m6A mRNA methylation-mediated MAPK signaling modulates the nasal mucosa inflammatory response in allergic rhinitis.

Background: Allergic rhinitis (AR) is a complex disease in which gene-environment interactions contribute to its pathogenesis. Epigenetic modifications, such as N6-methyladenosine (m6A) modification of mRNA, play important roles in regulating gene expression in multiple physiological and pathological processes. However, the function of m6A modification in AR and the inflammatory response is poorly understood. Methods: We used the ovalbumin (OVA) and aluminum hydroxide to induce an AR mouse model. Nasal symptoms, histopathology, and serum cytokines were examined. We performed combined m6A and RNA sequencing to analyze changes in m6A modification profiles. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and methylated RNA immunoprecipitation sequencing qPCR (MeRIP-qPCR) were used to verify differential methylation of mRNAs and the m6A methylation level. Knockdown or inhibition of Alkbh5 in nasal mucosa of mice was mediated by lentiviral infection or IOX1 treatment. Results: We showed that m6A was enriched in a group of genes involved in MAPK signaling pathway. Moreover, we identified a MAPK pathway involving Map3k8, Erk2, and Nfκb1 that may play a role in the disrupted inflammatory response associated with nasal inflammation. The m6A eraser, Alkbh5, was highly expressed in the nasal mucosa of AR model mice. Furthermore, knockdown of Alkbh5 expression by lentiviral infection resulted in high MAPK pathway activity and a significant nasal mucosa inflammatory response. Our findings indicate that ALKBH5-mediated m6A dysregulation likely contributes to a nasal inflammatory response via the MAPK pathway. Conclusion: Together, our data show that m6A dysregulation mediated by ALKBH5, is likely to contribute to inflammation of the nasal mucosa via the MAPK signaling pathway, suggesting that ALKBH5 is a potential biomarker for AR treatment.

Safety of Tonsillectomy and/or Adenoidectomy in Pediatric Patients with Prolonged Activated Partial Thromboplastin Time and Factor XII Deficiency.

Objective: To evaluate the safety and feasibility of tonsillectomy and/or adenoidectomy (T&A) in pediatric patients with prolonged activated partial thromboplastin time (APTT) and coagulation factor deficiency. Methods: A prospective study was admitted to the children undergoing T&A at our institution between October 2019 and January 2020, specifically focusing on preoperative coagulation function. Within this group, we identified 5 patients exhibiting prolonged APTT and coagulation factor deficiencies, constituting the experimental group, and 10 patients matched by gender and age with normal blood coagulation function were selected as the control group. Comparative analyses between the two groups were conducted, focusing on surgical duration, intraoperative bleeding volume, duration of hospital stay, and postoperative complications such as active bleeding across the groups. At the six-month postoperative mark, a reassessment of coagulation functions and factor assays was conducted within the experimental group. Results: No statistically significant differences were discovered in terms of surgical duration or bleeding volume when comparing the experimental subgroups with their respective control counterparts. Furthermore, there were no incidences of postoperative active bleeding observed in any of the groups. Notably, postoperative APTT values (32.7 ± 1.7s) exhibited a significant disparity compared to preoperative levels (43.7 ± 1.8s, p < 0.01). Coagulation factors demonstrated normalization, evidenced by a significant difference in postoperative Factor XII levels (40.2 ± 5.4%) compared to preoperative levels (63.1 ± 5.9%, p < 0.01). Conclusion: Prolonged APTT with FXII factor deficiency does not show a significant bleeding tendency and is not a contraindication for T&A surgery. Post T&A surgery, children with abnormal coagulation function and deficient clotting factors show significant improvement compared to pre-surgery. It is important to consider that chronic inflammation in adenoids and tonsils may contribute to the prolongation of APTT and the manifestation of Factor XII deficiency.

Transcriptomics Reveals the Mechanism of Purpureocillium lilacinum GZAC18-2JMP in Degrading Keratin Material.

Microbial degradation of keratin is characterized by its inherent safety, remarkable efficiency, and the production of copious degradation products. All these attributes contribute to the effective management of waste materials at high value-added and in a sustainable manner. Microbial degradation of keratin materials remains unclear, however, with variations observed in the degradation genes and pathways among different microorganisms. In this study, we sequenced the transcriptome of Purpureocillium lilacinum GZAC18-2JMP mycelia on control medium and the medium containing 1% feather powder, analyzed the differentially expressed genes, and revealed the degradation mechanism of chicken feathers by P. lilacinum GZAC18-2JMP. The results showed that the chicken feather degradation rate of P. lilacinum GZAC18-2JMP reached 64% after 216 h of incubation in the fermentation medium, reaching a peak value of 148.9 µg·mL-1 at 192 h, and the keratinase enzyme activity reached a peak value of 211 U·mL-1 at 168 h, which revealed that P. lilacinum GZAC18-2JMP had a better keratin degradation effect. A total of 1001 differentially expressed genes (DEGs) were identified from the transcriptome database, including 475 upregulated genes and 577 downregulated genes. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of the DEGs revealed that the metabolic pathways related to keratin degradation were mainly sulfur metabolism, ABC transporters, and amino acid metabolism. Therefore, the results of this study provide an opportunity to gain further insight into keratin degradation and promote the biotransformation of feather wastes.

