Objective:To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) through unsupervised clustering analysis.Methods:The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected, including 112 males and 43 females, aged from 7 to 87 years. Unsupervised clustering analysis was conducted using various clinical parameters, including age, gender, smoking and drinking history, local eosinophil (EOS) and neutrophil (NEU) counts, comorbid allergic rhinitis (AR), comorbid asthma, recurrence status, serum-specific IgE, total IgE, cytokine levels, peripheral blood EOS count and percentage, Lund-Mackay CT score, the ratio of CT scores for the maxillary sinus and ethmoid sinus (E/M ratio), visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and other common clinical indicators to elucidate the clinical characteristics of each cluster. Statistical analysis was conducted using GraphPad Prism 9.5 software.Results:Hierarchical clustering analysis identified four main clusters (Cluster A1-A4), showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels, nasal polyps accompanied by allergies and asthma, a subtype of nasal polyps with high recurrence rates dominated by neutrophils, and nasal polyps with high eosinophil levels. Further subset clustering revealed two clusters of mild polyps (Cluster B1-B2) featuring high cytokine expression and comorbid AR; and two clusters of severe polyps (Cluster B3-B4) presented with severe symptoms, high Lund-Mackay CT score, and high Lund-Kennedy endoscopic score. Variations between Cluster B3 and B4 included symptom complexity, the degree of eosinophil infiltration, and the probability of comorbid asthma. Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps. The comprehensive analysis of multi-index correlations demonstrated valuable insights into the relationships between common clinical parameters of nasal polyps, providing valuable information for a deeper understanding of the pathogenesis of CRSwNP.Conclusion:The clustering analysis in this study categorizes CRSwNP patients into different clusters based on clinical features and disease outcomes, providing a new perspective for more precise clinical treatment strategies.

Objective To investigate the expressions of glycolysis-related factors and changes in Notch1 signaling in endometrial tissues of adenomyosis(AM)and Ishikawa cells to explore the pathogenesis of AM.Methods Eutopic endometrial tissues were collected from 8 patients with AM and 8 patients with uterine fibroids matched for clinical characteristics(control group).The expressions of Notch1 signaling proteins and glycolysis-related factors in the collected tissues were detected using qRT-PCR and Western blotting,and the levels of glucose and lactic acid were determined.An Ishikawa cell model with lentivirus-mediated stable Notch1 overexpression was established for assessing cell survival rate with CCK-8 assay,cell migration and invasion abilities with Transwell migration and invasion assays,and glycolytic capacity by determining the extracellular acidification rate.Results Compared with those in the control group,the endometrial tissues in AM group showed significantly increased expression level of carbohydrate antigen 125(CA125),increased mRNA expression levels of Notch1,HK2 and PDHA and protein expressions of Notch1,GLUT1,HK2,PKM and PDHA,lowered glucose level and increased lactate level.The Ishikawa cell models with stable Notch1 overexpression exhibited significantly increased cell survival rate with attenuated cell migration and invasion abilities and decreased glycolysis capacity and reserve.Conclusion The Notch1 signaling pathway participates in the pathogenesis of AM possibly by regulating the proliferation,migration,invasion and glycolysis of endometrial cells.

Objective To investigate the expressions of glycolysis-related factors and changes in Notch1 signaling in endometrial tissues of adenomyosis(AM)and Ishikawa cells to explore the pathogenesis of AM.Methods Eutopic endometrial tissues were collected from 8 patients with AM and 8 patients with uterine fibroids matched for clinical characteristics(control group).The expressions of Notch1 signaling proteins and glycolysis-related factors in the collected tissues were detected using qRT-PCR and Western blotting,and the levels of glucose and lactic acid were determined.An Ishikawa cell model with lentivirus-mediated stable Notch1 overexpression was established for assessing cell survival rate with CCK-8 assay,cell migration and invasion abilities with Transwell migration and invasion assays,and glycolytic capacity by determining the extracellular acidification rate.Results Compared with those in the control group,the endometrial tissues in AM group showed significantly increased expression level of carbohydrate antigen 125(CA125),increased mRNA expression levels of Notch1,HK2 and PDHA and protein expressions of Notch1,GLUT1,HK2,PKM and PDHA,lowered glucose level and increased lactate level.The Ishikawa cell models with stable Notch1 overexpression exhibited significantly increased cell survival rate with attenuated cell migration and invasion abilities and decreased glycolysis capacity and reserve.Conclusion The Notch1 signaling pathway participates in the pathogenesis of AM possibly by regulating the proliferation,migration,invasion and glycolysis of endometrial cells.

