A greedy approach for mutual exclusivity analysis in cancer study.

The main challenge in cancer genomics is to distinguish the driver genes from passenger or neutral genes. Cancer genomes exhibit extensive mutational heterogeneity that no two genomes contain exactly the same somatic mutations. Such mutual exclusivity (ME) of mutations has been observed in cancer data and is associated with functional pathways. Analysis of ME patterns may provide useful clues to driver genes or pathways and may suggest novel understandings of cancer progression. In this article, we consider a probabilistic, generative model of ME, and propose a powerful and greedy algorithm to select the mutual exclusivity gene sets. The greedy method includes a pre-selection procedure and a stepwise forward algorithm which can significantly reduce computation time. Power calculations suggest that the new method is efficient and powerful for one ME set or multiple ME sets with overlapping genes. We illustrate this approach by analysis of the whole-exome sequencing data of cancer types from TCGA.

A forward selection algorithm to identify mutually exclusive alterations in cancer studies.

Mutual exclusivity analyses provide an effective tool to identify driver genes from passenger genes for cancer studies. Various algorithms have been developed for the detection of mutual exclusivity, but controlling false positive and improving accuracy remain challenging. We propose a forward selection algorithm for identification of mutually exclusive gene sets (FSME) in this paper. The method includes an initial search of seed pair of mutually exclusive (ME) genes and subsequently including more genes into the current ME set. Simulations demonstrated that, compared to recently published approaches (i.e., CoMEt, WExT, and MEGSA), FSME could provide higher precision or recall rate to identify ME gene sets, and had superior control of false positive rates. With application to TCGA real data sets for AML, BRCA, and GBM, we confirmed that FSME can be utilized to discover cancer driver genes.

lncRNA LIFR-AS1 suppresses invasion and metastasis of non-small cell lung cancer via the miR-942-5p/ZNF471 axis.

BACKGROUND: MicroRNA 942-5p (miR-942-5p) has been reported to promote migration and invasion in non-small cell lung cancer (NSCLC), but the underlying mechanism is not completely understood. The interplay between long non-coding RNAs (lncRNAs) and miRNAs plays a crucial role in tumor progression. METHODS: In the present study, we performed bioinformatic and biochemical analyses to identify miR-942-5p-interacting lncRNAs. The function and clinical significance of the candidate lncRNA(s) in NSCLC were determined. RESULTS: We identified LIFR-AS1 as a pivotal miR-942-5p-interacting lncRNA. Overexpression of miR-942-5p caused a reduction of LIFR-AS1 in NSCLC cells. LIFR-AS1 showed the ability to sponge miR-942-5p, leading to derepression of ZNF471. Functionally, LIFR-AS1 overexpression inhibited NSCLC cell migration and invasion, whereas LIFR-AS1 silencing yielded an opposite effect. In vivo studies confirmed that LIFR-AS1 overexpression suppressed lung metastasis of NSCLC cells. Rescue experiments demonstrated that enforced expression of miR-942-5p or depletion of ZNF471 restored the migration and invasion capacity of LIFR-AS1-overexpressing cells. Moreover, overexpression of ZNF471 restrained NSCLC cell invasion. Clinically, LIFR-AS1 downregulation was significantly correlated with TNM stage, lymph node metastasis, and reduced overall survival in NSCLC patients. CONCLUSIONS: we provide first evidence for the involvement of the LIFR-AS1/miR-942-5p/ZNF471 axis in NSCLC invasion and metastasis. LIFR-AS1 may represent a novel target for the treatment of NSCLC.

An epidemiological survey of laryngopharyngeal reflux disease at the otorhinolaryngology-head and neck surgery clinics in China.

