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1.  ICON: chronic rhinosinusitis 
Chronic rhinosinusitis (CRS) is a public health problem that has a significant socio-economic impact. Moreover, the complexity of this disease due to its heterogeneous nature based on the underlying pathophysiology - leading to different disease variants - further complicates our understanding and directions for the most appropriate targeted treatment strategies. Several International/national guidelines/position papers and/or consensus documents are available that present the current knowledge and treatment strategies for CRS. Yet there are many challenges to the management of CRS especially in the case of the more severe and refractory forms of disease. Therefore, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), a collaboration between EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus (ICON) on Chronic Rhinosinusitis. The purpose of this ICON on CRS is to highlight the key common messages from the existing guidelines, the differences in recommendations as well as the gaps in our current knowledge of CRS, thus providing a concise reference. In this document we discuss the definition of the disease, its relevance, pharmacoeconomics, pathophysiology, phenotypes and endotypes, genetics and risk factors, natural history and co-morbidities as well as clinical manifestations and treatment options in both adults and children comprising pharmacotherapy, surgical interventions and more recent biological approaches. Finally, we have also highlighted the unmet needs that wait to be addressed through future research.
doi:10.1186/1939-4551-7-25
PMCID: PMC4213581  PMID: 25379119
Chronic rhinosinusitis; Pharmacoeconomics; Pathophysiology; Phenotypes; Genetics; Co-morbidities; Treatment; Biologicals; Unmet needs
2.  The Development of Auditory Skills in Young Children with Mondini Dysplasia after Cochlear Implantation 
PLoS ONE  2014;9(9):e108079.
The aim of this study is to survey and compare the development of auditory skills in young children with Mondini dysplasia and profoundly-deaf young children with radiologically normal inner ears over a period of 3 years after cochlear implantation. A total of 545 young children (age 7 to 36 months) with prelingual, severe to profound hearing loss participated in this study. All children received cochlear implantation. Based on whether or not there was a Mondini dysplasia as diagnosed with CT scanning, the subjects were divided into 2 groups: (A) 514 young children with radiologically normal inner ears and (B) 31 young children with Mondini dysplasia. The Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) was used to assess the children's auditory skills that include vocalization changes, spontaneous alerting to sounds in everyday living environments, and the ability to derive meaning from sounds. The assessment was performed prior to surgery and at 1, 3, 6, 9, 12, 24, and 36 months after implant device switch-on. The mean scores for overall auditory skills were not significantly different between groups A and B at pre-surgery, 1, 12, 24, and 36 months post-surgery, but were significantly different at 3, 6, and 9 months post-surgery. The mean scores for all auditory skills in children with Mondini dysplasia showed significant improvement over time. The mean scores for the three subcategories of auditory skills in children with Mondini dysplasia also showed significant differences at pre-surgery, 1, 3, 6, and 9 months, however, there were no significant differences at 12, 24, and 36 months. Overall, the auditory skills of young children with Mondini dysplasia developed rapidly after cochlear implantation, in a similar manner to that of young children with radiologically normal inner ears. Cochlear implantation is an effective intervention for young children with Mondini dysplasia.
doi:10.1371/journal.pone.0108079
PMCID: PMC4172681  PMID: 25247792
3.  Suppression of Cytokine Release by Fluticasone Furoate vs. Mometasone Furoate in Human Nasal Tissue Ex-Vivo 
PLoS ONE  2014;9(4):e93754.
Background
Topical glucocorticosteroids are the first line therapy for airway inflammation. Modern compounds with higher efficacy have been developed, but head-to-head comparison studies are sparse.
Objective
To compare the activity of two intranasal glucocorticoids, fluticasone furoate (FF) and mometasone furoate (MF) with respect to the inhibition of T helper (Th)1, Th2 and Th17 cytokine release in airway mucosa.
Methods
We used an ex-vivo human nasal mucosal tissue model and employed pre- and post- Staphylococcus aureus enterotoxin B (SEB)-challenge incubations with various time intervals and drug concentrations to mimic typical clinical situations of preventive or therapeutic use.
