Publications by authors named "Jia-Wei Yang"

35 Publications

Potential therapeutic strategies for targeting Y-box-binding protein 1 in cancers.

Curr Cancer Drug Targets 2021 Aug 31. Epub 2021 Aug 31.

Department of Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012. China.

As one of the most conservative proteins in evolution, Y-box-binding protein 1 (YB-1) has long been considered as a potential cancer target. YB-1 is usually poorly expressed in normal cells and exerts cellular physiological functions such as DNA repair, pre-mRNA splicing and mRNA stabilizing. In cancer cells, the expression of YB-1 is up-regulated and undergoes nuclear translocation and contributes to tumorigenesis, angiogenesis, tumor proliferation, invasion, migration and chemotherapy drug resistance. During the past decades, a variety of pharmacological tools such as siRNA, shRNA, microRNA, circular RNA, lncRNA and various compounds have been developed to target YB-1 for cancer therapy. In this review, we describe the physiological characteristics of YB-1 in detail, highlight the role of YB-1 in tumors and summarize the current therapeutic methods for targeting YB-1 in cancer.
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http://dx.doi.org/10.2174/1568009621666210831125001DOI Listing
August 2021

The Controversy About the Effects of Different Doses of Corticosteroid Treatment on Clinical Outcomes for Acute Respiratory Distress Syndrome Patients: An Observational Study.

Front Pharmacol 2021 29;12:722537. Epub 2021 Jul 29.

Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Institute of Respiratory Medicine, Tongji University, Shanghai, China.

Corticosteroid usage in acute respiratory distress syndrome (ARDS) remains controversial. We aim to explore the correlation between the different doses of corticosteroid administration and the prognosis of ARDS. All patients were diagnosed with ARDS on initial hospital admission and received systemic corticosteroid treatment for ARDS. The main outcomes were the effects of corticosteroid treatment on clinical parameters and the mortality of ARDS patients. Secondary outcomes were factors associated with the mortality of ARDS patients. 105 ARDS patients were included in this study. Corticosteroid treatment markedly decreased serum interleukin-18 (IL-18) level (424.0 ± 32.19 vs. 290.2 ± 17.14; = 0.0003) and improved arterial partial pressure of oxygen/fraction of inspired oxygen (PaO/FiO) (174.10 ± 65.28 vs. 255.42 ± 92.49; < 0.0001). The acute physiology and chronic health evaluation (APACHE II) score (16.15 ± 4.41 vs. 14.88 ± 4.57, = 0.042) decreased significantly on the seventh day after systemic corticosteroid treatment. Interestingly, the serum IL-18 decreased significantly (304.52 ± 286.00 vs. 85.85 ± 97.22, < 0.0001), whereas the improvement of PaO/FiO (24.78 ± 35.03 vs. 97.17 ± 44.82, < 0.001) was inconspicuous after systemic corticosteroid treatment for non-survival patients, compared with survival patients. Furthermore, the receiver operating characteristic (ROC) model revealed, when equivalent methylprednisolone usage was 146.5 mg/d, it had the best sensitivity and specificity to predict the death of ARDS. Survival analysis by Kaplan-Meier curves presented the higher 45-day mortality in high-dose corticosteroid treatment group (logrank test < 0.0001). Multivariate Cox regression analyses demonstrated that serum IL-18 level, APACHE II score, D-dimer, and high-dose corticosteroid treatment were associated with the death of ARDS. Appropriate dose of corticosteroids may be beneficial for ARDS patients through improving the oxygenation and moderately inhibiting inflammatory response. The benefits and risks should be carefully weighed when using high-dose corticosteroid for ARDS. This work was registered in ClinicalTrials.gov. Name of the registry: Corticosteroid Treatment for Acute Respiratory Distress Syndrome. Trial registration number: NCT02819453. URL of trial registry record: https://register.clinicaltrials.gov.
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http://dx.doi.org/10.3389/fphar.2021.722537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358143PMC
July 2021

Albumin-Based LL37 Peptide Nanoparticles as a Sustained Release System against Lung Infection.

ACS Biomater Sci Eng 2021 05 31;7(5):1817-1826. Epub 2020 Aug 31.

Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.

(PA) has emerged as a pressing challenge to pulmonary infection and lung damage. The LL37 peptide is an efficient antimicrobial agent against PA strains, but its application is limited because of fast clearance , biosafety concerns, and low bioavailability. Thus, an albumin-based nanodrug delivery system with reduction sensitivity was developed by forming intermolecular disulfide bonds to increase LL37 performance against PA. Cationic LL37 can be efficiently encapsulated via electrostatic interactions to exert improved antimicrobial effects. The LL37 peptide exhibits greater than 48 h of sustained released from LL37 peptide nanoparticles (LL37 PNP), and prolonged antimicrobial effects were noted as the incubation time increased. Levels of inflammatory cytokines secreted by peritoneal macrophages, including TNF-α and IL-6, were reduced significantly after LL37 PNP treatment following PA stimulation, indicating that LL37 PNP inhibits PA growth and exerts anti-inflammatory effects . In a murine model of acute PA lung infection, LL37 PNP significantly reduced TNF-α and IL-1β expression and alleviated lung damage. The accelerated clearance of PA indicates that LL37 PNP could improve PA lung infection and the subsequent inflammation response more efficiently compared with free LL37 peptide. In conclusion, this excellent biocompatible LL37 delivery strategy may serve as an alternative approach for the application of new types of clinical treatment in future.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01084DOI Listing
May 2021

Targeting galectins in T cell-based immunotherapy within tumor microenvironment.

Life Sci 2021 Jul 27;277:119426. Epub 2021 Mar 27.

