Predictive Values of Serum IL-33 and sST2 in Endotypes and Postoperative Recurrence of Chronic Rhinosinusitis with Nasal Polyps.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disease with high heterogeneity and postoperative recidivation. The IL-33/ST2 axis is known to be involved in Th2 immune responses. This study is aimed at exploring levels of serum IL-33 and soluble ST2 (sST2) in CRSwNP patients and their potential for predicting CRSwNP endotypes and postoperative recurrence. Methods: The present study recruited 149 CRSwNP patients, 80 of whom were noneosinophilic (neCRSwNP) and 69 eosinophilic (eCRSwNP), as well as 60 healthy controls (HCs). Serum samples were collected from all participants, and sST2 and IL-33 concentrations were measured using ELISA. Multivariate analysis, receiver operating characteristic (ROC) curves, and Kaplan-Meier curves were used to evaluate the value of serum sST2 and IL-33 levels in distinguishing CRSwNP endotypes and predicting postoperative recurrence. Results: The levels of serum sST2 and IL-33 in CRSwNP patients were significantly higher than those in HCs, especially in the eCRSwNP group. Increased sST2 and IL-33 levels were associated with eosinophil counts and percentages in both tissue and blood. Multivariate regression and ROC curve analysis showed that serum sST2 and IL-33 exhibited potential for distinguishing CRSwNP endotypes, and the combination of serum IL-33 and sST2 showed even more predictive power. Finally, 124 CRSwNP patients completed the entire 3-year follow-up. Multivariate analysis and Kaplan-Meier curves showed that serum sST2 and IL-33 levels were associated with recurrence; serum sST2 and IL-33 each exhibited potential for predicting postoperative recurrence, and combining serum sST2 and IL-33 exhibited better accuracy and practicability. Conclusion: Our results suggested that serum sST2 and IL-33 levels were upregulated in CRSwNP patients and related to the degree of mucosal eosinophil infiltration and postoperative recurrence. Serum sST2 and IL-33 might serve as objective biomarkers for distinguishing phenotypes and predicting recurrence in CRSwNP, and their combined use outperformed either marker alone.

Serum Soluble ST2 Correlated with Symptom Severity and Clinical Response of Sublingual Immunotherapy for House Dust Mite-Induced Allergic Rhinitis Patients.

BACKGROUND: Suppressor of tumorigenicity 2 (ST2) is a key biomarker in inflammation and cardiovascular diseases, but limited data is available on its role in allergic rhinitis (AR). OBJECTIVE: The aim of this study is to explore the role of serum soluble ST2 (sST2) in evaluating disease severity and predicting the efficacy of sublingual immunotherapy (SLIT) in house dust mite- (HDM-) induced AR patients. METHODS: Eighty healthy controls (HC group) and 160 HDM-induced AR patients, including 40 mild patients (MAR group) and 120 moderate-severe patients (MSAR group), were recruited in this study. Serum was collected from all participants and levels of sST2 were determined by ELISA and the relationship between sST2 levels and disease severity was assessed. In the MSAR group, 109 patients received 3 years of SLIT, and the relationship between serum levels of sST2 and efficacy of SLIT was exampled. RESULTS: Serum sST2 levels were increased in HDM-induced AR patients compared to the HC group (P < 0.001), and the concentrations were higher in the MSAR group than in the MAR group and HC group (all P < 0.05). Moreover, sST2 levels positively correlated with the total nasal symptom score (TNSS), visual analogue scale (VAS), and specific IgE levels (P < 0.05). Seventy-eight MSAR patients accomplished SLIT, and they were divided into an effective group (n = 40) and an ineffective group (n = 38). The serum sST2 levels in the effective group were lower than those in the ineffective group (P < 0.001). In addition, patients in the effective group levels exhibited significantly lower sST2 levels post-SLIT than pre-SLIT (P < 0.001), but no statistic difference was observed in the ineffective group (P > 0.05). Receiver operating characteristic (ROC) curve showed promising accuracy for predicting clinical efficacy of SLIT in AR patients (area under the curve = 0.839, P < 0.001). CONCLUSION: Serum sST2 is a potential biomarker for assessing disease severity and may serve as a sensitive biomarker for predicting the therapeutic response of SLIT in HDM-induced AR patients.

Multi-wavelength optical data processing and recording based on azo-dyes doped organic-inorganic hybrid film.

