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Introduction Chronic obstructive pulmonary disease (COPD) is a global health concern and a leading cause of morbidity and mortality worldwide. COPD action plans help patients manage exacerbations by recognizing symptoms early and taking necessary steps. We found our COPD written action plan difficult to understand, potentially affecting the patient's ability to self-manage their COPD. Aims We aim to design a new COPD action plan to increase the knowledge scores of our patients during competency checks by 20%. Methods We employed the quality improvement methodology of needs analysis and root cause analysis and used a Pareto chart to identify the top four contributory factors to an ineffective COPD action plan. These include being too wordy, lacking pictorial illustrations, being only available in a single language (English), and too much medical jargon. Using the prioritization matrix to assess possible solutions, the team decided to implement a pictorial COPD action plan. After two cycles of Plan-Do-Study-Act, the final pictorial COPD plan was compared with the original written action plan. Results Ten English-speaking COPD patients from our outpatient respiratory clinics were surveyed with the original action plan while 11 more were surveyed after the introduction of the pictorial action plan. There was an improvement in mean knowledge scores by 92.8% (t(19) = 6.67, p < 0.01, at 95% CI). Patient satisfaction rates also increased from 44% to 100%. Sixty-three percent (63.6%) of patients surveyed said they referred back to the pictorial action plan 3 months after being introduced to it. Conclusion Pictorially enhanced COPD action plans have been shown to improve our patients' knowledge of COPD self-management., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tang et al.)

Objective: To explore the causal relationship between asthma, allergic rhinitis (AR), and chronic sinusitis (CRS), using two sample Mendelian randomization (MR) analysis, thereby providing foundational evidences for the pathogenesis and treatment of CRS. Methods: The genetic variations in AR and asthma were used as instrumental variables, with genetic data from the Integrated Epidemiology Unit (IEU) Open database. A total of 14 283 asthma and 18 934 AR cases were included, with 98 300 and 64 595 corresponding normal control cases, respectively. For CRS, there were 3 236 CRSwNP and 8 524 CRSsNP, respectively, with 167 849 and 167 849 corresponding normal control cases, respectively. The genetic data were analyzed using the inverse variance weighting method (IVW), MR Egger method, weighted median method, and Cochran's Q-test. Results: The IVW analysis showed that asthma increased the risk of both CRSwNP ( OR =482.8, 95% CI : 57.18-4 077.78, P <0.001) and CRSsNP ( OR =25.73, 95% CI : 9.79-67.56, P <0.001); AR significantly increased the risk of CRSsNP ( OR =5.40, 95% CI : 1.68-17.26, P =0.004), but not CRSwNP ( OR =7.38, 95% CI : 0.80-67.73, P =0.077). Conversely, neither CRSwNP nor CRSsNP increased the risk of asthma or AR. Conclusion: According to Mendelian genetic laws, asthma is a risk factor for CRSwNP and CRSsNP, while AR is a risk factor for CRSsNP.

This paper investigates achieving leader-following consensus in a class of multi-agent systems with nonlinear dynamics. Initially, it introduces a dynamic event-triggered strategy designed to effectively alleviate the strain on the system's communication resources. Subsequently, a distributed control strategy is proposed and implemented in the nonlinear leader-follower system using the dynamic event-triggered mechanism, aiming to ensure synchronization across all nodes at an exponential convergence speed. Thirdly, the research shows that under the dynamic event-triggered strategy the minimum event interval of any two consecutive triggers guarantees the elimination of Zeno behavior. Lastly, the validity of the calculation results is verified by a simulation example.

The latest research findings on bidirectional regulation of neuro-immunity through traditional neural circuits shed new light on the theoretical basis of the role of vidian neurectomy (VN). This article aims to provide a comprehensive understanding of VN, including the history of VN, the principle of neuroimmuno-interaction, the applied anatomy of VN as well as the methods of transnasal endoscopic surgery. Additionally, we introduce the concept of the nose-brain axis, which was proposed based on the advancement in the area of neuro-immune interactions.

Background: Plasma cell mastitis (PCM) is a benign breast disease that is refractory and difficult to cure. We integrated microwave ablation into the treatment of PCM to compare the clinical value of ultrasound-guided microwave ablation and traditional surgery in the treatment of PCM., Methods: A total of 68 patients with PCM who were admitted to 3 centers (Zhejiang Cancer Hospital, Hebei Province Hospital of Traditional Chinese Medicine, and Yantai Affiliated Hospital of Binzhou Medical university) from January 2017 to June 2019 were selected. All patients were diagnosed with PCM after pathological and clinical manifestations. Among these, 38 cases were treated with ultrasound-guided microwave ablation, and 30 cases were treated with traditional surgery. The operation time, hospitalization time, incision healing, intraoperative blood loss, postoperative pain degree, evaluation of breast shape effect, time taken for postoperative lesion disappearance, effective rate, and recurrence were recorded in the follow-up, and the clinical efficacy was compared and observed., Results: The effective rate of the ablation group was 86.8% (33/38), that of the operation group was 46.7% (14/30), and the difference was statistically significant (95% CI: 2.311-24.618; P<0.05). The average time of the lesion completely disappearing was 75.55±43.59 days in the ablation group and 103.87±45.98 days in the operation group, and the difference was statistically significant (P<0.05). The hospital stays, operation time, and intraoperative blood loss of patients in the ablation group were less than those of the operation group, and the difference was statistically significant (95% CI: -10.69 to -6.27, 95% CI: -77.06 to -51.26, and 95% CI: -21.54 to -13.64; P<0.05). The postoperative pain scoring, operative incision healing at 14 days after the operation, and breast appearance evaluation after treatment in the ablation group were better than those of the operation group, and the difference was statistically significant (P<0.05)., Conclusions: Compared with traditional surgery, ultrasound-guided microwave ablation is a more effective treatment option for PCM., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-21-1132/coif). All authors report that this study was funded by the Zhejiang Provincial Natural Science Foundation of China (No. LSD19H180001). The authors have no other conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Introduction: Protein corona (PCN) adsorbed on the surface of nanoparticles has brought new research perspectives for the interaction between nanoparticles and microorganisms. In this study, the responses of saccharomyces cerevisiae ' membrane lipid composition, the average length of the fatty acyl chains and the average number of unsaturation of fatty acids to ultrasound combined with nano-Fe 3 O 4 @PCN with time-limited proteolysis (nano-Fe 3 O 4 @TLP-PCN) was investigated., Methods: Lipidomic data was obtained using Ultra-high performance liquid chromatography coupled with a Q-Exactive plus mass spectrometer. The membrane potential, proton motive force assay and the membrane lipid oxidation were measured using Di-BAC 4 (3), DISC 3 (5) and C11-BODIPY 581/591 as the probes. Combined with the approach of feasible virtual samples generation, the back propagation artificial neural network (BP-ANN) model was adopted to establish the mapping relationship between lipids and membrane properties., Results: The time-limited proteolysis targeting wheat PCN-coated Fe 3 O 4 nanoparticles resulted in regular changes of hydrodynamic diameters, ζ-potentials, and surface hydrophobicity. In addition, with the prolongation of PCN proteolysis time, disturbances of 3 S.cerevisiae membrane characteristics, and membrane lipidomic remodeling in response to ultrasound+ nano-Fe 3 O 4 @PCN were observed. The analysis of relative importance which followed revealed that ergosterol, phosphatidylserine, and phosphatidylinositol phosphate had the greatest influence on membrane potential. For membrane lipid oxidation, ceramide, phosphatidylethanolamine, and sitosterol ester contribute 16.2, 14.9, and 13.1%, respectively. The relative contributions of six lysolecithins to the dissipation of proton motive force remained limited., Discussion: An adaptation mechanism of cell membrane to proteolyzed PCN, wherein lipidome remodeling could preserved functional membrane phenotypes was revealed. Furthermore, it is highlighted that the relative importances of SiE, Cer, PE and PIP in determining membrane potential, PMF dissipation and membrane lipid oxidation by establishing FVSG-BP-ANN model., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zheng, Xie, Tan and Liu.)

