Objective:To identify factors leading to delayed diagnosis of nasal cavity and paranasal sinus lymphoma （NSL） and to propose preventive strategies. Methods:A retrospective analysis of clinical data from 36 patients with lymphoma of sinonasal cavities admitted to the Otolaryngology Department of the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2024 was conducted. Results:Among 36 patients with non-Hodgkin's lymphoma（NHL）, the most common type was extranodal NK/T-cell lymphoma（ENKTL） in 23 cases（63.8%）, with a delayed diagnosis in 16 cases（69.6%）. The second most common type was diffuse large B-cell lymphoma（DLBCL） in 8 cases（22.2%）, with a delayed diagnosis in 5 cases（62.5%）. The main clinical presentation of ENKTL was nasal obstruction（87.0%）, primarily affecting the inferior turbinate（60.9%） and nasal septum（30.4%）. Endoscopic findings included neoplasms（65.2%）, extensive mucosal erosion and necrosis（17.4%）, and local scabbing/erosion/swelling（17.4%）. Patients in the local scabbing/erosion/swelling group had significantly longer intervals from onset to diagnosis than those in the neoplasms group（P<0.05）. MRI considered lymphoma in 7 cases（46.7%）, significantly higher than CT, which considered lymphoma in 2 cases（9.5%）（P<0.05）. Pathology often revealed lymphoid hyperplasia/infiltration with atypia and necrosis（79.4%）. Common initial misdiagnoses for delayed patients included rhinitis and sinusitis（50.0%）. For DLBCL, the most common clinical symptoms included ocular symptoms（50.0%）, nasal obstruction（50.0%）, and facial pain/swelling（50.0%）, with lesions primarily in the ethmoid sinus（75.0%）, orbit（50.0%）, and maxillary sinus（37.5%）. Endoscopy primarily revealed neoplasms（62.5%）. CT and MRI suggested lymphoma/malignant tumors to be 62.5% and 71.4%, respectively. Pathological findings frequently indicated intermediate to large cell diffuse infiltration and are often misdiagnosed as facial infections（40.0%） for delayed patients. Conclusion:Nasal cavity and sinus lymphoma, primarily ENKTL and DLBCL, often face delayed diagnosis. For ENKTL, clinicians should focus on patients with local crusting/erosion/swelling, combining CT and MRI for comprehensive assessment and timely tissue biopsy. For DLBCL, imaging examinations should be prioritized. Future research should focus on developing early screening and diagnostic tools to enhance efficiency.

Purpose:Although periostin has recently emerged as a new mediator in chronic allergic diseases, particularly in upper airway disease, its significance as a biomarker for allergic rhinitis (AR) is still unclear. Therefore, we aimed to assess the potential of periostin as a novel candidate biomarker for diagnosing and assessing the severity of AR. Patients and Methods:A total of 40 patients with AR and 22 healthy controls, all aged over 18 years, were recruited for the study. Participants underwent examinations to assess serum levels of total IgE (tIgE), specific IgE (sIgE), periostin, and remodeling-related factors, as well as fractional exhaled nitric oxide (FeNO) and fractional nasal nitric oxide (FnNO). Additionally, clinical characteristics questionnaire and nasal function assessments were completed by AR patients. Results:The levels of serum periostin were significantly higher in patients with AR compared to healthy controls (Z=-3.605, p<0.001). There was a notable positive correlation between serum periostin and FeNO (r=0.398, p=0.012), FnNO (r=0.379, p=0.017), as well as the visual analogue scale (VAS) score for ocular tearing (r=0.351, p=0.026) in AR patients. Furthermore, the serum periostin levels were higher in moderate-to-severe AR compared to mild AR cases (Z=-2.007, p=0.045). The level of serum periostin in AR patients showed a sequential increase corresponding to shortness of breath scores from 0 to 3 (Z=10.137, p=0.017). The predicted probability of serum periostin demonstrated moderate diagnostic accuracy in detecting AR (AUC=0.773, p<0.001). Conclusion:Serum periostin shows potential as a candidate biomarker for detecting AR and can serve as a surrogate biomarker for assessing airway inflammation in AR patients.