OBJECTIVE To investigate the effect and mechanism of α7 nicotinic acetylcholine receptor （α7nAChR） agonists PNU-282987 on cognitive function in temporal lobe epilepsy （TLE） model rats. METHODS Sixty rats were randomly divided into control group， model group， PNU-282987 group （3 mg/kg） and methyllycaconitine （MLA）+PNU-282987 group （6 mg/kg MLA+3 mg/kg PNU-282987）， with 15 rats in each group. Except for control group， the TLE model was established in the other groups. After the model was successfully established， each group was given relevant medicine or normal saline intraperitoneally， once a day， for two consecutive weeks. The epilepsy attack of rats was observed and scored， and the duration of seizures was recorded； the cognitive function of rats was detected； pathological morphology of neurons in CA1 region was observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in the hippocampus were detected； the positive expressions of ionized calcium-binding adapter molecule-1 （IBA-1）， α7nAChR， nuclear factor-κB （NF-κB） p65， p-NF-κB p65 in the hippocampus were detected. RESULTS Compared with model group， the score and duration of seizures， the number of IBA-1 positive cells， the levels of TNF- α， IL-6 and IL-1β， the expressions of NF- κB p65 and p-NF- κB p65 protein decreased significantly in the hippocampus （P＜0.05）； the escape latency time was shortened significantly （P＜0.05）， the time spent in the original platform quadrant and times of crossing the platform increased significantly （P＜0.05）； neuronal damage in the CA1 region of the hippocampus was significantly reduced； the expression of α7nAChR protein increased significantly in hippocampus （P＜0.05）. Compared with PNU-282987 group， the above indexes of rats in MLA+PNU-282987 group were reversed significantly （P＜0.05）. CONCLUSIONS PNU-282987 could improve cognitive dysfunction in TLE model rats， and its mechanism may be associated with inhibiting microglia-mediated inflammatory response through α7nAChR/NF- κB signaling pathway， thus reducing hippocampal neuronal damage.

Objective:To compare the difference on the positive detection rate of the main aeroallergens and food allergens specific IgE measured with the systems between fluorescence enzyme immunoassay(FEIA, referred to as ImmunoCAP system)and western blot(referred to as Allergy Screen system), in order to provide a basis for the rational application of methods and interpretation of the test results.Methods:The clinical information and sIgE test results data were collected from a total of 458 cases of allergic diseases from October 2017 to April 2019 in the outpatient clinic of Allergy Department in Beijing Children′s Hospital.All of the 458 cases were detected for a panel of common aeroallergens and food allergens sIgE level in their serum with the Allergy Screen system.Simultaneously, the above 141 cases were detected main aeroallergen and food allergen sIgE with ImmunoCAP system, while 303 cases only for aeroallergens and 14 cases only for food allergens.All of the cases were divided into three different phenotype groups according to the main target organ and diagnosis such as airway allergic disease group( N=293), skin allergic disease group( N=14)and multi-system allergic disease group( N=151). Meanwhile, three different age groups were referred to as <3 years old group( N=97), 3 to 6 years old group(3 years and 6 years included)( N=186)and >6 years old group( N=175). The same kinds of the allergens included in the two systems were house dust mite(HDM), cat dander, dog dander, egg white, milk, crab, shrimp, therefore data of sIgE to those seven allergens were compared. Results:In all the enrolled cases, the positive detection rate of HDM, egg white and milk sIgE detected by ImmunoCAP system were significantly higher than those by Allergy Screen system(30.6%, 36.1% and 43.2% vs 21.2%, 21.3% and 21.3%). Among the disease groups, the positive detection rate of HDM sIgE detected by ImmunoCAP system was significantly higher in the airway allergic disease group and multi-system allergic disease group than those by Allergy Screen system, respectively(33.7% and 24.6% vs 23.4% and 16.2%). The positive detection rate of egg white and milk sIgE detected by ImmunoCAP system in the multi-system allergic disease group was significantly higher than those by Allergy Screen system, respectively(47.6% and 47.6% vs 26.2% and 25.2%). There was no significant difference in the positive detection rate of cat dander, dog dander, crab and shrimp sIgE among the disease groups.The positive detection rate of HDM sIgE detected by ImmunoCAP system in all of the age groups were significantly higher than those by Allergy Screen system, respectively(14.9%, 26.9% and 42.3% vs 5.7%, 17.6% and 32.6%). The positive detection rate of cat dander sIgE detected by ImmunoCAP system in <3 years old group was significantly lower than that by Allergy Screen system(6.9% vs 16.1%). The positive detection rate of egg white sIgE detected by ImmunoCAP system in the <3 years old group and the 3 to 6 years old group were higher than those by Allergy Screen system, respectively(47.1% and 33.3% vs 32.4% and 15.0%). The difference in the positive detection rate of milk sIgE detected by these two methods in the <3 years old group and the 3 to 6 years old group was similar to the egg white.Conclusion:According to the analysis of seven kinds of major aeroallergen and food allergen sIgE results, there are differences between the two methods to detect HDM, cat dander, egg white and milk sIgE.It depends on the type of allergic disease and age.The positive detection rates of dog dander, crab, and shrimp sIgE detected by the two methods are consistent.In clinical application, comprehensive analysis should be made, testing methods should be selected rationally, and the results should be interpreted scientifically.

