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.

Controlled synthesized of ternary Cu-Co-Ni-S sulfides nanoporous network structure on carbon fiber paper: a superior catalytic electrode for highly-sensitive glucose sensing.

BACKGROUND: Efficient monitoring of glucose concentration in the human body necessitates the utilization of electrochemically active sensing materials in nonenzymatic glucose sensors. However, prevailing limitations such as intricate fabrication processes, lower sensitivity, and instability impede their practical application. Herein, ternary Cu-Co-Ni-S sulfides nanoporous network structure was synthesized on carbon fiber paper (CP) by an ultrafast, facile, and controllable technique through on-step cyclic voltammetry, serving as a superior self-supporting catalytic electrode for the high-performance glucose sensor. RESULTS: The direct growth of free-standing Cu-Co-Ni-S on the interconnected three-dimensional (3D) network of CP boosted the active site of the composites, improved ion diffusion kinetics, and significantly promoted the electron transfer rate. The multiple oxidation states and synergistic effects among Co, Ni, Cu, and S further promoted glucose electrooxidation. The well-architected Cu-Co-Ni-S/CP presented exceptional electrocatalytic properties for glucose with satisfied linearity of a broad range from 0.3 to 16,000 µM and high sensitivity of 6829 µA mM- 1 cm- 2. Furthermore, the novel sensor demonstrated excellent selectivity and storage stability, which could successfully evaluate the glucose levels in human serum. Notably, the novel Cu-Co-Ni-S/CP showed favorable biocompatibility, proving its potential for in vivo glucose monitoring. CONCLUSION: The proposed 3D hierarchical morphology self-supported electrode sensor, which demonstrates appealing analysis behavior for glucose electrooxidation, holds great promise for the next generation of high-performance glucose sensors.

Mitochondria targeted drug delivery system overcoming drug resistance in intrahepatic cholangiocarcinoma by reprogramming lipid metabolism.

The challenge of drug resistance in intrahepatic cholangiocarcinoma (ICC) is intricately linked with lipid metabolism reprogramming. The hepatic lipase (HL) and the membrane receptor CD36 are overexpressed in BGJ398-resistant ICC cells, while they are essential for lipid uptake, further enhancing lipid utilization in ICC. Herein, a metal-organic framework-based drug delivery system (OB@D-pMOF/CaP-AC, DDS), has been developed. The specifically designed DDS exhibits a successive targeting property, enabling it to precisely target ICC cells and their mitochondria. By specifically targeting the mitochondria, DDS produces reactive oxygen species (ROS) through its sonodynamic therapy effect, achieving a more potent reduction in ATP levels compared to non-targeted approaches, through the impairment of mitochondrial function. Additionally, the DDS strategically minimizes lipid uptake through the incorporation of the anti-HL drug, Orlistat, and anti-CD36 monoclonal antibody, reducing lipid-derived energy production. This dual-action strategy on both mitochondria and lipids can hinder energy utilization to restore drug sensitivity to BGJ398 in ICC. Moreover, an orthotopic mice model of drug-resistant ICC was developed, which serves as an exacting platform for evaluating the multifunction of designed DDS. Upon in vivo experiments with this model, the DDS demonstrated exceptional capabilities in suppressing tumor growth, reprogramming lipid metabolism and improving immune response, thereby overcoming drug resistance. These findings underscore the mitochondria-targeted DDS as a promising and innovative solution in ICC drug resistance.

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.

Unraveling the Molecular Landscape of Neutrophil Extracellular Traps in Severe Asthma: Identification of Biomarkers and Molecular Clusters.

Neutrophil extracellular traps (NETs) play a central role in chronic airway diseases. However, the precise genetic basis linking NETs to the development of severe asthma remains elusive. This study aims to unravel the molecular characterization of NET-related genes (NRGs) in severe asthma and to reliably identify relevant molecular clusters and biomarkers. We analyzed RNA-seq data from the Gene Expression Omnibus database. Interaction analysis revealed fifty differentially expressed NRGs (DE-NRGs). Subsequently, the non-negative matrix factorization algorithm categorized samples from severe asthma patients. A machine learning algorithm then identified core NRGs that were highly associated with severe asthma. DE-NRGs were correlated and subjected to protein-protein interaction analysis. Unsupervised consensus clustering of the core gene expression profiles delineated two distinct clusters (C1 and C2) characterizing severe asthma. Functional enrichment highlighted immune-related pathways in the C2 cluster. Core gene selection included the Boruta algorithm, support vector machine, and least absolute contraction and selection operator algorithms. Diagnostic performance was assessed by receiver operating characteristic curves. This study addresses the molecular characterization of NRGs in adult severe asthma, revealing distinct clusters based on DE-NRGs. Potential biomarkers (TIMP1 and NFIL3) were identified that may be important for early diagnosis and treatment of severe asthma.