BACKGROUND:The etiology of allergic rhinitis (AR), in which genetic and environmental factors are closely intertwined, has not yet been completely clarified. Programmed cell death 1 (PD-1) and its ligands (PD-L1 and PD-L2) regulate the immune and inflammatory responses during the development of immune-related and atopic diseases. To clarify the associations of genetic variants in PD-1, PD-L1 and PD-L2 with susceptibility to AR, gene-gene and gene-environment interactions were investigated. METHODS:A total of 452 AR patients and 495 controls were enrolled in this hospital-based case-control study. Eight single nucleotide polymorphisms (SNPs) in the PDCD1, PDCD1LG1 and PDCD1LG2 genes were genotyped. The correlations between SNPs and AR incidence, as well as gene-gene and gene-environment interactions were explored. Differentially expressed genes were screened by the Limma package in two Gene Expression Omnibus (GEO) datasets of AR patients. Expression qualitative trait locus (eQTL) analysis was performed via the Genotype-Tissue Expression (GTEx) database. RESULTS:The rs2297136 (A/G) in PDCD1LG1 was associated with a significantly increased risk of AR, whereas the PDCD1LG2 rs16923189 G allele was associated with a reduced risk of AR. In the subgroups according to AR-related phenotypes, the rs2297136 G allele increased, while the rs16923189 G allele reduced AR risk. Gene-gene interactions and gene-environment interactions (e.g., PDCD1LG1 polymorphisms with factors such as smoke, main road and cooking fumes) were verified in AR patients, but they were not significant after Bonferroni correction. CONCLUSION:PDCD1LG1 rs2297136 and PDCD1LG2 rs16923189 are associated with susceptibility to AR in this Chinese population. The PD-1/PD-L1 and PD-1/PD-L2 signaling pathways may regulate gene-gene and gene-environment interactions in the pathogenesis of AR.

Background: Compliance to sublingual immunotherapy (SLIT) is generally low, resulting in reduced short- and long-term clinical efficacy. Compliance is a critical factor determining the success of allergic rhinitis (AR) treatment. Objective: To analyze the compliance of patients with house dust mite (HDM)-induced AR to SLIT and the impact of coronavirus disease 2019 (COVID-19) on compliance. Methods: The clinical data of 3117 patients with HDM-induced AR who started SLIT between July 2018 and April 2022 were retrospectively reviewed. We assessed the reasons for non-compliance and the changes in non-compliance during the COVID-19 pandemic compared to the prepandemic period. Results: Of 3117 patients, 507 (16.27%) patients (ages, 5-67 years) were identified as noncompliant. The most common reason for non-compliance was poor efficacy (27.22%). The noncompliance rate was highest during 24-36 months of SLIT (28.13%, 153/544), followed by 12- 24 months (7.02%, 91/1296). Non-compliance was significantly higher in adolescents/adults than in children (P 1/4 0.000). Although the generalized linear model analysis indicated that compliance was affected by the COVID-19 pandemic during 3-6 months of SLIT, the overall compliance to SLIT was not significantly affected by the pandemic, according to the Kaplan-Meier survival analysis. Conclusions: The non-compliance rate of SLIT in this study was low, and poor efficacy was the most common reason for non-compliance. The compliance of adolescents/adults was lower than that of children. The COVID-19 pandemic did not significantly impact compliance to SLIT, which is an appropriate strategy for the home treatment of AR patients during major public health events.

教学查房是住院医师规范化培训(简称住培)重要的临床教学活动.基于目前住培已由制度建设逐步过渡为内涵和质量建设,强调核心胜任力的培养,该院耳鼻咽喉科专业基地教学查房以胜任力为导向进行相应的实践探索,包括目标、内容、流程、教学方法等,应用形成性评价,充分发挥教学小组的作用,不断提高教学查房质量,从而培养具有良好职业道德及岗位胜任力的耳鼻咽喉科住院医师.