Objective: To analyze the dynamic changes in the expression and function of peripheral type Ⅱ innate lymphoid cell (ILC2) subpopulation and the activity of signal transducers and activators of transcription (STAT6) in children with hay fever during pollen season. Methods: A total of 10 patients with hay fever, 10 patients with house dust mite (HDM)-sensitized asthma and 12 healthy controls (HC) were enrolled in this study. Changes in peripheral ILC2 and the intracellular expression of Th2-related cytokines were detected by flow cytometry during and outside the pollen season. Peripheral Lin^- cell population was isolated from each group and cultured with the presence of IL-25 or IL-33 for 7 d. The concentrations of IL-5 and IL-13 in culture supernatants were measured by ELISA. Expression of phospho-STAT6 at protein level was quantified by Western blot. Results: Within the pollen season, the percentage of peripheral ILC2 cells was significantly higher in children with hay fever [(23.09±7.86)%] than in children with HDM-sensitized asthma [(6.84±3.85)%, P<0.05] and healthy children[(1.69±0.87)%, P<0.05]. In the non-pollen season, the peripheral ILC2 cells in children with hay fever presented a decreasing trend [(11.30±2.45)%], but was still higher than that in HDM-sensitized asthmatics [(3.76±1.96)%, P<0.05] and HC [(1.32±0.91)%, P<0.05] at the same time point. Moreover, peripheral IL-13⁺ ILC2 cells in children with hay fever [(6.94±3.16)% vs(4.17±1.98)%, P<0.05] and in HDM-sensitized asthmatics [(1.89±0.70)% vs(1.44±0.55)%, P<0.05] during the pollen season were significantly higher than those in the non-pollen season. After the in vitro stimulation with IL25 or IL-33, the levels of IL-5 and IL-13 in culture supernatants were both increased in children with hay fever and HDM-sensitized asthmatics, and a synergistic action was observed when IL25 and IL-33 were used in combination. Meanwhile, the protein level of phospho-STAT4 in Lin^- cells was significantly up-regulated in the hay fever group after stimulation with IL25 and IL-33. Conclusions During the pollen season, the abnormal number and function of ILC2 subpopulation in children with hay fever might be another cause of the occurrence of clinical symptoms in a short period of time or acute exacerbation.

Objective:To construct the cardiac rehabilitation program for patients after percutaneous coronary intervention (PCI) from the perspective of self-determination theory (SDT) , and explore its effects.Methods:Totally 90 patients with coronary heart disease (CHD) who received PCI in the First Affiliated Hospital of Zhengzhou University between July and October 2018 were selected by convenient sampling. A total of 45 patients undergoing PCI between July and August 2018 were included in the control group, while 45 patients receiving PCI between September and October 2018 were included into the observation group. Patients in the control group received routine care, while patients in the observation group were treated with the cardiac rehabilitation program for patients after PCI from the perspective of SDT on the basis of routine care. Morisky Medication Adherence Scale (MMAS) and Coronary Heart Disease Self-Management Behavior Scale (CSMS) were used to evaluate the effect of intervention.Results:Totally 41 valid data were collected from the control group, while 43 valid data were collected from the observation group. After intervention, the medication adherence score of the observation group was higher than that of the control group, and the difference was statistically significant ( P<0.05) ; the CSMS scores of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The cardiac rehabilitation program for patients after PCI from the perspective of SDT can improve the medication adherence and self-management behavior of patients after PCI.

Objective To evaluate the effect of family doctor contracted service system in Shenzhen and explore the influencing factors for families to contract their family doctors. Methods A total of 480 residents were selected from 12 first-class community medical rehabilitation centers in Luohu, Futian and Nanshan districts of Shenzhen. The contents of the survey included the contracting status between the contracted and non-contracted residents, the utilization of four basic public health services, and the difference of satisfaction with community medical rehabilitation centers.Meanwhile, logistic regression was used to explore the important influencing factors of the contracted family doctors. Results The overall contracting rate of residents was 51.9% (248/478), and the lowest contracting rate was 23.1% (27/117) (P<0.05), found among patients under 40 years old.The utilization rate of contracted residents for growth and development examination, maternal health care as well as guidance of chronic disease prevention and treatment was higher than that of non-contracted residents ( P <0.05 ). fees and medical environment, service attitude,medical fees was higher than that of non-contracted residents(P<0.05).The satisfaction for convenience in medical environment, service attitude,medical fees and access to medical service was higher than that of non-contracted residents(P<0.05).The results of binary logistic regression analysis showed that age, education level, occupation ( retirement ) and chronic diseases were important factors affecting the signing of contracts.Conclusions The family doctors tend to be embraced by residents better than before. Family doctors contracted service system is conducive to improving the utilization rate of basic health services, acceptance rate of health services and satisfaction of residents. At the same time, the young population at large requires greater efforts before they can embrace the family doctor system.

