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Public databases have become invaluable resources for disease research, particularly in the realm of identifying and validating biomarkers, thus playing a significant role in enhancing our understanding of respiratory diseases. To facilitate this understanding, the development of user-friendly analytical tools and advanced systematic models that leverage the growing omics data and clinical information datasets is essential. Despite the importance of such resources, the research progress related to respiratory diseases is hindered by the absence of a centralized platform housing easily accessible datasets and accompanying visualization tools. In an effort to streamline and standardize information sharing across diverse respiratory research initiatives, we introduce Idbview, a specialized digital database focusing on respiratory conditions, offering interactive visualization functionalities powered by both Vue and R Shiny applications. Idbview brings together clinical data and various omics datasets, serving as a centralized repository, while also providing users with a suite of interactive tools to analyze and visualize data from multiple perspectives. As a comprehensive resource hub, Idbview aims to support the research community in conducting further studies in both clinical and bioinformatics domains, with the website accessible at https://idbview.com.

Abstract Uveal melanoma (UM) is the most common primary ocular malignancy in adults, and the 5‐year disease‐related mortality rate is 30%. MAL proteolipid family (MALs), including T‐cell differentiation protein (MAL), T‐cell differentiation protein 2 (MAL2), and T‐cell differentiation protein like (MALL), were involved in the progression and prognosis of many different cancers. However, the role of MALs in UM was not reported. UM samples were extracted from The Cancer Genome Atlas. R software (R3.6.3) was used to comprehensively analyze the roles of the MALs (significance threshold: p

Abstract Objective Asthma stands as one of the most prevalent chronic respiratory conditions in children, with its pathogenesis tied to the actived antigen presentation by dendritic cells (DCs) and the imbalance within T cell subgroups. This study seeks to investigate the role of the transcription factor EB (TFEB) in modulating the antigen presentation process of DCs and its impact on the differentiation of T cell subgroups. Methods Bone marrow dendritic cells (BMDCs) were activated using house dust mites (HDM) and underwent RNA sequencing (RNA-seq) to pinpoint differentially expressed genes. TFEB mRNA expression levels were assessed in the peripheral blood mononuclear cells (PBMCs) of both healthy children and those diagnosed with asthma. In an asthma mouse model induced by HDM, the TFEB expression in lung tissue DCs was evaluated. Further experiments involved LV-shTFEB BMDCs co-cultured with T cells to explore the influence of TFEB on DCs’ antigen presentation, T cell subset differentiation, and cytokine production. Results Transcriptomic sequencing identified TFEB as a significantly differentially expressed gene associated with immune system pathways and antigen presentation. Notably, TFEB expression showed a significant increase in the PBMCs of children diagnosed with asthma compared to healthy counterparts. Moreover, TFEB exhibited heightened expression in lung tissue DCs of HDM-induced asthmatic mice and HDM-stimulated BMDCs. Silencing TFEB resulted in the downregulation of MHC II, CD80, CD86, and CD40 on DCs. This action reinstated the equilibrium among Th1/Th2 and Th17/Treg cell subgroups, suppressed the expression of pro-inflammatory cytokines like IL-4, IL-5, IL-13, and IL-17, while augmenting the expression of the anti-inflammatory cytokine IL-10. Conclusion TFEB might have a vital role in asthma’s development by impacting the antigen presentation of DCs, regulating T cell subgroup differentiation, and influencing cytokine secretion. Its involvement could be pivotal in rebalancing the immune system in asthma. These research findings could potentially unveil novel therapeutic avenues for treating asthma.

BackgroundMycoplasma pneumoniae (MP) is a significant cause of community-acquired pneumonia with high macrolide resistance rates. Various COVID-19 pandemic restrictions have impacted the prevalence of MP.ObjectiveTo assess the changes in the pattern of MP infections among children before, during, and after the COVID-19 pandemic.MethodsA total of 36685 enrolled patients, aged 0-18 years, diagnosed with pneumonia and admitted to Children’s Hospital of Chongqing Medical University from January 2019 to December 2023, were retrospectively reviewed in this study. The epidemiological characteristics of pediatric MP infection were analyzed.ResultsAmong 36685 patients, 7610 (20.74%) tested positive for MP. The highest positive rate was observed among children aged over 6 years (55.06%). There was no gender disparity in MP infection across the three phases of the COVID-19 pandemic. Hospital stays were longest for children during the COVID-19 pandemic (P

IntroductionMycoplasma pneumoniae pneumonia (MPP) and Streptococcus pneumoniae pneumonia (SPP) are frequent causes of respiratory tract infection, the aims of the study were to explore the differences in clinical features between children with MPP and those with SPP.MethodsThis retrospective study included admitted children who were diagnosed with MPP or SPP over 5 years from January 2015 to January 2020. Children with MPP were compared to children with SPP in terms of clinical features.Results506 patients with MPP were compared to 311 patients with SPP in terms of clinical differences. The MPP group with a median age of 60 [29–89] months and the SPP group with a median age of 24 [10–40] months. Patients with MPP were older and had a higher occurrence of receiving antibiotics before admission, fever, dry cough, polypnea and diarrhea than patients with SPP (all p 48.5 months shown to be an independent predictive factor for the early evaluation and identification of MPP.DiscussionIn conclusion, patients with MPP and SPP usually present with fever, cough and some nonspecific symptoms. Our study showed that age, dry cough, polypnea, LDH levels, and PCT levels were independent predictive factors associated with MPP and SPP.

