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Neonatal pneumothorax in congenital diaphragmatic hernia:Be wary of high ventilatory pressures

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World Journal of Pediatric Surgery 2022年第3期5卷 154-161页

作者： Nathan Rubalcava Gabriella A Norwitz Aimee G Kim Gary Weiner Niki Matusko Meghan A Arnold George B Mychaliska Erin E Perrone Pediatric Surgery University of MichiganAnn ArborMichiganUSA Section of Neonatology Department of PediatricsUniversity of MichiganAnn ArborMichiganUSA department of Surgery University of MichiganAnn ArborMichiganUSA

Background Patients with congenital diaphragmatic hernia(CDH)require invasive respiratory support and higher ventilator pressures may be associated with barotrauma.We sought to evaluate the risk factors associated with pneumothorax in CDH neonates prior to repair.Methods Weretrospectivelyreviewednewborns born withCDHbetween 2014and 2019who developeda pneumothorax,and we matched these cases to patients with CDH without pneumothorax.Results Twenty-sixpatientswere included(n=13per group).The pneumothorax group required extracorporeal life support(ECLS)more frequently(85%vs 54%,p=0.04),particularly among type A/B defects(31%vs 7%,p=0.01).The pneumothorax group had higher positive end-expiratory pressure(PEEP)within 1 hour of birth(p=0.02),at pneumothorax diagnosis(p=0.003),and at ECLS(p=0.02).The pneumothorax group had a higher mean airway pressure(Paw)at birth(p=0.01),within 1 hour of birth(p=0.01),and at pneumothorax diagnosis(p=0.04).Using multiple logistic regression with cluster robust SEs,higher Paw(OR 2.2,95%Cl 1.08 to 3.72,p=0.03)and PEEP(OR 1.8,95%CI 1.15 to 3.14,p=0.007)were associated with an increased risk of developing pneumothorax.There was no difference in survival(p=0.09).Conclusions Development of a pneumothorax in CDH neonates is independently associated with higher Paw and higher PEEP.A pneumothorax increases the likelihood of treated with ECLS,even with smaller defect.

关键词： PEEP pneumothorax diagnosis

The collagen receptor,discoidin domain receptor 2,functions in Gli1-positive skeletal progenitors and chondrocytes to control bone development

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Bone Research 2022年第1期10卷 178-194页

作者： Fatma F.Mohamed Chunxi Ge Randy T.Cowling Daniel Lucas Shawn A.Hallett Noriaki Ono Abdul-Aziz Binrayes Barry Greenberg Renny T.Franceschi department of Periodontics&Oral Medicine University of MichiganAnn ArborMIUSA Division of Cardiovascular Medicine University of California at San DiegoSan DiegoCAUSA Division of Experimental Hematology and Cancer Biology Cincinnati Children’s Medical CenterCincinnatiOHUSA department of pediatrics Cincinnati Children’s HospitalCincinnatiOHUSA department of Orthodontics&Pediatric Dentistry University of MichiganAnn ArborMIUSA department of Prosthetic Dental Sciences College of DentistryKing Saud UniversityRiyadhSaudi Arabia department of Biological Chemistry School of MedicineUniversity of MichiganAnn ArborMIUSA department of Biomedical Engineering University of MichiganAnn ArborMIUSA

Discoidin Domain Receptor 2(DDR2)is a collagen-activated receptor kinase that,together with integrins,is required for cells to respond to the extracellular matrix.Ddr2 loss-of-function mutations in humans and mice cause severe defects in skeletal growth and development.However,the cellular functions of Ddr2 in bone are not understood.Expression and lineage analysis showed selective expression of Ddr2 at early stages of bone formation in the resting zone and proliferating chondrocytes and periosteum.Consistent with these findings,Ddr2^(+)cells could differentiate into hypertrophic chondrocytes,osteoblasts,and osteocytes and showed a high degree of colocalization with the skeletal progenitor marker,Gli1.A conditional deletion approach showed a requirement for Ddr2 in Gli1-positive skeletal progenitors and chondrocytes but not mature osteoblasts.Furthermore,Ddr2 knockout in limb bud chondroprogenitors or purified marrow-derived skeletal progenitors inhibited chondrogenic or osteogenic differentiation,respectively.This work establishes a cell-autonomous function for Ddr2 in skeletal progenitors and cartilage and emphasizes the critical role of this collagen receptor in bone development.