Department of Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, PR China. Electronic address:

Over the past few years, tumor immunotherapy has emerged as an innovative tumor treatment and owned incomparable advantages over other tumor therapy. With unique complexity and uncertainty, immunotherapy still need helper to apply in the clinic. Galectins, modulated in tumor microenvironment, can regulate the disorders of innate and adaptive immune system resisting tumor growth. Considering the role of galectins in tumor immunosuppression, combination therapy of targeted anti-galectins and immunotherapy may be a promising tumor treatment. This brief review summarizes the expression and immune functions of different galectins in tumor microenvironment and discusses the potential value of anti-galectins in combination with checkpoint inhibitors in tumor immunotherapy.
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http://dx.doi.org/10.1016/j.lfs.2021.119426DOI Listing
July 2021

Corticosteroids alleviate lipopolysaccharide-induced inflammation and lung injury via inhibiting NLRP3-inflammasome activation.

J Cell Mol Med 2020 11 25;24(21):12716-12725. Epub 2020 Sep 25.

Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

The role of corticosteroids in acute lung injury (ALI) remains uncertain. This study aims to determine the underlying mechanisms of corticosteroid treatment for lipopolysaccharide (LPS)-induced inflammation and ALI. We used corticosteroid treatment for LPS-induced murine ALI model to investigate the effect of corticosteroid on ALI in vivo. Moreover, LPS-stimulated macrophages were used to explore the specific anti-inflammatory effects of corticosteroids on NLRP3-inflammasome in vitro. We found corticosteroids attenuated LPS-induced ALI, which manifested in reduction of the alveolar structure destruction, the infiltration of neutrophils and the inflammatory cytokines release of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in Lung. In vitro, when NLRP3-inflammasome was knocked out, inflammatory response of caspase-1 activation and IL-1β secretion was obviously declined. Further exploration, our results showed that when corticosteroid preprocessed macrophages before LPS primed, it obviously inhibited the activation of caspase-1 and the maturation of IL-1β, which depended on inhibiting the nuclear factor-κB (NF-κB) signal pathway activation. However, when corticosteroids intervened the LPS-primed macrophages, it also negatively regulated NLRP3-inflammasome activation through suppressing mitochondrial reactive oxygen species (mtROS) production. Our results revealed that corticosteroids played a protection role in LPS-induced inflammation and ALI by suppressing both NF-κB signal pathway and mtROS-dependent NLRP3 inflammasome activation.
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http://dx.doi.org/10.1111/jcmm.15849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686976PMC
November 2020

Functionalized Mesoporous Silicon Nanomaterials in Inorganic Soil Pollution Research: Opportunities for Soil Protection and Advanced Chemical Imaging.

Curr Pollut Rep 2020 1;6(3):264-280. Epub 2020 Jul 1.

Department of Chemistry, University of Warwick, Coventry, CV4 7AL UK.

"Innovative actions towards a pollution free-planet" is a goal of the United Nations Environment Assembly (UNEA). Aided by both the Food and Agricultural Organisation (FAO) and its Global Soil Partnership under the 3rd UNEA resolution, a consensus from > 170 countries have agreed a need for accelerated action and collaboration to combat soil pollution. This initiative has been tasked to find new and improved solutions to prevent and reduce soil pollution, and it is in this context that this review provides an updated perspective on an emerging technology platform that has already provided demonstrable utility for measurement, mapping, and monitoring of toxic trace elements (TTEs) in soils, in addition to the entrapment, removal, and remediation of pollutant sources. In this article, the development and characteristics of functionalized mesoporous silica nanomaterials (FMSN) will be discussed and compared with other common metal scavenging materials. The chemistries of the common functionalizations will be reviewed, in addition to providing an outlook on some of the future directions/applications of FMSN. The use of FMSN in soil will be considered with some specific case studies focusing on Hg and As. Finally, the advantages and developments of FMSN in the widely used diffusive gradients-in-thin films (DGT) technique will be discussed, in particular, its advantages as a DGT substrate for integration with oxygen planar optodes in multilayer systems that provide 2D mapping of metal pollutant fluxes at submillimeter resolution, which can be used to measure detailed sediment-water fluxes as well as soil-root interactions, to predict plant uptake and bioavailability.
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http://dx.doi.org/10.1007/s40726-020-00152-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446291PMC
July 2020

Organ-on-a-Chip: Opportunities for Assessing the Toxicity of Particulate Matter.

Front Bioeng Biotechnol 2020 29;8:519. Epub 2020 May 29.

Department of Electrical and Computer Engineering, College of Electrical and Computer Engineering National Chiao Tung University, Hsinchu, Taiwan.

Recent developments in epidemiology have confirmed that airborne particulates are directly associated with respiratory pathology and mortality. Although clinical studies have yielded evidence of the effects of many types of fine particulates on human health, it still does not have a complete understanding of how physiological reactions are caused nor to the changes and damages associated with cellular and molecular mechanisms. Currently, most health assessment studies of particulate matter (PM) are conducted through cell culture or animal experiments. The results of such experiments often do not correlate with clinical findings or actual human reactions, and they also cause difficulty when investigating the causes of air pollution and associated human health hazards, the analysis of biomarkers, and the development of future pollution control strategies. Microfluidic-based cell culture technology has considerable potential to expand the capabilities of conventional cell culture by providing high-precision measurement, considerably increasing the potential for the parallelization of cellular assays, ensuring inexpensive automation, and improving the response of the overall cell culture in a more physiologically relevant context. This review paper focuses on integrating the important respiratory health problems caused by air pollution today, as well as the development and application of biomimetic organ-on-a-chip technology. This more precise experimental model is expected to accelerate studies elucidating the effect of PM on the human body and to reveal new opportunities for breakthroughs in disease research and drug development.
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http://dx.doi.org/10.3389/fbioe.2020.00519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272695PMC
May 2020

Assessing risk factors for SARS-CoV-2 infection in patients presenting with symptoms in Shanghai, China: a multicentre, observational cohort study.