The appearance of antiferroelectrics (AFE) in the ferrimagnetism (FM) system would give birth to a new type of multiferroic candidate, which is significant to the development of novel devices for energy storage. Here we demonstrate the realization of full antiferroelectrics in a magnetic La 0.5 Sr 0.5 Fe 12 O 19 system (AFE+FM), which also presents a strong magnetodielectric response (MD) and magnetoresistance (MR) effect. The antiferroelectric phase was achieved at room temperature by replacing 0.5 Sr 2+ ions with 0.5 La 2+ ions in the SrFe 12 O 19 compound, whose phase transition temperature of ferroelectrics (FE) to antiferroelectrics was brought down from 174 °C to -141 °C, while the temperature of antiferroelectrics converting to paraelectrics (PE) shifts from 490 °C to 234 °C after the substitution. The fully separated double P-E hysteresis loops reveal the antiferroelectrics in La 0.5 Sr 0.5 Fe 12 O 19 ceramics. The magnitude of exerting magnetic field enables us to control the generation of spin current, which induces MD and MR effects. A 1.1T magnetic field induces a large spin current of 15.6 n A in La 0.5 Sr 0.5 Fe 12 O 19 ceramics, lifts up dielectric constants by 540%, and lowers the resistance by -89%. The magnetic performance remains as usual. The multiple functions in one single phase allow us to develop novel intelligent devices.

Background: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far., Summary: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations., Key Messages: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically., (© 2023 S. Karger AG, Basel.)

Nasopharyngeal carcinoma (NPC) is the most common nasopharyngeal squamous cell carcinoma, and recurrence and metastasis are still difficult problems in its current treatment. This study aimed to investigate the effect of SUMO modification of STAT1 protein on the proliferation and invasion of NPC, and to reveal the underlying mechanism. Two gene expression profiles (GSE12452 and GSE53819) of 49 nasopharyngeal carcinomas and 28 normal controls were analyzed to identify differentially expressed genes. In total, 448 up-regulated genes and 622 down-regulated genes were identified. In addition, 16 SUMO-related molecules in the NPC dataset GSE102349 with survival data were analyzed, and it was found that the high expression of SENP1 and SENP2 was closely related to the poor prognosis of NPC. GO and GSEA analysis suggested that immune-related biological processes, IFN-γ-STAT signaling pathway and protein modification-related molecules were significantly enriched in NPC, resulting in poor survival prognosis. In order to verify the results of bioinformatics analysis and explore its underlying molecular mechanisms, western blot, Immunofluorescence, Immunoprecipitation and Immunohistochemistry are conducted in NPC cells, animals and clinical samples. SENP1 and STAT protein levels were increased in NPC tissues. SENP1 inhibited SUMOylation of STAT1, thereby promoting the protein level of STAT1 and the nuclear translocation. SENP1 promoted the proliferation and invasion of NPC by inducing STAT1. Overall, SENP1-induced deSUMOylation of STAT1, resulting in an increased proliferation and invasion of nasopharyngeal carcinoma., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Background: Introducing a de-novo home haemodialysis (HHD) program often raises safety concerns as errors could potentially lead to serious adverse events. Despite the complexity of performing haemodialysis at home without the supervision of healthcare staff, HHD has a good safety record. We aim to pre-emptively identify and reduce the risks to our new HHD program by risk assessment and using failure mode and effects analysis (FMEA) to identify potential defects in the design and planning of HHD., Methods: We performed a general risk assessment of failure during transitioning from in-centre to HHD with a failure mode and effects analysis focused on the highest areas of failure. We collaborated with key team members from a well-established HHD program and one HHD patient. Risk assessment was conducted separately and then through video conference meetings for joint deliberation. We listed all key processes, sub-processes, step and then identified failure mode by scoring based on risk priority numbers. Solutions were then designed to eliminate and mitigate risk., Results: Transitioning to HHD was found to have the highest risk of failure with 3 main processes and 34 steps. We identified a total of 59 areas with potential failures. The median and mean risk priority number (RPN) scores from failure mode effect analysis were 5 and 38, with the highest RPN related to vascular access at 256. As many failure modes with high RPN scores were related to vascular access, we focussed on FMEA by identifying the risk mitigation strategies and possible solutions in all 9 areas in access-related medical emergencies in a bundled- approach. We discussed, the risk reduction areas of setting up HHD and how to address incidents that occurred and those not preventable., Conclusions: We developed a safety framework for a de-novo HHD program by performing FMEA in high-risk areas. The involvement of two teams with different clinical experience for HHD allowed us to successfully pre-emptively identify risks and develop solutions., (© 2022. The Author(s).)

A novel virus named Aconitum amalgavirus 1 (AcoAV-1) was identified in Chinese aconite (Aconitum carmichaelii) plants. The complete genome of AcoAV-1 is 3,370 nucleotides long, containing two partially overlapping open reading frames encoding a putative coat protein and a RNA-dependent RNA polymerase, respectively. Its fusion protein shares 34.9%-50.7% amino acid sequence identity with other amalgaviruses. Phylogenetic analysis showed that this virus formed a clade with blueberry latent virus and four other related viruses, suggesting that it belongs to the genus Amalgavirus in the family Amalgaviridae., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Regulating the physical properties such as the quantum phase and the Kondo effect of molecular electronic devices near critical points may play a key role in increasing the robustness of quantum memory, which is a crucial component in quantum information processing. Molecules with a triangular topology are ideal prototypes to reveal the competition among magnetic frustration, Kondo screening, and local inter-molecule exchange interactions. Herein, motivated by a recent work investigating the single-electron tunneling through a redox-active edge-fused porphyrin trimer by using a Hubbard dimer model [J. O. Thomas, J. K. Sowa, B. Limburg, X. Bian, C. Evangeli, J. L. Swett, S. Tewari, J. Baugh, G. C. Schatz, G. A. D. Briggs, H. L. Anderson and J. A. Mol, Chem. Sci., 2021, 12, 11121], we studied the phase transition, the electronic transport, and the thermodynamical properties of a real molecular trimer structure organized in a triangular topology, with and without an external magnetic field, and at zero and non-zero temperatures. Both the Hubbard electron-electron interaction and the Heisenberg exchange interaction are fully taken into account, with the aid of the state-of-the-art numerical renormalization group method. Various kinds of Kondo behaviors and quantum phase transitions are demonstrated, due to the competition among the Ruderman-Kittel-Kasuya-Yosida interaction, the direct exchange coupling, and the Zeeman effect. Our findings may offer deep insights into the manipulation of the quantum phase and the Kondo behavior in a molecular trimer with a triangular topology.