Thermosensitive gel-nano system against esophageal cancer via restoring p53 activity and boosting T-cell immunity.

In esophageal cancer (EC), clinical specimen testing has uncovered a significant increase in BTB and CNC homolog 1 (BACH1) expression and a shift towards an immunosuppressive environment, alongside a notable decrease in p53 protein expression. Therefore, therapeutic strategies focusing on BACH1 inhibition and p53 upregulation appear promising. Traditional oral treatments for EC lack precision and efficacy. Here, we propose a novel approach employing tumor-targeted nanoparticles (NPs) for drug delivery. However, the formation of a drug reservoir at the esophageal site, crucial for the sustained release of therapeutics, presents significant challenges in nano-delivery systems for EC treatment. To address this, we developed a thermosensitive hydrogel composed of F127 and tannic acid, serving as a vehicle for NP loading. These NPs, synthesized through the emulsion/volatization methods of mPEG-PLGA-PLL-cRGD, facilitate in situ drug delivery. Upon contacting esophageal tissue, the hydrogel transitions to a gel, adhering to the lining and enabling sustained release of encapsulated therapeutics. The formulation encompasses NPs laden with small interfering RNA targeting BACH1 (siBACH1) and the p53 activator PRIMA-1, creating a cohesive gel-nano system. Preliminary biological assessments demonstrate that this injectable, thermosensitive gel-nano system adheres effectively to esophageal tissue and targets EC cells. For better modeling clinical outcomes, a patient-derived organoid xenograft (PDOX) model was innovated, involving transplantation of EC-derived organoids into humanized mice, reconstructed with peripheral blood mononuclear cells (PBMCs). Post-treatment analysis showed substantial EC growth inhibition (89.51% tumor inhibition rate), significant BACH1 level reduction, restored anti-tumor immune responses, and pronounced tumor apoptosis. In summary, our study introduces a thermosensitive gel-nano system for EC treatment via restoring p53 activity and boosting T-cell immunity, with potential for clinical application.

Domiciliary monitoring of exhaled nitric oxide in the management of asthma: a pilot study.

BACKGROUND: Whether asthma patients could benefit from home monitoring for fractional exhaled nitric oxide (flow of 50 mL/s, FeNO50) is unknown. We explore the application value of home monitoring FeNO50 in daily asthma management. METHODS: Twenty-two untreated, uncontrolled asthma patients were selected. Medical history, blood and sputum samples, pulmonary function, Asthma Control Test (ACT), and other clinical data of the subjects were collected. All subjects underwent daily monitoring for four weeks using a FeNO50 monitor and mobile spirometry (mSpirometry). The diurnal differences and dynamic changes were described. Compare the effect-acting time and the relative plateau of treatment between FeNO50 and mSpirometry monitoring. RESULTS: In the first two weeks, the morning median (IQR) level of FeNO50 was 44 (35, 56) ppb, which was significantly higher than the evening median level [41 (32, 53) ppb, P = 0.028]. The median (IQR) effect-acting time assessed by FeNO50 was 4 (3, 5) days, which was significantly earlier than each measure of mSpirometry (P < 0.05). FeNO50 reached the relative plateau significantly earlier than FEV1 (15 ± 2 days vs. 21 ± 3 days, P < 0.001). After treatment, the daily and weekly variation rates of FeNO50 showed a gradually decreasing trend (P < 0.05). The ACT score, sputum eosinophils, and blood eosinophils also significantly improved (P ≤ 0.01). CONCLUSIONS: The daily home monitoring of FeNO50 in asthmatic patients showed significant circadian rhythm, and the sensitivity of FeNO50 in evaluating the response to treatment was higher than mSpirometry. The daily and weekly variation rates of FeNO50 change dynamically with time, which may be used to assess the condition of asthma.

Nanosystem Delivers Senescence Activators and Immunomodulators to Combat Liver Cancer.