Lancet Digit Health 2020 06 14;2(6):e323-e330. Epub 2020 May 14.

Department of Respiratory and Critical Medicine, Shanghai Tenth People's Hospital, Shanghai, China.

Background: The outbreak of COVID-19 has led to international concern. We aimed to establish an effective screening strategy in Shanghai, China, to aid early identification of patients with COVID-19.

Methods: We did a multicentre, observational cohort study in fever clinics of 25 hospitals in 16 districts of Shanghai. All patients visiting the clinics within the study period were included. A strategy for COVID-19 screening was presented and then suspected cases were monitored and analysed until they were confirmed as cases or excluded. Logistic regression was used to determine the risk factors of COVID-19.

Findings: We enrolled patients visiting fever clinics from Jan 17 to Feb 16, 2020. Among 53 617 patients visiting fever clinics, 1004 (1·9%) were considered as suspected cases, with 188 (0·4% of all patients, 18·7% of suspected cases) eventually diagnosed as confirmed cases. 154 patients with missing data were excluded from the analysis. Exposure history (odds ratio [OR] 4·16, 95% CI 2·74-6·33; p<0·0001), fatigue (OR 1·56, 1·01-2·41; p=0·043), white blood cell count less than 4 × 10 per L (OR 2·44, 1·28-4·64; p=0·0066), lymphocyte count less than 0·8 × 10 per L (OR 1·82, 1·00-3·31; p=0·049), ground glass opacity (OR 1·95, 1·32-2·89; p=0·0009), and having both lungs affected (OR 1·54, 1·04-2·28; p=0·032) were independent risk factors for confirmed COVID-19.

Interpretation: The screening strategy was effective for confirming or excluding COVID-19 during the spread of this contagious disease. Relevant independent risk factors identified in this study might be helpful for early recognition of the disease.

Funding: National Natural Science Foundation of China.
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http://dx.doi.org/10.1016/S2589-7500(20)30109-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255260PMC
June 2020

Graphene Oxide-Based Nanomaterials: An Insight into Retinal Prosthesis.

Int J Mol Sci 2020 Apr 22;21(8). Epub 2020 Apr 22.

Department of Electrical and Computer Engineering, College of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu 300, Taiwan.

Retinal prosthesis has recently emerged as a treatment strategy for retinopathies, providing excellent assistance in the treatment of age-related macular degeneration (AMD) and retinitis pigmentosa. The potential application of graphene oxide (GO), a highly biocompatible nanomaterial with superior physicochemical properties, in the fabrication of electrodes for retinal prosthesis, is reviewed in this article. This review integrates insights from biological medicine and nanotechnology, with electronic and electrical engineering technological breakthroughs, and aims to highlight innovative objectives in developing biomedical applications of retinal prosthesis.
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http://dx.doi.org/10.3390/ijms21082957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216005PMC
April 2020

Graphene Oxide-Based Biosensors for Liquid Biopsies in Cancer Diagnosis.

Nanomaterials (Basel) 2019 Dec 3;9(12). Epub 2019 Dec 3.

Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu 300, Taiwan.

Liquid biopsies use blood or urine as test samples, which are able to be continuously collected in a non-invasive manner. The analysis of cancer-related biomarkers such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), microRNA, and exosomes provides important information in early cancer diagnosis, tumor metastasis detection, and postoperative recurrence monitoring assist with clinical diagnosis. However, low concentrations of some tumor markers, such as CTCs, ctDNA, and microRNA, in the blood limit its applications in clinical detection and analysis. Nanomaterials based on graphene oxide have good physicochemical properties and are now widely used in biomedical detection technologies. These materials have properties including good hydrophilicity, mechanical flexibility, electrical conductivity, biocompatibility, and optical performance. Moreover, utilizing graphene oxide as a biosensor interface has effectively improved the sensitivity and specificity of biosensors for cancer detection. In this review, we discuss various cancer detection technologies regarding graphene oxide and discuss the prospects and challenges of this technology.
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http://dx.doi.org/10.3390/nano9121725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956293PMC
December 2019

The Development of Controllable Magnetic Driven Microphysiological System.

Front Cell Dev Biol 2019 7;7:275. Epub 2019 Nov 7.

Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu, Taiwan.

Current research has enabled the use of microphysiological systems and creation of models for alveolar and pulmonary diseases. However, bottlenecks remain in terms of medium- and long-term regulation of cell cultures and their functions in microchannel systems, as well as in the enhancement of representation of alveolar models and reference values of the data. Currently used systems also require on-chip manufacturing of complex units, such as pumps, tubes, and other cumbersome structures for maintaining cells in culture. In addition, system simplification and minimization of all external and human factors major challenges facing the establishment of alveolar models. In this study, a magnetically driven dynamic alveolus cell-culture system has been developed to use controlled magnetic force to drive a magnetic film on the chip, thereby directing the fluid within it to produce a circulating flow. The system has been confirmed to be conducive with regard to facilitating uniform attachment of human alveolar epithelial cells and long-term culture. The cell structure has been recapitulated, and differentiation functions have been maintained. Subsequently, reactions between silica nanoparticles and human alveolar epithelial cells have been used to validate the effects and advantages of the proposed dynamic chip-based system compared to a static environment. The innovative concept of use of a magnetic drive has been successfully employed in this study to create a simple and controllable yet dynamic alveolus cell-culture system to realize its functions and advantages with regard to tissue construction.
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http://dx.doi.org/10.3389/fcell.2019.00275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853840PMC
November 2019

The clinical characteristics and prognosis of ABPA are closely related to the mucus plugs in central bronchiectasis.