Combined analysis of the transcriptome and proteome of Eucommia ulmoides Oliv. (Duzhong) in response to Fusarium oxysporum.

Eucommia ulmoides Oliv. (Duzhong), a valued traditional herbal medicine in China, is rich in antibacterial proteins and is effective against a variety of plant pathogens. Fusarium oxysporum is a pathogenic fungus that infects plant roots, resulting in the death of the plant. In this study, transcriptomic and proteomic analyses were used to explore the molecular mechanism of E. ulmoides counteracts F. oxysporum infection. Transcriptomic analysis at 24, 48, 72, and 96 h after inoculation identified 17, 591, 1,205, and 625 differentially expressed genes (DEGs), while proteomics identified were 66, 138, 148, 234 differentially expressed proteins (DEPs). Meanwhile, GO and KEGG enrichment analyses of the DEGs and DEPs showed that they were mainly associated with endoplasmic reticulum (ER), fructose and mannose metabolism, protein processing in the ER, type II diabetes mellitus, the ribosome, antigen processing and presentation, and the phagosome. In addition, proteome and transcriptome association analysis and RT-qPCR showed that the response of E. ulmoides to F. oxysporum was likely related to the unfolded protein response (UPR) of the ER pathway. In conclusion, our study provided a theoretical basis for the control of F. oxysporum.

[Presentation and management of allergic fungal rhinosinusitis in children].

Objective:To assess the presentation of allergic fungal rhinosinusitis（AFRS） in children and the role of long-term comprehensive therapy of endoscopic surgery combined with drug therapy. Methods:The 3 children with AFRS were routinely examined by nasal endoscopy, CT scan, MRI scan and allergen detection before surgery, and mycological and histomathological examination were performed on the secretions in the sinus and the mucosa of the affected sinuses. All the 3 patients underwent endoscopic surgery, preoperative and postoperative treatment with oral and nasal corticosteroid, nasal irrigation, and individualized anti-allergy therapy and immunotherapy. The patients were followed up for 3 to 12 months. Results:All 3 children had nasal polyps and headache, and 2 children had exophthalmos and facial asymmetry. There were typical CT and MRI findings on imaging. Serum total IgE were all elevated, and 2 cases were positive for fungal SIgE. All 3 children underwent endoscopic surgery. Fungal hyphae and spores were found in 1 child, and other fungi tests were positive in another 2 children. Postoperative facial asymmetry was relieved spontaneously, and mucosal swelling and polypoid changes were observed in 2 children. Conclusion:AFRS is a specific type of chronic rhinosinusitis that is not uncommon in children. Early diagnosis, prompt operation, standardized treatment and long-term follow-up are very important in the diagnosis and treatment of AFRS in children.

Application of intraoperative hypothermic saline to relieve postoperative pain for pediatric coblation tonsillectomy.

OBJECTIVES: To evaluate the effect of hypothermic saline application for pediatric coblation tonsillectomy on postoperative pain. METHODS: Forty-eight children with adenotonsillar hyperplasia underwent tonsillectomy ± adenoidectomy. 24 children were in the HTS group (which used hypothermic saline as the coblation medium in operation), the other 24 children with the same age were in the control NTS group (who use normothermic saline as the coblation medium). All children and their parents were asked to complete a daily questionnaire for 7 days following their surgery. RESULTS: Significant differences were observed when comparing the two outlet water temperatures of the coblation wand both at ablation power and at coagulation power (p = 0.000). Children in HTS group got lower scores than those in the NTS group (p < 0.05). No side effects were observed. CONCLUSIONS: Using hypothermic normal saline as the media of coblation wand is potential for reduce postoperative pain in pediatric patients while also having no detrimental financial or medical effects on said patients.

Pediatric Epistaxis and Its Correlation Between Air Pollutants in Beijing From 2014 to 2017.

