Exploration of the pathophysiology of high myopia via proteomic profiling of human corneal stromal lenticules.

This study aimed to investigate the underlying pathophysiology of high myopia by analyzing the proteome of human corneal stromal lenticule samples obtained through small incision lenticule extraction (SMILE). A total of thirty-two patients who underwent SMILE were included in the study. Label-free quantitative proteomic analysis was performed on corneal stromal lenticule samples, equally representing high myopia (n = 10) and low myopia (n = 10) groups. The identified and profiled lenticule proteomes were analyzed using in silico tools to explore biological characteristics of differentially expressed proteins (DEPs). Additionally, LASSO regression and random forest model were employed to identify key proteins associated with the pathophysiology of high myopia. The DEPs were found to be closely linked to immune activation, extracellular matrix, and cell adhesion-related pathways according to gene ontology analysis. Specifically, decreased expression of COL1A1 and increased expression of CDH11 were associated with the pathogenesis of high myopia and validated by western blotting (n = 6) and quantitative real time polymerase chain reaction (n = 6). Overall, this study provides evidence that COL1A1 and CDH11 may contribute to the pathophysiology of high myopia based on comparative proteomic profiling of human corneal stromal lenticules obtained through SMILE.

Study on the biological properties of SMILE-derived corneal stromal lenticules after long-term cryopreservation in nutrient capsules.

PURPOSE: To investigate the long-term preservation effects of nutrient capsules on the physiological activity, collagen fiber structure and transmittance of corneal stromal lenticules derived from small incision lenticule extraction (SMILE). METHODS: A new nutrient capsule was constructed for long-term preservation of SMILE-derived corneal stromal lenticules. The lenticules were randomly divided into 99% anhydrous glycerol, and hydrogel nutrient capsules. After preserving for 1 year at -80 °C, lenticules were compared with fresh lenticules. The optical transmittance, tissue morphology, ultrastructure, cells activity and immunogenicity of the lenticules was detected and compared between different groups. RESULTS: The rate of apoptotic cells was significantly higher in the glycerol group compared with the nutrient capsule group (P < 0.0001). More viable cells were present in the lenticules after nutrient capsule preservation compared to the glycerol group (P = 0.0003). The mean transmittance of the lenticules in the glycerol group (50 ± 18%) was significantly lower (P = 0.0008) compared to the control group (75 ± 11%), and the lenticules transmittance of the nutrient capsule group (64 ± 15%) after long-term preservation was not significantly different (P = 0.23) compared to the control group. The structure of HE staining showed that the collagen fibers in the nutrient capsule group were arranged in parallel and neatly, and a few cavitation vesicles were visible inside the tissue. There was no significant difference in the number of lenticular collagen fibers in the nutritional capsule group compared to the fresh lenticule group (P = 0.06). HLA-DR, HLA-ABC, CD45, CD25 and CD69 expression was low in all groups of lenticules after preservation. CONCLUSIONS: Nutrient capsules can preserve lenticules for a long time and maintain the transmission structure and cells activity of lenticules.

Comparison of axial length and anterior segment parameters of patients with myopia measured using 2 fourier-domain optical coherent biometry devices.