Clin Respir J 2020 Feb 5;14(2):140-147. Epub 2019 Dec 5.

Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Introduction: The characteristics of Allergic Bronchopulmonary Aspergillosis (ABPA) based on its radiological classification is still unclear.

Objectives: To investigate the clinical significances of ABPA patients with central bronchiectasis (ABPA-CB) by different radiological classifications of mucus plugs.

Methods: ABPA-CB patients from a pulmonary hospital between 2008 and 2015 were retrospectively included and analysed. According to the chest imaging in their first visit to physician, the ABPA-CB patients were divided into two groups based on the presence of high-attenuation mucus (HAM) or low-attenuation mucus (LAM). The primary endpoint was ABPA relapse within 1 year since the glucocorticoid withdrawal. The relationship between the imaging findings and the clinical prognosis was illuminated.

Results: A total of 125 ABPA patients were analysed in this study. Compared to the LAM group, the HAM group presented higher blood eosinophil cells counts, higher rates of Aspergillus detection isolated in sputum and expectoration of brownish-black mucus plugs, more affected lobes and segments, poorer pulmonary function and higher rate of relapse.

Conclusions: The clinical characteristics and prognosis of ABPA-CB patients are closely related to its radiological phenotype of mucus plugs in the central bronchiectasis. Clinicians should promote a diversity of personalized treatments for different patients with different radiological characteristics.
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http://dx.doi.org/10.1111/crj.13111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028037PMC
February 2020

One-Pot Fabrication of TiO₂ Rutile Nanorods/Anatase Nanoparticles: Mixed Crystal Phase and Morphology-Control for Enhanced Photovoltaic Performance.

J Nanosci Nanotechnol 2019 12;19(12):7714-7720

Department of State Key Laboratory of Materials-Oriented Chemical Engineering, Jiangsu National Synergetic Innovation Center for Advanced Materials, College of Chemical Engineering, Nanjing Tech University (former Nanjing University of Technology), Nanjing 210009, P. R. China.

The formation of nanocrystals with a controlled composition and desirable nanostructure is a prominent challenge in many science and technology fields. In this study, rutile TiO₂ nanorods coexisting with anatase TiO₂ nanoparticles were fabricated via a mild one-pot hydrothermal process. Results indicate an interesting phenomenon wherein adding an appropriate amount of oxalic acid can realize proportional regulation of anatase and the rutile phase. An increasing quantity of oxalic acid changes the crystalline phase from rutile to anatase accompanied by morphological changes from TiO₂ nanorods to nanoparticles. The optimized anatase/rutile crystalline phase and TiO₂ nanorods/nanoparticles morphology enhance the light-scattering and electron transfer ability. When the percentage of anatase phase increased to 67%, the composite architecture grew by 60% in photoelectric conversion efficiency and 0.1 V in open-circuit voltage. This study opens a door to the fabrication of the controllable mixed crystal composition and the designed micro-nano structure for the improvement on the photovoltaic performance.
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http://dx.doi.org/10.1166/jnn.2019.16847DOI Listing
December 2019

Remote Magnetic Control of Autophagy in Mouse B-Lymphoma Cells with Iron Oxide Nanoparticles.

Nanomaterials (Basel) 2019 Apr 4;9(4). Epub 2019 Apr 4.

Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan.

Autophagy is the spontaneous degradation of intracellular proteins and organelles in response to nutrient deprivation. The phagocytosis of iron oxide nanoparticles (IONPs) results in intracellular degradation that can be exploited for use in cancer treatment. Non-invasive magnetic control has emerged as an important technology, with breakthroughs achieved in areas such as magneto-thermal therapy and drug delivery. This study aimed to regulate autophagy in mouse B-lymphoma cells (A20) through the incorporation of IONPs-quantum dots (QDs). We hypothesized that with the application of an external magnetic field after phagocytosis of IONPs-QDs, autophagy of intracellular IONPs-QDs could be regulated in a non-invasive manner and subsequently modulate the regulation of inflammatory responses. The potential of this approach as a cancer treatment method was explored. The application of IONPs and an external magnetic force enabled the non-invasive regulation of cell autophagy and modulation of the self-regulatory function of cells. The combination of non-invasive magnetic fields and nanotechnology could provide a new approach to cancer treatment.
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http://dx.doi.org/10.3390/nano9040551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524120PMC
April 2019

Noninvasive Glucose Monitoring with a Contact Lens and Smartphone.

Sensors (Basel) 2018 Sep 22;18(10). Epub 2018 Sep 22.

Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu 300, Taiwan.

Diabetes has become a chronic metabolic disorder, and the growing diabetes population makes medical care more important. We investigated using a portable and noninvasive contact lens as an ideal sensor for diabetes patients whose tear fluid contains glucose. The key feature is the reversible covalent interaction between boronic acid and glucose, which can provide a noninvasive glucose sensor for diabetes patients. We present a phenylboronic acid (PBA)-based HEMA contact lens that exhibits a reversible swelling/shrinking effect to change its thickness. The difference in thickness can be detected in a picture taken with a smartphone and analyzed using software. Our novel technique offers the following capabilities: (i) non-enzymatic and continuous glucose detection with the contact lens; (ii) no need for an embedded circuit and power source for the glucose sensor; and (iii) the use of a smartphone to detect the change in thickness of the contact lens with no need for additional photo-sensors. This technique is promising for a noninvasive measurement of the glucose level and simple implementation of glucose sensing with a smartphone.
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http://dx.doi.org/10.3390/s18103208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210255PMC
September 2018

Printable Graphene Oxide Micropatterns for a Bio-Subretinal Chip.