Abstract The aim of this study is to research the expression of the transient receptor potential canonical channel 3 (TRPC3) in a neonatal hyperoxic lung injury model of bronchopulmonary dysplasia (BPD), and to further investigate the role of the TRPC3/nuclear factor‐κB (NF‐κB) signaling pathway in hyperoxia‐induced BPD by a TRPC3 agonist (GSK1702934A). The hyperoxic lung injury model of BPD was established in Sprague–Dawley neonatal rats. Hematoxylin and eosin (HE) staining and radial alveolar count (RAC) values showed that the hyperoxic lung injury model of BPD was successfully established in the neonatal rats, and pulmonary edema was found in the neonatal rats with BPD. The results of reference transcriptome sequencing, Quantitative real‐time PCR (qPCR), and western blot showed lower pulmonary expression of TRPC3 in the BPD group than in the control group. Immunofluorescence showed predominant expression of TRPC3 in airways and pulmonary vessels, and the fluorescence intensity of the BPD group was lower than that of the control group. Lung dry‐to‐wet weight ratio, HE staining, and RAC value showed that the lung histomorphology significantly improved in the BPD + TRPC3 agonist group compared with the BPD group on day 14 but did not revert to the level of the control group. According to qPCR results, compared with the control group, the expression of NF‐κB1 decreased and the expression of NF‐κBiz increased in the BPD group, whereas the expression of NF‐κBiz decreased in the BPD + TRPC3 agonist group. Therefore, we draw the conclusion that TRPC3 may activate NF‐κB by inhibiting NF‐κBiz to promote cell proliferation and lung growth and development.

Abstract Background Asthma is a common respiratory disease. In asthma, the small airways have more intensive inflammation and prominent airway remodelling, compared to the central airways. We aimed to investigate the predictive value of risk factors and the fractional concentration of exhaled nitric oxide (FeNO) for persistent small airway dysfunction (p-SAD), and compare the effects of different treatment modalities. Methods This retrospective cohort study included 248 children with asthma (aged 4–11 years). Binary logistic regression was used to analyse the risk factors for p-SAD. Correlations among FEV1/FVC, small airway function parameters, and FeNO levels in patients with asthma were analysed using Spearman’s rank correlation. The receiver operating characteristic curve and the Delong test were used to analyse the predictive value of FeNO for p-SAD. Differences in the treatment effects of inhaled corticosteroids (ICS) and ICS with a long-acting beta-agonist (ICS/LABA) on p-SAD were analysed using Fisher’s exact test. Results Asthmatic children with older age of receiving the regular treatment (OR 1.782, 95% CI 1.082–2.935), with younger age at the time of onset of suspected asthma symptoms (OR 0.602, 95% CI 0.365–0.993), with longer duration of using ICS or ICS/LABA (OR 1.642, 95% CI 1.170–2.305) and with worse asthma control (OR 3.893, 95% CI 1.699–8.922) had increased risk for p-SAD. Significant negative correlations of small airway function parameters with FeNO at a 200 mL/s flow rate (FeNO200), and the concentration of nitric oxide in the alveolar or acinar region (CaNO) were observed. The areas under the curve of FeNO200 (cut-off:10.5ppb), CaNO (cut-off:5.1ppb), and FeNO200 combined with CaNO were 0.743, 0.697, and 0.750, respectively, for asthma with p-SAD. After using ICS or ICS/LABA, switching to ICS/LABA was easier than continuing with ICS to improve small airway dysfunction (SAD) in the 8th month. Conclusions Paediatric asthma with p-SAD is associated with older age at receiving regular treatment, younger age at the time of onset of suspected asthma symptoms, longer duration of using ICS or ICS/LABA, worse asthma control, and higher FeNO200 and CaNO levels, all of which can be combined with small airway function indicators to distinguish p-SAD from asthma. ICS/LABA improves SAD better than ICS alone.

