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Background: Extensive knowledge of allergic multimorbidities is required to improve the management of allergic diseases with the industrialization of China. However, the demography and allergen distribution patterns of allergic multimorbidities in China remain unclear, despite the increasing prevalence of allergies. Methods: This was a real-world, cross-sectional study of 1273 outpatients diagnosed with one or more allergic diseases in Guangzhou, the most populated city of southern China, with leading industrial and commercial centers, between April 2021 and March 2022. Seven allergic diseases (allergic rhinitis (AR), asthma (AS)/cough variant asthma (CVA), atopic dermatitis (AD)/eczema, food allergy (FA), allergic conjunctivitis (AC), drug allergy (DA), and anaphylaxis) were assessed. Positive rates of sensitization to different allergens were measured using an allergen detection system of the UniCAP (Pharmacia Diagnostics, Sweden) instrument platform to compare the groups of allergic multimorbidities against a single entity. Results: There were 659 (51.8%) males and 614 (48.2%) females aged from 4 months to 74 years included in the analysis. The study participants who were diagnosed with allergic diseases had an average of 1.6 diagnoses. Overall, 46.5% (592 of 1273) of the patients had more than one allergic condition, and allergic rhinitis was the most common type of multimorbidity. Women were more likely to suffer from an allergic disease alone, whereas allergic multimorbidities were more likely to be diagnosed in men (p = 0.005). In addition, allergic multimorbidities were common in all age groups, with an incidence ranging from 37.1% to 57.4%, in which children and adolescents were more frequently diagnosed with allergic multimorbidities than adults (18–60 years old) (all p < 0.05). Allergic multimorbidity was observed throughout the year. A difference in the positive rate of allergens sensitization and total immunoglobulin E (tIgE) levels between different allergic multimorbidities was observed. Conclusions: Allergic multimorbidities were very commonly found in nearly half of all patients with allergies. The proportion of allergic multimorbidities varied with the type of disease, sex, age, and allergen distribution pattern. These findings may help clinicians to develop "One health" strategies for the clinical management of allergic diseases. [ABSTRACT FROM AUTHOR]

Summary: Vibrio alginolyticus threatens both humans and marine animals, but hosts respond to V. alginolyticus infection is not fully understood. Here, functional metabolomics was adopted to investigate the metabolic differences between the dying and surviving zebrafish upon V. alginolyticus infection. Tryptophan was identified as the most crucial metabolite, whose abundance was decreased in the dying group but increased in the survival group as compared to control group without infection. Concurrently, the dying zebrafish displayed excessive immune response and produced higher level of reactive oxygen species (ROS). Interestingly, exogenous tryptophan reverted dying rate through metabolome re‐programming, thereby enhancing the survival from V. alginolyticus infection. It is preceded by the following mechanism: tryptophan fluxed into the glycolysis and tricarboxylic acid cycle (TCA cycle), promoted adenosine triphosphate (ATP) production and further increased the generation of NADPH. Meanwhile, tryptophan decreased NADPH oxidation. These together ameliorate ROS, key molecules in excessive immune response. This is further supported by the event that the inhibition of pyruvate metabolism and TCA cycle by inhibitors decreased D. reiro survival. Thus, our data indicate that tryptophan is a key metabolite for the host to fight against V. alginolyticus infection, representing an alternative strategy to treat bacterial infection in an antibiotic‐independent way. [ABSTRACT FROM AUTHOR]

Background: The implementation of allergen immunotherapy (AIT) requires extensive knowledge of allergen distribution in the region to identify high-risk regions for AIT utilization. However, the geographical distribution patterns of the major Dermatophagoides allergens in China remain unclear despite the increasing prevalence of these allergens. Methods: We performed comprehensive database searches of articles demonstrating the distribution patterns of Dermatophagoides-sensitized allergic rhinitis (AR) and allergic asthma (AA) in China, published between 1990 and 2017. Results: We retrieved 163 articles encompassing 114,302 allergen-positive cases to generate the distribution maps. The rate of sensitization to Dermatophagoidespteronyssinus(D. pteronyssinus)and Dermatophagoidesfarinae (D. farinae) was similar in patients with AR (75.1 vs. 75.2%, p > 0.05) but not in those with AA (78.5 vs. 77.7%, p = 0.041). Patients with AR and AA shared similar regional distribution patterns of both D. pteronyssinus and D. farinae sensitization, which were highest in the southern and central parts of China and lowest in the northern regions, especially in the Northwest. The overall rate of sensitization to D. pteronyssinus and D. farinae was significantly higher in patients with AA (p < 0.001). Additionally, the annual mean temperature and humidity were the 2 major determinants of D. pteronyssinus and D. farinae sensitization in AR and of D. pteronyssinus sensitization in AA, whereas the annual mean temperature was the sole determinant for D. farinae sensitization in AA. Conclusion: These findings may inform clinicians of the strategies for the prevention of Dermatophagoides sensitization and may be of benefit to the future clinical management of allergic diseasesassociated with sensitization to Dermatophagoides mites. [ABSTRACT FROM AUTHOR]