Background:Allergic rhinitis (AR) is a nasal inflammatory disease resulting from a complex interplay between genetic and environmental factors. The association between Toll-like receptor (TLR) signaling pathway and environmental factors in AR pathogenesis remains to be explored. This study aims to assess the genetic association of AR with single nucleotide polymorphisms (SNPs) in TLR signaling pathway, and investigate the roles of gene-gene and gene-environment interactions in AR.Methods:A total of 452 AR patients and 495 healthy controls from eastern China were enrolled in this hospital-based case-control study. We evaluated putatively functional genetic polymorphisms in TLR2, TLR4 and CD14 genes for their association with susceptibility to AR and related clinical phenotypes. Interactions between environmental factors (such as traffic pollution, residence, pet keeping) and polymorphisms with AR were examined using logistic regression. Models were stratified by genotype and interaction terms, and tested for the significance of gene-gene and gene-environment interactions.Results:In the single-locus analysis, two SNPs in CD14, rs2563298 (A/C) and rs2569191 (C/T) were associated with a significantly decreased risk of AR. Compared with the GG genotype, the GT and GT/TT genotypes of TLR2 rs7656411 (G/T) were associated with a significantly increased risk of AR. Gene-gene interactions (eg, TLR2 rs7656411, TLR4 rs1927914, and CD14 rs2563298) was associated with AR. Gene-environment interactions (eg, TLR4 or CD14 polymorphisms and certain environmental exposures) were found in AR cases, but they were not significant after Bonferroni correction.Conclusion:The genetic polymorphisms of TLR2 and CD14 and gene-gene interactions in TLR signaling pathway were associated with susceptibility to AR in this Han Chinese population. However, the present results were limited to support the association between gene-environment interactions and AR.

Background Genetic variants in GARP (also known as LRRC32) have been reported to have significant associations with asthma and eczema in special populations, but little is known about allergic rhinitis. This study purposes to evaluate the association of single nucleotide polymorphisms (SNPs) in GARP with house dust mite (HDM)-sensitized persistent allergic rhinitis (PER) in a population of Han Chinese. Methods In this hospital-based case–control study, 534 HDM-sensitized PER patients and 451 healthy controls were recruited from East China. In this population, six SNPs in GARP were identified. Serum total and specific IgE levels were measured with ImmunoCAP. Secondary structure and minimum free energy were predicted by RNAfold. Results rs79525962 was associated with the risk of HDM-sensitized PER (P < 0.05). The individuals with CT+TT genotype demonstrated a higher risk of HDM-sensitized PER than those with CC genotype (adjusted OR = 1.393, 95% CI = 1.019–1.904). The homozygous genotype CC of rs3781699 rendered a lower risk of HDM-sensitized PER than the wild-type genotype AA (adjusted OR = 0.646, 95% CI = 0.427–0.976); however, the genotype and allele frequencies of rs3781699 demonstrated no associations with HDM-sensitized PER (P > 0.05). rs79525962 increased the risk of HDM-sensitized PER in the subgroup aged ≥16 years (adjusted OR = 1.745, 95% CI = 1.103–2.760), and this high risk was also found in the females (adjusted OR = 1.708, 95% CI = 1.021–2.856). The G-C haplotype of rs1320646-rs3781699 rendered a lower risk of HDM-sensitized PER than the common haplotype G-A (adjusted OR = 0.819, 95% CI = 0.676–0.993). The secondary structure of GARP altered in response to different genotypes of rs79525962 and rs3781699. Conclusion SNP rs79525962 in the GARP gene marks a risk locus of HDM-sensitized PER in Chinese Hans.

BACKGROUND:The polymorphisms inside microRNA target sites locating in the 3'-UTR region may introduce the micro-RNA-binding changes, which may regulate the gene expression and correlate with the potential diseases. OBJECTIVES:We aimed to investigate whether the polymorphisms in microRNA target sites of transforming growth factor beta (TGF-β) signaling pathway genes are associated with the susceptibility of mite-sensitized allergic rhinitis (AR) in a Han Chinese population. METHODS:In this case-control study, 454 AR patients and 448 healthy controls were recruited. Three HapMap single-nucleotide polymorphisms (SNPs) were mapped to putative microRNA recognition sites and genotyped by TaqMan allelic discrimination assay. RESULTS:The genotype and allele frequencies of 3 SNPs (rs1590 in TGFBR1; rs1434536 and rs17023107 in BMPR1B) showed lack of significant association with AR. However, in the subgroup analysis, the TG, GG, and TG/GG genotypes of rs1590 exhibited significantly increased risk of AR in the male subgroup (TG: adjusted OR = 1.57, 95% CI = 1.08-2.31; GG: adjusted OR = 1.76, 95% CI = 1.09-2.86; TG/GG: adjusted OR = 1.62, 95% CI = 1.13-2.33). The CT genotypes of rs17023107 might have potential to protect against AR in the patients age of <15 years (adjusted OR = 0.37, 95% CI = 0.14-0.95) and the males (adjusted OR = 0.48, 95% CI = 0.25-0.95). No significant association was found between SNPs and the total serum IgE level. CONCLUSIONS:In a Han Chinese population, stratified by age and gender, susceptibility to mite-sensitized AR may be associated with 2 SNPs (rs1590 and rs17023107) in microRNA target sites of TGF-β signaling pathway genes.