CD47 blockade has emerged as a promising immunotherapy against liver cancer. However, the optimization of its antitumor effectiveness using efficient drug delivery systems or combinations of therapeutic agents remains largely incomplete. Here, patients with liver cancer co-expressing CD47 and CDC7 (cell division cycle 7, a negative senescence-related gene) are found to have the worst prognosis. Moreover, CD47 is highly expressed, and senescence is inhibited after the development of chemoresistance, suggesting that combination therapy targeting CD47 and CDC7 to inhibit CD47 and induce senescence may be a promising strategy for liver cancer. The efficacy of intravenously administered CDC7 and CD47 inhibitors is limited by low uptake and short circulation times. Here, inhibitors are coloaded into a dual-targeted nanosystem. The sequential release of the inhibitors from the nanosystem under acidic conditions first induces cellular senescence and then promotes immune responses. In an in situ liver cancer mouse model and a chemotherapy-resistant mouse model, the nanosystem effectively inhibited tumor growth by 90.33% and 85.15%, respectively. Overall, the nanosystem in this work achieved the sequential release of CDC7 and CD47 inhibitors in situ to trigger senescence and induce immunotherapy, effectively combating liver cancer and overcoming chemoresistance.

Long-acting anti-inflammatory injectable DEX-Gel with sustained release and self-healing properties regulates TH1/TH2 immune balance for minimally invasive treatment of allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a prevalent immune-related allergic disease, and corticosteroid nasal sprays serve as the primary treatment for this patient population. However, their short duration of efficacy and frequent administration pose challenges, leading to drug wastage and potential adverse effects. To overcome these limitations, we devised a novel approach to formulate DEX-Gel by incorporating dexamethasone (DEX) into a blend of Pluronic F127, stearic acid (SA), and polyethylene glycol 400 (PEG400) to achieve sustained-release treatment for AR. RESULTS: Following endoscopic injection into the nasal mucosa of AR rats, DEX-Gel exhibited sustained release over a 14-day period. In vivo trials employing various assays, such as flow cytometry (FC), demonstrated that DEX-Gel not only effectively managed allergic symptoms but also significantly downregulated helper T-cells (TH) 2 and TH2-type inflammatory cytokines (e.g., interleukins 4, 5, and 13). Additionally, the TH1/TH2 cell ratio was increased. CONCLUSION: This innovative long-acting anti-inflammatory sustained-release therapy addresses the TH1/TH2 immune imbalance, offering a promising and valuable approach for the treatment of AR and other inflammatory nasal diseases.

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.

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.

Guideline on treating community-acquired pneumonia with Chinese patent medicines.

Community-acquired pneumonia (CAP) is one of the most common infectious diseases, and its morbidity and mortality increase with age. Resistance and mutations development make the use of anti-infective therapy challenging. Chinese patent medicines (CPMs) are often used to treat CAP in China and well tolerable. However, currently there are no evidence-based guideline for the treatment of CAP with CPMs, and the misuse of CPMs is common. Therefore, we established a guideline panel to develop this guideline. We identified six clinical questions through two rounds of survey, and we then systematically searched relevant evidence and performed meta-analyses, evidence summaries and GRADE decision tables to draft recommendations, which were then voted on by a consensus panel using the Delphi method. Finally, we developed ten recommendations based on evidence synthesis and expert consensus. For the treatment of severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Xuebijing injection, Shenfu injection, and Shenmai injection respectively. For the treatment of non-severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Lianhua Qingwen capsule/granule, Qingfei Xiaoyan Pill and Shufeng Jiedu capsule respectively. CPMs have great potential to help in the fight against CAP worldwide, but more high-quality studies are still needed to strengthen the evidence.

Biomechanical effects of S1 sacroiliac screws versus S2 sacroiliac screws on sacroiliac screws combined with a lumbar iliac fixation in the treatment of vertical sacral fractures: a biomechanical finite element analysis.