Results
At a fixed concentration of 10−10 M, FF had significantly higher suppressive effects on interferon (IFN)-γ, interleukin (IL)-2 and IL-17 release, but not IL-5 or tumor necrosis factor (TNF)-α, vs. MF. While the maximal suppressive activity was maintained when FF was added before or after tissue stimulation, the cytokine suppression capacity of MF appeared to be compromised when SEB-induced cell activation preceded the addition of the drug. In a pre-challenge incubation setting with removal of excess drug concentrations, MF approached inhibition of IL-5 and TNF-α after 6 and 24 hours while FF maximally blocked the release of these cytokines right after pre-incubation. Furthermore, FF suppressed a wider range of T helper cytokines compared to MF.
Conclusion
The study demonstrates the potential of our human mucosal model and shows marked differences in the ability to suppress the release of various cytokines in pre- and post-challenge settings between FF and MF mimicking typical clinical situations of preventive or therapeutic use.
doi:10.1371/journal.pone.0093754
PMCID: PMC3977874  PMID: 24710117
4.  Prevalence of Allergic Rhinitis in China 
Allergic rhinitis (AR) is a serious systemic allergic disease, which together with comorbid asthma causes major illness and disability worldwide. Recent epidemiological studies have revealed wide variations in the increasing prevalence of AR and allergies globally, including in China. Despite a markedly higher population than western countries, and a landmass close to Europe in area, little epidemiological data is available on AR in China. Thus, the present study reviewed the prevalence, comorbid allergic diseases, trends and pattern of sensitizing allergens in adults and children suffering from AR in China. Available data indicated that despite variations in the prevalence of AR in different regions of the country, the prevalence of AR has increased in both adults and children over the last 2 decades. Similarly, there has been an increase in a "western"-type lifestyle, industrialization and air pollution over this period, which may have contributed to the increased prevalence of AR observed in China.
doi:10.4168/aair.2014.6.2.105
PMCID: PMC3936037  PMID: 24587945
Allergic rhinitis; prevalence; China; asthma; allergen; epidemiology; adult; children
5.  Staphylococcal enterotoxin B influences the DNA methylation pattern in nasal polyp tissue: a preliminary study 
Staphylococcal enterotoxins may influence the pro-inflammatory pattern of chronic sinus diseases via epigenetic events. This work intended to investigate the potential of staphylococcal enterotoxin B (SEB) to induce changes in the DNA methylation pattern. Nasal polyp tissue explants were cultured in the presence and absence of SEB; genomic DNA was then isolated and used for whole genome methylation analysis. Results showed that SEB stimulation altered the methylation pattern of gene regions when compared with non stimulated tissue. Data enrichment analysis highlighted two genes: the IKBKB and STAT-5B, both playing a crucial role in T- cell maturation/activation and immune response.
doi:10.1186/1710-1492-9-48
PMCID: PMC3867657  PMID: 24341752
Staphylococcus aureus enterotoxin B; Chronic rhinosinusitis and nasal polyps; DNA methylation; MBD2; Whole genome methylation analysis; Hypermethylation
6.  Assessment of the feasibility and coverage of a modified universal hearing screening protocol for use with newborn babies of migrant workers in Beijing 
BMC Pediatrics  2013;13:116.
Background
Although migrant workers account for the majority of newborns in Beijing, their children are less likely to undergo appropriate universal newborn hearing screening/rescreening (UNHS) than newborns of local non-migrant residents. We hypothesised that this was at least in part due to the inadequacy of the UNHS protocol currently employed for newborn babies, and therefore aimed to modify the protocol to specifically reflect the needs of the migrant population.
Methods
A total of 10,983 healthy babies born to migrant mothers between January 2007 and December 2009 at a Beijing public hospital were investigated for hearing abnormalities according to a modified UNHS protocol. This incorporated two additional/optional otoacoustic emissions (OAE) tests at 24–48 hours and 2 months after birth. Infants not passing a screening test were referred to the next test, until any hearing loss was confirmed by the auditory brainstem response (ABR) test.
Results
A total of 98.91% (10983/11104) of all newborn children underwent the initial OAE test, of which 27.22% (2990/10983) failed the test. 1712 of the failed babies underwent the second inpatient OAE test, with739 failing again; thus significantly decreasing the overall positive rate for abnormal hearing from 27.22% to 18.36% ([2990–973 /10983)]; p = 0). Overall, 1147(56.87%) babies underwent the outpatient OAE test again after1-month, of whom 228 failed and were referred for the second outpatient OAE test (i.e. 2.08% (228/10983) referral rate at 1month of age). 141 of these infants underwent the referral test, of whom 103 (73.05%) tested positive again and were referred for a final ABR test for hearing loss (i.e. final referral rate of 1.73% ([228-38/10983] at 2 months of age). Only 54 infants attended the ABR test and 35 (0.32% of the original cohort tested) were diagnosed with abnormal hearing.