Purpose: Epithelial-mesenchymal transition (EMT) involved in asthmatic airway remodeling. Thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine, was a key component in airway immunological response in asthma. But the role of TSLP in the EMT process was unknown. We aimed to access whether TSLP could induce EMT in airway epithelia and its potential mechanism. Materials and Methods: Human bronchial epithelial (HBE) cells were incubated with TSLP or transforming growth factor beta 1 (TGF-β1) or both. SB431542 was used to block TGF-β1 signal while TSLP siRNA was used to performed TSLP knockdown. Changes in E-cadherin, vimentin, collagen I and fibronectin level were measured by real-time PCR, western blot and immunofluorescence staining. Expressions of TGF-β after TSLP administration were measured by real-time PCR, western blot and ELISA. Results: TSLP induced changes of EMT relevant markers alone and promoted TGF-β1-induced EMT in HBEs. Intracellular and extracellular expression of TGF-β1 were upregulated by TSLP. SB431542 blocked changes of EMT relevant markers induced by TSLP. Knockdown of TSLP not only reduced TSLP and TGF-β1 expression but also inhibited changes of EMT relevant markers induced by TGF-β1 in HBEs. Conclusions: TSLP could induce early stage of EMT in airway epithelial cells through upregulation of TGF-β1. This effect may act as a targeting point for suppression of asthma. [ABSTRACT FROM AUTHOR]

Summary: Aims: West syndrome (WS) is a classic form of early infantile epileptic encephalopathy (EIEE) characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on electroencephalography. Genetic defects play a critical role in the pathology of WS, and 54 EIEE genes have been identified till date. This study was designed to uncover new candidate genes for West syndrome. Methods: In this study, we recruited 56 Chinese families with WS of unknown etiology. Whole exome sequencing (WES) was performed to identify Mendelian inheritance rare or novel variants. The association between candidate genes and WS was analyzed from many aspects, including recurrent genes in patients, predicted variant effect on genes, human tolerance to deficient genes, gene expression in the nervous system, coexpression with EIEE genes, mutual interaction with known EIEE proteins, genes related to ion channel or fragile X mental retardation protein function, and mouse models with manifestation of seizures. Genes with supporting evidence from those aspects were defined as highlight candidate genes. Results: Whole exome sequencing identified 112 candidate variants in 89 genes. Among the candidate genes, 33 were autosomal dominant, 22 were autosomal recessive, and 34 were X‐linked. Complex bioinformatic analysis revealed 17 highlight candidate genes: ATP2A2, CD99L2, CLCN6, CYFIP1, CYFIP2, GNB1, GPT2, HUWE1, KMT2D, MYO18A, NOS3, RYR1, RYR2, RYR3, TAF1, TECTA, and UBA1. The majority of highlight candidate genes are calcium‐signaling pathway and mental retardation genes. Conclusions: This is the first WES study of Chinese WS patients with unknown etiology. This combination of phenotypic and genomic data will enable further testing to elucidate mechanisms underlying the pathogenesis of WS. [ABSTRACT FROM AUTHOR]