BACKGROUND: This study assessed the agreement of ocular parameters of patients with myopia measured using Colombo intraocular lens (IOL) 2 and IOLMaster 700. METHODS: Eighty patients (male, 22; average age, 29.14 ± 7.36 years) with myopia (159 eyes) were included in this study in May 2023. The participants' axial length (AXL), central corneal thickness (CCT), lens thickness (LT), white-to-white distance (WTW), front flat (K1), steep (K2), mean (Km) corneal keratometry, astigmatism (Astig), J0 vector, and J45 vector were measured using the IOLMaster 700 and Colombo IOL 2. The measurements from both devices were compared using the generalized estimating equation, correlation analysis, and Bland-Altman plots. RESULTS: With the Colombo IOL 2, lower values for K2 and J0 (odds ratio [OR] = 0.587, p = 0.033; OR = 0.779, p < 0.0001, respectively), and larger values for WTW, Astig, and J45 (OR = 1.277, OR = 1.482, OR = 1.1, all p < 0.0001) were obtained. All ocular measurements by both instruments showed positive correlations, with AXL demonstrating the strongest correlation (r = 0.9996, p < 0.0001). The intraclass correlation coefficients for AXL and CCT measured by both instruments was 0.999 and 0.988 (both p < 0.0001), and Bland-Altman plot showed 95% limits of agreement (LoA) of -0.078 to 0.11 mm and - 9.989 to 13.486 µm, respectively. The maximum absolute 95% LoA for LT, WTW, K1, K2, and J0 were relatively high, achieving 0.829 mm, 0.717 mm, 0.983 D, 0.948 D, and 0.632 D, respectively. CONCLUSIONS: In young patients with myopia, CCT and AXL measurements obtained with the Colombo IOL 2 and IOLMaster 700 were comparable. However, WTW, LT, corneal refractive power, and astigmatism values could not be used interchangeably in clinical practice.

Autostereoscopic 3D viewing can change the dimensions of the crystalline lens in myopes.

PURPOSE: Autostereoscopic displays have become increasingly common, but their impact on ocular dimensions remains unknown. We sought to identify changes in the crystalline lens dimensions induced by autostereoscopic three-dimensional (3D) viewing. METHODS: Forty young adults (age: 22.6 ± 2.0 years, male/female: 15/25) were consecutively enrolled and randomly divided into two groups (3D and two-dimensional [2D] viewing groups) to watch a 30-min movie clip displayed in 3D or 2D mode on a tablet computer. The lens thickness (LT), diameter, curvature, decentration and tilt were measured with anterior segment optical coherence tomography under both non-accommodating (static) and accommodating conditions. RESULTS: In the static condition, the LT decreased by 0.03 ± 0.03 mm (p < 0.001) and the anterior radius of curvature (ARC) increased by 0.49 ± 0.59 mm (p = 0.001) post-3D viewing. In contrast, following 2D viewing, the ARC decreased by 0.23 ± 0.25 mm (p = 0.001). Additionally, the increase in the steep ARC post-3D viewing was greater in high-myopic eyes than low to moderate myopic eyes (p = 0.04). When comparing the accommodative with the static (non-accommodative) condition, for 3D viewing the lens decentration decreased (-0.03 ± 0.05 mm, p = 0.02); while for 2D viewing, the posterior curvature radius (-0.14 ± 0.20 mm, p = 0.006) and diameter (-0.13 ± 0.20 mm, p = 0.01) decreased. CONCLUSIONS: Viewing with the autostereoscopic 3D tablet could temporally decrease the thickness and curvature of the lens under non-accommodating conditions. However, its long-term effect requires further exploration.

Eosinophil extracellular traps in asthma: implications for pathogenesis and therapy.

Asthma is a common, chronic inflammatory disease of the airways that affects millions of people worldwide and is associated with significant healthcare costs. Eosinophils, a type of immune cell, play a critical role in the development and progression of asthma. Eosinophil extracellular traps (EETs) are reticular structures composed of DNA, histones, and granulins that eosinophils form and release into the extracellular space as part of the innate immune response. EETs have a protective effect by limiting the migration of pathogens and antimicrobial activity to a controlled range. However, chronic inflammation can lead to the overproduction of EETs, which can trigger and exacerbate allergic asthma. In this review, we examine the role of EETs in asthma.

Corneal thickness measurements with the RTVue, Casia-2, and Pentacam devices in patients with mild-to-moderate keratoconus: a comparative study.