关键词： Gli1 progenitor skeletal

Procedural Sedation and Analgesia in Children in Emergency department—Role of Adjunct Therapies

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Open Journal of Anesthesiology 2017年第11期7卷 371-380页

作者： Nirupama Kannikeswaran Ahmad Farooqi Cindy Chidi Deepak Kamat carman and ann adam department of pediatrics Children’s Hospital of Michigan Detroit MI USA Wayne State University School of Medicine Detroit MI USA

Objective: To compare sedation efficacy and parent/consultant satisfaction between standard sedation, sedation with music listening, and sedation with Certified Child life Specialists (CCLS) in children undergoing procedural sedation in the Pediatric Emergency department (PED). Methods: Eligible children, aged 3 - 18 years, were randomly allocated to one of 3 groups: 1) standard sedation;2) sedation with music listening;3) sedation with CCLS intervention. All 3 groups received intravenous ketamine. The child life group received age appropriate comforting measures, while the music group listened to music of their choice during the procedure. The primary outcome was sedation efficacy, measured by Ramsay Sedation scale, FACES-P scale and need for re-dosing. The secondary outcome was parent/consultant satisfaction. Results: Fifty nine patients were analyzed (standard sedation: 20;sedation with music listening: 20;and sedation with CCLS: 19). There was no significant difference in mean initial ketamine dosing (1.58 ± 0.44 vs. 1.68 ± 0.36 vs. 1.42 ± 0.47, p = 0.26). There was no significant difference in median Ramsay Sedation scores [6(IQR:4,6) vs. 6 (IQR:4,6) vs. 6 (IQR:5,6)], FACES-R pain score [0 (IQR:0.0) vs. 0 (IQR:0.0) vs. 0 (IQR:0.0)] and need for re-dosing [9/20 (45%) vs. 4/20 (20%) vs. 8/19 (42.1%)] amongst the 3 groups. Parent and consultant satisfaction was high in all 3 groups. Conclusion: Our pilot study did not demonstrate a difference in sedation efficacy or parent/consultant satisfaction when adjunct therapies were used during PSA. Further studies with a large sample size are needed to define the role for such adjunct therapies during procedural sedation in PED.

关键词： Procedural Sedation Music Therapy Certified Child Life Specialists Emergency department Children

Latitudinal and longitudinal regulation of tissue macrophages in inflammatory diseases

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Genes & Diseases 2022年第5期9卷 1194-1207页

作者： XiaoYi He Stephanie Tan Zhong Shao Xiao Wang department of Neurology Affiliated Zhongshan Hospital of Dalian UniversityDalianLiaoning 116001PR China The Third Hospital of Fushun FushunLiaoning 113004PR China Stanley Manne Children’s Research Institute Ann&Robert H.Lurie Children’s Hospital of ChicagoChicagoIL 60611USA department of pediatrics Feinberg School of MedicineNorthwestern UniversityChicagoIL 60611USA

Macrophages are dominant innate immune cells.They demonstrate remarkable het-erogeneity and plasticity that are essential for homeostasis and host defense.The heterogeneity of tissue macrophages is shaped by the ontogeny,tissue factors,and environmental signals,a pattern in a tissue-associated latitudinal manner.At the same time,macrophages have long been considered as mainly plastic cells.These cells respond to stimulation quickly and in a stimulus-specific way by utilizing a longitudinal cascaded activation,including coordination of signal trans-ducer,epigenetic elements,and transcription factors,conclusively determine the macrophage phenotypes and functions.With the development of cutting-edge technologies,such as fate-mapping,single-cell transcriptomics,ipsc platform,nanotherapeutic materials,etc.,our under-standing of macrophage biology and the roles in the pathogenesis of diseases is much advanced.This review summarizes recent progress on the latitudinal and longitudinal regulation of tissue macrophages in inflammatory diseases.The latitudinal regulation covers the tissue macrophage or-igins,tissue factors,and environmental signals,reflecting the macrophage heterogeneity.The lon-gitudinal regulation focuses on how multiple factors shape the phenotypes and functions of macrophage subsets to gain plasticity in inflammatory diseases(i.e.,inflammatory bowel disease).In addition,how to target macrophages as a potential therapeutic approach and cutting edge-technologies for tissue macrophage study are also discussed in this review.