Objective: Fibrocyte localization to the airways and thymic stromal lymphopoietin (TSLP) overexpression in the lung are features of severe asthma. The aim of this study was to determine whether TSLP contributes to fibrocyte trafficking and airway remodeling in a mouse model of allergic asthma. Methods: We established a chronic asthma animal model by administering house dust mite (HDM) extracts intranasally for up to 5 consecutive weeks. Mouse anti-TSLP monoclonal antibody (mAb) was given intraperitoneally starting the 4th week. Fluorescence-labeled CD34/collagen I (Col I)-dual-positive fibrocytes were examined by confocal microscopy. The level of TGF-β1 in the bronchoalveolar lavage (BAL) fluid was determined by ELISA. Results: We found significantly increased levels of TSLP and TGF-β1 in the lung of the mice subjected to repeated allergen exposure, which was accompanied by increased number of fibrocytes in the sub-epithelial zone and the BAL fluid. However, blocking TSLP markedly decreased the production of TGF-β1, reduced the number of fibrocytes and subsequently prevented alterations of both airway and vascular structures. Conclusions: Our data suggested that TSLP might function in airway remodeling by promoting circulating fibrocyte recruitment to the lung in the mice subjected to chronic allergen exposure. These results provide a better rationale for targeting the interaction between TSLP and fibrocytes as a therapeutic approach for chronic allergic asthma. [ABSTRACT FROM AUTHOR]

Objective: To investigate the alterative spectrum and trends of aeroallergens sensitization in children with allergic rhinitis (AR) in Guangzhou, China in the past 10 years.Participants and Methods: In this retrospective study, 4,111 children with complaints of nasal hyper-reactivity who visited the Pediatric Department and/or Otolaryngology Department from January 2007 to November 2016 were enrolled. Serum specific immunoglobulin E was measured and positive detection was made in 3,328 patients, who were, therefore, diagnosed with AR. Positive rates and trends of different aeroallergens sensitization were assessed. The tendency of positive rates changing over the years, and the difference and trends in positive rate of aeroallergen sensitization that occurred in subgroups of gender, age, and season were determined and analyzed with logistic regression.Results: The percentage of detected common aeroallergens in AR children was (from high to low) 81.07%, 34.44%, 14.72%, 11.81%, 6.04%, and 3.70% for house dust mites (HDMs), cat-dog dander, cockroach, mold mixture, tree pollen mixture, and herb pollen mixture, respectively. An ascending trend of aeroallergens sensitization or AR (odds ratio [OR] =1.116, 95% CI: 1.086-1.146) was found. Interestingly, an increasing trend of cat-dog dander and mold sensitization was found in AR children (OR =1.164, 95% CI: 1.133-1.196; OR =1.169, 95% CI: 1.120-1.223) in this retrospective study, while HDMs sensitization held a steady trend (OR =0.983, 95% CI: 0.961-1.007).Conclusion: In the increasing trend of aeroallergens sensitization or AR, HDMs sensitization still held the majority. But emphasis should be made on pet allergy for young children with AR in the context of ascending trend of sensitization to cat-dog dander. [ABSTRACT FROM AUTHOR]

Fulminant myocarditis (FM) is a life-threatening disease in children. With a rapid, progressive course of deterioration, it causes refractory cardiorespiratory failure even with optimal clinical intervention. We present the case of a 9-year-old girl with FM complicated by cardiogenic shock, malignant arrhythmia, and refractory cardiac arrest. She received effective cardiopulmonary resuscitation, therapeutic hypothermia, and other supportive treatments. However, the patient rapidly worsened into pulseless ventricular tachycardia and refractory cardiac arrest. Therefore, we performed extracorporeal membrane oxygenation (ECMO) to establish spontaneous circulation after the failure of standard resuscitation measures. The girl recovered with intact cardiac and neurocognitive functions after continued ECMO treatment for 221 hours. Therefore, ECMO is an effective rescue therapeutics for FM, especially when complicated with refractory cardiac arrest. [ABSTRACT FROM AUTHOR]

The synthesis of [N-MeA]2[M(mnt)2] (N-MeA=N-methylacridine; M=Ni (II), Zn (II), Cu (II) and Cd (II); mnt=maleonitriledithiolate) and crystal structure analysis of the Ni (1) and Zn (2) complexes are reported. The conductivities of almost all the complexes under 4 MPa pressure are above 10−5 S cm−1, which are characteristic of intrinsic semi-conductors. The complexes exhibit charge transfer transitions in both their absorption spectra and fluorescence spectroscopy. [Copyright &y& Elsevier]