While single wavelength all-optical information encoding through optically induced orientation of azobenzene dyes is being extensively pursued, we propose multi-wavelength optical data processing and recording based on disperse red 1 (DR1) and 4-(4-hydroxybutyloxy) azobenzene doped organic-inorganic hybrid films to increase the density of recording data. By investigating the change of absorbance spectrum of the doped film under different irradiations, results indicate a laser pulses around 470 nm would be suitable as the probe beam. In the measurement of optical data processing and recording, two cw lasers pulse at 532 nm and 355 nm induce trans-cis isomerization of the azo-dyes in the film, while the output of the probe beam record the processed data as {(-1), (0), (1)} according to different inputs of the pump beams. Since the light induced isomerization has a sensitive response in the as-prepared solid organic-inorganic matrix system, the films is promising as recording and monitoring element in all-optical devices over a wide range of repetition rates.

Serum exosome-derived miR-146a-3p promotes macrophage M2 polarization in allergic rhinitis by targeting VAV3 via PI3K/AKT/mTOR pathway.

BACKGROUND: Our previous study showed that miR-146a-3p was elevated in serum exosomes of allergic rhinitis (AR) patients, but the underlying mechanisms were unclarified. This study was to investigate the impact of exosome-derived miR-146a-3p on macrophage polarization in the pathology of AR. METHOD: We detected the expression of miR-146a-3p in nasal tissues of AR patients and healthy controls (HCs), and investigated its correlation with macrophage polarization markers. The impact of miR-146a-3p derived from AR serum exosomes on macrophage polarization was examined. Transcriptome sequencing was performed on macrophages treated with a miR-146a-3p inhibitor, and target genes of miR-146a-3p were explored through a combination of bioinformatics analysis and experimental validation. RESULTS: The expressions of miR-146a-3p and macrophage polarization markers were increased in the AR nasal tissues, and a positive association was observed between the expressions of miR-146a-3p and the levels of CD163 and CD206. The AR serum exosomes could be uptake by macrophages, and promote M2 polarization and cytokine secretions. Mechanistically, miR-146a-3p regulation could impact both macrophage M2 polarization and cytokine secretion. Inhibition of miR-146a-3p altered the gene transcriptions within macrophages. Bioinformatics analysis and clinical pathological specimen research confirmed that VAV3 was a target gene of miR-146a-3p, and it exerted a detrimental effect on macrophage M2 polarization via the PI3K/AKT/mTOR pathway. Functional recovery experiments and dual-luciferase reporter gene assays confirmed that miR-146a-3p could selectively target and inhibit the expression of VAV3, thereby promoting macrophage M2 polarization through the PI3K/AKT/mTOR pathway. CONCLUSION: Serum exosome-derived miR-146a-3p facilitated macrophage M2 polarization in AR by targeting VAV3 through the PI3K/AKT/mTOR pathway. These findings implied that miR-146a-3p and VAV3 could serve as potential targets for the development of novel therapeutic strategies in AR management.

Serum exosomal miR-146a-3p associates with disease severity and efficacy of sublingual immunotherapy in allergic rhinitis.

BACKGROUND: Sublingual immunotherapy (SLIT) is an effective treatment for allergic rhinitis (AR), but its efficacy is variable among individuals. This study aimed to characterize serum exosome-derived microRNAs (miRNAs) and evaluate their abilities in predicting the efficacy of SLIT in AR. METHODS: RNA sequencing was performed to explore differentially expressed exosomal miRNAs in serum exosomes between AR patients and healthy controls (HCs). Sequencing analysis results were verified in an independent cohort, and the correlations between the levels of exosome-derived miRNAs and disease severity were evaluated. The most promising miRNAs were further tested in two AR cohorts treated with SLIT to assess their abilities in predicting short and long-term efficacy, respectively. RESULTS: The exosome-derived miRNAs profiling in the AR group was significantly different from the HC group, and differentially expressed genes were enriched and clustered in pathways such as PI3K-Akt and ErbB signalling pathways. The top three most significant miRNAs were verified by reverse transcription-polymerase chain reaction (qRT-PCR), and results showed that miR-146a-3p levels were significantly elevated in the AR group and correlated with the total and specific gE levels, the visual analogue scale of the total nasal symptom score (all p < 0.05). Further data in the first validation cohort suggested that miR-146a-3p levels were significantly downregulated in the effective group, and logistic regression showed that miR-146a-3p levels were associated with the short-term efficacy of SLIT(p < 0.05). The receiver operating characteristic (ROC) curve showed that miR-146a-3p could early predict SLIT efficacy (AUC = 0.669, p = 0.047). In the second validation cohort, miR-146a-3p levels were also decreased in the effective group and the ROC curve further confirmed its reliable accuracy in predicting the long-term efficacy of SLIT in AR patients (AUC = 0.749, p < 0.001). CONCLUSION: Serum exosome-derived miRNAs may be involved in the development of AR and associated with its disease severity. Serum exosome-derived miR-146a-3p seems to be a novel biomarker for predicting the short and long-term efficacies of SLIT in AR patients.