Unicompartmental knee arthroplasty (UKA) is an effective treatment for end-stage anteromedial osteoarthritis of the knee. Medial tibial plateau fracture or femoral condyle fracture may occur after UKA, and its treatment is very challenging. The causes leading to this complication include: surgical technique errors, such as the weakening of posterior cortical strength of the tibial platform during operation, the reduction of bone mass due to too much tibial osteotomy, and the stress concentration in the bone bed due to bad alignment of the prosthesis, etc. Prosthesis design factors, such as press-fit fixation design of cementless UKA prosthesis, and multiple nail holes fixation for tibial osteotomy guide, etc. And the morphology of tibial plateau, such as tibial platform in Asian people with narrow and small shap and medial overhanging condyles. Correct selection of patients, strict surgical principles and standardized surgical techniques are the keys to prevent periprosthetic fractures during and after medial UKA. After the diagnosis is confirmed, the treatment choice mainly depends on the fracture pattern and the stability of the prosthesis.

The COVID-19 pandemic has been an unprecedented health crisis for the general population as well as for patients with chronic illnesses such as those requiring maintenance dialysis. Patients suffering from chronic kidney disease requiring dialysis are considered a high-risk population. Multiple reports have highlighted an increased need for intensive care and higher death rates among this group of patients. Most maintenance dialysis patients are in-centre haemodialysis patients who receive treatment in shared facilities (community dialysis centres). The inability to maintain social distancing in these facilities has led to case clustering among patients and staff. This poses a substantial risk to the patients, their household members, and the wider community. To mitigate the risks of COVID-19 transmission, telemedicine was rapidly adopted in the past year by nephrologists and other allied-health staff to provide care via remote consultations and reviews. Telemedicine poses unique challenges even in an era where so much is performed online with a high degree of success and satisfaction. In applying distant clinical care for maintenance haemodialysis patients via telemedicine, there is a need to ensure adequate protection for the health and safety of patients as well as understand the ethical and legal implications of telemedicine. We discussed, in this article, these three core aspects of patient safety and quality, ethics and legal implications in telemedicine, and how each of these is crucial to the safe and effective delivery of care in general as well as unique aspects of this in Singapore.

A novel enamovirus was identified in common bean plants with disease symptoms. Its genome of 5,781 nucleotides (nt) contains five open reading frames. This virus and other members of the genus Enamovirus share 50.4-68.4% nucleotide sequence identity in the complete genome and 19.9-51.9% amino acid sequence identity in the P0 protein, 24.9-52.5% in P1, 33.4-62.9% in P1-P2, 30.6-81.1% in P3, and 32.3-74.2% in P3-P5. Phylogenetic analysis showed that the virus is most closely related to alfalfa enamovirus 1 and pea enation mosaic virus 1 in the genus Enamovirus of the family Solemoviridae. These results suggest that this virus, tentatively named "bean enamovirus 1", should be classified as a member of a new species in the genus Enamovirus., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Introduction: Non-cystic fibrosis bronchiectasis (NCFB) is a highly heterogenous disease. We describe the clinical characteristics of NCFB patients and evaluate the performance of Bronchiectasis Severity Index (BSI) in predicting mortality., Methods: Patients attending the bronchiectasis clinic between August 2015 and April 2020 with radiologically proven bronchiectasis on computed tomography were recruited. Clinical characteristics, spirometry, radiology, microbiology and clinical course over a median period of 2.4 years is presented., Results: A total of 168 patients were enrolled in this prospective cohort study. They were predominantly women (67.8%), Chinese (87.5%) and never-smokers (76.9%). Median age of diagnosis was 64 years (interquartile range 56-71) and the most common aetiology was "idiopathic" bronchiectasis (44.6%). Thirty-nine percent had normal spirometries. Compared to female patients, there were more smokers among the male patients (53.8% versus 8.5%, P <0.001) and a significantly larger proportion with post-tuberculous bronchiectasis (37.0% vs 15.8%, P =0.002). Fifty-five percent of our cohort had a history of haemoptysis. Lower body mass index, presence of chronic obstructive pulmonary disease, ever-smoker status, modified Reiff score, radiological severity and history of exacerbations were risk factors for mortality. Survival was significantly shorter in patients with severe bronchiectasis (BSI>9) compared to those with mild or moderate disease (BSI<9). The hazard ratio for severe disease (BSI>9) compared to mild disease (BSI 0-4) was 14.8 (confidence interval 1.929-114.235, P =0.01)., Conclusion: The NCFB cohort in Singapore has unique characteristics with sex differences. Over half the patients had a history of haemoptysis. The BSI score is a useful predictor of mortality in our population.

Background and Objective: Simulation enhances a physician's competency in procedural skills by accelerating ascent of the learning curve. Training programmes are moving away from the Halstedian model of 'see one, do one, teach one', also referred as medical apprenticeship. We aimed to determine if a 3-month structured bronchoscopy curriculum that incorporated simulator training could improve bronchoscopy competency among pulmonary medicine trainees., Methods: We prospectively recruited trainees from hospitals with accredited pulmonary medicine programmes. Trainees from hospitals (A, B and C) were assigned to control group (CG) where they received training by traditional apprenticeship while trainees from hospital D were assigned to intervention group (IG) where they underwent 3-month structured curriculum that incorporated training with the bronchoscopy simulator. Two patient bronchoscopy procedures per trainee were recorded on video and scored independently by two expert bronchoscopists using the modified Bronchoscopy Skills and Tasks Assessment Tool (BSTAT) forms. A 25 multiple choice questions (MCQ) test was administered to all participants at the end of 3 months., Results: Eighteen trainees participated; 10 in CG and eight in IG with equal female:male ratio. Competency assessed by modified BSTAT and MCQ tests was variable and not driven by volume as IG performed fewer patient bronchoscopies but demonstrated better BSTAT, airway anaesthesia and MCQ scores. Bronchoscopy simulator training was the only factor that correlated with better BSTAT (r = 0.80), MCQ (r = 0.85) and airway anaesthesia scores (r = 0.83), and accelerated the learning curve of IG trainees., Conclusion: An intensive 3-month structured bronchoscopy curriculum that incorporated simulator training led to improved cognitive and technical skill performance as compared with apprenticeship training., (© 2021 Asian Pacific Society of Respirology.)

Telemedicine has gained popularity during the recent COVID-19 pandemic. Regular and timely physician review is an essential component of care for the maintenance of hemodialysis patients. While it is widely acknowledged that telemedicine cannot fully replace the role of physical review in this group of patients with organ failure, it can perhaps reduce the reliance on physical review or serve as a filter and triage in determining which patient requires actual physical review. The use of technology in any healthcare setting should always align with existing clinical workflow and protocols. We discuss the safety and quality aspects of this new concept applied to the satellite dialysis unit., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Haroon, Lau, Tan and Davenport.)