BACKGROUND: To compare the characteristics of corneal thickness measurements among the RTVue, Casia-2, and Pentacam in patients with mild-to-moderate keratoconus. METHODS: We recruited 46 eyes of 46 patients diagnosed with mild-to-moderate keratoconus at our hospital between January and March 2022. The central corneal thickness (CCT) and thinnest corneal thickness (TCT) were measured using two optical coherence tomography (OCT) instruments (RTVue and Casia-2) and the more conventional Pentacam. Differences and correlations between the CCTs and TCTs, based on the device and influencing factors, were explored. RESULTS: The CCTs were highly consistent among the groups (p = 0.434) and correlated with one another (p < 0.001). The TCTs measured by OCTs were thinner than those measured by the Pentacam (p < 0.001); however, all three devices were highly correlated (p < 0.001). The thinnest point location measurements with RTVue and Casia-2 differed significantly from the measurements with the Pentacam. Bland-Altman plots demonstrated a significant agreement between Pentacam and OCTs in TCT measurement (p < 0.001); the 95% limits of agreement were - 3.1 µm to + 33.1 µm for Pentacam and RTVue and - 8.6 µm to + 36.5 µm for Pentacam and Casia-2. RTVue and Casia-2 showed no difference in corneal thickness (p = 0.633) and thinnest point location measurement (p > 0.05). Multivariate analysis identified that the TCT measurement difference between the RTVue and Pentacam was related to the difference between the CCT and TCT (b = 0.490, 95% confidence interval [CI]: 0.033 to 0.948, p = 0.036), whereas the difference between the Casia-2 and Pentacam was related to the anterior radius for curvature (A) grade (b = 3.9, 95% CI: 1.753 to 6.074, p = 0.001), corneal pachymetry at the thinnest (C) grade (b = - 7.875, 95% CI: - 11.404 to - 4.346, p < 0.001), and the difference between the CCT and TCT (b = 0.425, 95% CI: 0.1 to 0.751, p = 0.012). CONCLUSIONS: CCTs in patients with mild-to-moderate keratoconus were similar among all three devices, but the TCTs and the thinnest point locations were not. Furthermore, the TCT measurement differences between the OCT devices and the Pentacam were more pronounced in keratoconus cases with a steeper anterior surface, thicker TCTs, and a larger difference between the CCT and TCT. TRIAL REGISTRATION: Number: 2021118-1. Retrospectively registered: September 01, 2021.

Theoretical Investigations on the Detecting Mechanism of a Typical 2,4,6-Trinitrophenol Fluorescence Sensor and Its Design Strategy.

Fluorescence sensors based on small organic molecules are drawing increasing attention. In this contribution, the underlying detection mechanism of a typical fluorescence sensor for 2,4,6-trinitrophenol (TNP) based on fluorescence quenching is comprehensively investigated. The TNP molecule is proved to plant an intermolecular electron transfer state (dark state) below the bright state. Strong π-π interaction is observed between the sensor and TNP, which provides considerable orbital overlaps between the sensor and analyte. Electron transfer from the sensor to analyte is facilitated by such a strong interaction, which quenches the sensor's fluorescence. The design strategy for such TNP sensors is proposed based on the detection mechanism, and a series of new sensors is designed, which is likely to have better sensitivity than the original sensor.

Exploring the Photophysics of a Zn2+ Fluorescence Sensor and Its Sensing Mechanism.

Sensor X is a turn-on sensor, which is applied in the fluorescence detection of Zn2+ ions. Its photophysical process is comprehensively investigated to clarify its weak fluorescence. With the aid of density functional theory (DFT) and time-dependent density functional theory (TDDFT), the potential energy surfaces (PES) of X on both ground and first excited states are studied. Excited-state intramolecular proton transfer (EPT) processes as well as molecule twisting motion are observed, which induces several minima on the excited-state PES. Transition states as well as rate constants for these dynamic processes are obtained to evaluate their occurrences. The twisting motion of the sensor is an ultrafast process, which is initiated by a specific EPT process and leads to a nonemissive twisted intramolecular charge transfer (TICT) state. The fluorescence of the sensor is barely observable because of the easily attainable TICT state on the excited PES. This mechanism is trustworthy and intrinsically different from the previously proposed mechanism. After clarifying the photophysical process of the sensor, the Zn2+ sensing mechanism is uncovered. Also, the selectivity against Cd2+ and Hg2+ is fully discussed.