Abstract: Escherichia coli endotoxin LPS regulates blood–brain barrier permeability by disrupting the tight junction (TJ) complex between brain endothelial cells. This study used Bend.3 cells to examine the signaling networks involved in the hyperpermeability of the brain endothelial barrier caused by LPS. The LPS-induced alterations in the brain endothelial barrier were associated with PKC (a, β, ζ) and RhoA, but were independent of PI3K and the tyrosine kinase pathway. Inhibition of PKC (a, β, ζ) and RhoA activity using shRNA and dominant negative mutants diminished the effects of LPS on the brain’s endothelial TJs. The interactions between the PKC and Rho pathways were therefore examined. PKC-a and PKC-ζ, but not PKC-β interacted with RhoA in Bend.3 cells stimulated by LPS. PKC-a acted as the upstream molecule for Rho and PKC-ζ acted as the downstream target for Rho. Comparing the effect of double inhibition of “Rho and PKC” and single inhibition of “Rho” or “PKC” confirmed that this interaction is critical for LPS-induced brain endothelial cell hyperpermeability. Collectively these data are the first to suggest that LPS affects the brain’s endothelial TJ barrier via PKC (a, β, ζ)- and RhoA, independent of the PI3K and tyrosine kinase pathways. In addition, PKC-a and PKC-ζ, respectively, act as the upstream and downstream regulator for RhoA in the process. [Copyright &y& Elsevier]

Background: Diabetic peripheral neuropathy causes significant pain to patients. Umbilical cord mesenchymal stem cells have been shown to be useful in the treatment of diabetes and its complications. The aim of this study was to investigate whether human umbilical cord mesenchymal stem cells treated with interferon-gamma can ameliorate nerve injury associated with diabetes better than human umbilical cord mesenchymal stem cells without interferon-gamma treatment., Methods: Human umbilical cord mesenchymal stem cells were assessed for adipogenic differentiation, osteogenic differentiation, and proliferation ability. Vonfry and a hot disc pain tester were used to evaluate tactile sensation and thermal pain sensation in mice. Hematoxylin-eosin and TUNEL staining were performed to visualize sciatic nerve fiber lesions and Schwann cell apoptosis in diabetic mice. Western blotting was used to detect expression of the apoptosis-related proteins Bax, B-cell lymphoma-2, and caspase-3 in mouse sciatic nerve fibers and Schwann cells. Real-Time Quantitative PCR was used to detect mRNA levels of the C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 2, C-X-C motif chemokine ligand 9, and C-X-C motif chemokine ligand 10 in mouse sciatic nerve fibers and Schwann cells. Enzyme-linked immunosorbent assay was used to detect levels of the inflammatory cytokines, interleukin- 1β, interleukin-6, and tumor necrosis factor-α in serum and Schwann cells., Results: The adipogenic differentiation capacity, osteogenic differentiation capacity, and proliferation ability of human umbilical cord mesenchymal stem cells were enhanced after interferon-gamma treatment. Real-Time Quantitative PCR revealed that interferon-gamma promoted expression of the adipogenic markers, PPAR-γ and CEBP-α, as well as of the osteogenic markers secreted phosphoprotein 1, bone gamma-carboxyglutamate protein, collagen type I alpha1 chain, and Runt-related transcription factor 2. The results of hematoxylin-eosin and TUNEL staining showed that pathological nerve fiber damage and Schwann cell apoptosis were reduced after the injection of interferon-gamma-treated human umbilical cord mesenchymal stem cells. Expression of the apoptosis-related proteins, caspase-3 and Bax, was significantly reduced, while expression of the anti-apoptotic protein B-cell lymphoma-2 was significantly increased. mRNA levels of the cell chemokines, C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 2, C-X-C motif chemokine ligand 9, and C-X-C motif chemokine ligand 10, were significantly reduced, and levels of the inflammatory cytokines, interleukin-1β, interleukin-6, and tumor necrosis factor-α, were decreased. Tactile and thermal pain sensations were improved in diabetic mice., Conclusion: Interferon-gamma treatment of umbilical cord mesenchymal stem cells enhanced osteogenic differentiation, adipogenic differentiation, and proliferative potential. It can enhance the ability of human umbilical cord mesenchymal stem cells to alleviate damage to diabetic nerve fibers and Schwann cells, in addition to improving the neurological function of diabetic mice., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Bacterial metabolic environment influences antibiotic killing efficacy. Thus, a full understanding for the metabolic resistance mechanisms is especially important to combat antibiotic-resistant bacteria., Methods: Isobaric tags for relative and absolute quantification-based proteomics approach was employed to compare proteomes between ceftazidime-resistant and -sensitive Edwarsiella tarda LTB4 (LTB4-R CAZ and LTB4-S, respectively)., Results: This analysis suggested the possibility that the ceftazidime resistance mediated by depressed glucose is implemented through an inefficient metabolic flux from glycolysis, the pyruvate cycle, glutamate metabolism to purine metabolism. The inefficient flux was demonstrated by the reduced expression of genes and the decreased activity of enzymes in the four metabolic pathways. However, supplement upstream glucose and downstream guanosine separately restored ceftazidime killing, which not only supports the conclusion that the inefficient metabolic flux is responsible for the resistance, but also provides an effective approach to reverse the resistance. In addition, the present study showed that ceftazidime is bound to pts promoter in E. tarda ., Discussion: Our study highlights the way in fully understanding metabolic resistance mechanisms and establishing metabolites-based metabolic reprogramming to combat antibiotic resistance., Competing Interests: X-xP was employed by the Guangdong Litai Pharmaceutical Co., Ltd. The remaining 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 Xiang, Wang, Tao, Ye, Liang, Peng, Yang and Li.)