Adv Healthc Mater 2018 09 26;7(18):e1800365. Epub 2018 Jul 26.

Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu, 300, Taiwan.

Recently, implantable artificial subretinal chips using electronic components have replaced photoreceptors to serve as the most feasible treatment for retinal diseases. As such a chip that is meant to be implanted and used for very long periods, growing retinal cells on it to improve the electrical stimulation efficiency and attraction of neuronal elements remains a challenge. Here, an inkjet printing technology is employed to create graphene oxide (GO) micropatterns onto microelectrodes of a photovoltaic-powered implantable retinal chip. These GO micropatterns allow human retinal pigment epithelium (RPE) cells to specially attach and grow in each microelectrode. In addition, the cell proliferation, viability, and tight junction of RPE cells are improved during culturing. The development of a simple surface-coating technology would pave the way for the development of the first fully integrated and encapsulated retinal prostheses with biocompatible on-chip microelectrodes for long-term implantation, which could be effectively applied in retina tissue engineering and therapy.
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http://dx.doi.org/10.1002/adhm.201800365DOI Listing
September 2018

Enhanced Osteogenic Differentiation of Stem Cells on Phase-Engineered Graphene Oxide.

ACS Appl Mater Interfaces 2018 Apr 9;10(15):12497-12503. Epub 2018 Apr 9.

Optical Materials Engineering Laboratory , ETH Zurich , Zurich 8092 , Switzerland.

Graphene oxide (GO) has attracted significant interest as a template material for multiple applications due to its two-dimensional nature and established functionalization chemistries. However, for applications toward stem cell culture and differentiation, GO is often reduced to form reduced graphene oxide, resulting in a loss of oxygen content. Here, we induce a phase transformation in GO and demonstrate its benefits for enhanced stem cell culture and differentiation while conserving the oxygen content. The transformation results in the clustering of oxygen atoms on the GO surface, which greatly improves its ability toward substance adherence and results in enhanced differentiation of human mesenchymal stem cells toward the osteogenic lineage. Moreover, the conjugating ability of modified GO strengthened, which was examined by auxiliary osteogenic growth peptide conjugation. Overall, our work demonstrates GO's potential for stem cell applications while maintaining its oxygen content, which could enable further functionalization and fabrication of novel nano-biointerfaces.
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http://dx.doi.org/10.1021/acsami.8b02225DOI Listing
April 2018

Simultaneous drug delivery and cellular imaging using graphene oxide.

Biomater Sci 2018 Mar;6(4):813-819

Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu, Taiwan 30010.

Graphene oxide (GO), a derivative of graphene, and its related nanomaterials have attracted much attention in recent years due to the excellent biocompatibility and large surface area of GO with abundant oxygen functional groups, which further enable it to serve as a nano-bio interface. Herein, we demonstrate the induction of blue fluorescence in GO suspensions via a mild thermal annealing procedure. Additionally, this procedure preserves the oxygen functional groups on the graphene plane which enables the conjugation of cancer drugs without obvious cytotoxicity. Consequently, we demonstrate the capability of GO to simultaneously play the dual-role of a: (i) cellular imaging agent and (ii) drug delivery agent in CT26 cancer cells without the need for additional fluorescent protein labeling. Our method offers a simple, controllable strategy to tune and enhance the fluorescence property of GO, which shows potential for biomedical applications and fundamental studies.
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http://dx.doi.org/10.1039/c7bm01192jDOI Listing
March 2018

[Effects of exogenous MeJA, SA and two kinds of endophytic fungi on physiology and total phenols content of seedlings of Bletilla striata].

Zhongguo Zhong Yao Za Zhi 2016 Aug;41(15):2794-2801

College of Hortriculture, Nanjing Agricultural University, Nanjing 210095, China.

Tissue culture seedlings of Bletilla striata were treated with MeJA, SA and two kinds of endophytic fungi in order to study the effects of those treatments on the physiology and total phenols content. The method of tissue culture was used to culture seeds into seedlings, and then different treatments were applied on them to observe and measure the changes of physiology and total phenols content. We find that the growth of seedlings treated with SA was poor, which treated with 40 μmol•L⁻¹ MeJA, 50 mL•L⁻¹ Hypocrea koningii and 10 mL•L⁻¹ Trichoderma koningiopsis showed better. The activity of SOD, POD and CAT was at a high level under SA treatment of each concentration. The activity of SOD and POD increased as the rise of MeJA concentration, while CAT was highest at 80 μmol•L⁻¹. The activity of SOD and POD increased with the increasing of the concentration of H. koningii treatment, while CAT reached the highest at 1 mL•L⁻¹. The activity of SOD, POD and CAT increased first and then declined with the concentration of T. koningiopsis increasing, and the highest activity was at 10 mL•L⁻¹. The contents of MDA, soluble protein and proline were increased more or less under the four treatments. The content of polysaccharide was at a high level under 60 μmol•L⁻¹ of MeJA. The total phenols content was at a high level under 40 μmol•L⁻¹ of MeJA, 60 μmol•L⁻¹ of SA, 1 mL•L⁻¹ of H. koningii and 10 mL•L⁻¹ of T. koningiopsis. The results indicated that the addition of exogenous MeJA, SA and endophytic fungi under certain concentrations could improve the resistance of B. striata and increase the content of total phenols at some degree and the trearment of MeJA, H. koningii and T. koningiopsis could promote the growth of seedlings under certain concentrations.
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http://dx.doi.org/10.4268/cjcmm20161508DOI Listing
August 2016

Macrolides protect against infection via inhibition of inflammasomes.