Conclusions
Our study shows that it is feasible and practical to achieve high coverage rates for screening hearing loss and decrease the referral rates in newborn babies of migrant workers, using a modification of the currently employed UNHS protocol.
doi:10.1186/1471-2431-13-116
PMCID: PMC3750515  PMID: 23926962
Auditory brainstem response (ABR); Migrant people; Newborn babies; Otoacoustic emissions (OAE); Universal newborn hearing screening (UNHS)
8.  Interaction between IGF-IR and ER Induced by E2 and IGF-I 
PLoS ONE  2013;8(5):e62642.
Estrogen receptor (ER) is a nuclear receptor and the insulin-like growth factor-I (IGF-I) receptor (IGF-IR) is a transmembrane tyrosine kinase receptor. Estrogen and IGF-I are known to have synergistic effects on the growth of breast cancer cells. Recently, non-nuclear effects of ER have been under investigation. To study the mechanism involved in this process, we have used MCF-7 breast cancer cell lines transfected with IGF-IR anti-sense cDNA (SX13, MCF-7SX13) that resulted in 50% reduction of IGF-IR. In MCF-7 cells, estradiol (E2) and IGF-I induced the rapid association of ER to IGF-IR, however, the interaction was abrogated in MCF-7SX13 cells. In addition, NWTB3 cells (NIH3T3 cells overexpressing IGF-IR) were transiently transfected with ERα, the ER-IGF-IR interaction was induced by both E2 and IGF-I. Moreover, ERα regulated the IGF-I signaling pathways through phosphorylation of ERK1/2 and Akt and the interaction of ER-IGF-IR potentiated the cell growth. Finally, E2 and IGF-I stimulated translocation of ER from the nucleus to the cytoplasm. Taken together, these findings reveal that the interaction of the ER and IGF-IR is important for the non-genomic effects of ER.
doi:10.1371/journal.pone.0062642
PMCID: PMC3660452  PMID: 23704881
9.  The effects of vitamins C and B12 on human nasal ciliary beat frequency 
Background
This study was designed to investigate the effects of the vitamins C and B12 on the regulation of human nasal ciliary beat frequency (CBF).
Methods
Human nasal mucosa was removed endoscopically and nasal ciliated cell culture was established. Changes of CBF in response to different concentrations of vitamin C or vitamin B12 were quantified by using high-speed (240 frames per second) digital microscopy combined with a beat-by-beat CBF analysis.
Results
At the concentrations of 0.01% and 0.10%, vitamin C induced an initial increase, followed by a gradual decrease of CBF to the baseline level, while 1.00% vitamin C induced a reversible decrease of CBF. Vitamin B12, at the concentrations of 0.01% and 0.10%, did not influence CBF during the 20-min observation period, while a 1.00% vitamin B12 treatment caused a time-dependent but reversible decrease of CBF.
Conclusions
Treatment with vitamin C or vitamin B12 caused a concentration-dependent but reversible decrease of CBF in cultured human nasal epithelial cells. Therefore, it is necessary to choose a concentration that is safe, effective, and non-ciliotoxic when applying these drugs topically in the nasal cavity.
doi:10.1186/1472-6882-13-110
PMCID: PMC3663725  PMID: 23688196
Ciliary beat frequency; Vitamin C; Vitamin B12; Nasal epithelial cell
10.  The Association between Polymorphisms in the MRPL4 and TNF-α Genes and Susceptibility to Allergic Rhinitis 
PLoS ONE  2013;8(3):e57981.
Background
Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa, involving a complex interaction between genetic and environmental factors. Evidence suggests that polymorphisms in the gene coding for mitochondrial ribosomal protein L4 (MRPL4), located in close proximity to intercellular adhesion molecule-1 (ICAM-1) gene on chromosome location 19p13.2, may influence the risk factor for the development of AR.
Objective
The aim of our study was to investigate any association between AR susceptibility and polymorphisms in ICAM-1 gene, as well as associations between AR risk and polymorphisms in MRPL4, nuclear factor-kappaB (NF-κB) and tumor necrosis factor alpha(TNF-α) genes, associated with ICAM-1 expression.