关键词： Epigenetic regulation Inflammatory disease microRNA Macrophage origin Macrophage polarization Single-cell RNA-sequencing Tissue macrophage

Anteroposterior Airway Diameter during Sedation for Brain MRI in Children with and without Developmental Disabilities

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Open Journal of Anesthesiology 2014年第8期4卷 191-196页

作者： Nirupama Kannikeswaran Swati Mody Xinguang Chen Marwan Zidan Lalitha Sivaswamy Wayne State University School of Medicine Carman and Ann Adams Department of Pediatrics Division of Emergency Medicine Children’s Hospital of Michigan Detroit MI USA Wayne State University School of Medicine Carman and Ann Adams Department of Pediatrics Division of Neurology Children’s Hospital of Michigan Detroit MI USA Wayne State University School of Medicine Carman and Ann Adams Department of Pediatrics Division of Pediatric Radiology Children’s Hospital of Michigan Detroit MI USA Wayne State University School of Medicine Detroit MI USA Wayne State University Detroit MI USA

Objective: Our study objective was to compare the anteroposterior (AP) oropharyngeal airway diameter measured using static MRI images in children with and without developmental disabilities during sedation. Methods: We performed a secondary analysis on a prospective, observational age-matched, 1:2 case-control study of children aged 3 - 10 years who were sedated for brain MRI. AP airway diameters were determined at the level of soft palate (airway_SP) and tongue (airway_T) from midline sagittal images by a single blinded radiologist. Results: Airway diameter was evaluated in 134 controls (C) and 68 cases (D). There was no difference in the overall adverse events (D: 30% C: 32.9%;p = 0.7) as well as hypoxia (D: 10%;C: 9.3%, p = 0.9). There was no significant difference in mean airway_T (D: 10.62 ± 3.48 vs. C: 10.38 ± 3.47;p = 0.64) and airway_SP diameter (D: 4.59 ± 2.36 vs. C: 5.17 ± 3.9;p = 0.14) between the two groups. There was no significant difference in airway_T and airway_SP diameters amongst those who experienced and those who did not experience hypoxia in cases. Amongst controls however, the airway_SP was smaller in those who experienced hypoxia compared to those who did not experience hypoxia. Conclusions: There was no difference in the AP airway_T and airway_SP diameter during sedation using static MRI images in children with and without developmental disabilities. Changes in airway_SP was associated with hypoxia amongst controls in our study cohort.

关键词： Sedation Magnetic Resonance Imaging Airway Diameter Developmental Disabilities Children

Estimated prevalence and trends in smoking among adolescents in South Korea,2005-2021:a nationwide serial study

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World Journal of pediatrics 2023年第4期19卷 366-377页

作者： Hyoin Shin Sangil Park Hyunju Yon Chae Yeon Ban Stephen Turner Seong Ho Cho Youn Ho Shin Jung U.Shin Ai Koyanagi Louis Jacob Lee Smith Chanyang Min Young Joo Lee So Young Kim Jinseok Lee Rosie Kwon Min Ji Koo Guillaume Fond Laurent Boyer Jong Woo Hahn Namwoo Kim Sang Youl Rhee Jae Il Shin Ho Geol Woo Hyeowon Park Hyeon Jin Kim Yoonsung Lee Man S.Kim Eléa Lefkir Vlasta Hadalin Jungwoo Choi Seung Won Lee Dong Keon Yon Sunyoung Kim department of Medicine Kyung Hee University College of MedicineSeoulSouth Korea department of Neurology Kyung Hee University College of MedicineSeoulSouth Korea Maternity and Child Health Division NHS Grampian AberdeenAberdeenUK Division of Allergy-Immunology University of South Florida Morsani College of MedicineTampaFLUSA department of pediatrics CHA Gangnam Medical CenterCHA University School of MedicineSeoulSouth Korea department of Dermatology CHA Bundang Medical CenterCHA University School of MedicineSeongnamSouth Korea Research and Development Unit Parc Sanitari Sant Joan de DeuCIBERSAMISCIIIBarcelonaSpain Catalan Institution for Research and Advanced Studies(ICREA) Pg.Lluis CompanysBarcelonaSpain Faculty of Medicine University of Versailles Saint-Quentin-en-YvelinesMontigny-Le-BretonneuxFrance Centre for Health Performance and WellbeingAnglia Ruskin UniversityCambridgeUK Center for Digital Health Medical Science Research InstituteKyung Hee University Medical CenterKyung Hee University College of Medicine23 Kyungheedae-RoDongdaemun-GuSeoul02447South Korea department of Obstetrics and Gynecology Kyung Hee University College of MedicineSeoulSouth Korea department of Otorhinolaryngology-Head and Neck Surgery CHA Bundang Medical CenterCHA University School of MedicineSeongnamSouth Korea department of Biomedical Engineering Kyung Hee UniversityYonginSouth Korea department of Biomedical Engineering University of MichiganAnn ArborMIUSA department of Human Biology University of TorontoTorontoONCanada AP-HM Aix-Marseille Univ.CEReSS—Health Service Research and Quality of Life CenterMarseilleFrance FondaMental Foundation CreteilFrance department of pediatrics Seoul National University College of MedicineSeoulSouth Korea department of Neuropsychiatry Seoul National University College of MedicineSeoulSouth Korea department of Endocrinology and Metabolism Kyung Hee University School of MedicineSeoulSouth Korea department of pediatrics Yonsei University College of