Molecular magnetic compounds, which combine the advantages of nanoscale behaviors with the properties of bulk magnetic materials, are particularly attractive in the fields of high-density information storage and quantum computing. Before molecular electronic devices can be fabricated, a crucial task is the measurement and understanding of the transport behaviors. Herein, we consider a magnetic molecular trimer sandwiched between two metal electrodes, and, with the aid of the sophisticated full density matrix numerical renormalization group (FDM-NRG) technique, we study the effect of magnetic anisotropy on the charge transport properties, illustrated by the local density of states (LDOS, which is proportional to the differential conductance), the Kondo effect, and the temperature and inter-monomer hopping robustness. Three kinds of energy peaks are clarified in the LDOS: the Coulomb, the Kondo and the Ruderman-Kittel-Kasuya-Yosida (RKKY) peaks. The local magnetic moment and entropy go through four different regimes as the temperature decreases. The Kondo temperature TK could be described by a generalized Haldane's formula, revealing in detail the process where the local moment is partially screened by the itinerant electrons. A relationship between the width of the Kondo resonant peak WK and TK is built, ensuring the extraction of TK from WK in an efficient way. As the inter-monomer hopping integral varies, the ground state of the trimer changes from a spin quadruplet to a magnetically frustrated phase, then to an orbital spin singlet through two first order quantum phase transitions. In the first two phases, the Kondo peak in the transmission coefficient reaches its unitary limit, while in the orbital spin singlet, it is totally suppressed. We demonstrate that magnetic anisotropy may also induce the Kondo effect, even without Coulomb repulsion, hence it is replaceable in the many-body behaviours at low temperature.

Nasopharyngeal carcinoma (NPC) is an epithelial cancer emerging from the lining of nasopharyngeal mucosa, with extremely frequent occurrence in east and southeast Asia. For the purpose of exploring roles of the dysregulated long non-coding RNA (lncRNA) in NPC, we identified a novel lncRNA LINC00669 with an apparent negative correlation to the overall survival from human NPC mRNA expression profiling databases. We further performed RNA pulldown coupled with mass spectrum to find out its target protein, and applied a series of in vitro and in vivo loss-and-gain-of function assays to investigate its oncogenic roles in NPC tumor development and progression. Our results demonstrated that LINC00669 competitively binds to the key JAK/STAT signaling pathway suppressor SOCS1, and insulates it from imposing ubiquitination modification on the pathway component of STAT1, which leads to its abnormal stabilization and activation. The activated STAT1 is then transferred into the nucleus and initiates the transcription of genes related to proliferation and invasion. In summary, our study reveals that the cytoplasmic resident lncRNA LINC00669 confers malignant properties on NPC cancer cells by facilitating a persistent activation of the JAK/STAT signaling pathway. Findings in the current study shed lights on prospects for treating NPC using strategies targeting the novel regulator of the JAK/STAT signaling.

Alpha-1 antitrypsin deficiency (AATD) is a cause of bronchiectasis. Guidelines for bronchiectasis from the British Thoracic Society do not recommend to routinely test patients for AATD. In contrast, guidelines for AATD recommend routine screening. This contradiction, in part, results from the lack of data from large studies performing comprehensive screening. We screened 1600 patients with bronchiectasis at two centres in the UK from 2012 to 2016. In total, only eight individuals with AATD were identified representing 0.5% of the overall population. We conclude that routine screening for AATD in bronchiectasis in the UK has a low rate of detection. Further studies are required in different geographical regions, which may have a higher prevalence of AATD., Competing Interests: Competing interests: ML declares personal fees from Grifols, Bayer, Polyphor and Astrazeneca. JDC declares research grants or personal fees from Glaxosmithkline, Boehringer-Ingelheim, Astrazeneca, Pfizer, Bayer, Grifols, Aradigm, Napp and Insmed outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the clinical significance of endoscopic vidian neurectomy (EVN) on outcomes in patients with coexisting refractory allergic rhinitis (AR) and bronchial asthma, and to analyze its influence factor. Methods: Clinical data of 109 patients with moderate to severe persistent intractable AR and bronchial asthma who were allocated to the bilateral EVN group (surgery group, 70 cases) or conservative medication group (drug group, 39 cases) from 1 May 2008 to 30 April 2013 in Department of Otorhinolaryngology Head and Neck Surgery, Third Xiangya Hospital, Central South University were retrospectively analyzed, including 47 cases of male and 62 cases of female aged (32.7±6.8) years.Ninety-five patients were followed up for at least 3 years. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Visual Analog Scale (VAS), Asthma Quality of Life Questionnaire (AQLQ), Total Asthma Symptom Score (TASS), forced expiratory volume in 1 second of predicted (FEV1) and medication scores were evaluated at 6 months, 1 year and 3 years after undergoing the initial treatments in the two groups. Multiple factor analysis was used to determine the factors influencing the improvement after EVN. Results: Postoperative scores of RQLQ were significantly lower than preoperative scores during follow-up in surgery group (the preoperative score and postoperative score at 6 months, 1 year, 3 years after operation was 2.39±0.61 ( x ± s ), 0.81±0.43, 0.89±0.32, 1.06±0.24, respectively, all P< 0.001). Postoperative scores of VAS were significantly lower than preoperative scores during follow-up in surgery group (the preoperative score and postoperative score at 6 months, 1 year,3 years after operation was 7.13±1.04, 2.52±1.47, 2.70±1.42, 2.85±1.64, respectively, all P< 0.05). Scores of RQLQ and VAS in surgery group were significantly lower than those of drug group. Postoperative scores of AQLQ were significantly higher than preoperative scores during follow-up in surgery group (the preoperative score and postoperative score at 6 months, 1 year, 3 years after operation was 3.78±0.81, 4.99±0.45, 4.75±0.71, 4.62±0.64, respectively, all P< 0.05), and were significantly higher than those of drug group. The TASS and FEV1 were not significantly changed in surgery group. The postoperative medication scores for AR were gradually reduced after surgery (the preoperative score and postoperative score at 6 months, 1 year, 3 years after operation was 0.99±0.21, 0.37±0.12, 0.39±0.26, 0.45±0.11, respectively, all P< 0.05), and the postoperative medication scores for Asthma were gradually reduced after surgery too (the preoperative score and postoperative score at 6 months, 1 year, 3 years after operation was 1.27±0.31, 0.82±0.29, 0.85±0.23, 0.96±0.19, respectively, all P< 0.05), and all the postoperative medication scores were significantly lower than those of drug group. At the end of the follow-up, the improvement rates for AR and asthma were 90.6% (58/64) and 45.3% (29/64), respectively. Asthma outcomes were significantly improved by controlling rhinitis symptoms in patients whose asthma attacks were induced by "rhinitis onset" or "climate change" . Conclusion: For patients with AR and bronchial asthma, EVN can significantly control AR symptoms, and improve asthma outcomes in patients whose asthma attacks are induced by rhinitis onset and/or climate change.