PURPOSE: Using the Reflux Symptom Index (RSI), this nationwide study aimed to investigate the incidence, diagnostic status, risk factors, and common symptoms of adult laryngopharyngeal reflux disease (LPRD) at otorhinolaryngology-head and neck surgery (OHNS) clinics in China. METHODS: This multicenter cross-sectional survey began at the different institutions ranged from July to October 2017, and the duration was 12 months. A total of 90,440 eligible patients were finally enrolled from 72 medical institutions in China. All these patients completed the questionnaire based on RSI. In this study, LPRD was defined as RSI > 13. RESULTS: There were 9182 with LPRD among the 90,440 eligible participants (10.15%). However, only 1294 had a history of LPRD diagnosis among those with LPRD (14.09%). There were regional differences in the frequency of LPRD (P < 0.001). The proportions of patients with LPRD in males (vs. females), middle- and old-aged patients (vs. young), with current smoking history (vs. no smoking), and current drinking history (vs. no drinking) were significantly higher (all P < 0.001). Middle and old age, current smoking, and drinking history were independent predictors of LPRD (all P < 0.001, OR 1.240, 1.261, and 1.481, respectively). "Sensations of something stuck in throat or a lump in throat", "clearing throat", and "excess throat mucus or postnasal drip" were the most frequent clinical symptoms in patients with LPRD. CONCLUSIONS: LPRD has a high incidence at the OHNS clinics in China. However, the diagnostic status of this disease is not optimistic. Older age, smoking, and drinking history were risk factors for LPRD.

Weighted Transmission Disequilibrium Test for Family Trio Association Design.

BACKGROUND: Family-based design is one of the most popular designs in genetic studies. Transmission disequilibrium test (TDT) for family trio design is optimal only under the additive trait model and may lose power under the other trait models. The TDT-type tests are powerful only when the underlying trait model is correctly specified. Usually, the true trait model is unknown, and the selection of the TDT-type test is problematic. Several methods, which are robust against the mis-specification of the trait model, have been proposed. In this paper, we propose a new efficiency robust procedure for family trio design, namely, the weighted TDT (WTDT) test. METHODS: We combine information of the largest two TDT-type tests by using weights related to the three TDT-type tests and take the weighted sum as the test statistic. RESULTS: Simulation results demonstrate that WTDT has power close to, but much more robust than, the optimal TDT-type test based on a single trait model. WTDT also outperforms other efficiency robust methods in terms of power. Applications to real and simulated data from Genetic Analysis Workshop (GAW15) illustrate the practical application of the WTDT method. CONCLUSION: WTDT is not only efficiency robust to model mis-specifications but also efficiency robust against mis-specifications of risk allele.

Poisson Approximation-Based Score Test for Detecting Association of Rare Variants.

Genome-wide association study (GWAS) has achieved great success in identifying genetic variants, but the nature of GWAS has determined its inherent limitations. Under the common disease rare variants (CDRV) hypothesis, the traditional association analysis methods commonly used in GWAS for common variants do not have enough power for detecting rare variants with a limited sample size. As a solution to this problem, pooling rare variants by their functions provides an efficient way for identifying susceptible genes. Rare variant typically have low frequencies of minor alleles, and the distribution of the total number of minor alleles of the rare variants can be approximated by a Poisson distribution. Based on this fact, we propose a new test method, the Poisson Approximation-based Score Test (PAST), for association analysis of rare variants. Two testing methods, namely, ePAST and mPAST, are proposed based on different strategies of pooling rare variants. Simulation results and application to the CRESCENDO cohort data show that our methods are more powerful than the existing methods.

CircNRIP1 promotes proliferation, migration and phenotypic switch of Ang II-induced HA-VSMCs by increasing CXCL5 mRNA stability via recruiting IGF2BP1.