Methods
A cohort of 414 patients with AR and 293 healthy controls was enrolled from the Han Chinese population in Beijing, China. Blood was drawn for DNA extraction and total serum immunoglobulin E (IgE). A total of 14 single nucleotide polymorphisms (SNPs) in ICAM-1, NF-κB, TNF-α, and MRPL4 genes were selected using the CHB genotyping data from the International Haplotype Mapping (HapMap) and assessed for differences in frequencies of the alleles and genotypes between the AR patients and control subjects.
Results
TNF-α SNP rs1799964 and MRPL4 SNP rs11668618 were found to occur in significantly greater frequencies in the AR group compared to control group. There were no significant associations between SNPs in NF-κB, ICAM-1 and AR. The SNP-SNP interaction information analysis further indicated that there were no synergistic effects among the selected sets of polymorphisms.
Conclusions
Our results suggest a strong association between AR risk and polymorphisms of MRPL4 and TNF-α genes in Han Chinese population.
doi:10.1371/journal.pone.0057981
PMCID: PMC3589466  PMID: 23472126
11.  Prediction of significant coronary artery disease in patients undergoing operations for rheumatic mitral valve disease 
OBJECTIVE
This study aims to develop a logistic regression model and a simple score system for the prediction of significant coronary artery disease (CAD) in patients undergoing operations for rheumatic mitral valve disease.
METHODS
A total of 1241 rheumatic patients (mean age 57 ± 6 years), who underwent routine coronary angiography (CAG) before mitral valve operations between 1998 and 2009, was analyzed. To identify low-risk (≤5%) patients, a bootstrap refined logistic regression model on the basis of clinical risk factors was developed, from which an additive model was derived. Receiver operating characteristic (ROC) curves were used to compare discrimination, and precision was quantified by the Hosmer–Lemeshow statistic. Significant coronary atherosclerosis was defined as 50% or more luminal narrowing in one or more major epicardial vessels by means of CAG.
RESULTS
One hundred twenty-seven (10.2%) patients had significant coronary atherosclerosis. Independent predictors of significant CAD include age, male sex, hypertension, angina, smoking, and hypercholesterolemia. Five hundred and fifty patients were designated as low risk according to our logistic regression and additive models. Of these patients, only 6 (1.1%) had single-vessel disease, and none had multivessel disease. Our models proved more efficient than established regression models.
CONCLUSIONS
Our logistic regression model could estimate the risk of significant CAD in rheumatic patients undergoing mitral valve operations, while the additive simple score system could reliably identify the low-risk patients in whom routine preoperative angiography might be safely avoided.
doi:10.1016/j.ejcts.2011.04.018
PMCID: PMC3241135  PMID: 21641813
Rheumatic heart valve disease; Mitral valve disease; CAD; Risk factor; Logistic regression model
12.  Single nucleotide polymorphisms in thymic stromal lymphopoietin gene are not associated with allergic rhinitis susceptibility in Chinese subjects 
BMC Medical Genetics  2012;13:79.
Background
Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine, implicated in the development and progression of allergic diseases. Recent studies have demonstrated significantly increased expression and synthesis of TSLPin nasal mucosa of patients with allergic rhinitis (AR), compared with nonallergic control subjects. Also, there is significant correlation between the level of TSLP mRNA and symptom severity in AR patients. In this study, we investigated whether polymorphisms in the TSLP gene were associated with increased risk of AR in the Chinese population.
Methods
In a candidate gene association study, we tested 11 single nucleotide polymorphisms (SNPs) in the TSLP gene in 368 AR and 325 control adult Han Chinese subjects from Beijing. The 11 SNPs were selected from the Chinese HapMap genotyping dataset to ensure complete genetic coverage. AR was established by questionnaire and clinical examination, and blood was drawn from all subjects for DNA extraction. The PLINK software package was used to perform statistical testing.
Results
In the single-locus analysis of AR risk, no significant differences in allele and genotype frequencies were found between AR and control subjects. Further logistic regression analyses adjusted for age and gender also failed to reveal significant associations between AR and the selected SNPs. Similarly, analysis stratified by gender, and haplotype or diplotype did not reveal any association with AR risk.