Identification of genetic determinants of hemolytic activity of Riemerella anatipestifer using random transposon mutagenesis.

Riemerella anatipestifer causes epizootic infectious disease in poultry resulting in serious economic losses especially to the duck industry. In our previous study, R. anatipestifer was found to lyse duck erythrocytes in vitro. In the present study, a random Tn4351 mutagenesis library of hemolytic R. anatipestifer strain SX containing 4000 mutants was constructed to investigate the genetic basis of hemolytic activity. Thirty mutants with reduced hemolytic activity and one with increased hemolytic activity were screened and insertions in 24 genes were identified. Of these genes, four were predicted to encode outer membrane proteins, one encoded a cytoplasmic membrane protein, 11 encoded cytoplasmic proteins, and eight encoded proteins with unknown locations. Based on current annotations of the R. anatipestifer genomes, of the 24 genes, 7 (29.17%) were involved in iron utilization. The hemolytic activities of the complemented strains M2 (pRES-Riean_0790) and M18 (pRES-Riean_0653) were restored, indicating that both Riean_0653 and Riean_0790 are involved in the hemolytic activity of strain SX. However, the recombinant proteins rRiean_0317, rRiean_0790, rRiean_0653, rRiean_1027, rRiean_1143, and rRiean_1561 had no hemolytic activity, suggesting that none were hemolysins.

Role of the Weak Interactions during the 2,4,6-Trinitrophenol Detecting Process of a Fluorescein-Based Sensor.

Achieving fast and precise fluorescence sensing of 2,4,6-trinitrophenol (TNP) is of fundamental importance for homeland security and environment protection. Weak interactions between the sensor and an analyte always play a critical role, which is capable of affecting the photophysics of the sensor. This study performs a thorough investigation on the effects of the weak interaction between TNP and a typical fluorescein-based sensor. The photophysics of the sensor before and after interacting with TNP is fully discussed by analyzing the potential energy surface (PES) of the sensor and rate constants of the excited-state dynamic processes. TNP is found to affect the PES greatly, which plants an intermolecular electron transfer state (dark state) below the bright state. The π-π interaction is proved to induce considerable orbital overlaps between the analyte and the sensor, which facilitates the electron transfer process and generates the dark state.

Characterization of the hemolytic activity of Riemerella anatipestifer.

Riemerella anatipestifer infection causes serious economic losses in the duck industry worldwide. Acute septicemia and high blood bacterial loading in R. anatipestifer infected ducks indicate that R. anatipestifer may be able to obtain iron and other nutrients by lysing duck erythrocytes to support its rapid growth and proliferation in the blood. However, so far, little is known about the hemolytic activity of R. anatipestifer to duck erythrocytes. In this study, 29 of 52 R. anatipestifer strains showed hemolytic activity on duck blood agar, whereas all the tested dba+ (with hemolytic activity on duck blood agar) and dba- strains created pores in the duck red blood cells, with 4.35-9.03% hemolytic activity in a liquid hemolysis assay after incubation for 24 h. The concentrated culture supernatants of all the tested R. anatipestifer strains and the extracted outer membrane proteins (OMPs) from dba+R. anatipestifer strains showed hemolytic activity on duck blood agar. These results, together with the median lethal dose (LD50) of some dba+ and dba-R. anatipestifer strains in ducklings, suggested that there was no direct relationship between the hemolytic capacity of R. anatipestifer on duck blood agar and its virulence.

Theoretical Investigations on the Excited-State Dynamics of an Al3+ Fluorescence Sensor.

Twisted internal charge transfer (TICT) states are of fundamental importance during the photo-physical processes of dyes and sensors. In this contribution, excited-state dynamics of an Al3+ fluorescence sensor 1-{[(2-hydroxyphenyl)-imino]methyl}naphthalen-2-ol based on the turn-on signal is clarified. Two different dark TICT states are observed by exploring the excited-state potential energy surface. With the twist of the C2-N bond, the two dark states can be reached facilely, which induce the experimentally observed weak fluorescence of the sensor. The sensing mechanism is then uncovered by investigating the electronic coupling between the sensor and analyte. Al3+ is proved to form strong coordination bonds with the sensor, which restricts the motion of the C2-N bond. Consequently, the TICT states are eliminated, which generate the turn-on signal. This sensing mechanism is trustworthy and intrinsically different from the previously proposed one, which would shed some light on the design of turn-on sensors.