Circular RNA (circRNA) has been found to be differentially expressed and involved in regulating the processes of human diseases, including thoracic aortic dissection (TAD). However, the role and mechanism of circNRIP1 in the TAD process are still unclear. GEO database was used to screen the differentially expressed circRNA and mRNA in type A TAD patients and age-matched normal donors. Angiotensin II (Ang II)-induced human aortic vascular smooth muscle cells (HA-VSMCs) were used to construct TAD cell models. The expression levels of circNRIP1, NRIP1, CXC-motif chemokine 5 (CXCL5) and IGF2BP1 were detected by quantitative real-time PCR. Cell proliferation and migration were determined by EdU assay, transwell assay and wound healing assay. The protein levels of synthetic phenotype markers, contractile phenotype markers, CXCL5 and IGF2BP1 were tested by western blot analysis. The interaction between IGF2BP1 and circNRIP1/CXCL5 was confirmed by RIP assay, and CXCL5 mRNA stability was assessed by actinomycin D assay. CircNRIP1 was upregulated in TAD patients and Ang II-induced HA-VSMCs. Knockdown of circNRIP1 suppressed Ang II-induced proliferation, migration and phenotypic switch of HA-VSMCs. Also, high expression of CXCL5 was observed in TAD patients, and its knockdown could inhibit Ang II-induced HA-VSMCs proliferation, migration and phenotypic switch. Moreover, CXCL5 overexpression reversed the regulation of circNRIP1 knockdown on Ang II-induced HA-VSMCs functions. Mechanistically, circNRIP1 could competitively bind to IGF2BP1 and subsequently enhance CXCL5 mRNA stability. CircNRIP1 might contribute to TAD progression by promoting CXCL5 mRNA stability via recruiting IGF2BP1.

Correcting for differential genotyping error in genetic association analysis.

Differential genotype error in case-control association studies occurs when cases and controls are genotyped under different conditions. Existence of differential errors can considerably bias the association test, resulting in inflation of type I error and spurious significance. With the availability of high-throughput genotyping technologies such as the SNPchip, null markers that are unlinked with the disease can be used to correct for the bias caused by differential errors. A similar method, known as the genomic control, had been used to correct for population stratification in association studies. In this paper, we show that the same idea can be used to correct for the bias caused by differential errors, under the assumption that the null markers and the candidate marker are subject to the same or similar genotyping error model. The variance inflation is shown to be minor and the bias in the association test is the major source of type I error inflation in the presence of differential errors. Our method centralizes the test statistic by deducting the bias estimated from null markers through a quadratic regression method, which adjusts for the variability of null marker allele frequencies. Simulation results show that the proposed method performs very well in correcting for the type I error inflations.

Symptom clusters and characteristics of cervical cancer patients receiving concurrent chemoradiotherapy: A cross-sectional study.

Background: Cervical cancer patients have a high symptom burden during concurrent chemoradiotherapy (CCRT) and urgently need precise symptom management strategies. Nonetheless, the symptom profile and influencing factors are unclear. Methods: A total of 234 patients with cervical cancer who underwent CCRT in a tertiary care hospital clinical oncology center in Guangxi Zhuang Autonomous Region from March 2022 to March 2023 were included in the study. The general information questionnaire, M.D. Anderson symptom inventory, Fatigue Scale-14, Pittsburgh Sleep Quality Index, and grip strength test were used for the investigation. Symptom clusters were extracted by exploratory factor analysis, and latent profile analysis was performed using Mplus 8.0 software. Multinomial logistic regression was used to explore the factors influencing the potential categories of symptom clusters. Results: Exploratory factor analysis extracted four symptom clusters: a fatigue-related symptom cluster, a gastrointestinal-related symptom cluster, a mood-related symptom cluster, and a physical-related symptom cluster, of which the fatigue-related symptom cluster was more severe and was divided into three potential categories: low fatigue-good muscle fitness type (25.63%), general fatigue-moderate muscle fitness type (68.37%) and high fatigue-low muscle fitness type (6%). Multinomial logistic regression analysis showed that hemoglobin levels, tumor stage, absence of complications, and unemployment were factors influencing the fatigue-related symptom cluster in patients undergoing CCRT for cervical cancer. Conclusions: Cervical cancer patients experience multiple symptom clusters during CCRT. Different characteristics appeared in different clusters. Among them, fatigue-related symptom clusters were more severe and heterogeneous. In clinical practice, we should pay attention to and use high symptom feature predictors, focusing on the core symptoms that play a dominant role, achieving early identification and management, and reducing patients' symptom burden.

[Risk factors of recurrence and canceration for premalignant vocal fold lesions after surgery].