Am J Physiol Lung Cell Mol Physiol 2017 Oct 6;313(4):L677-L686. Epub 2017 Jul 6.

Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China;

Macrolides antibiotics have been effectively used in many chronic diseases, especially with infection. The mechanisms underlying the therapeutic effects of macrolides in these diseases remain poorly understood. We established a mouse model of chronic lung infection using agar-beads, with azithromycin treatment or placebo. Lung injury, bacterial clearance, and inflammasome-related proteins were measured. In vitro, the inflammasomes activation induced by flagellin or ATP were assessed in LPS-primed macrophages with or without macrolides treatment. Plasma IL-18 levels were determined from patients who were diagnosed with bronchiectasis isolated with or without and treated with azithromycin for 3-5 days. Azithromycin treatment enhanced bacterial clearance and attenuated lung injury in mice chronically infected with , which resulted from the inhibition of caspase-1-dependent IL-1β and IL-18 secretion. In vitro, azithromycin and erythromycin inhibited NLRC4 and NLRP3 inflammasomes activation. Plasma IL-18 levels were higher in bronchiectasis patients with isolation compared with healthy controls. Azithromycin administration markedly decreased IL-18 secretion in bronchiectasis patients. The results of this study reveal that azithromycin and erythromycin exert a novel anti-inflammatory effect by attenuating inflammasomes activation, which suggests potential treatment options for inflammasome-related diseases.
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http://dx.doi.org/10.1152/ajplung.00123.2017DOI Listing
October 2017

Efficacy and safety of long-term inhaled antibiotic for patients with noncystic fibrosis bronchiectasis: a meta-analysis.

Clin Respir J 2016 Nov 2;10(6):731-739. Epub 2015 Mar 2.

Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Background And Aims: The evidence supported the use of nebulized antibiotics in non-cystic fibrosis (non-CF) bronchiectasis is indefinite. A meta-analysis was performed to determine the efficacy and safety of long-term inhaled antibiotics for patients with non-CF bronchiectasis.

Methods: PubMed, Embase, Web of Science and Cochrane Library databases were searched up to March 20, 2014. Reduction of sputum bacterial density, eradication of sputum Pseudomonas aeruginosa, the risk of exacerbations and other clinical outcomes related to inhalation treatment were analyzed.

Results: Three hundred seventy articles were searched. Eight randomized controlled trials recruiting 539 patients were included in this meta-analysis. Long-term inhaled antibiotics showed an obvious reduction of the sputum bacterial density [weighted mean difference = 2.85, 95% confidence interval (CI): 1.6-4.09, P < 0.00001] and augment eradication of sputum P. aeruginosa [odds ratio (OR) = 6.6, 95% CI: 2.93-14.86, P < 0.00001]. No evidences showed higher risk of P. aeruginosa resistance after inhaled therapy. In addition, nebulized therapy reduced the amount of patients with exacerbation (OR = 0.46, 95% CI: 0.21-1.00, P = 0.05). However, patients with inhaled antibiotics were more likely to suffer wheeze (OR = 6.74, 95% CI: 2.22-20.52, P = 0.0008) and bronchospasm (OR = 2.84, 95% CI: 1.11-7.25, P = 0.03).

Conclusion: For patients with non-CF bronchiectasis, long-term inhaled antibiotics can effectively reduce the sputum bacterial density, increase P.A eradication and attenuate the risk of exacerbation, however, accompanied with higher risk of wheeze and bronchospasm.
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http://dx.doi.org/10.1111/crj.12278DOI Listing
November 2016

Combined inhaled corticosteroid and long-acting β2-adrenergic agonist therapy for noncystic fibrosis bronchiectasis with airflow limitation: An observational study.

Medicine (Baltimore) 2016 Oct;95(42):e5116

Department of Respiratory and Critical Care Medicine Department of Pulmonary function test, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Background And Objective: There is presently no clear evidence on the effect of combined treatment for non-cystic fibrosis (non-CF) bronchiectasis with inhaled corticosteroid (ICS) and long-acting β2-adrenergic agonist (LABA). The objective of this study is to assess the efficacy and safety of salmeterol-fluticasone combined inhaled therapy for non-CF bronchiectasis with airflow limitation.

Methods: An observational study was performed in 120 non-CF bronchiectasis patients diagnosed by high-resolution computed tomography (HRCT) scanning of the chest. Patients received either routine therapy or salmeterol-fluticasone (100/500 μg daily) combined inhaled therapy on the basis of routine therapy. Clinical symptoms, health-related quality of life (HRQL), lung function, short-acting β2-adrenergic agonist (SABA) use, and safety were monitored throughout the study.

Results: OF the 120 subjects, 60 received combined inhaled therapy and 60 received routine therapy. Compared to the control group, the combined inhaled therapy group showed significant improvement in their clinical symptom scores (-2.21 vs. -0.31, P = 0.002) and a reduction in number of weekly SABA usage (-4.2 vs. 0.1, P < 0.01). In addition, patients in the inhaled therapy group achieved a significant improvement in HRQL based on mMRC (-1.51 vs. -0.31, P < 0.005) and SGRQ (-7.83 vs. -2.16, P < 0.01) scoring accompanied with no severe adverse events. There were fewer exacerbation frequencies in the combined inhaled therapy group over the 12 months of treatment compared to the control group (1 [0-2] vs. 2 [1-4], P = 0.017). Furthermore, stratified analysis indicated that combined inhaled therapy partially improve lung function for patients for whom it is severely impaired and those with pseudomonas aeruginosa isolated.