Objective: To explore effect of mobile platform in improving compliance and efficacy of subcutaneous immunotherapy（SCIT） in children with allergic rhinitis（AR）. Method: From January to June 2018, 86 children diagnosed with AR and receiving SCIT were selected as research objects. According to the random sequence generated by the computer, the research objects were randomly assigned to the experimental group and the control group, with 43 cases in each group. The control group received conventional SCIT management, while the experimental group received mobile platform SCIT management relying on smart phones and computers. The SCIT shedding rate at the initial stage and the time taken to reach the maintenance period were compared between the two groups, as well as the visual simulation scale of rhinitis symptoms, four-point score and rhinoconjunctivia-related quality of life scores before and at the 6th month after the intervention. Result: There was no statistically significant difference in the initial SCIT shedding rate between the two groups（ P >0.05）, and the average duration of the maintenance period of the experimental group was shorter than that of the control group, with statistically significant difference（ P <0.05）. At the 6th month after intervention, there was no statistically significant difference in the scores of rhinitis symptoms by the four-point method between the two groups（ P >0.05）, and there were statistically significant differences in the visual simulation scale of rhinitis symptoms and the scores of children's rhinoconjunctivia-related quality of life（ P <0.05）. Conclusion: This study confirmed that the application of a mobile platform is of great significance for improving compliance and the treatment effects of SCIT in children with AR., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

The number of patients with allergic rhinitis (AR) have been increasing in the world. Establishment of AR model in mice is an important method for the study of this disease. However, there is still no consensus standard for the modeling methods, selection of allergens and adjuvants, and evaluation parameter of AR modeling. Here, we introduce the advancement of AR mouse model in recent years from the above, and provide evidence of references for the standardized process of AR mouse model establishment.

Many studies have shown that (5R)-5-hydroxytriptolide is the optimal modified analogue of triptolide, possessing comparable immunosuppressive activity but much lower cytotoxicity than triptolide. Whether (5R)-5-hydroxytriptolide has preventive effects on neuroinflammation is unclear. This study was designed to pretreat primary astrocytes from the brains of neonatal Sprague-Dawley rats with 20, 100 and 500 nM (5R)-5-hydroxytriptolide for 1 hour before establishing an in vitro neuroinflammation model with 1.0 μg/mL lipopolysaccharide for 24 hours. The generation of nitric oxide was detected by Griess reagents. Astrocyte marker glial fibrillary acidic protein was measured by immunohistochemical staining. The levels of tumor necrosis factor-α and interleukin-1β in the culture supernatant were assayed by enzyme linked immunosorbent assay. Nuclear factor-κB/p65 expression was examined by immunofluorescence staining. The phosphorylation of inhibitor of nuclear factor IκB-α and the location of nuclear factor-κB/P65 were determined using western blot assay. Our data revealed that (5R)-5-hydroxytriptolide inhibited the generation of nitric oxide, tumor necrosis factor-α and interleukin-1β from primary astrocytes activated by lipopolysaccharide, decreased the positive reaction intensity of glial fibrillary acidic protein, reduced the expression of tumor necrosis factor alpha and interleukin-1β in culture supernatant, inhibited the phosphorylation of IκB-α and the translocation of nuclear factor-κB/P65 to the nucleus. These results have confirmed that (5R)-5-hydroxytriptolide inhibits lipopolysaccharide-induced glial inflammatory response and provides cytological experimental data for (5R)-5-hydroxytriptolide in the treatment of neurodegenerative diseases., Competing Interests: None

Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease, and cystic fibrosis; however, its presence, frequency, and clinical significance in non-cystic fibrosis bronchiectasis remain unclear., Objectives: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis., Methods: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles ("immunoallertypes"), were determined., Measurements and Main Results: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. "Sensitized bronchiectasis" was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome., Conclusions: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a "treatable trait" permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.

Background and Objective: A major challenge with the treatment of obstructive sleep apnoea (OSA) is adherence to continuous positive airway pressure (CPAP) therapy. Mask tolerability is an important determinant of adherence, however evidence to guide selection of mask interfaces is lacking., Methods: We conducted a randomized crossover trial of mask interfaces in CPAP therapy for moderate-to-severe OSA to assess adherence and efficacy of CPAP therapy with nasal mask, nasal pillow and oronasal masks. Demographic data, Nasal Obstruction Symptom Evaluation (NOSE) scores and craniofacial measurements were also analysed for associations with adherence with oronasal masks., Results: Eighty-five patients were included in the study (mean ± SD age: 46 ± 12 years; body mass index: 29.9 ± 5.6 kg/m 2 ; apnoea-hypopnoea index (AHI): 53.6 ± 24.0 events/h). Patients had better adherence with nasal masks (average night use: 3.96 ± 2.26 h/night) compared to oronasal masks (3.26 ± 2.18 h/night, P < 0.001) and nasal pillows (3.48 ± 2.20 h/night, P = 0.007). Residual AHI was higher with oronasal masks (7.2 ± 5.2) compared to nasal masks (4.0 ± 4.2, P < 0.001) and nasal pillows (4.1 ± 3.3, P < 0.001). Twenty-two (25.9%) patients had the best adherence with oronasal masks (4.22 ± 2.14 vs 2.93 ± 2.12 h/night, P = 0.016). These patients had lower NOSE scores (15 (0-35) vs 40 (10-55), P = 0.024) and larger menton-labrale inferioris/biocular width ratios (31 ± 3% vs 28 ± 4%, P = 0.019)., Conclusion: Nasal masks are the preferred interface during CPAP initiation. Patients with less nasal obstruction and a proportionally increased chin-lower lip distance to mid-face width may have better CPAP adherence with an oronasal mask interface., (© 2018 Asian Pacific Society of Respirology.)

Non-cystic fibrosis bronchiectasis (NCFB) characterized by permanent bronchial dilatation and recurrent infections has been clinically managed by long-term intermittent inhaled antibiotic therapy among other treatments. Herein we investigated dry powder inhaler (DPI) formulation of ciprofloxacin (CIP) nanoplex with mannitol/lactose as the excipient for NCFB therapy. The DPI of CIP nanoplex was evaluated against DPI of native CIP in terms of their (1) dissolution characteristics in artificial sputum medium, (2) ex vivo mucus permeability in sputum from NCFB and healthy individuals, (3) antibacterial efficacy in the presence of sputum against clinical Pseudomonas aeruginosa strains (planktonic and biofilm), and (4) cytotoxicity towards human lung epithelial cells. Despite their similarly fast dissolution rates in sputum, the DPI of CIP nanoplex exhibited superior mucus permeability to the native CIP (5-7 times higher) attributed to its built-in ability to generate highly supersaturated CIP concentration in the sputum. The superior mucus permeability led to the CIP nanoplex's higher antibacterial efficacy (>3 log 10 CFU/mL). The DPI of CIP nanoplex exhibited similar cytotoxicity towards the lung epithelial cells as the native CIP indicating its low risk of toxicity. These results established the promising potential of DPI of CIP nanoplex as a new therapeutic avenue for NCFB., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a "research priorities" consensus statement for bronchiectasis.Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S-28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific quantitative PCR for detection of and conidial quantification for a range of airway Aspergillus species was performed. Sputum galactomannan, Aspergillus specific IgE, IgG and TARC (thymus and activation regulated chemokine) levels were measured systemically and associated to clinical outcomes.The bronchiectasis mycobiome is distinct and characterised by specific fungal genera, including Aspergillus , Cryptococcus and Clavispora Aspergillus fumigatus (in Singapore/Kuala Lumpur) and Aspergillus terreus (in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies of Aspergillus- associated disease including sensitisation and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles, and associated with more severe disease, poorer pulmonary function and increased exacerbations.The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening for Aspergillus -associated disease should be considered even in apparently stable patients., Competing Interests: Conflict of interest: F.T. Chew reports personal fees from Sime Darby Technology Center, Olam International and First Resources Ltd, outside the submitted work. J.D. Chalmers reports grants from AstraZeneca, grants and personal fees from GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Bayer Healthcare and Grifols, and personal fees from Napp, outside the submitted work., (Copyright ©ERS 2018.)