Objective:To analyze the risk factors of recurrence and canceration for premalignant vocal fold lesions after surgery, and to provide a reasonable basis for preoperative evaluation and postoperative follow-up. Methods:This study retrospective analyzed the relationship between clinicopathological factors and clinical outcome（recurrence, canceration, recurrence-free survival, and canceration-free survival） in 148 patients undergoing surgical treatment in Chongqing General Hospital from 2014 to 2017. Results:The five-year overall recurrence rate was 14.86% and the overall recurrence rate was 8.78%. Univariate analysis showed that smoking index, laryngopharyngeal reflux and lesion range were significantly associated with recurrence（P<0.05）, and smoking index and lesion range were significantly associated with canceration（P<0.05）. Multivariate logistic regression analysis showed that smoking index ≥600 and laryngopharyngeal reflux were independent risk factors for recurrence（P<0.05）, and smoking index ≥600 and lesion range ≥1/2 vocal cord were independent risk factors for canceration（P<0.05）. The mean carcinogenesis interval for the postoperative smoking cessation group was significantly longer（P<0.05）. Conclusion:Excessive smoking, laryngopharyngeal reflux and a wide range of lesions may be related to postoperative recurrence or malignant progression of precancerous lesions in the vocal cord, and further large-scale multi-center prospective randomized controlled studies are needed to clarify the effects of the above factors on recurrence and malignant changes in the future.

A Clinical Study to Assess the Efficacy and Safety of MP-AzeFlu Nasal Spray in Comparison to Commercially Available Azelastine Hydrochloride and Fluticasone Propionate Nasal Sprays in Chinese Volunteers with Allergic Rhinitis.

INTRODUCTION: The objective of the present study was to evaluate the efficacy and safety of MP-AzeFlu nasal spray in comparison to commercially available azelastine hydrochloride and fluticasone propionate sprays in Chinese patients with moderate-to-severe allergic rhinitis (AR). METHODS: We conducted a 14-day multicenter, randomized, double-blind, active controlled prospective clinical study in adult and adolescent patients with AR, who had moderate-to-severe symptoms. The primary efficacy endpoint was the change from baseline in combined 12-h reflective total nasal symptom score (rTNSS) (morning [AM] + afternoon [PM]). The safety profile of the study medications was assessed through the recording, reporting, and analysis of baseline medical conditions, adverse events (AEs), vital signs, and focused nasal examination. Three hundred patients per treatment group were randomized, which led to a total sample size estimation of 900 patients. RESULTS: MP-AzeFlu group showed significantly higher symptom reduction for the entire 2-week treatment period in rTNSS when compared with the AZE group (LS mean difference: - 1.96; 95% CI: - 2.53, - 1.39; p < 0.0001), or the FLU group (LS mean difference: - 0.98; 95% CI: - 1.55, - 0.41; p = 0.0007). The results of adult RQLQ showed improvement in QoL in all treatment groups. Except for dysgeusia (bitter taste) that was reported by more patients (13 [4.3%]) in the MP-AzeFlu group, the incidence of all other TEAEs in the MP-AzeFlu group was comparable or even lower than in other treatment groups. CONCLUSIONS: MP-AzeFlu, when administered as one spray per nostril twice daily for 14 days, alleviated AR symptoms in Chinese patients with moderate-to-severe AR. TRIAL REGISTRATION: Clinicaltrials.gov; NCT03599791, Registered June 29, 2018, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03599791 .

The CUSUM statistics of change-point models based on dependent sequences.

In this paper, we investigate the mean change-point models based on associated sequences. Under some weak conditions, we obtain a limit distribution of CUSUM statistic which can be used to judge the mean change-mount δ n is satisfied or dissatisfied n 1 / 2 δ n = o ( 1 ) . We also study the consistency of sample covariances and change-point location statistics. Based on Normality and Lognormality data, some simulations such as empirical sizes, empirical powers and convergence are presented to test our results. As an important application, we use CUSUM statistics to do the mean change-point analysis for a financial series.

Coexistence of Basaloid Squamous Cell Carcinoma and Large Cell Neuroendocrine Carcinoma in the Larynx: A Case Report and Literature Review.