Background: Circular RNAs (circRNAs) are involved in inflammation; however, their role in allergic rhinitis (AR) remains unclear. In this study, we analyzed circRNA expression and identified a circRNA-miRNA-mRNA network through which circRNAs regulate AR pathogenesis. Methods: We analyzed circRNA, miRNA, and mRNA expression profiles in the nasal mucosa by high-throughput sequencing (HTS), using a fold-change >1.5 and p-value < 0.05 to pinpoint significantly differentially expressed (DE) circRNAs, miRNAs, and mRNAs in AR. A DEcircRNA-DEmiRNA-DEmRNA crosstalk network was then constructed using bioinformatics and statistical analysis. Gene ontology and Kyoto encyclopedia of genes and genomes pathway analyses were performed to identify the biological terms enriched in the network; whereas RT-PCR and Sanger sequencing were used to confirm the circRNAs. Results: A total of 264 DEcircRNAs were identified by HTS, including 120 upregulated and 144 downregulated in AR compared to controls. A DEcircRNA-DEmiRNA-DEmRNA crosstalk network was constructed with 17 miRNAs, 11 circRNAs, 29 mRNAs, and 64 interaction pairs. These genes were involved in the Wnt signaling pathway, TNF biosynthesis, inflammatory responses, the PI3K-Akt signaling pathway, and Toll-like receptors. Of the 11 DEcircRNAs, hsa_circ_0008668 and circTRIQK were upregulated, whereas hsa_circ_0029853 and circRNA_01002 were down-regulated in AR tissues. Sanger sequencing confirmed the back-splicing junctions of these circRNAs. Conclusions: We constructed a novel DEcircRNA-DEmiRNA-DEmRNA network for AR that pro -vides a basis for future studies to investigate its underlying molecular mechanisms.

Abstract Background House dust mite (HDM)‐induced allergic rhinitis (AR) is a highly prevalent disease with bothersome symptoms. Genetic variants of the Hippo pathway genes play a critical role in the respiratory disease. However, no study has reported associations between variants of the Hippo pathway genes and HDM‐induced AR risk. Methods Forty‐three key genes in the Hippo pathway were selected from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome pathway database, and previous reported studies. A case‐control study of 222 cases and 237 controls was performed to assess the associations between 121 genetic variants in these genes and HDM‐induced AR risk. DNeasy Blood & Tissues Kits were used for extracting genomic DNA from the venous blood and Infinium Asian Screening Array BeadChips for performing genotyping. A logistic regression model was applied to evaluate the effects of variants on HDM‐induced AR risk. The false discovery rate (FDR) method was utilized to correct for multiple testing. The receiver operating characteristic (ROC) curve was plotted to obtain the cut‐off value of total IgE for the diagnosis of HDM‐induced AR. Histone modification and transcription factor binding sites were visualized by UCSC genome browser. Moreover, expression qualitative trait loci (eQTL) analysis was obtained from Genotype‐Tissue Expression (GTEx) database. Results We found that rs754466 in DLG5 was significantly associated with a decreased HDM‐induced AR risk after FDR correction (adjusted odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.36–0.74, p = 3.25 × 10−4, P FDR = 3.93 × 10−2). The rs754466 A allele reduced the risk of HDM‐induced AR in the subgroup of moderate/severe total nasal symptom score (TNSS). Furthermore, rs754466 was associated with a high mRNA expression of DLG5. Additionally, histone modification and transcription factor binding sites were rich in the region containing rs754466. Conclusion Our findings indicated that rs754466 in DLG5 decreased the susceptibility to HDM‐induced AR.