Objective To analyze the effects on control rate and the outcome of pulmonary function in children with bronchial asthma (abbreviated asthma) who were received the two years standardized treatment and management,and to explore the sensitive parameters of control effects in children with asthma.Methods Using the retrospective analysis,asthmatic children were selected from January 2014 to January 2015 in Beijing Children's Hospital,allergy and asthma outpatient clinics.All the patients were received asthma control treatment and management according to GINA guidelines (2014 version).They were assessed on asthma control level at one year and two years follow up visits respectively and their pulmonary function were evaluated at the same time.According to response status to therapy and adjustment of step up and down,children were divided into two groups,the stable control group and the difficult to control group.The parameters of sex,age,asthma,combined with rhinitis,allergen sensitization and pulmonary function were compared between the two groups.Results A total of 149 patients were enrolled in this study.The treatment levels were 20.2％,67.1％ and 12.7％ respectively at grade 2,grade 3 and ≥ 4 grade.After Treatment management for one year and two years,the asthma control level were assessed as good control was 81.8％ and 83.2％ respectively (P ＜ 0.05) Each parameter of pulmonary function excepted FEV1/FVC at the one year visit point after treatment and management was significantly higher than that at enrollment (P ＜ 0.05).After two years of treatment and management,PEF％ pred and FEF25 ％ pred was higher than that at first follow up visit (P ＜ 0.05).There were no significantly different on the distribution of sex,age,course of asthma,allergic rhinitis,allergen sensitization and initial control treatment level between the stable control and the difficult to control groups.Asthma control stability status assessment and analysis at the one year follow up visits showed that PEF％ pred was significantly higher in the group of stable control than that in group of difficult to control (97.3 ± 14.3 vs 93.1 ± 15.1,P ＜ 0.05).Asthma control stability starus assessment and analysis at two years follow up visits showed that the positive rate of allergen sensitization was significantly lower in the group of stable control than that in group of difficult to control (P ＜ 0.05),while FEV1/FVC was significantly higher in the group of stable control than that in group of difficult to control (81.0 ± 9.47vs77.4 ± 8.95,P＜0.05).Conclusion School age children asthma control level were improved with longer time regular treatment and management as well as the pulmonary function improvement.Multiple allergenic sensitization and lower PEF％ pred value and FEV1/FVC are suggestive parameters for children with difficult to control asthma.

Objective To investigate the levels and significance of Th17 cells and regulatory T cells (Treg) in peripheral blood of children with allergic rhinitis during pollen and non-pollen seasons.Methods Thirteen children with hay fever, 10 children with house dust mite(HDM)-allergic asthma and 10 healthy children were recruited into this study.Percentages of Th17 and Treg cells were detected by flow cytometry.Levels of IL-17, IL-10 and TGF-β in cell culture supernatants were measured by ELISA.Results (1) The percentages of Th17 cells in children with allergic rhinitis [(3.4±2.4)%] were significantly higher than those in HDM-allergic asthmatics [(2.1±1.6)%] and those in healthy children [(0.5±0.3)%] during pollen season (both P<0.05).The levels of Treg cells in allergic rhinitis group [(2.1±1.3)%] and in HDM-allergic asthma group [(3.6±1.9)%] were significantly lower than those in healthy control group [(5.5±2.8)%] (both P<0.05).The levels of Th17 cells [(3.0±1.9)% vs (3.4±2.4)%, P<0.05] and ratios of Th17/Treg cells [(1.4±1.0)% vs (1.7±1.5)%, P<0.05] in children with allergic rhinitis were significantly decreased during non-pollen season as compared with those during pollen season, but the levels of Treg cells were up-regulated [(2.4±1.6)% vs (2.1±1.3)%, P<0.05].(2) Correlation analysis revealed that the ratios of Th17/Treg cells were positively correlated with the concentrations of FeNO (fractional concentration of exhaled NO) (r=0.321, P<0.05) and the counts of circulating eosinophils (r=0.198, P<0.05) in children with allergic rhinitis during pollen season.Conclusion The imbalanced Th17 and Treg cells in children with allergic rhinitis during pollen season might play a vital role in the regulation of allergic airway inflammation.