BACKGROUND: Epistaxis is a common symptom in children. The effect of air pollution on epistaxis is not yet clear. OBJECTIVES: To explore the characteristics of pediatric epistaxis in Beijing and its correlation with air pollutants. MATERIAL AND METHODS: Data were collected from 2014 to 2017 in Otolaryngology Department of Capital Institute of Pediatrics. Children diagnosed with epistaxis with relevant information with the same period of municipal air pollutants' concentration were compared. RESULTS: The annual visits of epistaxis showed a bimodal trend. The incidence of epistaxis in infants was low, increased with age, reached the peak between the ages of 4 to 5, and then gradually decreased with age. In different age groups, male patients were more than females. From 2014 to 2017 in Beijing, particulate matter less than 2.5 µm in diameter (PM2.5), particulate matter less than 10 µm in diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) showed a downtrend, lower in summer than in the other 3 seasons. Ozone (O3) was significantly higher in 2016 and 2017, showed an increase trend in summer. The incidence of epistaxis was negatively correlated with PM2.5, PM10, SO2, NO2 and CO, which was positively correlated with O3 (P < .05). CONCLUSIONS: Pediatric epistaxis in Beijing changes with age and has obvious seasonal variation. There are some correlations between air pollutants and the incidence of epistaxis in children.

Pediatric coblation total tonsillectomy: intracapsular or extracapsular?

OBJECTIVES: To compare the results of coblation intracapsular total tonsillectomy (CITT) with those of conventional coblation extracapsular total tonsillectomy (CETT) in the treatment of tonsillar hypertrophy in children with regards to efficacy and complications. METHODS: Ninety children with adenotonsillar hyperplasia underwent tonsillectomy ± adenoidectomy (48 CITT and 42 CETT). Intraoperative situation was observed and recorded. Patients were reexamined regarding recovery condition and tonsil regrowth, and were followed for at least one year. RESULTS: Significant differences were observed in four clinical features when the CITT group was compared with the CETT group: intraoperative bleeding score, intraoperative tonsillar fossa score, color of white membrane one day postoperatively, and visual analogue scale (VAS) value one week postoperatively (p < .05). There were statistical correlations between intraoperative bleeding score and age, course of disease, surgery method, number of acute tonsillitis attacks per year, and intraoperative tonsillar fossae score (p < .05). Two significant differences were noted when the tonsil hypertrophy group was compared with the chronic tonsillitis group: color of white membrane at one day and one week postoperatively (p < .05). No regrowth of tonsil was found. CONCLUSIONS: Compared with conventional extracapsular tonsillectomy, CITT has the advantages of decreased pain and bleeding, and promote healing of wounds. No tonsillar regrowth was observed after at least one year of follow-up.

[Treatment of obstructive sleep apnea-hypopnea syndrome for children refractory asthma].

OBJECTIVE: The aim of this study was to understand the effect of different treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS) for refractory asthma in children. METHODS: Fifty two children (32 in surgical group, 20 in conservative group) with refractory asthma and OSAHS were included in the study. All children received asthma condition assessment and polysomnography (PSG) examination before and after treatment, and were followed up for 6 months. RESULTS: All children got improved in PSG values 3 months after treatment, more significant improvement was achieved in surgical group than in conservative group (P < 0.05). While compared of OSAHS treatment, there were 2 cure, 6 notable effective, 9 effective, 3 in vain cases in conservative group, 8 cure, 16 notable effective, 8 effective, 0 in vain cases in surgery group. There was significant difference between the two groups (χ² = 8.91, P = 0.031). All children got improved in asthma condition evaluation parameters and decreased the use number of short acting ß2 agonists after 6 months treatment. More significant improvement was achieved in surgical group than in conservative group. The differences of all the items had statistical significance (P < 0.05). There was statistical correlation between days mutation rate of peak expiratory flow (PEF) and apnea hypopnea index (r = 0.712, P < 0.01), and between days mutation rate of PEF and lowest oxygen saturation (r = 0.726, P < 0.01). CONCLUSIONS: Active treatment of OSAHS can improve asthma symptoms and reduce asthma medication effectively. The curative effect of surgical treatment is superior to conservative treatment.

Upper airway cough syndrome in children and two inflammatory factors: TRPV1 and TGF-ß2.

OBJECTIVES: The aim of the study was to investigate upper airway cough syndrome (UACS) in children and to determine alternative methods to explore the relationships among TRPV1, TGF-ß2, and UACS. METHODS: In 2012, 104 children with adenoid hypertrophy aged 2-13 years who were admitted to the otolaryngology department, Capital Institute of Pediatrics-affiliated children's hospital, were included in this study. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) studies for TRPV1 and TGF-ß2 were performed to understand the relationship between the two inflammatory factors, and the correlations among the indices and UACS. The research was divided into three stages. In stage 1, 72 children (24 UACS and 48 controls) were enrolled in the study, and ELISAs for TRPV1 and TGF-ß2 were performed. In stage 2, 32 children (16 UACS and 16 controls) were enrolled in the study and both ELISA and IHC for TRPV1 and TGF-ß2 were performed. In stage 3, 41 children were enrolled in this research who had thick mucus secretions in the posterior nasal apertures in stage 1 and 2 (23 cases with chief complaint (or history) of chronic cough and 18 cases without). The difference between the TRPV1 and TGF-ß2 serum values and the clinical factors was determined. RESULTS: The levels of TRPV1 and TGF-ß2 were significantly increased in the UACS cases. OSAHS and thick mucus secretions correlated with a diagnosis of UACS. A history of asthma and thick mucus secretions correlated with elevation of the two inflammatory factors. There was no statistical correlation between ELISA and IHC testing. Among the children with thick mucus secretions, some had a higher possibility of chronic coughing including those who had higher levels of the two indices, larger tonsils and a history of chronic tonsillitis. CONCLUSION: The detections of TRPV1 and TGF-ß2 from serum and adenoid body specimens are valuable for UACS auxiliary diagnosis. Tonsil hypertrophy and chronic tonsillitis history are independent risk factors of UACS.