Temperature influences fish's susceptibility to infectious disease through an immune response. However, the mechanism underlying this regulation is yet to be elucidated. In this study, we compared the susceptibility of crucian carp that were grown at 18°C and 33°C, respectively, to Aeromonas sobrial infection and found that crucian carp was more susceptible when grown at 33°C. These distinct susceptibilities of fish at different temperatures to infection may partially be explained by their differences in the metabolism as revealed by comparative metabolomics profiling: crucian carp demonstrated enhanced TCA cycle but reduced fatty acid biosynthesis; Our study also found that maltose was the most suppressed metabolite in fish grown at 33°C. Importantly, exogenous injection of maltose enhances crucian carp survival grown at 33°C by 30%. Further study showed that exogenous maltose downregulated the production of several cytokines but enhanced the lysozyme ( lyz ) and complement component c3 , which involves the humoral innate immunity. Our results suggest that maltose promotes the survival of crucian carp likely through fine tuning the immune gene expression, and this finding provides a novel approach to manage bacterial infection.

Cellular senescence is a complicated process featured by irreversible cell cycle arrest and senescence-associated secreted phenotype (SASP), resulting in accumulation of senescent cells, and low-grade inflammation. Cellular senescence not only occurs during the natural aging of normal cells, but also can be accelerated by various pathological factors. Cumulative studies have shown the role of cellular senescence in the pathogenesis of chronic lung diseases including chronic obstructive pulmonary diseases (COPD) and idiopathic pulmonary fibrosis (IPF) by promoting airway inflammation and airway remodeling. Recently, great interest has been raised in the involvement of cellular senescence in asthma. Limited but valuable data has indicated accelerating cellular senescence in asthma. This review will compile current findings regarding the underlying relationship between cellular senescence and asthma, mainly through discussing the potential mechanisms of cellular senescence in asthma, the impact of senescent cells on the pathobiology of asthma, and the efficiency and feasibility of using anti-aging therapies in asthmatic patients., (Copyright © 2020 Wang, Su, Yang, Yang, Yang, Yan and Chen.)

Thymic stromal lymphopoietin (TSLP) activates lung dendritic cells (DCs) to promote a T helper type 2 lymphocyte (Th2) response in animal models. However, the mechanism behind this process remains unclear. In this study, we investigate the role of a nuclear factor for activated T-cells 1 (NFATc1) in the TSLP-induced polarisation towards a Th2 response. A cluster of differentiated (CD)14 + peripheral blood mononuclear cells (PBMCs) and naïve T cells were isolated from blood collected from healthy human volunteers, and TSLP was used to induce DC maturation. The effects of TSLP-DCs and treatments with FK506, an NFATc1 inhibitor, on naïve T cell differentiation were monitored by measuring the interleukin (IL)-4, IL-13, and interferon-γ (IFN-γ) expression levels. In addition, the mRNA levels of T-box expression in T cells (T-bet), GATA binding protein 3 (GATA-3), TSLP, and NFATc1 were measured for the same purpose. IL-4, IL-13, and mRNA levels of GATA-3 and NFATc1 significantly increased with TSLP-DC induction ( P <0.01), indicating polarization towards the Th2 response. These changes were reversed by treatment with FK506 ( P <0.01). Our findings suggest that NFATc1 plays a key role in the TSLP-induced differentiation of T cells to Th2, and NFATc1 is a potential therapeutic target for treating allergic diseases., (© 2019 by the Association of Clinical Scientists, Inc.)