Conclusion: Our results show that salmeterol-fluticasone combined inhaled therapy should be effective and safe for non-CF bronchiectasis patients especially for those patients with poor lung function or pseudomonas aeruginosa isolated.
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http://dx.doi.org/10.1097/MD.0000000000005116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079324PMC
October 2016

Asthma and risk of bronchiectasis exacerbation: we still need more evidence.

Eur Respir J 2016 10;48(4):1247-1248

Dept of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Dept of Medicine, Soochow University, Suzhou, China

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http://dx.doi.org/10.1183/13993003.00979-2016DOI Listing
October 2016

Reduced global functional connectivity of the medial prefrontal cortex in major depressive disorder.

Hum Brain Mapp 2016 09 4;37(9):3214-23. Epub 2016 May 4.

Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.

Background: Major depressive disorder is a disabling neuropsychiatric condition that is associated with disrupted functional connectivity across brain networks. The precise nature of altered connectivity, however, remains incompletely understood. The current study was designed to examine the coherence of large-scale connectivity in depression using a recently developed technique termed global brain connectivity.

Methods: A total of 82 subjects, including medication-free patients with major depression (n = 57) and healthy volunteers (n = 25) underwent functional magnetic resonance imaging with resting data acquisition for functional connectivity analysis. Global brain connectivity was computed as the mean of each voxel's time series correlation with every other voxel and compared between study groups. Relationships between global connectivity and depressive symptom severity measured using the Montgomery-Åsberg Depression Rating Scale were examined by means of linear correlation.

Results: Relative to the healthy group, patients with depression evidenced reduced global connectivity bilaterally within multiple regions of medial and lateral prefrontal cortex. The largest between-group difference was observed within the right subgenual anterior cingulate cortex, extending into ventromedial prefrontal cortex bilaterally (Hedges' g = -1.48, P < 0.000001). Within the depressed group, patients with the lowest connectivity evidenced the highest symptom severity within ventromedial prefrontal cortex (r = -0.47, P = 0.0005).

Conclusions: Patients with major depressive evidenced abnormal large-scale functional coherence in the brain that was centered within the subgenual cingulate cortex, and medial prefrontal cortex more broadly. These data extend prior studies of connectivity in depression and demonstrate that functional disconnection of the medial prefrontal cortex is a key pathological feature of the disorder. Hum Brain Mapp 37:3214-3223, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/hbm.23235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980239PMC
September 2016

Asthma and bronchiectasis exacerbation.

Eur Respir J 2016 06 13;47(6):1680-6. Epub 2016 Apr 13.

Dept of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Dept of Medicine, Soochow University, Suzhou, China

Bronchiectasis and asthma are common respiratory diseases worldwide. However, the influence of asthma on bronchiectasis remains unclear. The objective of this study is to analyse the effects of asthma on bronchiectasis exacerbation.Data from inpatients diagnosed with bronchiectasis with or without asthma at Shanghai Pulmonary Hospital (Shanghai, China) between January 2013 and December 2014 were retrospectively collected and analysed. 249 patients with only bronchiectasis and 214 patients with both bronchiectasis and asthma were included in the study. Follow-up records were used to evaluate the effect of asthma on bronchiectasis exacerbation.The variables found to be independently associated with bronchiectasis exacerbations were age (OR 1.07, 95% CI 1.03-1.11; p<0.001), duration of symptoms (OR 1.06, 95% CI 1.03-1.09; p<0.001), the presence of asthma (OR 2.6, 95% CI 1.15-5.88; p=0.021), forced expiratory volume in 1 s <50% predicted (OR 4.03, 95% CI 1.75-9.26; p=0.001), isolation of Pseudomonas aeruginosa in sputum (OR 2.41, 95% CI 1.00-5.79; p=0.05) and lung lesion extension to more than two lobes (OR 2.73, 95% CI 1.16-6.45; p=0.022).The existence of asthma was associated with an independent increase in risk of bronchiectasis exacerbation.
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http://dx.doi.org/10.1183/13993003.01862-2015DOI Listing
June 2016

RNA-seq transcriptome analysis of a Pseudomonas strain with diversified catalytic properties growth under different culture medium.

Microbiologyopen 2016 08 6;5(4):626-36. Epub 2016 Apr 6.

School of Pharmacy, Zunyi Medical University, Zunyi, 563000, China.

Biocatalysis is an emerging strategy for the production of enantio-pure organic molecules. However, lacking of commercially available enzymes restricts the widespread application of biocatalysis. In this study, we report a Pseudomonas strain which exhibited versatile oxidation activity to synthesize chiral sulfoxides when growing under M9-toluene medium and reduction activity to synthesize chiral alcohols when on Luria-Bertani (LB) medium, respectively. Further comparative transcriptome analysis on samples from these two cultural conditions has identified 1038 differentially expressed genes (DEG). Gene Ontology (GO) enrichment and KEGG pathways analysis demonstrate significant changes in protein synthesis, energy metabolism, and biosynthesis of metabolites when cells cultured under different conditions. We have identified eight candidate enzymes from this bacterial which may have the potential to be used for synthesis of chiral alcohol and sulfoxide chemicals. This work provides insights into the mechanism of diversity in catalytic properties of this Pseudomonas strain growth with different cultural conditions, as well as candidate enzymes for further biocatalysis of enantiomerically pure molecules and pharmaceuticals.
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http://dx.doi.org/10.1002/mbo3.357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985596PMC
August 2016

Distribution of Major Pathogens from Sputum and Bronchoalveolar Lavage Fluid in Patients with Noncystic Fibrosis Bronchiectasis: A Systematic Review.

