examination revealed dullness topercussion and a decrease in breath sound. Chest radiogra-phy was consistent with air space consolidation (Picture 1)and computed tomography scan of chest revealed a largethick wall cavity abutting the chest wall in the right upperlung (Picture 2). Hemoglobin A1c was 13.8%. Direct exami-nation of bronchial biopsy (Picture 3) led to the diagnosis ofpulmonary mucormycosis.Mucormycosis is a life-threatening fungal infection thatoccurs primarily in patients with various immunocom-promised states (1). In the present case, there was a predi-lection for involvement of the upper lobes, but none of theradiological findings were characteristic (2). Fiberoptic bron-choscopy was a useful diagnostic method, and histopa-thologic examination was more sensitive than fungal cul-tures (2). The clinical disease of mucormycosis is very simi-lar to invasive pulmonary aspergillosis. The fungus is non-septate with short stubby side branches at a 90-degree angleand this is a diagnostic feature. The fungus invades theblood vessels and causes distal ischemic necrosis. Successfulmanagement continues to be early diagnosis, followed bysystemic antifungal therapy and surgical resection combinedwith control of the underlying disease.

Although many risk models have been tested in patients who undergo extracorporeal membrane oxygenation, few have been assessed for patients who received veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support in the emergency department (ED). This study aimed to successfully predict outcomes of patients with cardiac or noncardiac failure who received VA-ECMO in the ED within 24 hours of arrival at the ED. This retrospective, observational cohort study included 154 patients, who were classified as cardiac (n = 127) and noncardiac (n = 27) patients and received VA-ECMO within 24 hours after arrival at the China Medical University Hospital ED in Taiwan between January 2009 and September 2014. We recorded mechanical ventilation settings, arterial blood gases, laboratory parameters including plasma lactate level, requirement of catecholamines, and risk scores at time of ECMO initiation. ECMO and mechanical ventilation support duration, length of stay in the hospital, and 90-day mortality data were also examined. The overall mortality rate was 64.9 %. We used “survival after veno-arterial ECMO (SAVE)” scores to assess survival prediction in survival and nonsurvival groups, which was statistically different (–3.2 vs. –8.3, p