Background Although smoking is classified as a risk factor for severe COVID-19 outcomes,there is a scarcity of studies on prevalence of smoking during the COVID-19 pandemic.Thus,this study aims to analyze the trends of prevalence of smoking in adolescents over the COVID-19 pandemic period.Methods The present study used data from middle to high school adolescents between 2005 and 2021 who participated in the Korea Youth Risk Behavior Web-based Survey(KYRBS).We evaluated the smoking prevalence(ever or daily)by year groups and estimated the slope in smoking prevalence before and during the pandemic.Results A total of 1,137,823 adolescents participated in the study[mean age,15.04 years[95%confidence interval(CI)15.03-15.06];and male,52.4%(95%CI 51.7-53.1)].The prevalence of ever smokers was 27.7%(95%CI 27.3-28.1)between 2005 and 2008 but decreased to 9.8%(95%CI 9.3-10.3)in 2021.A consistent trend was found in daily smokers,as the estimates decreased from 5.4%(95%CI 5.2-5.6)between 2005 and 2008 to 2.3%(95%CI 2.1-2.5)in 2021.However,the downward slope in the overall prevalence of ever smokers and daily smokers became less pronounced in the COVID-19 pandemic period than in the pre-pandemic period.In the subgroup with substance use,the decreasing slope in daily smokers was significantly more pronounced during the pandemic than during the pre-pandemic period.Conclusions The proportion of ever smokers and daily smokers showed a less pronounced decreasing trend during the pandemic.The findings of our study provide an overall understanding of the pandemic's impact on smoking prevalence in adolescents.

关键词： Adolescent COVID-19 Daily smokers Ever smokers Pandemic Smoking

National trends in alcohol and substance use among adolescents from 2005 to 2021:a Korean serial cross‑sectional study of one million adolescents

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World Journal of pediatrics 2023年第11期19卷 1071-1081页