Conclusion
Although TSLP presents itself as a good candidate for contributing to allergy, this study failed to find an association between specific SNPs in the TSLP gene and AR susceptibility in the Han Chinese population.
doi:10.1186/1471-2350-13-79
PMCID: PMC3459694  PMID: 22973903
Allergic rhinitis; Chinese subjects; Genotyping; Thymic stromal lymphopoietin; Single nucleotide polymorphism
13.  Multiple Osteomas in Middle Ear 
Case Reports in Otolaryngology  2012;2012:685932.
Since the first description of middle ear osteomas by Thomas in 1964, only few reports were published within the English literatures (Greinwalid et al., 1998; Shimizu et al., 2003; Cho et al., 2005; and Jang et al., 2009), and only one case of the multiple osteomas in middle ear was described by Kim et al., 2006, which arose from the promontory, lateral semicircular canal, and epitympanum. Here we describe a patient with multiple middle ear osteomas arising from the promontory, incus, Eustachian tube, and bony semicanal of tensor tympani muscle. This patient also contracted the chronic otitis media in the ipsilateral ear. The osteomas were successfully removed by performing type III tympanoplasty in one stage.
doi:10.1155/2012/685932
PMCID: PMC3420700  PMID: 22928138
14.  Herpes Simplex Virus Type 1 Infection Facilitates Invasion of Staphylococcus aureus into the Nasal Mucosa and Nasal Polyp Tissue 
PLoS ONE  2012;7(6):e39875.
Background
Staphylococcus aureus (S. aureus) plays an important role in the pathogenesis of severe chronic airway disease, such as nasal polyps. However the mechanisms underlying the initiation of damage and/or invasion of the nasal mucosa by S. aureus are not clearly understood. The aim of this study was to investigate the interaction between S. aureus and herpes simplex virus type 1 (HSV1) in the invasion of the nasal mucosa and nasal polyp tissue.
Methodology/Principal Findings
Inferior turbinate and nasal polyp samples were cultured and infected with either HSV1 alone, S. aureus alone or a combination of both. Both in turbinate mucosa and nasal polyp tissue, HSV1, with or without S. aureus incubation, led to focal infection of outer epithelial cells within 48 h, and loss or damage of the epithelium and invasion of HSV1 into the lamina propria within 72 h. After pre-infection with HSV1 for 24 h or 48 h, S. aureus was able to pass the basement membrane and invade the mucosa. Epithelial damage scores were significantly higher for HSV1 and S. aureus co-infected explants compared with control explants or S. aureus only-infected explants, and significantly correlated with HSV1-invasion scores. The epithelial damage scores of nasal polyp tissues were significantly higher than those of inferior turbinate tissues upon HSV1 infection. Consequently, invasion scores of HSV1 of nasal polyp tissues were significantly higher than those of inferior turbinate mucosa in the HSV1 and co-infection groups, and invasion scores of S. aureus of nasal polyp tissues were significantly higher than those of inferior turbinate tissues in the co-infection group.
Conclusions/Significance
HSV1 may lead to a significant damage of the nasal epithelium and consequently may facilitate invasion of S. aureus into the nasal mucosa. Nasal polyp tissue is more susceptible to the invasion of HSV1 and epithelial damage by HSV1 compared with inferior turbinate mucosa.
doi:10.1371/journal.pone.0039875
PMCID: PMC3387208  PMID: 22768151
15.  Polymorphisms in RYBP and AOAH Genes Are Associated with Chronic Rhinosinusitis in a Chinese Population: A Replication Study 
PLoS ONE  2012;7(6):e39247.
Background
The development of CRS is believed to be the result of combined interactions between the genetic background of the affected subject and environmental factors.
Objectives
To replicate and extend our recent findings from genetic association studies in chronic rhinosinusitis (CRS) performed in a Canadian Caucasian population in a Chinese population.
Methods
In a case-control replication study, DNA samples were obtained from CRS with (n = 306; CRSwNP) and without (n = 332; CRSsNP) nasal polyps, and controls (n = 315) in a Chinese population. A total of forty-nine single nucleotide polymorphisms (SNPs) selected from previous identified SNPs associated with CRS in Canadian population, and SNPs from the CHB HapMap dataset were individually genotyped.