Objective: Laryngeal cancer is a common malignant tumor in the head and neck, which affects swallowing, breathing, and pronunciation function. In recent years, many long non-coding RNAs (lncRNAs) have been shown to be involved in the progression of cancer with the development of gene sequencing, transcriptomics, and bioinformatics. LncRNA Dleu2 is a cancer-related lncRNA that down-regulates tumor progression in a variety of cancers. However, its possible effects and related signaling pathway in the development of laryngeal cancer are not clear., Patients and Methods: Real-time PCR was applied to test lncRNA Dleu2 and microRNA-16-1 (miR-16-1) expressions in laryngeal carcinoma tissues. LncRNA Dleu2 and miR-16-1 levels were over-expressed by transfection. Cell proliferation was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell migration was evaluated by using wound-healing assay. Cell invasion was determined by using transwell assay., Results: LncRNA Dleu2 and miR-16-1 levels were significantly declined in the laryngeal carcinoma tissue compared to para-carcinoma tissue (p < 0.05). LncRNA Dleu2 and miR-16-1 up-regulation significantly reduced cell proliferation, migration, and invasion compared to the control group (p < 0.05). Ago-miR16-1 transfection significantly enhanced the luciferase activity of wild-type Dleu2 compared to control group (p < 0.05), suggesting their interaction with each other., Conclusions: LncRNA Dleu2 influences the proliferation, migration, and invasion of laryngeal cancer cells through miR-16-1. Therefore, lncRNA Dleu2 and miR-16-1 may serve as potential biomarkers and targets for laryngeal cancer diagnosis and treatment.

Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

Background: Studies on diagnostic tests for exercise-induced bronchoconstriction (EIB) have centered around the asthmatic and elite athletic population. Traditionally, the exercise challenge test (ET) was recommended to assess EIB. We aimed to compare the performance of surrogate testing, mainly the hypertonic saline (HS) test, and methacholine challenge test (MCT) versus ET in identifying EIB among non-athletic subjects., Methods: We prospectively recruited subjects who did not have confirmed active asthma, but who reported exercise-induced dyspnoea. The participants underwent HS and ET on separate days within two weeks. MCT performed within one year were obtained retrospectively from medical records. The sensitivity, specificity, and accuracy of each diagnostic test were calculated using ET as the gold standard., Results: We recruited 27 participants (mean age 20.6±2.5 years; 92.6% male). Five (18.5%) had a history of self-reported asthma prior to recruitment. Eleven participants (40.7%) had a positive ET test. The sensitivity, specificity and accuracy of HS in diagnosing EIB was 90.9%, 62.5% and 74.1%; while that of MCT was 88.9%, 83.3% and 85.7% respectively. Six subjects were positive to HS but had negative ET test., Conclusions: Both HS and MCT were found to be suitable alternatives to ET in screening for EIB in the non-athletic population in this pilot study. Further large scale studies are required to confirm this finding. These tests have the potential to replace ET for the diagnosis of EIB in centres without ET equipment or facilities., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Chronic lung disease is recognized as an important risk factor for developing pulmonary aspergillosis. The development of specific aspergillus-associated syndromes depends on host immunity and underlying lung disease. In the setting of asthma, hypersensitivity to Aspergillus can lead to allergic bronchopulmonary aspergillosis (ABPA) or severe asthma with fungal sensitization (SAFS). Chronic use of systemic or inhaled corticosteroids coupled with recurrent antibiotic use for exacerbations prevalent in chronic obstructive pulmonary disease (COPD) predisposes to chronic pulmonary aspergillosis (CPA). Prior pulmonary tuberculosis is a risk factor for CPA, a syndrome with a wide range of presentations including a simple aspergilloma, chronic cavities, necrosis or fibrosis. Accumulating evidence suggests that the presence of or colonization by Aspergillus in the setting of chronic lung disease can worsen clinical course and outcomes even in the absence of overt pulmonary aspergillosis. We propose that understanding the complex interplay between host and fungi may provide key insights into the pathogenesis of Aspergillus -associated pulmonary syndromes in the setting of chronic lung disease, and provide novel therapeutic approaches to improve its identification and management.

Background: Accurate diagnosis is critical to both therapeutic decisions and prognostication in interstitial lung diseases (ILD). However, surgical lung biopsies carry high complication rates. Fibred confocal fluorescence microscopy (FCFM) offers an alternative as it can visualize lung tissue in vivo at the cellular level with minimal adverse events. We wanted to investigate the diagnostic utility, and safety of using FCFM for patients with ILD., Methods: In patients with suspected ILD, FCFM images were obtained from multiple bronchopulmonary segments using a miniprobe inserted through the working channel of a flexible bronchoscope. The procedure was performed under moderate sedation in an outpatient setting. Morphometric measurements and fibre pattern analyses were co-related with computed tomography (CT) findings and patients' final diagnoses based on multi-disciplinary consensus., Results: One hundred and eighty four segments were imaged in 27 patients (18 males) with a median age of 67 years (range, 24-79 years). They were grouped into chronic fibrosing interstitial pneumonia (16 patients) and other ILDs. Six distinct FCFM patterns were observed: normal, increased fibres, densely packed fibres, hypercellular, thickened fibres and others/non-specific. The pattern resembling densely packed fibres was seen in at least one segment in 68.8% patients with chronic fibrosing interstitial pneumonia, but only 36.4% in other ILD (P=0.097). An association between inflammatory patterns on CT and a hypercellular pattern on FCFM was also found (P<0.001)., Conclusions: Our study shows the potential of FCFM in classifying ILD, but its role in further diagnosis remains limited., Competing Interests: The authors have no conflicts of interest to declare.

The mutual control of the electric and magnetic properties of a multiferroic solid is of fundamental and great technological importance. In this article, the synthesis procedure of La 0.2 Pb 0.7 Fe 12 O 19 ceramics was briefly described and the data acquired for the materials characterization is presented. This data article is related to the research article-Acta Mater. 2016, 121, 144 (j.actamat.2016.08.083). Electric polarization hysteresis loop and I-V curve, which help to confirm the ferroelectricity of La 0.2 Pb 0.7 Fe 12 O 19 ceramics, were presented. Strong magnetic polarization data was also presented. The great variation of the dielectric constants along with the magnetic field has been presented which helped to demonstrat the giant magnetocapacitance of La 0.2 Pb 0.7 Fe 12 O 19 . All the datasets were collected at room temperature. Large ferroelectricity, strong magnetism and colossal magneto-capacitance effect have been all realized in one single phase La 0.2 Pb 0.7 Fe 12 O 19 at room temperature.