作者： Sangil Park Hyunju Yon Chae Yeon Ban Hyoin Shin Seounghyun Eum Seung Won Lee Youn Ho Shin Jung UShin Ai Koyanagi Louis Jacob Lee Smith Chanyang Min AbdullahÖzgür Yeniova So Young Kim Jinseok Lee Vlasta Hadalin Rosie Kwon Min Ji Koo Guillaume Fond Laurent Boyer Sunyoung Kim Jong Woo Hahn Namwoo Kim Eléa Lefkir Victoire Bondeville Sang Youl Rhee Jae Il Shin Dong Keon Yon Ho Geol Woo department of Neurology Kyung Hee University Medical Center23 Kyungheedae‑roDongdaemun‑guSeoul 02447South Korea department of Medicine Kyung Hee University College of MedicineSeoulSouth Korea department of Precision Medicine Sungkyunkwan University School of MedicineSuwonSouth Korea department of pediatrics CHA Gangnam Medical CenterCHA University School of MedicineSeoulSouth Korea department of Dermatology CHA Bundang Medical CenterCHA University School of MedicineSeongnamSouth Korea Research and Development Unit Parc Sanitari Sant Joan de DeuCIBERSAMISCIIIBarcelonaSpain Catalan Institution for Research and Advanced Studies(ICREA) Pg.Lluis CompanysBarcelonaSpain Faculty of Medicine University of Versailles Saint-Quentin-en-YvelinesMontigny‑le‑BretonneuxFrance Centre for Health Performance and WellbeingAnglia Ruskin UniversityCambridgeUK Center for Digital Health Medical Science Research InstituteKyung Hee University Medical CenterKyung Hee University College of MedicineSeoulSouth Korea Division of Gastroenterology Department of Internal MedicineFaculty of MedicineTokat Gaziosmanpaşa UniversityTokatTurkey department of Otorhinolaryngology‑Head&Neck Surgery CHA Bundang Medical CenterCHA University School of MedicineSeongnamSouth Korea department of Biomedical Engineering Kyung Hee UniversityYonginSouth Korea Faculty of Medicine University of LjubljanaLjubljanaSlovenia department of Biomedical Engineering University of MichiganAnn ArborMIUSA department of Human Biology University of TorontoTorontoONCanada AP-HM Aix-Marseille UniversityCEReSS-Health Service Research and Quality of Life CenterMarseilleFrance FondaMental Foundation CreteilFrance department of Family Medicine Kyung Hee University College of MedicineSeoulSouth Korea department of pediatrics Seoul National University Bundang HospitalSeongnamSouth Korea department of Neuropsychiatry Seoul National University HospitalSeoulSouth Korea Faculty of Medicine University of Rennes 1RennesFrance department

Background Although previous studies have provided data on early pandemic periods of alcohol and substance use in adolescents,more adequate studies are needed to predict the trends of alcohol and substance use during recent periods,including the mid-pandemic period.This study investigated the changes in alcohol and substance use,except tobacco use,throughout the pre-,early-,and mid-pandemic periods in adolescents using a nationwide serial cross-sectional survey from South Korea.Methods Data on 1,109,776 Korean adolescents aged 13–18 years from 2005 to 2021 were obtained in a survey operated by the Korea Disease Control and Prevention Agency.We evaluated adolescents’alcohol and substance consumption prevalence and compared the slope of alcohol and substance prevalence before and during the COVID-19 pandemic to see the trend changes.We define the pre-COVID-19 period as consisting of four groups of consecutive years(2005–2008,2009–2012,2013–2015,and 2016–2019).The COVID-19 pandemic period is composed of 2020(early-pandemic era)and 2021(midpandemic era).Results More than a million adolescents successfully met the inclusion criteria.The weighted prevalence of current alcohol use was 26.8%[95%confidence interval(CI)26.4–27.1]from 2005 to 2008 and 10.5%(95%CI 10.1–11.0)in 2020 and 2021.The weighted prevalence of substance use was 1.1%(95%CI 1.1–1.2)from 2005 to 2008 and 0.7%(95%CI 0.6–0.7)between 2020 and 2021.From 2005 to 2021,the overall trend of use of both alcohol and drugs was found to decrease,but the decline has slowed since COVID-19 epidemic(current alcohol use:βdiff 0.167;95%CI 0.150–0.184;substance use:βdiff 0.152;95%CI 0.110–0.194).The changes in the slope of current alcohol and substance use showed a consistent slowdown with regard to sex,grade,residence area,and smoking status from 2005 to 2021.Conclusion The overall prevalence of alcohol consumption and substance use among over one million Korean adolescents from the early and mid-stage(2020–2021)of the COVID-19 pandemic showed a slower decline than expect

关键词： Alcohol Adolescent Corona virus disease 2019 South Korea Substance use

Nighttime feeding in Turkish children and its association with anemia

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Open Journal of pediatrics 2012年第1期2卷 67-72页

作者： Metin Trabzon Melih Abdullah Turunckapi Oner Ozdemir Melike Sultan Ozgonenel Damla Ince Bülent Ozgonenel department of pediatrics Okmeydani Training and Research HospitalIstanbulTurkey Family Health Center of Ilgaz CankiriTurkey department of pediatrics Goztepe Research and Training HospitalIstanbulTurkey Hematology/Oncology Carman and Ann Adams Children’s Hospital of MichiganWayne State UniversityDetroitUSA