Results
We identified two SNPs respectively in RYBP (rs4532099, p = 2.15E–06, OR = 2.59) and AOAH (rs4504543, p = 0.0001152, OR = 0.58) significantly associated with whole CRS cohort. Subgroup analysis for the presence of nasal polyps (CRSwNP and CRSsNP) displayed significant association in CRSwNP cohorts regarding to one SNP in RYBP (P = 3.24E–006, OR = 2.76). Evidence of association in the CRSsNP groups in terms of 2 SNPs (AOAH_rs4504543 and RYBP_rs4532099) was detected as well. Stratifying analysis by gender demonstrated that none of the selected SNPs were associated with CRSwNP as well as CRSsNP. Meanwhile 3 SNPs (IL1A_rs17561, P = 0.005778; IL1A_rs1800587, P = 0.009561; IRAK4_rs4251513, P = 0.03837) were associated with serum total IgE level.
Conclusions
These genes are biologically plausible, with roles in regulation of transcription (RYBP) and inflammatory response (AOAH). The present data suggests the potential common genetic basis in the development of CRS in Chinese and Caucasian population.
doi:10.1371/journal.pone.0039247
PMCID: PMC3378692  PMID: 22723975
16.  Cost-effectiveness analysis of neonatal hearing screening program in china: should universal screening be prioritized? 
Background
Neonatal hearing screening (NHS) has been routinely offered as a vital component of early childhood care in developed countries, whereas such a screening program is still at the pilot or preliminary stage as regards its nationwide implementation in developing countries. To provide significant evidence for health policy making in China, this study aims to determine the cost-effectiveness of NHS program implementation in case of eight provinces of China.
Methods
A cost-effectiveness model was conducted and all neonates annually born from 2007 to 2009 in eight provinces of China were simulated in this model. The model parameters were estimated from the established databases in the general hospitals or maternal and child health hospitals of these eight provinces, supplemented from the published literature. The model estimated changes in program implementation costs, disability-adjusted life years (DALYs), average cost-effectiveness ratio (ACER), and incremental cost-effectiveness ratio (ICER) for universal screening compared to targeted screening in eight provinces.
Results and discussion
A multivariate sensitivity analysis was performed to determine uncertainty in health effect estimates and cost-effectiveness ratios using a probabilistic modeling technique. Targeted strategy trended to be cost-effective in Guangxi, Jiangxi, Henan, Guangdong, Zhejiang, Hebei, Shandong, and Beijing from the level of 9%, 9%, 8%, 4%, 3%, 7%, 5%, and 2%, respectively; while universal strategy trended to be cost-effective in those provinces from the level of 70%, 70%, 48%, 10%, 8%, 28%, 15%, 4%, respectively. This study showed although there was a huge disparity in the implementation of the NHS program in the surveyed provinces, both universal strategy and targeted strategy showed cost-effectiveness in those relatively developed provinces, while neither of the screening strategy showed cost-effectiveness in those relatively developing provinces. This study also showed that both strategies especially universal strategy achieve a good economic effect in the long term costs.
Conclusions
Universal screening might be considered as the prioritized implementation goal especially in those relatively developed provinces of China as it provides the best health and economic effects, while targeted screening might be temporarily more realistic than universal screening in those relatively developing provinces of China.
doi:10.1186/1472-6963-12-97
PMCID: PMC3353179  PMID: 22510223
17.  Association Pattern of Interleukin-1 Receptor-Associated Kinase-4 Gene Polymorphisms with Allergic Rhinitis in a Han Chinese Population 
PLoS ONE  2011;6(6):e21769.
Objective
Interleukin-1 receptor-associated kinase-4 (IRAK-4) encodes a kinase that is essential for NF-kB activation in Toll-like receptor and T-cell receptor signaling pathways, indicating a possible crosstalk between innate and acquired immunities. We attempted to determine whether the polymorphisms in the Interleukin-1 receptor-associated kinase-4 (IRAK-4) gene are associated with allergic rhinitis (AR) in the Han Chinese population.
Methods
A population of 379 patients with AR and 333 healthy controls was studied. Blood was drawn for DNA extraction and total serum immunoglobulin E (IgE). A total of 11 single nucleotide polymorphisms (SNPs) in IRAK-4 were selected and individually genotyped.
Results
Significant allelic differences between cases and controls were obtained for the SNP of rs3794262 in the IRAK-4 gene. In the stratified analysis for gender, two SNPs (rs4251431 and rs6582484) in males appeared as significant associations. Subgroup analysis for the presence of different allergen sensitivities displayed associations only in the house dust mite-allergic cohorts (rs3794262, rs4251481). None of the selected SNPs in IRAK-4 was associated with total IgE level. The haplotype analyisis indicated GCCTGCGA was significantly associated with AR. The SNP-SNP interaction information analysis indicated that the selected sets of polymorphisms had no synergistic effect.