Background: Advanced technology has become a valuable tool in etiological studies of intellectual disability/global developmental delay (ID/GDD). The present study investigated the role of genetic analysis to confirm the etiology in ID/GDD patients where the cause of the disease was uncertain in central China., Methods: We evaluated 1051 ID/GDD children aged 6 months to 18 years from March 2009 to April 2017. Data concerning basic clinical manifestations were collected, and the method of etiology confirmation was recorded. Genome-wide copy number variations (CNVs) detection and high-throughput sequencing of exons in the targeted regions was performed to identify genetically-based etiologies. We compared the incidence of different methods used to confirm ID/GDD etiology among groups with differing degrees of ID/GDD using the Chi-square or Fisher exact probability test., Results: We recruited 1051 children with mild (367, 34.9%), moderate (301, 28.6%), severe (310, 29.5%), and profoundly severe (73, 6.9%) ID/GDD. The main causes of ID/GDD in the children assessed were perinatal factors, such as acquired brain injury, as well as single gene imbalance and chromosomal gene mutation. We identified karyotype and/or CNVs variation in 46/96 (47.9%) of cases in severe ID/GDD patients, which was significantly higher than those with mild and moderate ID/GDD of 34/96 (35.4%) and 15/96 (15.6%), respectively. A total of 331/536 (61.8%) patients with clear etiology have undergone genetic analysis while 262/515 (50.9%) patients with unclear etiology have undergone genetic analysis (χ = 12.645, P < 0.001). Gene structure variation via karyotype analysis and CNV detection increased the proportion of children with confirmed etiology from 51.0% to 56.3%, and second-generation high-throughput sequencing dramatically increased this to 78.9%. Ten novel mutations were detected, recessive mutations in X-linked genes (ATPase copper transporting alpha and bromodomain and WD repeat domain containing 3) and dominant de novo heterozygous mutations in X-linked genes (cyclin-dependent kinase like 5, protocadherin 19, IQ motif and Sec7 domain 2, and methyl-CpG binding protein 2) were reported in the study., Conclusions: The present study indicates that genetic analysis is an effective method to increase the proportion of confirmed etiology in ID/GDD children and is highly recommended, especially in ID/GDD children with uncertain etiology.

Background: Aberrant epithelial remodeling and/or abnormalities in mucociliary apparatus in airway epithelium contribute to infection and inflammation. It is uncertain if these changes occur in both large and small airways in non-cystic fibrosis bronchiectasis (non-CF bronchiectasis). In this study, we aim to investigate the histopathology and inflammatory profile in the epithelium of bronchi and bronchioles in bronchiectasis., Methods: Excised lung tissue sections from 52 patients with non-CF bronchiectasis were stained with specific cellular markers and analyzed by immunohistochemistry and immunofluorescence to assess the epithelial structures, including ciliated cells and goblet cells morphology. Inflammatory cell counts and ciliary proteins expression levels of centrosomal protein 110 (CP110) and dynein heavy chain 5, axonemal (DNAH5) were assessed., Results: Epithelial hyperplasia is found in both bronchi and bronchioles in all specimens, including hyperplasia and/or hypertrophy of goblet cells. The median cilia length is longer in hyperplastic epithelium [bronchi: 8.16 (7.03-9.14) µm, P<0.0001; bronchioles: 7.46 (6.41-8.48) µm, P<0.0001] as compared to non-hyperplastic epithelium (bronchi: 5.60 µm; bronchioles: 4.89 µm). Hyperplastic epithelium is associated with overexpression of CP110 and decreased intensity of DNAH5 expression in both bronchial and bronchiolar epithelium. Though infiltration of neutrophils is predominant (63.0% in bronchi and 76.7% in bronchioles), eosinophilic infiltration is also present in the mucosa of bronchi (30.8%) and bronchioles (54.8%)., Conclusions: Aberrant epithelial remodeling with impaired mucociliary architecture is present in both large and small airways in patients with refractory non-CF bronchiectasis. Future studies should evaluate the interplay between these individual components in driving chronic inflammation and lung damage in patients., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Airway remodeling is a hallmark of bronchial asthma. Our group has previously reported that the thymic stromal lymphopoietin (TSLP), an airway epithelial-derived cytokine, has a central role in the pathogenesis of airway remodeling, and that toll-like receptor (TLR) 4 signaling in epithelial cells may trigger T-helper 2 (Th2) immune responses by overexpression of TSLP. However, it is currently unclear whether TLR4 is a target in the treatment of airway remodeling in asthma. The present study established a house dust mite (HDM)-induced chronic asthmatic model in female BALB/c mice and treated the HDM-exposed mice with 3 mg/kg TAK242, as a TLR4 antagonist, 30 min prior to HDM challenge for up to 2 weeks. General structural changes in the airways were subsequently evaluated and the levels of TSLP in the bronchoalveolar lavage fluid (BALF) and interleukin (IL)-4, IL-13 and interferon (IFN)-γ in the blood serum were determined. Results indicated that TAK242 treatment markedly reduced pathological changes in the airways of HDM-induced asthmatic mice, as demonstrated by reductions in airway wall thickening, peribronchial collagen deposition and subepithelial fibrosis. Furthermore, airway hyperresponsiveness to inhaled methacholine and the levels of TSLP in the BALF and IL-4, IL-13 and IFN-γ in the peripheral blood were significantly reduced by TAK242 treatment (P<0.05). Furthermore, the shift in the IFN-γ/IL-4 ratio induced by HDM treatment was significantly reversed following TAK242 pretreatment, which indicated that TAK242 modulated Th1/Th2 immune homeostasis in the chronic asthma mouse model. The present findings in a chronic asthma mouse model suggest that TAK242 may be an efficient treatment for airway remodeling, possibly through the inhibition of TSLP overexpression and Th2 airway inflammation.