Basaloid squamous cell carcinoma and large cell neuroendocrine carcinoma are not common in head and neck, these tumors rarely occur in the larynx but both have highly aggressive clinical behavior and a high mortality rate. The diagnosis is complicated by these tumors' atypical clinical and pathological features. This case details a coexistence of basaloid squamous cell carcinoma and large cell neuroendocrine carcinoma of a woman in the larynx. The patient underwent endoscopy- and coblation-assisted transoral microsurgery to achieve hyoid horizontal epiglottidectomy and has no recurrence after 12 months of follow-up.

Trace metals in sediment from Chaohu Lake in China: Bioavailability and probabilistic risk assessment.

Bioavailability-based probabilistic risk assessment is an effective approach for risk characterization of trace metals towards aquatic species. However, it has not been routinely applied in lake management due to limited research. In this study, Chaohu Lake (Anhui Province, China) was selected as a case study, and total and bioavailable concentrations of trace metals in surface sediment were investigated using chemical extraction and diffusive gradients in thin films (DGT). Probabilistic risk assessment (PRA) was performed using Monte Carlo simulation. In addition, the species sensitivity distribution (SSD) was constructed using acute toxicity data to model the sensitivity of aquatic species towards metals. Three evaluation methods, namely, toxic units based on total content, modified potential ecological risk index (RI) based on chemical fractionation and DGT-SSD coupled PRA, were implemented and compared. Results showed that trace metals, especially Cd, were significantly affected by anthropogenic activities. Chemical fractionation analysis revealed that the majority of Cd was readily available to aquatic organisms, while Cr was stable under normal conditions. Toxic units based on the total content demonstrated that metals in sediment were at 91.6 % low and 8.4 % medium toxicity levels, while the modified RI based on chemical fractionation found toxicity levels of 84.1 % low and 15.9 % medium. Furthermore, the combined toxicity calculated from DGT-SSD coupled PRA showed that trace metals in sediment had a 24.8 % probability of toxic effects towards aquatic organisms, with Cu, Zn, Cd, and Ni being the main contributors. Comparative analysis suggested that the DGT-SSD coupled PRA could provide a more objective and scientific evidence for lake management with regard to metal contamination.

Factors affecting cadmium accumulation in the soil profiles in an urban agricultural area.

Soil Cd pollution is a serious environmental issue associated with human activities. However, the factors determining exogenous Cd dynamics in the soil profile in a complex environment are not well understood. Based on regional observations from 169 soil profiles across the Chengdu Plain, this study explored the key factors controlling Cd accumulation in the soil profile under actual field conditions. Results showed that total soil Cd contents decreased from 0.377 to 0.196 mg kg-1 with increasing soil depth. The effects of phosphate fertilizer rates, road density and precipitation on the difference in total soil Cd content were only observed in topsoil, while agricultural land-use type and topography had no impact. In contrast, significant differences in the total soil Cd content among different parent material types were found in the 0-20, 40-60 and 60-100 cm soil depths. One sample t-tests showed that significant Cd accumulation occurred in the whole soil profile in soils formed from Q4 (Quaternary Holocene) grey alluvium, while soils formed from Q3 (Quaternary Pleistocene) old alluvium and Q4 grey-brown alluvium showed significant Cd accumulation only in the 0-40 cm soil layers. In the topsoil, acid soluble Cd accounted for the largest proportion of the total Cd in soils formed from Q4 grey alluvium, reducible Cd was the main fraction in soils formed from Q4 grey-brown alluvium, while reducible Cd and residual Cd contributed the largest proportion of the total soil Cd in soils formed from Q3 old alluvium. The above results indicated that parent material was the decisive factor determining the magnitudes and depths of exogenous Cd accumulation in the soil profile due to its impacts on the Cd fraction distributions. These findings suggested that the parent material-induced Cd fraction distributions and accumulation should be considered for effectively exploring targeted remediation strategies for Cd pollution.

Divergent responses of cropland soil organic carbon to warming across the Sichuan Basin of China.