Multiple-Cytokine Profiling: A Novel Method for Early Prediction of the Efficacy of Sublingual Immunotherapy in Allergic Rhinitis Patients.

BACKGROUND: Allergic rhinitis (AR) is a common inflammatory airway disease, and allergen-specific immunotherapy (AIT) is the only disease-modifying treatment for it. However, not all AR patients respond to AIT, and early prediction of patient response is extremely important. This study aimed to example serum levels of multiple cytokines in AR and explore their association with the efficacy of AIT. METHODS: A total of 74 AR patients treated with sublingual immunotherapy (SLIT) were prospectively recruited. Serum samples were obtained before the onset of SLIT and cytokine levels detected by multiplex analysis. All patients were followed for >1 year, and associations between cytokine levels and the early efficacy of SLIT were evaluated. Significantly distinctive cytokines were further verified in another independent cohort. RESULTS: Sixty patients completed the visit schedule set: 35 patients were put into a responder group and 25 a nonresponder group. Multiple-cytokine profiling showed that cytokine levels differed significantly between the two groups. The responder group had higher concentrations of BAFF and CCL11 and lower levels of CCL2, CCL7, IFNγ, IL8, IL10, IL16, and IL33 than the nonresponder group (P<0.05). Receiver-operating characteristic curves highlighted that serum BAFF, IFNγ, IL10, and IL33 levels were strongly predictive of the efficacy of SLIT (area under the curve <0.7, P<0.05). Serum IL10 and IL33 were overexpressed in nonresponders in the validation cohort. Patients in the responder group exhibited significantly higher IL10 levels and lower IL33 post-SLIT than pre-SLIT (P<0.05), but no statistical difference was found in nonresponders (P<0.05). CONCLUSION: Our data indicated that serum multiple-cytokine profiling was associated with response to SLIT and that IL10 and IL33 might serve as novel biomarkers for early prediction of efficacy and be involved in the therapeutic mechanisms of SLIT in AR patients.

Anterior wall resection plus radiofrequency ablation versus simple aspiration in the treatment of auricular pseudocyst: a retrospective study.

OBJECTIVE: To compare the efficacy of two different treatment approaches for auricular pseudocyst. METHODS: This retrospective study reviewed data from patients with auricular pseudocyst that were treated with either anterior wall resection plus radiofrequency ablation compression (surgical group) or simple aspiration and compression suturing (control group). The following outcomes were compared between the two groups: therapeutic response (cure, good or none), duration of postoperative medication (antibiotics) use, duration of postoperative pain, duration of recovery of appearance and rate of complications (infection, auricular thickening, incision swelling and recurrence). RESULTS: A total of 386 patients were enrolled in the study: 218 in the surgical group and 168 in the control group. Duration of postoperative medication use, duration of postoperative pain, duration of recovery of appearance and rate of postoperative complications were significantly lower in the surgical group compared with the control group. The overall therapeutic response (cure and good response) was significantly greater in the surgical group than in the control group. CONCLUSION: Auricular pseudocyst can be effectively treated by both of these methods, but anterior wall resection plus radiofrequency ablation compression might be more effective.

Broadband High-Efficiency Grating Couplers for Perfectly Vertical Fiber-to-Chip Coupling Enhanced by Fabry-Perot-like Cavity.

We propose a broadband high-efficiency grating coupler for perfectly vertical fiber-to-chip coupling. The up-reflection is reduced, hence enhanced coupling efficiency is achieved with the help of a Fabry-Perot-like cavity composed of a silicon nitride reflector and the grating itself. With the theory of the Fabry-Perot cavity, the dimensional parameters of the coupler are investigated. With the optimized parameters, up-reflection in the C-band is reduced from 10.6% to 5%, resulting in an enhanced coupling efficiency of 80.3%, with a 1-dB bandwidth of 58 nm, which covers the entire C-band. The minimum feature size of the proposed structure is over 219 nm, which makes our design easy to fabricate through 248 nm deep-UV lithography, and lowers the fabrication cost. The proposed design has potential in efficient and fabrication-tolerant interfacing applications, between off-chip light sources and integrated chips that can be mass-produced.

Efficiency Enhanced Grating Coupler for Perfectly Vertical Fiber-to-Chip Coupling.