Background and Purpose: Early or primary application of high-frequency oscillatory ventilation (HFOV) has been recently suggested not to offer benefit to patients with acute respiratory distress syndrome (ARDS). However, the rescue effects of HFOV on severe pediatric acute respiratory distress syndrome (PARDS) with hypoxemia refractory to conventional mechanical ventilation (CMV) remain unclear. This study aimed to determine whether severe PARDS children would benefit from HFOV when oxygenation deteriorated on CMV and to identify any potential risk factors related to mortality., Patients and Methods: In a retrospective and observational study, 48 children with severe PARDS between January 2009 and July 2015 were divided into two groups: 26 in HFOV group and 22 in CMV group. Data regarding demographic, underlying conditions, arterial blood gases and clinical outcomes were collected and analyzed., Results: The arterial partial pressure of oxygen (PaO 2 )/fraction of inspiration oxygen (FiO 2 ) ratio and PaO 2 improved significantly during HFOV, whereas arterial partial pressure of carbon dioxide (PaCO 2 ) and oxygenation index decreased. There was no statistical difference in the in-hospital mortality between the groups ( P =0.367). The odds ratio of survival in HFOV group was 2.74 (95% confidence interval 0.52 to 14.58, P =0.237). The pediatric intensive care unit length of stay and total ventilation duration were longer in HFOV group ( P =0.048 and P =0.000, respectively). Vasoactive agents were used more frequently in HFOV group ( P =0.007). The incidence of new air leak was similar between the two groups ( P =0.674). The presence of multiple organ dysfunction syndrome and heavier body weight were identified as predictors of mortality in the HFOV group ( P =0.006 and P =0.020, respectively)., Conclusion: HFOV as an efficient alternative therapy could significantly improve hypoxemia and promote CO 2 removal in severe PARDS children when oxygenation progressively worsens on CMV., Competing Interests: The authors report no conflicts of interest in this work.

Recent studies have proposed that susceptibility to chronic obstructive pulmonary disease (COPD) might be related with the polymorphisms of some genes encoding antioxidant enzymes, such as heme oxygenase-1 (HOX-1) and microsomal epoxide hydrolase (mEPH). We examined these polymorphisms in 256 patients with COPD and 266 healthy smokers from Han population in Southwest China. The frequencies of each allele were compared both individually and in combination between patients and controls. Polymorphisms of HOX-1 gene could be grouped into three classes: S (or=32 repeat). The allele frequencies of class L and the genotypic frequencies of the group with L were significantly higher in COPD than in controls. Our findings also showed that the proportion of slow mEPH activity was significantly higher in COPD than in controls. Conversely, the proportion of fast mEPH activity was significantly lower in COPD. In combined analysis, the frequency of the individuals having at least one L allele in the HOX-1 gene promoter and slow or very slow activity genotype for mEPH was higher in COPD than in control. Genetic polymorphisms in HOX-1 and mEPH genes are associated with the development of COPD in Southwest China.