[Analysis of intractable cough in 128 children].

OBJECTIVE: To disclose the etiological factors and to investigate the therapeutical effect on nasal disorders in 128 children with intractable cough. METHODS: One hundred and twenty-eight children with intractable cough were consulted by ENT doctors using electronic nasopharyngoscope, for those children with nasal diseases, relevant treatment was given. RESULTS: Among 128 children, one hundred and sixteen had nasal disorders. Upper airway cough syndrome (UACS) was diagnosed in 92 cases (71.9%), nasal disorders without UACS was diagnosed in 24 cases (18.7%), no nasal disorders were found in 12 cases (9.4%). Among children with UACS, allergic rhinitis was diagnosed in 76 cases, rhino-sinusitis in 39 cases, adenoid hypertrophy in 54 cases, and chronic rhinitis in 8 cases. However, for those children without UACS, 10 cases had chronic rhinitis and 14 cases had allergic rhinitis. Clinical symptoms, signs and the findings of electronic nasopharyngoscope were analyzed in 92 children with UACS. The results showed that regular cough occurred in 62 cases, nasal disease in 65 cases, subjective feeling of postnasal discharge in 18 cases, mouth breathing or snoring in 32 cases, purulent secretion in nasal meatus in 61 cases, retropharyngeal folliculosis in 58 cases, purulent secretion in pharynges detected from pharynx in 41 cases, and purulent or viscosity secretion were found in 91 cases by first electronic nasopharyngoscopy. After 14 days of treatment, the children with UACS (90/92) had significant higher remission rate (chi² = 32.21, P = 0.000) in cough than those who had nasal disorders but without UACS (13/24). CONCLUSIONS: The nasal disorders, especially for UACS, were common in children with intractable cough. The therapy to nasal disorders could release the chronic cough symptoms in children with intractable cough.

[Analysis of the causes of pediatric rhino-source diseases].

OBJECTIVE: To analyze clinical features of pediatric rhino-source diseases for reducing missed diagnosis and misdiagnosis. METHOD: Data of 3588 children with rhino-source diseases seen from April 2005 to May 2006 were retrospectively analyzed in this study in order to disclose the relationship of etiological factor, clinical features and diagnosis. RESULT: Among all these cases, 2090 complained of nasal discomfort including nasal obstruction, discharge, rhinalgia and epistaxis. However 1498 cases (41.76%) did not, of whom 470 cases had snoring and apnea, 332 cases of otalgia and otorrhea, 145 cases had chronic cough, 138 had headache and 92 had lower respiratory infection. CONCLUSION: A high percentage of children who suffered from pediatric rhino-source disease did not develop nasal symptoms. Pediatric rhino-source disease should be considered for patients in whom the therapeutic effect is unexpectedly poor.

[Clinical observation on treatment of cervicogenic headache with turtle-probing needling at Tianzhu (BL 10)].

OBJECTIVE: To observe therapeutic effect of turtle-probing needling at Tianzhu (BL 10) on cervicogenic headache. METHODS: Seventy cases were randomly divided into a treatment group (n=36) and a control group (n= 34). The treatment group were treated with turtle-probing needling at Tianzhu (BL 10) on the affected side, first perpendicularly needling the point and then penetration-needling homolateral Fengchi (GB 20), Fengfu (GV 16), below cervical Jiaji points (EX-B2), and occipital tuberosity in order. And the control group were treated with acupuncture at Fengchi (GB 20),Tianzhu (BL 10), Shuaigu (GB 8), Touwei (ST 8) and corresponding cervical Jiaji points (EX-B2), Houxi (SI 3), Ashi points at the affected side with routine needling manipulation. Treatment was given once each day, 6 sessions constituting one course. RESULTS: There was no significant difference between the two groups in therapeutic effect (P > 0.05), but the cured and markedly effective rates for analgesic effect in the observation group at the first three sessions were higher than those in the control group (P < 0.05). CONCLUSION: The turtle-probing needling method and the routine needling have a similar therapeutic effect, but the turtle-probing needling method more rapidly produces the analgesic effect.