OBJECTIVE: To examine the impact of sacroiliac screw position and length on the biomechanical properties of triangular osteosynthesis in treating unilateral vertical sacral fractures and provide a clinical reference. METHODS: Unilateral Denis type II sacral fractures were modelled using finite elements to represent Tile C pelvic ring injuries. Six sacroiliac screws were used with iliolumbar fixation patterns to fix the sacral fractures, and the sacral stability, maximum pressure, and stress distribution were compared among the internal fixation modalities. RESULTS: The best vertical stability of the internal fixation model was achieved when the S1 segment was fixed with lengthened sacroiliac screws, followed by when the S1 segment was fixed using normal sacroiliac screws. There was no significant difference in vertical stability between the S1 + S2 dual-segment fixation model and the S1-segment fixation model. The maximum pressure under a vertical force of 600 N showed a trend of L5LS1 < L5NS1 < L5LS12 < L5LS2 < L5NS2 < L5NS12. CONCLUSIONS: In unilateral vertical sacral fractures (Denis II) treated with triangular osteosynthesis using triangular jointing combined with unilateral iliolumbar + sacroiliac screw fixation, the use of a single lengthened sacroiliac screw for the S1 segment is recommended to achieve the best vertical stability of the sacrum with less maximum compression on the internal fixation components. If it is not possible to apply a lengthened sacroiliac screw, the use of a normal sacroiliac screw for the S1 segment is recommended. Adding an S2 screw does not significantly increase the vertical stability of the sacrum.

Identification of cough-variant asthma phenotypes based on clinical and pathophysiologic data.

BACKGROUND: Cough-variant asthma (CVA) may respond differently to antiasthmatic treatment. There are limited data on the heterogeneity of CVA. OBJECTIVE: We aimed to classify patients with CVA using cluster analysis based on clinicophysiologic parameters and to unveil the underlying molecular pathways of these phenotypes with transcriptomic data of sputum cells. METHODS: We applied k-mean clustering to 342 newly physician-diagnosed patients with CVA from a prospective multicenter observational cohort using 10 prespecified baseline clinical and pathophysiologic variables. The clusters were compared according to clinical features, treatment response, and sputum transcriptomic data. RESULTS: Three stable CVA clusters were identified. Cluster 1 (n = 176) was characterized by female predominance, late onset, normal lung function, and a low proportion of complete resolution of cough (60.8%) after antiasthmatic treatment. Patients in cluster 2 (n = 105) presented with young, nocturnal cough, atopy, high type 2 inflammation, and a high proportion of complete resolution of cough (73.3%) with a highly upregulated coexpression gene network that related to type 2 immunity. Patients in cluster 3 (n = 61) had high body mass index, long disease duration, family history of asthma, low lung function, and low proportion of complete resolution of cough (54.1%). TH17 immunity and type 2 immunity coexpression gene networks were both upregulated in clusters 1 and 3. CONCLUSION: Three clusters of CVA were identified with different clinical, pathophysiologic, and transcriptomic features and responses to antiasthmatics treatment, which may improve our understanding of pathogenesis and help clinicians develop individualized cough treatment in asthma.

Efficacy of artesunate in asthma: based on network pharmacology and molecular docking.

Background: Asthma has brought great economic burdens to community. Artesunate has shown certain effects on asthma experimentally, but relevant mechanisms are not clear. This study aims to systemically evaluate the efficacy and safety of artesunate and its metabolite, dihydroartemisinin (DHA), in asthma, based on network pharmacology and molecular docking. Methods: All the information before March 1st, 2022 was collected. We evaluated the physicochemistry and Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of artesunate and DHA by SwissADME and ADMETlab, identified targets of artesunate and DHA from SwissTargetPrediction and PharmMapper, and acquired genes participating in asthma from GeneCards and DisGeNET. Overlapping targets and hub genes were identified with Maximal Clique Centrality (MCC) algorithm in Cytoscape, cytoHubba. Enrichment analyses were performed to analyze the potential mechanisms and target sites. Molecular docking was utilized to investigate the receptor-ligand interactions on Autodock Vina and visualized in PyMOL. Results: Artesunate and DHA showed acceptable druglikeness and safety for clinical application. A total of 282 targets of compounds and 7,997 targets of asthma were identified. 172 overlapping targets were visualized in a compound-target and protein-protein interaction network. Biofunction analysis showed the clustering associations with biosynthesis and metabolism of and response to steroid hormone, immune and inflammatory response, airway hyperresponsiveness, airway remodeling and cell survival and death regulation. CCND1, CASP3, MTOR, ERBB2, MAPK3, EGFR, MAP2K1, PTGS2, JAK2, and CASP8 were identified as the hub targets. Molecular docking indicated 10 stable receptor-ligand interactions, except for CASP3. Conclusions: Artesunate has the potential to be a potent and safe anti-asthmatic agent based on diverse therapeutic mechanisms and acceptable safety.

Role of clinical biomarkers in predicting the effectiveness of omalizumab.