Background: Insertion of a carotid chimney graft during thoracic endovascular aortic repair (Ch-TEVAR) is a recognized technique to extend the proximal landing zone into the aortic arch in the treatment of thoracic aortic disease. Conventional technique requires surgical exposure of the carotid artery for insertion of the carotid chimney graft., Methodology: We describe our experience in the use of a suture-mediated closure device in percutaneous Ch-TEVAR in four patients., Results: Successful hemostasis was achieved in all four patients. No complications related to the carotid puncture were recorded., Conclusion: We conclude that using suture-mediated closure device for carotid closure appears feasible and deserves further studies as a potential alternative to conventional surgical approach.

Neurodegenerative disorders are one of the leading causes of death among the elderly. Therapeutic approaches with a single target have proven unsuccessful in treating these diseases. Structural combination of multi-functional compounds may lead to a molecule with multiple properties. In this study, we designed and synthesized T-006, a novel analog derived from two multi-functional neuroprotective chemicals, tetramethylpyrazine and J147. The methoxyphenyl group of J147 was replaced by tetramethylpyrazine. Bioactivity evaluation showed that T-006 at very low concentrations had multi-functional neuroprotective effects including rescuing iodoacetic acid-induced neuronal loss, preventing oxidative stress-induced neurotoxicity and reducing glutamate-induced excitotoxicity in vitro. Most importantly, T-006 significantly ameliorated memory impairments in APP/PS1 transgenic mice. These multiple functions of a single molecule suggest that T-006 is a promising novel neuroprotective agent for treating various neurodegenerative disorders, including and in particular Alzheimer's disease.

Mutations in epidermal growth factor receptor (EGFR) rendering it constitutively active is one of the major causes for metastatic non-small-cell lung cancer (NSCLC), and EGFR-targeted therapies utilizing tyrosine kinase inhibitors (TKIs) are often used clinically as the first-line treatment. But approximately half of NSCLC patients develop resistance to these therapies, where the MET proto-oncogene is amplified by EGFR through the hypoxia-inducible factor (HIF)-1α. Here we report that endothelial PAS domain-containing protein 1 (EPAS1), with 48% sequence identity to HIF-1α, specifically binds to TKI-resistant T790M EGFR, but not to wild-type EGFR, in NSCLC cell lines. Expression of EPAS1 enhances amplification of MET when simultaneously expressed with T790M EGFR but not with wild-type EGFR, and this enhancement is independent of ligand binding domain of EGFR. MET amplification requires EPAS1, since EPAS1 knock-down reduced MET levels. When NSCLC cells expressing T790M EGFR were treated with TKIs, reduced EPAS1 levels significantly enhanced the drug effect, whereas over-expression of EPAS1 increased the drug resistant effect. This EPAS1-dependent TKI-resistance was abolished by knocking-down MET, suggesting that EPAS1 does not cause TKI-resistance itself but functions to bridge EGFR and MET interactions. Our findings suggest that EPAS1 is a key factor in the EGFR-MET crosstalk in conferring TKI-resistance in NSCLC cases, and could be used as a potential therapeutic target in TKI-resistant NSCLC patients.

Background: A subset of severe asthma patients has fixed airways obstruction, which is characterized by incomplete reversibility to bronchodilator challenge. We aimed to elucidate the factors associated with fixed airways obstruction in a cohort of patients with severe asthma in Singapore., Methods: 245 patients from the Singapore General Hospital-Severe Asthma Phenotype Study (SGH-SAPS) were screened. These patients fulfilled World Health Organization criteria for "treatment-resistant severe asthma" and were all on combination of high-dose inhaled corticosteroids and long-acting beta2 agonists. 76 patients had pre- and postbronchodilator lung function tests and were selected for analysis. They were divided into two groups based on postbronchodilator (Post BD) forced expiratory volume in one second, PostBDFEV1 % predicted: ≥70% (Non-Fixed Obs) and < 70% (Fixed Obs). We compared clinical and demographic parameters between the two groups., Results: Patients in the Fixed Obs group were more frequently past or current smokers and had a higher pack-year smoking history. Overall, pack-year smoking history had a modest negative correlation with PostBDFEV1 % predicted. Atopy, allergen sensitization (type and numbers), comorbidities, symptoms, health care utilization and medication use did not differ between the two groups. The prebronchodilator FEV1 % predicted, FEV1/FVC and FVC % predicted were significantly lower in the Fixed Obs group. In addition, prebronchodilator FVC % predicted accounted for more variability than FEV1/FVC in predicting PostBDFEV1% predicted., Conclusion: Smoking is associated with fixed airways obstruction in patients with treatment-resistant severe asthma in Singapore. Furthermore, our results suggest that both small and large airways obstruction contribute independently to fixed airways obstruction in severe asthma.

As one of the human activities that transform nature, construction of dams and dykes may impose significant effects on lake ecosystems. Due to lacking of comparative data for ecological monitoring, how the changes of phytoplankton community structure respond to altered hydrological connectivity between lakes and other water bodies is still unknown. This work chose Junshan Lake, the typical isolated lake from Poyang Lake floodplain, to investigate the succession in phytoplankton communities responding to altered connectivity. Phytoplankton samples were collected during the wet and dry seasons in Junshan Lake, to analyze the phytoplankton community structure. The results showed that, fifty three genera from six phyta were identified in Junshan Lake, with Chlorophyta (47.2%), Bacillariophyta (22.2%), Cyanophyta (14.8%) and Euglenophyta (9.3%) being the main phyta. The dominant species were Ceratium hirundinella (20.5%), Anabeana spp. (18.5%) and Microcystis spp. (12.9%) during the wet seasons. Cryptomonas ovate (38.4%), Aulacoseira granulata (15.2%) and Microcystis spp. (10.5%) dominated during the whole dry seasons. The total phytoplankton abundance was mainly composed of Cyanophyta (85.4% -87.0%). The total phytoplankton biomass was dominantly made up of Cyanophyta (45.0%), Dinophyta (21.1%), Bacillariophyta (15.6%) and Chlorophyta (11.5%) during the wet seasons. Cryptophyta (38.2%), Bacillariophyta (31.3%) and Cyanophyta (21.1%) were the main contributors of the total phytoplankton biomass during the dry seasons. The phytoplankton community structure changed from Dinophyta-Bacillariophyta type during the wet seasons of 2007-2008 to Cyanophyta- Dinophyta type during the wet seasons of 2012-2013, and changed from Dinophyta- Bacillariophyta type during the dry seasons of 2007-2008 to Cryptophyta- Bacillariophyta- Cyanophyta type during the dry seasons of 2012-2013. The abundance and biomass increased from 2.66 x 10(6) cell L(-1) during 2007-2008 to 6.77 x 10(7) cell x L(-1) during 2012- 2013, and from 0.72 mg x L(-1) during 2007-2008 to 12.30 mg x L(-1) during 2012-2013, respectively. The succession pattern of phytoplankton community in the Junshan Lake showed a decrease in the proportion of oligotrophic species as Chrysophyta and Dinophyta, and an increase in eutrophic species as Cyanophyta and Cryptophyta. Thus, being isolated from Poyang Lake might alter hydrologic factors so that the water exchange time became longer and the water flow became slower which could promote the growth and aggregation of phytoplankton eutrophication indicator species in Junshan Lake.