Objective:To compare the clinical characteristics of chronic rhinosinusitis(CRS) with nasal polyps(CRSwNP) and without nasal polyps(CRSsNP), and to provide evidence for formulating rational treatment strategies.Methods:The clinical data of 225 patients suffering from CRS in Jiangsu and Anhui provinces who were hospitalized for endoscopic sinus surgery from November 2018 to December 2019, which included the preoperative blood routine, blood biochemistry, serum total IgE(tIgE), allergen specific IgE(sIgE), paranasal sinus CT, and postoperative histopathological examinations, were retrospectively analyzed for statistical analysis.Results:Of the 225 patients, 148(65.8%) were in the CRSwNP group and 77(34.2%) in the CRSsNP group. There were no significant differences in gender, age, length of hospital stay, differential leucocyte counts and biochemical indexes in peripheral blood between the two groups( P>0.05). In patients with CRSwNP and CRSsNP, the positive rate of serum sIgE against at least one of allergen was 34.5% and 40.3% respectively( P>0.05), among which dust mites were most common with a positive rate of 23.0% and 26.0% respectively( P>0.05). There were also no statistically significant differences in positive rates of serum tIgE and sIgE against 20 common allergens, as well as inhaled and ingested allergens between the CRSwNP and CRSsNP groups( P>0.05). In addition, no significant difference was found in distribution of serum allergen-sIgE concentrations between these two groups( P>0.05). However, the Lund-Mackay scores of paranasal sinus CT scans were significantly higher in the CRSwNP group than those in the CRSsNP group in terms of the sinuses, ostiomeatal complex and the total scores( P<0.05). Moreover, the positive rate of lymphocyte and plasma cell infiltration in the tissue were more than 60% in both groups, while eosinophil infiltration was significantly higher in the CRSwNP group(43.2%) than that in the CRSsNP group(22.1%; P<0.05). Conclusion:At present, lymphocyte and plasma cell inflammation is still dominant in patients with CRS in this region. However, the positive rate of eosinophil infiltration in polyp tissues was 43.2% in patients with CRSwNP, which needs to arouse our recognition and further attention. The total positive rate of allergen sensitization in CRSwNP and CRSsNP patients was 34.5% and 40.3% respectively, with no significant difference. And the major allergen is dust mites.

Background Polymorphism –509C/T in the promoter of transforming growth factor beta1 ( TGFB1) gene is implicated in the pathogenesis of asthma. This polymorphism might also act to regulate the development of allergic rhinitis (AR). Objectives To investigate whether –509C/T is associated with AR susceptibility and severity in a Han Chinese population. Methods The study enrolled 263 patients with persistent AR and 249 healthy controls. AR patients were classified as mild or moderate/severe AR groups according to the Allergic Rhinitis and its Impact on Asthma classification. TGFB1 gene polymorphism –509C/T was genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum total Immunoglobulin E (IgE) and specific IgE levels were determined using an ImmunoCAP. Results Significant difference was found in the allele frequency of TGFB1 –509C/T between AR patients and healthy controls ( P = .027) but not in the genotype frequency ( P =.051). However, the genotype frequency of TGFB1 –509C/T showed significant difference between the mild AR group, the moderate/severe AR group, and the control group ( P = .012); between the moderate/severe AR group and the control group ( P =.036); between the mild AR group and the moderate/severe AR group ( P = .038); but not between the mild AR group and the control group ( P =.075). Conclusion TGFB1 promoter polymorphism –509C/T may be associated with the susceptibility and the severity of persistent AR of Han Chinese, but the functional relationship still needs clarification.

患者女,64岁,因"声嘶逐渐加重1年余"于2017年11月13日入院.患者自诉于1年前无明显诱因下出现声音嘶哑,逐渐加重,用嗓过度后明显加重,伴咽痛、咽部异物感,无吞咽痛,无呼吸困难及痰中带血,当地医院予以中成药治疗后,症状稍改善,停药后加重.遂于2017年10月18日就诊于外院,行喉部CT检查示:声门上区喉腔后缘脂性密度影,颈部小淋巴结.