Chin Med J (Engl) 2015 Oct;128(20):2792-7

Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.

Objective: Noncystic fibrosis (non-CF) bronchiectasis remains as a common health problem in Asia. Pathogens' distribution in airways of patients with non-CF bronchiectasis is important for doctors to make right decision.

Data Sources: We performed this systematic review on the English language literatures from 1966 to July 2014, using various search terms included "pathogens" or "bacteria" or "microbiology" and "bronchiectasis" or "non-cystic fibrosis bronchiectasis" or "non-CF bronchiectasis" or "NCFB."

Study Selection: We included studies of patients with the confirmed non-CF bronchiectasis for which culture methods were required to sputum or bronchoalveolar lavage fluid (BALF). Weighted mean isolation rates for Haemophilus influenzae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Stapylococcus aureus, Moxarella catarrhails were compared according to different methodology.

Results: The total mean bacterial culture positive rates were 63%. For studies using sputum samples, the mean positive culture rates were 74%. For studies using BALF alone or BALF and sputum, it was 48%. The distributions of main bacterial strains were 29% for H. influenzae, 28% for P. aeruginosa, 11% for S. pneumoniae, 12% for S. aureus, and 8% for M. catarrhails with methodology of sputum. Meanwhile, the bacterial distributions were 37% for H. influenzae, 8% for P. aeruginosa, 14% for S. pneumoniae, 5% for S. aureus, and 10% for M. catarrhails with methodology of BALF alone or BALF and sputum. Analysis of the effect of different methodology on the isolation rates revealed some statistically significant differences.

Conclusions: H. influenzae accounted for the highest percentage in different methodology. Our results suggested that the total positive culture rates and the proportion of P. aeruginosa from sputum and BALF specimens had significant differences, which can be used in further appropriate recommendations for the treatment of non-CF bronchiectasis.
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http://dx.doi.org/10.4103/0366-6999.167360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736878PMC
October 2015

Short-term Exposure to Ambient Fine Particulate Matter Increases Hospitalizations and Mortality in COPD: A Systematic Review and Meta-analysis.

Chest 2016 Feb 12;149(2):447-458. Epub 2016 Jan 12.

Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China; Soochow University, Suzhou, China. Electronic address:

Background: Many epidemiologic studies have documented variable relationships between ambient particulate matter (PM) and COPD hospitalizations and mortality in cities worldwide.

Methods: Comprehensive and systematic searches were performed in the electronic reference databases (PubMed, EMBASE, Google Scholar, Ovid, and Web of Science) with specific search terms and selection criteria for relevant studies. Summary ORs and 95% CIs were calculated to evaluate the relationship between short-term exposure to PM with aerodynamic diameters ≤ 2.5 μm (PM2.5) and COPD hospitalizations and mortality. The sources of heterogeneity and the effect of potential confounders were explored using subgroup analyses. Study findings were analyzed using a random effects model and a fixed effects model in COPD hospitalizations and mortality, respectively.

Results: The search yielded 12 studies suitable for meta-analysis of hospitalizations and six studies suitable for the mortality meta-analysis until April 15, 2015. A 10-μg/m(3) increase in daily PM2.5 (lag days 0-7) was associated with a 3.1% (95% CI, 1.6%-4.6%) increase in COPD hospitalizations and a 2.5% (95% CI, 1.5%-3.5%) increase in COPD mortality. Significant publication bias was not found in studies focusing on the relationship between short-term PM2.5 exposure and COPD hospitalizations and mortality.

Conclusions: Our combined analysis indicated that short-term exposure to a 10-μg/m(3) increment of ambient PM2.5 is associated with increased COPD hospitalizations and mortality. Further study is needed to elucidate to what extent this relationship is causal, together with other factors, and to elucidate the mechanism by which PM2.5 induces activation of cellular processes promoting COPD exacerbations.
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http://dx.doi.org/10.1378/chest.15-0513DOI Listing
February 2016

The existence of bronchiectasis predicts worse prognosis in patients with COPD.

Sci Rep 2015 Jun 16;5:10961. Epub 2015 Jun 16.

1] Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, China [2] Soochow University, Suzhou, China.

Bronchiectasis is prevalent in patients with COPD. The objective of this study was to assess the clinical characteristics and prognostic value of bronchiectasis in patients with COPD in China. Data from patients diagnosed with COPD at the Shanghai Pulmonary Hospital between January 2009 and December 2013 were retrospectively collected and analyzed. SPSS statistical software was used to analyze the data. Data from 896 patients with COPD were analyzed. Bronchiectasis was present in 311 patients. The isolation of pseudomonas aeruginosa (PA) from sputum was the variable most significantly associated with the presence of bronchiectasis in patients with COPD (hazard ratio (HR), 2.93; 95% confidence interval (CI), 1.35-6.37; P = 0.007). During follow-up (median of 21 months; interquartile range: 10-39 months), there were 75 deaths, of which 39 were in the bronchiectasis group. The presence of bronchiectasis (HR, 1.77; 95% CI, 1.02-3.08; P = 0.043) was associated with an increase in all-cause mortality in patients with COPD. These results suggest that bronchiectasis in patients with COPD was associated with the isolation of PA from the sputum. Bronchiectasis was an independent risk factor for all-cause mortality in patients with COPD.
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http://dx.doi.org/10.1038/srep10961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468518PMC
June 2015
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