The current-voltage characteristics of Ni contacts with the surfaces of ZnO thin films as well as single crystal (0001) ZnO substrate are investigated. The ZnO thin film shows a conversion from Ohmic to rectifying behavior when annealed at 800°C. Similar findings are also found on the Zn-polar surface of (0001) ZnO. The O-polar surface, however, only shows Ohmic behavior before and after annealing. The rectifying behavior observed on the Zn-polar and ZnO thin film surfaces is associated with the formation of nickel zinc oxide (Ni1-xZnxO, where x = 0.1, 0.2). The current-voltage characteristics suggest that a p-n junction is formed by Ni1-xZnxO (which is believed to be p-type) and ZnO (which is intrinsically n-type). The rectifying behavior for the ZnO thin film as a result of annealing suggests that its surface is Zn-terminated. Current-voltage measurements could possibly be used to determine the surface polarity of ZnO thin films.

Objective: To evaluate the efficacy of an electromagnetic device for correct bedside placement of nasojejunal feeding tube for patients in intensive care unit (ICU)., Methods: The clinical data of 109 patients in ICU who accepted bedside nasojejunal feeding tube placement from January 2010 to September 2012 were retrospectively analyzed. All the patients were divided into three groups according to the difference in type of nasojejunal feeding tube and the placement technique: control group 1 (n=48, Flocare feeding tube and bedside blind insertion group), control group 2 (n=28, Corflo(®) feeding tube and bedside blind insertion group), observation group (n=33, Corflo(®) feeding tube and electromagnetic tube placement device group). The success rate, the times of placement, duration of nasojejunal feeding, and safety were compared among three groups., Results: The success rate of control group 2 and observation group were higher than control group 1 (71.43%, 90.91% vs. 33.33%), rate of partial success and failure rate were lower than those of control group 1 (partial success rate: 17.86%, 3.03% vs. 35.42%; failure rate: 10.71%, 6.06% vs. 31.25%, all P<0.05), and no differences were found between control group 2 and observation group. The average times for successful placement in observation group was lower than that of control group 1 and control group 2 (1.6±0.5 vs. 6.6±3.2, 5.8±2.3, both P<0.05), and the average time for successful placement was shorter in observation group than that of control group 1 and control group 2 (12.48±3.78 minutes vs. 25.27±3.61 minutes, 23.58±4.87 minutes, both P<0.05), but there was no difference between control group 1 and control group 2. No complications occurred in all three groups., Conclusion: Placement of a nasojejunal tube with the aid of an electromagnetic device is an excellent method for enteral nutrition, as it is safer, more efficient, with high successful rate, less time spending, and easier to master for beginners.

A new class of ratiometric fluorescence sensors composed of rare-earth (RE) compound nanotubes is described. Polyethylenimine-coated yttrium hydroxide fluoride nanotubes (YHF NTs) that were synthesized hydrothermally exhibit highly efficient fluorescence when doped with RE ions. The polyethylenimine on the NTs facilitates the incorporation of phosphors such as quantum dots or organic dyes onto the NT surface to produce dual-emitting nanocomposites which are excellent ratiometric fluorescence sensors. The phosphor layer and underlying tubes in the nanocomposites act as the indicator and reference probes, respectively. This ratiometric fluorescence method which can be applied to the detection of heavy metals in solutions, temperature sensing, and pH sensing boasts high sensitivity and selectivity as well as better accuracy than traditional intensity-based fluorescence methods.

Chlorhexidine and mupirocin are used in health care facilities to eradicate methicillin-resistant Staphylococcus aureus (MRSA) carriage. The objective of this study was to assess the frequency of chlorhexidine and mupirocin resistance in isolates from nares carriers in multiple nursing homes and to examine characteristics associated with resistance. Nasal swab samples were collected from approximately 100 new admissions and 100 current residents in 26 nursing homes in Orange County, CA, from October 2008 to May 2011. MRSA isolates were tested for susceptibility by using broth microdilution, disk diffusion, and Etest; for genetic relatedness using pulsed-field gel electrophoresis; and for qac gene carriage by PCR. Characteristics of the nursing homes and their residents were collected from the Medicare Minimum Data Set and Long-Term Care Focus. A total of 829 MRSA isolates were obtained from swabbing 3,806 residents in 26 nursing homes. All isolates had a chlorhexidine MIC of ≤4 μg/ml. Five (0.6%) isolates harbored the qacA and/or qacB gene loci. Mupirocin resistance was identified in 101 (12%) isolates, with 78 (9%) isolates exhibiting high-level mupirocin resistance (HLMR). HLMR rates per facility ranged from 0 to 31%. None of the isolates with HLMR displayed qacA or qacB, while two isolates carried qacA and exhibited low-level mupirocin resistance. Detection of HLMR was associated with having a multidrug-resistant MRSA isolate (odds ratio [OR], 2.69; P = 0.004), a history of MRSA (OR, 2.34; P < 0.001), and dependency in activities of daily living (OR, 1.25; P = 0.004). In some facilities, HLMR was found in nearly one-third of MRSA isolates. These findings may have implications for the increasingly widespread practice of MRSA decolonization using intranasal mupirocin.

Cigarette smoking is associated with an increased incidence of chronic obstructive pulmonary disease (COPD). In this study, we hypothesized that liquiritin apioside (LA), a main flavonoid component from Glycyrrhiza uralensis, had antioxidant properties by inducing glutathione (GSH) biosynthesis via the inhibition of cytokines and protected lung epithelial cells against cigarette smoke-mediated oxidative stress. A549 cells were treated with cigarette smoke extract (CSE) and/or LA. ICR mice were exposed to cigarette smoke (CS) for four days with increasing exposure time for up to 6 h per day to elicit epithelial cells injury. One hour before smoke exposure, mice were treated with LA by gavage; 18 h after the last CS exposure all examinations were performed. Treatment with LA concentration-dependently prevented CSE-induced cytotoxicity, increase of TGF-β and TNF-α mRNA expression, depletion of GSH and apoptosis in A549 cells. LA at doses 3, 10 and 30 mg/kg dose-dependently inhibited pulmonary neutrophil and macrophage inflammation. Lung sections of the CS-exposed LA treated mice showed an apparently reduced pulmonary inflammation and a significant inhibitory effect on mucus containing goblet cells in the large airways. Furthermore, the CS-induced pulmonary release of TGF-β, TNF-α and myeloperoxidase activity was reduced, and superoxide dismutase activity was enhanced.These results indicate that protective roles of LA on CS-induced the lung epithelial cell injury are mediated by inhibiting TGF-β and TNF-α expression and increasing anti-oxidative levels of GSH, suggesting that LA might be effective as protective agent against epithelial injury in COPD., (© 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.)