目的 Toll样受体(TLR)信号通路一直是变应性鼻炎(AR)和哮喘等变态反应性疾病的研究热点,研究TLR通路基因单核苷酸多态性(SNPs)与AR发病的相关性及机制.方法 采用基于医院的病例-对照研究,选择持续性AR患者452例及正常人群495例.通过生物信息学数据库系统筛选TLR通路基因6个SNPs,分别是TLR2的rs7656411、rs76112010、rs7682814,CD14的rs2563298、rs2569190、rs2569191.采用TaqMan技术对SNPs进行分型,ImmunoCAP100变应原体外检测系统测定血清总IgE、特异性IgE,分析SNPs与AR发病率的相关性,并探讨基因-基因相互作用.结果 CD14的rs2563298、rs2569191基因分布在AR组与对照组比较有统计学意义(P<0.05).TLR2的rs7656411和CD14的rs2563298、rs2569191在AR伴随哮喘组与正常对照组中基因分布有明显差异.此外TLR2的rs7656411在AR男性组和有家族史组与对照组的基因分布有明显差异,CD14的rs2563298、rs2569191在AR分组中与对照组均有明显差异.基因交互发现rs7656411,rs2563298、rs2569191三个位点存在阳性关联.结论 TLR通路基因TLR2、CD14多态性与AR发病风险及其临床表型存在一定相关性.

近年来,随着教育国际化的迅速发展,来我国接受医学教育的留学生日益增多,南京医科大学自1975年开始留学生教育,于2004年开始留学生学历生规模化招生和培养,现已建成1门国家级精品课程,5门省级精品课程以及7门校级精品课程.同时,学校借鉴欧美发达国家医学人才培养经验,使得我校留学生教学更进一步与国际接轨.

基于器官系统的综合课程(organ system-based integrated curriculum)、以问题为基础的教学(prob-lem based learning,PBL)、临床客观能力考试(objec-tive structured clinical examination,OSCE)和多选题(multiple choice questions,MCQ)被称作是现代四大医学教育理念[1],分别体现了现代医学教学中课程设置、教学模式和考核考试手段的创新.

Objective To report application of heterogeneous acellular dermal matrix grafts in skin defect repair af-ter resection of external ear neoplasms. Methods From January 2013 to March 2016, 32 patients (14 with auricular neo-plasms and 18 with external auditory canal neoplasms) received heterogeneous acellular dermal matrix grafts for skin de-fect repair after removal of external ear neoplasms, and were followed-up for 6 months. Results The wound healed well in all patients, with no obvious scar or contracture, external auditory canal atresia or stenosis, nor reject reaction of trans-plantation. None of the 32 patients showed significant systemic adverse reaction. Conclusions Heterogeneous dermal acellular matrix transplant can be used as a simple, safe and reliable method for repairing skin defect after removal of ex-ternal ear neoplasms, and is worth broad clinical applications.

Background: The ADAM33 gene has been identified as a potentially important asthma candidate gene and polymorphisms in this gene have been shown to be associated with asthma and seasonal allergic rhinitis.Objective: To assess whether the ADAM33 polymorphisms are associated with persistent allergic rhinitis (PER) due to house dust mites in a Chinese population.Methods: In a hospital-based case-control study of 515 patients with mite-sensitized PER and 495 healthy controls, we genotyped seven single nucleotide polymorphisms (SNPs) in ADAM33. Serum levels of eosinophil cationic protein, total IgE and allergen-specific IgE against Dermatophagoides pteronyssinus and Dermatophagoides farinae were measured by the ImmunoCAP assays.Results: In the single-locus analysis, three polymorphisms, rs3918392 (F1), rs528557 (S2) and rs2787093, were significantly associated with mite-sensitized PER. SNP S2 was associated with significantly increased risk both of asthmatic and nonasthmatic mite-sensitized PER. In the combined genotypes analysis, individuals with 2-4 risk alleles had a significantly higher risk of mite-sensitized PER (adjusted OR = 1.99, 95% CI = 1.50-2.62) than those with 0-1 risk alleles. Haplotype-based association analysis revealed that the ACAGCCT haplotype might have potential to protect against mite-sensitized PER (adjusted OR = 0.67; 95% CI = 0.49-0.90).Conclusions: Polymorphisms in the ADAM33 gene may contribute to susceptibility of mite-sensitized PER in this Chinese population.