Conclusions
Our findings did not support the potential contribution of the IRAK-4 gene to serum IgE levels. However, the results demonstrated a gender- and allergen-dependant association pattern between polymorphisms in IRAK-4 and AR in Chinese population.
doi:10.1371/journal.pone.0021769
PMCID: PMC3128076  PMID: 21738793
18.  SNPs in the FCER1A Gene Region Show No Association with Allergic Rhinitis in a Han Chinese Population 
PLoS ONE  2010;5(12):e15792.
Background
Immunoglobulin E (IgE) is a central player in the allergic response, and raised total IgE levels are considered as an indicator of atopy or potential development of atopy. A recent genome-wide scan in a German population-based cohort of adults identified the gene encoding the alpha chain of the high affinity receptor for IgE (FCER1A) as a susceptibility locus influencing total serum IgE levels. The aim of this study was to investigate whether the polymorphisms in the FCER1A gene are associated with allergic rhinitis (AR) in a Han Chinese population.
Methodology/Principal Findings
A population of 378 patients with AR and 288 healthy controls was studied. Precise phenotyping of patients was accomplished by means of a questionnaire and clinical examination. Blood was drawn for DNA extraction and total serum immunoglobulin E (IgE) measurement. A total of 16 single nucleotide polymorphisms (SNPs) in FCER1A were selected and individually genotyped. None of the SNPs in the FCER1A showed an association with AR. Similarly, the lack of association was also evident in subgroup analysis for the presence of different allergen sensitivities. None of the selected SNPs in FCER1A was associated with total IgE level.
Conclusions
Although FCER1A presents itself as a good candidate for contributing to total serum IgE, this study failed to find an association between SNPs in the FCER1A gene region and IgE level or AR susceptibility.
doi:10.1371/journal.pone.0015792
PMCID: PMC3013135  PMID: 21209833
19.  Age-specific PSA reference ranges in Chinese men without prostate cancer 
Asian Journal of Andrology  2008;11(1):100-103.
This study is to determine age-specific prostate-specific antigen (PSA) distributions in Chinese men without prostate cancer (PC) and to recommend reference ranges for this population after comparison with other studies. From September 2003 to December 2006, 9 374 adult men aged from 18 to 96 years agreed to participate in the study. After all cases of PC were excluded, 8 422 adult men participated in statistical analysis and were divided into five age groups. Simple descriptive statistical analyses were carried out and quartiles and 95th percentiles were calculated for each age group. The age-specific PSA reference ranges are as follows: 40–49 years, 2.15 ng mL−1; 50–59 years, 3.20 ng mL−1; 60–69 years, 4.10 ng mL−1; 70–79 years, 5.37 ng mL−1. The results indicate that the ethnic differences in PSA levels are obvious. The currently adopted Oesterling's age-specific PSA reference ranges are not appropriate for Chinese men. The reference ranges of this study should be more suitable to Chinese men.
doi:10.1038/aja.2008.17
PMCID: PMC3735217  PMID: 19050693
age; prostate cancer; prostate-specific antigen
20.  The Ciliary Rootlet Maintains Long-Term Stability of Sensory Cilia 
Molecular and Cellular Biology  2005;25(10):4129-4137.
The striated ciliary rootlet is a prominent cytoskeleton originating from basal bodies of ciliated cells. Although a familiar structure in cell biology, its function has remained unresolved. In this study, we carried out targeted disruption in mice of the gene for rootletin, a component of the rootlet. In the mutant, ciliated cells are devoid of rootlets. Phototransduction and ciliary beating in sensory and motile cilia initially exhibit no apparent functional deficits. However, photoreceptors degenerate over time, and mutant lungs appear prone to pathological changes consistent with insufficient mucociliary clearance. Further analyses revealed a striking fragility at the ciliary base in photoreceptors lacking rootlets. In vitro assays suggest that the rootlet is among the least dynamic of all cytoskeletons and interacts with actin filaments. Thus, a primary function of the rootlet is to provide structural support for the cilium. Inasmuch as photoreceptors elaborate an exceptionally enlarged sensory cilium, they are especially dependent on the rootlet for structural integrity and long-term survival.
doi:10.1128/MCB.25.10.4129-4137.2005
PMCID: PMC1087714  PMID: 15870283

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