In this work, a bidirectional grating coupler for perfectly vertical coupling is proposed. The coupling efficiency is enhanced using a silicon nitride (Si3N4) layer above a uniform grating. In the presence of Si3N4 layer, the back-reflected optical power into the fiber is diminished and coupling into the waveguide is increased. Genetic algorithm (GA) is used to optimize the grating and Si3N4 layer simultaneously. The optimal design obtained from GA shows that the average in-plane coupling efficiency is enhanced from about 57.5% (-2.5 dB) to 68.5% (-1.65 dB), meanwhile the average back-reflection in the C band is reduced from 17.6% (-7.5 dB) to 7.4% (-11.3 dB). With the help of a backside metal mirror, the average coupling efficiency and peak coupling efficiency are further increased to 87% (-0.6 dB) and 89.4% (-0.49 dB). The minimum feature size of the designed device is 266 nm, which makes our design easy to fabricate through 193 nm deep-UV lithography and lowers the fabrication cost. In addition, the coupler proposed here shows a wide-band character with a 1-dB bandwidth of 64 nm and 3-dB bandwidth of 96 nm. Such a grating coupler design can provide an efficient and cost-effective solution for vertical fiber-to-chip optical coupling of a Wavelength Division Multiplexing (WDM) application.

Management of traumatic tympanic membrane perforation: a comparative study.

This prospective study was conducted to evaluate the efficacy of sea buckthorn oil patches in treating traumatic tympanic membrane (TM) perforations. We enrolled 370 patients with traumatic TM perforations of different sizes. These patients were randomly assigned to control group and treatment group. In the treatment group, a sterile cotton patch with sea buckthorn oil was used to cover the TM perforations. In the control group, patients were treated with a sterile cotton patch. The healing rate and time were compared between the two groups. We found that the overall healing rate was significantly higher in the treatment group than in the control group. For middle and large TM perforations, sea buckthorn oil treatment led to a significant increase in the healing rate. At 2 months after injury, the duration of healing was, generally, shorter in the treatment group than in the control group (P<0.05). In conclusion, sea buckthorn oil patches are effective in treating middle and large TM perforations, which results in increased healing rates and decreased healing time.

[Bio-modification of polyhydroxyalkanoates and its biocompatibility with chondrocytes].

OBJECTIVE: To study the hydrophilicity and the cell biocompatibility of the poly(3-hydroxybutyrate-co- 3-hydroxyvalerate) (PHBV) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) coated with a fusion protein polyhydroxyalkanoates granule binding protein (PhaP) fused with Arg-Gly-Asp (RGD) peptide (PhaP-RGD). METHODS: PHBV and PHBHHx films were fabricated by solvent evaporation. Scanning electronic microscope (SEM) was used to study the morphology of the films. PhaP-RGD fusion proteins were expressed and purified by the technology of protein engineering; PHBV and PHBHHx films were immersed in the PhaP-RGD with an amount of 3.5 mg/mL protein/per sample respectively. The hydrophilicity of the surface were detected by the contact angle measurements. Septal cartilage cells obtained from human septal cartilage were cultured in vitro. The 2nd passage chondrocytes were incubated on PHBV unmodified with PhaP-RGD in group A1, PHBV modified with PhaP-RGD in group A2, PHBHHx unmodified with PhaP-RGD in group Bl, PHBHHx modified with PhaP-RGD in group B2, and on the cell culture plates in group C. After cultured for 3 days, the proliferation of cells was detected by the DAPI staining; the proliferation viability of cells was detected by the MTT assay after cultured for 3 and 7 days; after cultured for 7 days, the adhesion and morphology of the cells on the surface of the biomaterial films were observed by SEM and the matrix of the cells was detected through the toluidine blue staining. RESULTS: SEM observation showed that PHBV and PHBHHx films had porous structures. The contact angle of the surface of the PHBV and PHBHHx films modified with PhaP-RGD fusion proteins were significantly reduced when compared with the films unmodified with PhaP-RGD fusion proteins (P < 0.05). Chondrocytes of human nasal septal cartilage incubated on the films could grow in all groups. After 3 days of cultivation in vitro, the cell proliferation and viability of group B2 were the strongest among all groups (P < 0.05); the cell proliferation after cultured for 7 days was significantly stronger than that after cultured for 3 days in groups A1, A2, B1, and B2 (P < 0.05); and the cell proliferation was significantly stronger in groups B1 and B2 than groups A1, A2 and C, in group B2 than group B1, and in group A1 than group A2 (P < 0.05). The results of toluidine blue staining showed that blue metachromasia matrixes were observed in groups A1, A2, B1, and B2; group A1 and group A2 had similar staining degree, and the staining of group B2 was deeper than that of group B1. The adhesion of cells in all groups was good through SEM observation; and the connection of cells formed and stretched into the pores of the materials. CONCLUSION: The biomaterial films of PHBHHx modified with PhaP-RGD fusion protein can promote its biocompatibility with chondrocytes.