Cropland soils are considered to have the potential to sequester carbon (C). Warming can increase soil organic C (SOC) by enhancing primary production, but it can also cause carbon release from soils. However, the role of warming in governing cropland SOC dynamics over broad geographic scales remains poorly understood. Using over 4000 soil samples collected in the 1980s and 2010s across the Sichuan Basin of China, this study assessed the warming-induced cropland SOC change and the correlations with precipitation, cropland type and soil type. Results showed mean SOC content increased from 11.10 to 13.85 g C kg-1. Larger SOC increments were observed under drier conditions (precipitation < 1050 mm, dryland and paddy-dryland rotation cropland), which were 1.67-2.23 times higher than under wetter conditions (precipitation > 1050 mm and paddy fields). Despite the significant associations of SOC increment with crop productivity, precipitation, fertilization, cropland type and soil type, warming also acted as one of major contributors to cropland SOC change. The SOC increment changed parabolically with the rise in temperature increase rate under relatively drier conditions, while temperature increase had no impact on cropland SOC increment under wetter conditions. Meanwhile, the patterns of the parabolical relationship varied with soil types in drylands, where the threshold of temperature increase rate, the point at which the SOC increment switched from increasing to decreasing with warming, was lower for clayey soils (Ali-Perudic Argosols) than for sandy soils (Purpli-Udic Cambosols). These results illustrate divergent responses of cropland SOC to warming under different environments, which were contingent on water conditions and soil types. Our findings emphasize the importance of formulating appropriate field water management for sustainable C sequestration and the necessity of incorporating environment-specific mechanisms in Earth system models for better understanding of the soil C-climate feedback in complex environments.

Awareness about laryngopharyngeal reflux disease among Chinese otolaryngologists: a nationwide survey.

OBJECTIVES: This study aimed to investigate the status of the current knowledge about laryngopharyngeal reflux disease (LPRD) among Chinese otolaryngologists. DESIGN: Multi-centre cross-sectional survey. SETTING: 220 medical centres in different regions of China. PARTICIPANTS: A total of 2254 otolaryngologists from 220 medical centres in China who were successfully on-site surveyed between November 2019 and December 2020. MAIN OUTCOME MEASURES: Awareness about LPRD included knowledge about risk factors, symptoms, laryngoscope signs, related diseases, current diagnostic methods and treatments. RESULTS: The percentage of participants who had heard of LPRD was 96.4%, with academic conferences as the most common source of information (73.3%). The most commonly known risk factor, symptom, laryngoscope sign, related disease, diagnostic method and treatment were alcohol consumption (44.0%), pharyngeal foreign body sensation (66.9%), hyperaemia (52.4%), pharyngolaryngitis (54.8%), pH monitoring (47.6%) and medication (82.1%), respectively. Only 28.3% of all participants knew that 24 h pH or multichannel intraluminal impedance pH monitoring was the most accurate diagnostic test. As many as 73.1% of all participants knew that proton pump inhibitors were the first-line treatment drugs. An analysis of the overall status of awareness using a scoring system suggested that otolaryngologists were better aware owing to more access, working at 3A hospitals, and postgraduate or above educational background (all p<0.05). CONCLUSION: Although the majority of Chinese otolaryngologists had heard of LPRD, their overall awareness about the disease was not encouraging. More efforts are needed to increase the knowledge about LPRD among this group of physicians. TRIAL REGISTRATION NUMBER: ChiCTR1900025581.

CHFR­mediated epithelial­to­mesenchymal transition promotes metastasis in human breast cancer cells.

Checkpoint with FHA and RING finger domains (CHFR) is a G2 phase/mitosis checkpoint. Several studies have reported that CHFR is downregulated in multiple cancer types and serves a tumor suppressor role. However, the biological function of CHFR in breast cancer (BRCA), particularly regarding metastasis, are yet to be elucidated. In the present study, it was revealed that CHFR is upregulated in BRCA compared with normal tissues, according to The Cancer Genome Atlas database. In addition, subgroup analysis of BRCA revealed that CHFR was upregulated in both human epidermal growth factor receptor 2­positive and triple­negative BRCA. Meanwhile, patients with high expression levels of CHFR exhibited poorer overall survival rates. Furthermore, the present data revealed that the overexpression of CHFR in SKBR3 cells resulted in enhanced cell migration and invasiveness, and also significantly upregulated mesenchymal markers, such as N­cadherin, vimentin, transcription factor Slug and tight junction protein claudin­1. Furthermore, knockdown of CHFR in MDA­MB­231 cells significantly inhibited cell migration and invasiveness, and also downregulated mesenchymal markers, such as N­cadherin, vimentin and tight junction protein claudin­1. In conclusion, the current results indicated that CHFR expression was associated with cell metastasis in BRCA by mediating epithelial­to­mesenchymal transition.