Background: Children who continue to wake up at night to be fed after 6 months of age are called trained nighttime feeders. Nighttime feeding may be associated with dental and medical complications, in addition to causing sleep deprivation in children and parents, as well as with iron-poor nutrition. Methods: We surveyed 614 Turkish children aged 6 months to 5 years from three centers (2 urban and 1 rural) to determine the prevalence of nighttime feeding. We also sought to determine factors associated with continuation of nighttime feedings after 6 months of age. Results: Fifty percent of the participants were night- time feeders. Nighttime feedings were given once, twice, and three times or more to 19.9%, 15.6%, and 14.5% of the participants, respectively. The rural population had a higher rate of nighttime feeding (57.0% rural vs 46.6% urban, p = 0.016). 168 urban children (median age 25 months) had blood count data. Fifty percent of these children were given night-time feedings: 19.6% once, 17.9% twice, and 12.5% three times or more. Nighttime meals were breast-feeding in 51.2%, cow’s milk by bottle in 33.3%, and other in 15.5%. Mean hemoglobin level of nighttime feeders was significantly lower: 11.3 ± 1.3 g/dL vs 12.2 ± 1.0 g/dL in non-nighttime feeders (p < 0.001), even dropping to 10.8 ± 1.4 g/dL in those that were fed 3 times or more at night (p < 0.001). 31.0% of nighttime-feeders were anemic compared to 17.9% in those that did not receive nighttime feedings (p = 0.048). We also noted that intense nighttime feeding was associated with lower MCV (p < 0.001) and lower ferritin levels (p < 0.001). Conclusions: Nighttime feeding is prevalent among Turkish children, especially among the rural population. Nighttime feeding was also noted to be associated with anemia in this study. Nighttime feeding should be screened for and treated in children after 6 months of age.

关键词： Survey Nighttime Feeding Pediatric Sleep Disorder Anemia Iron Deficiency

Insoluble β-glucan from the cell wall of Candida albicans induces immune responses of human THP-1 monocytes through Dectin-1

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Chinese Medical Journal 2009年第5期122卷 496-501页

作者： LI Min LIU Ze-hu CHEN Qing ZHOU Wu-qing YU Mei-wen Lü Gui-xia LU Xue-lian SHEN Yong-nian LIU Wei-da WU Shao-xi department of Medical Mycology Institute of Dermatology Chinese Academy of Medical Science & Peking Union Medical College Nanjing 210042 China Developmental Therapeutics Program Barbara Ann Karmanos Cancer Institute departments of pediatrics Wayne State University School of Medicine Detroit MI 48201 USA (Chen Q)

Background β-glucan is the major structure component of Candida albicans （C. albicans） cell wall. It has been demonstrated that Dectin-1 as the principal C-type lectin pattern-recognition receptor （PRR） can recognize fungal β-glucan and induce immune responses. In this study, we sought to clarify whether insoluble β-glucan from the cell wall of C. albicans （CalG） could induce immune responses in human THP-1 monocytes （a human acute monocytic leukemia cell line） and to determine the underlying mechanisms. Methods Human THP-1 monocytes were challenged with CalG in vitro. The mRNA expression of Dectin-1, Toll-like receptors （TLR2）, proinflammatory cytokine （TNF-a） and chemokine （IL-8） was assayed by real-time reverse transcription polymerase chain reaction （RT-PCR）. The secretion of TNF-a and IL-8 were measured by enzyme-linked immunosorbent assay （ELISA）. H2O2 release was determined by microplate fluorescent assay. Western blotting was used to analyze IKB-a phosphorylation and degradation. Results Exposure of THP-1 monocytes to CalG led to increased gene expression and secretion of TNF-a and IL-8. CalG induced H2O2 release in a time-dependent manner. CalG hydrolyzed with zymolyase failed to induce gene expression and secretion of TNF-a, IL-8 and H2O2 release. CalG up-regulated the mRNA of Dectin-1, whereas the mRNA level of TLR2 was not altered. THP-1 monocytes challenged with CalG resulted in the activation of NF-KB in a time-dependent manner. Dectin-1 inhibitor laminarin blocked the CalG-induced production of TNF-a and H2O2 in THP-1 monocytes, but no such effect was observed in pretreatment with anti-TLR2 neutralizing antibody and the LPS inhibitor （polymyxin B）. Conclusion CalG may play a role in activation of immune responses in human THP-1 cells throuah Dectin-1, not TLR2.

关键词： Candida albicans monocytes insoluble β-glucan Dectin-1 cytokines hydrogen peroxide