OBJECTIVE: To explore whether baseline clinical biomarkers and characteristics can be used to predict the responsiveness of omalizumab. METHODS: We retrospectively analyzed a cohort of patients with severe asthma who received omalizumab treatment and collected their baseline data and relevant laboratory examination results along with case records of omalizumab treatment responsiveness after 16 weeks. We compared the differences in variables between the group of patients that responded to omalizumab therapy and the non-responder group, and then performed univariate and multivariate logistic regression. Finally, we analyzed the difference in response rate for subgroups by selecting cut-off values for the variables using Fisher's exact probability method. RESULTS: This retrospective, single-center observational study enrolled 32 patients with severe asthma who were prescribed daily high-dose inhaled corticosteroids and long-acting ß2 receptor agonists on long-acting muscarinic receptor antagonists with or without OCS. Data on age, sex, BMI, bronchial thermoplasty, FeNO, serum total IgE, FEV1, blood eosinophils, induced sputum eosinophils, blood basophils, and complications were not significantly different between the responder and non-responder groups. In the univariate and multivariate logistic regression, all the variants were not significant, and we were unable to build a regression model. We used normal high values and the mean or median of variables as cut-off values to create patient subgroups for the variables and found no significant difference in the omalizumab response rate between the subgroups. CONCLUSION: The responsiveness of omalizumab is not associated with pretreatment clinical biomarkers, and these biomarkers should not be used to predict the responsiveness of omalizumab.

Artesunate inhibits airway remodeling in asthma via the MAPK signaling pathway.

Background: Artesunate (ART), is a semi-synthetic water-soluble artemisinin derivative extracted from the plant Artemisia annua, which is often used to treating malaria. In vivo and in vitro studies suggested it may help decrease inflammation and attenuate airway remodeling in asthma. However, its underlying mechanism of action is not elucidated yet. Herein, an attempt is made to investigate the ART molecular mechanism in treating asthma. Methods: The BALB/c female mice sensitized via ovalbumin (OVA) have been utilized to establish the asthma model, followed by carrying out ART interventions. Lung inflammation scores by Haematoxylin and Eosin (H&E), goblet cell hyperplasia grade by Periodic Acid-Schiff (PAS), and collagen fibers deposition by Masson trichrome staining have been utilized for evaluating how ART affected asthma. RNA-sequencing (RNA-seq) analyses were performed to identify differentially expressed genes (DEGs). The DEGs were analyzed by Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and Protein-Protein interaction (PPI) function analyses. Hub clusters were found by Cytoscape MCODE. Subsequently, Real-Time quantitative PCR (RT-qPCR) verified the mRNA expression profiles of DEGs. Finally, immunohistochemistry (IHC) and western blots have validated the relevant genes and potential pathways. Results: ART considerably attenuated inflammatory cell infiltration, mucus secretion, and collagen fibers deposition. KEGG pathway analysis revealed that the ART played a protective role via various pathways including the mitogen-activated protein kinase (MAPK) pathway as one of them. Moreover, ART could alleviate the overexpression of found in inflammatory zone 1(FIZZ1) as revealed by IHC and Western blot analyses. ART attenuated OVA-induced asthma by downregulating phosphorylated p38 MAPK. Conclusion: ART exerted a protective function in a multitarget and multi-pathway on asthma. FIZZ1 was a possible target for asthma airway remodeling. The MARK pathway was one of the key pathways by which ART protected against asthma.

Application of Digital Orthopedic Technology in Orthopedic Trauma.

In order to solve the limitation of auxiliary treatment means in the process of orthopedic trauma surgery, and further improve the effective integration of orthopedic trauma clinical surgery and computer technology, a new orthopedic trauma auxiliary treatment means based on digital orthopedic technology was proposed with the aid of virtual digital technology. The method builds a 3D model of fracture fragments through 3D orthopedic modeling and obtains a high-quality 3D model through processing. Later clinical tests verify the feasibility of this auxiliary treatment method. The test results show that the precision of the 3D reconstruction model based on custom option fitting is higher than that based on optimal option fitting, and the precision difference is within 0.2%. This result also indicates that the 3D model obtained by 3D reconstruction has higher accuracy. The results show that three-dimensional finite element modeling technology can accurately simulate the stress of the spine of orthopedic patients and can reduce the incidence of complications through preoperative diagnosis, curative effect prediction, and trauma surgery, which has a good aid for postoperative recovery.