[Analysis of allergen distribution and clinical characteristics of autumn allergic rhinitis in Changchun and surrounding areas].

Objective:To investigate the allergen characteristics, allergen distribution and clinical symptoms of autumn allergic rhinitis in Changchun and surrounding areas. Methods:The allergen test results of 1080 allergic rhinitis（AR） suspected patients from Changchun and surrounding areas were collected, from August to October 2019 and August to October 2020 in the Department of Otorhinolaryngology Head and Neck Surgery, the Second Hospital of Jilin University. The positive rates of major allergens and their differences in gender, age, different years and clinical symptom were compared and analyzed. Results:①Among the 1080 suspected AR patients, 804 patients（74.44%） had positive allergens. ②The top 3 allergens of autumn AR in Changchun and surrounding areas were Artemisia（36.20%）, Dwarf ragweed（33.24%） and Candida/Penicillium notarum/Cladosporium/Alternaria/Aspergillus niger（19.81%）. The positive rates of Artemisia and Dwarf ragweed were higher in men than in women（P<0.05）. ③Artemisia was the major allergen of autumn AR in juvenile group, youth group and middle-aged group. ④The positive rate of two or more allergens was 2.39 times that of single allergen. ⑤Patients with positive autumn pollen allergens had more severe symptoms of nasal congestion, red eye/eye itching and epiphora than those in other groups. Conclusion:Seasonal AR had typical clinical symptom characteristics. Major allergens in autumn AR in Changchun and surrounding areas are autumn pollen allergens（Artemisia, Dwarf ragweed, Humulus）. The distribution of those allergens was different in gender, age, and different years.

[Analysis of Spatial Distribution and Influencing Factors of Nitrogen and Phosphorus Fertilizer Application Intensity in Chengdu Plain].

The spatial distribution of fertilization intensity and its influencing factors are significant for the accurate management of fertilization and pollution prevention and control. Previous studies are mostly limited to the discussion of human factors that influences the spatial distribution of fertilization intensity while ignoring natural geographical factors. Based on the chemical fertilizer survey data collected from 23492 sites in Chengdu Plain and combined with Geostatistics analysis and Geographic Information System (GIS) technology, the spatial distribution characteristics and influencing factors of average nitrogen and phosphorus fertilizer application intensity from 2010 to 2015 in this region were explored. The results show that:① the average annual application intensity of nitrogen and phosphorus fertilizer in the study area from 2010 to 2015 is generally in the low and medium risk intensity of 120-360 kg·hm-2 and 60-180 kg·hm-2. The high risk intensity is mainly distributed in the grain (fruit) and vegetable growing areas such as Pidu, Pengzhou, Shifang, Longquanyi and Jintang, while the relatively low value areas are mostly distributed in the south and northeast. ② the nugget coefficients of nitrogen and phosphorus fertilizer application intensities are 66.17% and 41.60%. Their spatial distribution is determined by structural and random factors, showing a moderate spatial autocorrelation. ③ both human and natural factors have significant effects on the application intensity of nitrogen and phosphorus fertilizer. The crop type (fine classification) can explain the spatial variation of nitrogen fertilizer and phosphorus fertilizer respectively by 12.90% and 25.10%, which is the main controlling factor affecting the spatial distribution of nitrogen and phosphorus application intensity; the importance of soil parent material is second only to the planting crop type, and the independent explanation ability of phosphorus application intensity is about 3.6 times higher than that of nitrogen application intensity. When the type of planting crop plays a decisive role, the soil parent material still deeply restricts and affects the spatial distribution of nitrogen and phosphorus fertilizer application intensity in the study area. Therefore, the comprehensive effects of planting crop types and soil parent materials should be considered in fertilization management and environmental risk analysis, and the effects of soil parent material should also be taken into account in the application of phosphate fertilizer.