Electron transfer and intersystem crossing triggered fluorescence quenching detection of mercury ions.

Via a specific fluorescence quenching response, organic compound L serves as an excellent probe for Hg2+ in aqueous solution. The underlying detection mechanism is proposed based on the analyses of orbital interactions between probe L and Hg2+, which is new and intrinsically different from the previously proposed one. By investigating the excitation process and the excited state deactivation process of the organometallic compound formed by L and Hg2+, two non-emissive channels, namely intermolecular electron transfer and intersystem crossing, are observed. The co-effect of the two channels leads to the significant fluorescence quenching of L. Hopefully, the newly proposed mechanism can inspire experimentalists to encapsulate the two channels into one probe to achieve accurate detection of metal ions.

Roles of the TonB1 and TonB2 proteins in haemin iron acquisition and virulence in Riemerella anatipestifer.

Two TonB systems in Riemerella anatipestifer were found and characterized as ExbB1-ExbD1-TonB1 and ExbB2-ExbD2-ExbD2'-TonB2, but the significance of two sets of TonB complexes in R. anatipestifer is not clear. In this study, by deleting the tonB1 or tonB2 gene of R. anatipestifer strain CH3, we investigated the roles of the TonB1 and TonB2 proteins in iron acquisition and virulence. The results showed that strain CH3 could utilize haemin as the sole iron source in the presence of l-cysteine, but haemin iron acquisition was defective in the CH3ΔtonB1 mutant, and the deletion of either tonB1 or tonB2 significantly reduced adhesion to and invasion of Vero cells. Animal experiments indicated that the LD50 of the CH3ΔtonB1 and CH3ΔtonB2 mutants in ducklings was ∼224- and ∼87-fold, respectively, higher than that of the WT CH3 strain. Additional analysis indicated that blood bacterial loading of ducklings infected with CH3ΔtonB1 or CH3ΔtonB2 decreased significantly compared with that found for WT CH3-infected ducklings. Thus, our results indicated that the TonB1, but not TonB2 protein, is involved in haemin iron acquisition and that both TonB proteins are necessary for optimal bacterial virulence.

Precision medicine for severe asthma - Biological targeted therapy.

Severe asthma is a complex and heterogeneous chronic airway inflammatory disease. Current treatment strategies are increasingly focused on disease classification, facilitating the transition towards personalized medicine by integrating biomarkers and monoclonal antibodies for tailored therapeutic approaches. Several approved biological agents, including anti-immunoglobulin E (IgE), anti-interleukin (IL)-4, anti-IL-5, and anti-thymic stromal lymphopoietin (TSLP) monoclonal antibodies, have demonstrated significant efficacy in reducing asthma exacerbations, eosinophil counts, improving lung function, minimizing oral corticosteroid usage, and enhancing patients' quality of life. The utilization of these biological agents has brought about profound transformations in the management of severe asthma. This article provides a comprehensive review on biomarkers and biological agents for severe asthma while emphasizing the increasing importance of further research into its pathogenesis and novel treatment modalities.

Clarithromycin attenuates airway epithelial-mesenchymal transition in ovalbumin-induced asthmatic mice through modulation of Kv1.3 channels and PI3K/Akt signaling.

Airway epithelial-mesenchymal transition (EMT) is the important pathological feature of airway remodeling in asthma. While macrolides are not commonly used to treat asthma, they have been shown to have protective effects on the airways, in which mechanisms are not yet fully understood. This study aims to investigate the impact of clarithromycin on airway EMT in asthma and its potential mechanism. The results revealed an increase in Kv1.3 expression in the airways of ovalbumin (OVA)-induced asthmatic mice, with symptoms and pathological changes being alleviated after treatment with the Kv1.3 inhibitor 5-(4-phenoxybutoxy)psoralen (PAP-1). Clarithromycin was found to attenuate airway epithelial-mesenchymal transition through the inhibition of Kv1.3 and PI3K/Akt signaling. Further experiments in vitro confirmed that PAP-1 could mitigate EMT by modulating the PI3K/Akt signaling in airway epithelial cells undergoing transformation into mesenchymal cells. These findings confirmed that clarithromycin might have a certain protective effect on asthma-related airway remodeling and represent a promising treatment strategy.

Hydroxyproline Concentration and Associated Factors of Preserved Small Incision Lenticule Extraction-Derived Corneal Stromal Lenticules.

PURPOSE: To evaluate changes of hydroxyproline concentration and its influencing factors of small incision lenticule extraction (SMILE)-derived corneal stromal lenticules with different preservation methods. METHODS: A total of 390 corneal stromal lenticules of 195 patients were derived from SMILE surgeries. Thirty of the lenticules were classified as the fresh (control) group, and the rest were randomly and evenly divided and stored in anhydrous glycerol, silicone oil, Optisol, and cryopreservation for 1 day, 1 week, or 1 month. A hydroxyproline assay kit (ab222941, Abcam) was used to measure the hydroxyproline concentration in each preservation method. Concentrations of MMP-2, TIMP-2, TNFα, TGFß2, and reactive oxygen species were also evaluated. RESULTS: In the anhydrous glycerol group, the concentration of hydroxyproline decreased within 1 week (fresh: 1 dΔ = 0.229, P < 0.001*; 1 d - 1 wΔ = 0.055, P < 0.001*) while that in the silicone oil group remained stable in 1 week (1 d - 1 wΔ = -0.005, P = 0.929) and decreased significantly in 1 m (1 m - 1 wΔ = -0.041, P = 0.003*). The sequence of hydroxyproline concentration in the Optisol group was 1 m > 1 day > 1 week. Hydroxyproline concentration in the cryopreservation group decreased within 1 m. Hydroxyproline concentration was highest in the Optisol group and lowest in the anhydrous glycerol group under the same preservation time. Hydroxyproline concentration was negatively correlated with MMP-2 (r = -0.16, P = 0.421) and TIMP-2 (r = -0.56, P = 0.002*) while MMP-2 and TNFα (r = 0.17, P = 0.242), TIMP-2 and TGFß2 (r = 0.21, P = 0.207), and TNFα and reactive oxygen species (r = 0.52, P = 0.007*) were positively correlated. CONCLUSIONS: More collagen was retained in SMILE lenticules preserved in Optisol under the same preservation time. The mechanism of the changes of collagen in preserved SMILE-derived lenticules and oxidative stress requires additional investigation.

The {332}<113> Twinning Behavior of a Ti-15Mo Medical Alloy during Cyclic Deformation and Its Effect on Microstructure and Performance.

In this study, the microstructural evolution of a Ti-15Mo medical alloy was investigated, when the in situ cyclic tensile strain had 2% amplitude and the tension-compression cyclic deformation had 1%, 2%, and 3% amplitude. The Vickers hardness and wear resistance of the alloy were also optimized due to the grain-refining effect after cyclic deformation and annealing. The twinning-induced plasticity (TWIP) was considered the main deformation mechanism of the Ti-15Mo alloy during the tensile-compressive cycle deformation with suitable strain amplitude. The {332}<113> twins and boundaries were the main contributors to the grain refinement. The optimal microstructure, hardness, and wear resistance were obtained in the alloy deformed by tension-compression cyclic strain with a 3% strain amplitude. The wear resistance of the annealed alloy in Hank's solution was excellent in contrast to the original Ti-15Mo alloy due to its reasonable microstructure and hardness. It is clear that abundant twins were formed and retained in the coarse grains of the original alloy after cyclic deformation and annealing, which provided the expected refined grains and performance.

Xingbei antitussive granules ameliorate cough hypersensitivity in post-infectious cough guinea pigs by regulating tryptase/PAR2/TRPV1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xingbei antitussive granules (XB) is a classic Chinese Medicine prescription for treating post-infectious cough(PIC), based on the Sanao Decoction from Formularies of the Bureau of People's Welfare Pharmacies in the Song Dynasty and Jiegeng decoction from Essentials of the Golden Chamber in the Han Dynasty. However, the therapeutic effects and pharmacological mechanisms are still ambiguous. In the present study, we endeavored to elucidate these underlying mechanisms. AIMS OF THE STUDY: This study aimed to explore the potential impact and mechanism of XB on PIC, and provide a scientific basis for its clinical application. MATERIALS AND METHODS: Cigarette smoking (CS) combined with lipopolysaccharide (LPS) nasal drops were administered to induce the PIC guinea pig with cough hypersensitivity status. Subsequently, the model guinea pigs were treated with XB and the cough frequency was observed by the capsaicin cough provocation test. The pathological changes of lung tissue were assessed by HE staining, and the levels of inflammatory mediators, mast cell degranulating substances, and neuropeptides were detected. The protein and mRNA expression of transient receptor potential vanilloid type 1(TRPV1), proteinase-activated receptor2(PAR2), and protein kinase C (PKC) were measured by Immunohistochemical staining, Western blot, and RT-qPCR. Changes in the abundance and composition of respiratory bacterial microbiota were determined by 16S rRNA sequencing. RESULTS: After XB treatment, the model guinea pigs showed a dose-dependent decrease in cough frequency, along with a significant alleviation in inflammatory infiltration of lung tissue and a reduction in inflammatory mediators. In addition, XB high-dose treatment significantly decreased the levels of mast cell Tryptase as well as ß-hexosaminidase (ß-Hex) and downregulated the expression of TRPV1, PAR2, and p-PKC. Simultaneously, levels of neuropeptides like substance P (SP), calcitonin gene-related peptide (CGRP), neurokinin A (NKA), and nerve growth factor (NGF) were improved. Besides, XB also can modulate the structure of respiratory bacterial microbiota and restore homeostasis. CONCLUSION: XB treatment alleviates cough hypersensitivity and inflammatory responses, inhibits the degranulation of mast cells, and ameliorates neurogenic inflammation in PIC guinea pigs whose mechanism may be associated with the inhibition of Tryptase/PAR2/PKC/TRPV1 and the recovery of respiratory bacterial microbiota.

Assessment of Keratoconus Risk in Very Asymmetric Ectasia Using Corneal Tomographic and Biomechanical Parameters.

Purpose: To investigate the relationship between corneal tomographic or biomechanical parameters and risk of keratoconus in very asymmetric ectasia (VAE). Methods: This retrospective case-control single-centre study included patients with VAE and normal controls. The VAE group had clinical ectasia in one eye and normal topography (VAE-NT) in the fellow eye; VAE-NT eyes were selected for analysis. The control group was selected from corneal refractive surgery candidates; the right eye was enrolled. Scheimpflug-based corneal tomography (Pentacam) and corneal biomechanical assessment (Corvis ST) were performed. Univariate and multivariable logistic regression were performed using Cox proportional hazards models to evaluate keratoconus-associated risk factors. A two-piecewise linear regression model was applied to examine the threshold effect of selected vital paragmeters on the risk of keratoconus according to a smoothing plot. Results: Threshold effect between tomographic integration and risk of keratoconus was observed. Discrepancy between the central corneal thickness and thinnest corneal thickness (discrepancy CCT vs TCT) greater than 5 µm, discrepancy between the apex corneal thickness and thinnest corneal thickness (discrepancy ACT vs TCT) greater than 3 µm, vector distance between CCT and TCT (distance CCT vs TCT) greater than 0.65 mm indicated a significant increased risk of keratoconus. Risk of keratoconus decreased when distance CCT vs TCT was less than 0.65 mm. Conclusion: Discrepancy CCT vs TCT, discrepancy ACT vs TCT, and distance CCT vs TCT can be used as indicators for risk assessment of early keratoconus.