Abstract Background Metastasis is one of the leading cause contributes to treatment failure and poor prognosis of hepatocellular carcinoma (HCC) patients. The underlying mechanism of HCC metastasis remains to be determined. Although several RNA binding proteins (RBPs) have been found to participate in tumorigenesis and progression of liver cancer, the role of RBPs in HCC patients with extrahepatic metastases is poorly understood. Methods By performing RNA-seq of primary HCC tissues (including HCC with extrahepatic metastasis and those did not develop metastasis), we identified a set of HCC metastasis-associated RBPs candidates. Among which, ribosomal protein S7 (RPS7) was found to be remarkably increased in HCC tissues and be strongly related to HCC poor survival. Overexpression or CRISPR-Cas9–mediated knockout were applied to investigate the role of RPS7 on the metastasis-associated phenotypes of HCC cells. RNA sequencing, RIP, RNA-pull down, dual luciferase reporter assay, nascent RNA capture assay, and RNA decay and so on, were applied to reveal the underlying mechanism of RPS7 induced HCC metastasis. Results Gain- and loss- of function analyses revealed that RPS7 promoted HCC cells adhesion, migration and invasion capabilities, as well as lung metastasis. Mechanistically, we uncovered that lysyl oxidase-like 2 (LOXL2) was a critical downstream target of RPS7. RPS7 could stabilize LOXL2 mRNA by binding to AUUUA motifs in the 3155–3375 region of the 3’UTR of LOXL2 mRNA, thus increased LOXL2 expression via elevating LOXL2 mRNA abundance. Further research revealed that LOXL2 could accelerate focal adhesion formation through maintaining the protein stability of ITGB1 and activating ITGB1-mediated FAK/SRC signaling pathway, and thereby contribute to the pro-metastasis effect of RPS7. Conclusions Taken together, our data reveal a novel function of RPS7 in HCC metastasis, also reveal the critical roles of the RPS7/LOXL2/ITGB1 axis in HCC metastasis and shed new light on the exploration of molecular drugs against HCC.

Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis-related hospitalizations among children under 5 years of age, with reinfection being common throughout life. Maternal vaccination has emerged as a promising strategy, delivering elevated antibody levels to newborns for immediate protection. However, limited research has explored the protective efficacy of maternal antibodies (matAbs) against secondary RSV infections in offspring. To address this gap, we employed a mouse model of maternal RSV vaccination and secondary infection of offspring to evaluate lung pathology following RSV reinfection in mice with varying levels of maternal antibody (matAb). Additionally, we aimed to investigate the potential causes of exacerbated lung inflammation in offspring with high matAb levels following secondary RSV exposure. Our findings revealed that offspring with elevated levels of maternal pre-F antibody demonstrated effective protection against lung pathology following the initial RSV infection. However, this protection was compromised upon reinfection, manifesting as heightened weight loss, exacerbated lung pathology, increased expression of RSV-A N genes, eosinophilia, enhanced IL-5, IL-13, MUC5AC, and eosinophils Major Basic Protein (MBP) production in lung tissue compared to offspring lacking matAbs. Importantly, these unexpected outcomes were not attributed to antibody-dependent enhancement (ADE) resulting from declining matAb levels over time. Notably, our findings showed a decline in secretory IgA (sIgA), mucosal IgA, and mucosal IgG levels in offspring with high matAb levels post-primary RSV challenge. We propose that this decline may be a critical factor contributing to the ineffective protection observed during secondary RSV exposure. Overall, these findings offer valuable insights into maternal vaccination against RSV, contributing to a comprehensive understanding and mitigation of potential risks associated with maternal RSV vaccination.

Abstract The common human coronaviruses (HCoVs) HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 which are members of the coronavirus family are long co-existed with humans and widely distributed globally. Common HCoVs usually cause mild, self-limited upper respiratory tract infections (URTI), and also associated with lower respiratory tract infections (LRTI), especially in children. However, there are little multicentre studies have been conducted in children of several different areas in China, and the epidemic potential of common HCoVs remains unclear. Understanding of the common HCoVs is valuable for clinical and public health. Herein, we retrospectively analysed the medical records of children with acute lower respiratory tract infection admitted to 9 hospitals from different regions in China from 2014 to 2019. Of the 124 patients who tested positive for coronaviruses, OC43 was the predominant type, accounting for 36.3% (45/124) of the detections. Children aged ≤ 6 months and 12–23 months had the highest detection rate of common HCoVs, and the detection rate gradually declined after 2 years old. These four HCoVs could be detected all year round. Among the areas of our study, the overall positive rate was higher in southern China, especially in Guangzhou (29/124, 23.4%). Moreover, common HCoV-positive patients were codetected with 9 other common respiratory pathogens. 229E (11/13, 84.6%) was the most frequently associated with codetection, with EV/RhV was the most frequently codetected virus. Cough (113/124, 91.1%) and fever (73/124, 58.9%) were the most common symptoms of common HCoVs infection.

In order to research the effect of viscosity modifying admixture (VMA) on the rebar rust resistance in self-compacting concrete, stereoscopic microscope, linear polarization, electrochemical impedance spectroscopy and Tafel polarization test method were utilized to study the effect of three commonly used viscosity modifying admixtures, polyacrylamide (PAM), hydroxypropyl methyl cellulose (HPMC) and hydroxyethyl cellulose (HEC) on the rebar rust resistance performance in simulated concrete pore solution. Results showed that PAM, HPMC and HEC could effectively inhibit the corrosion of rebar in simulated concrete pore solution. With the content of VMAs increasing, the corrosion resistance of rebar was enhanced. The rust resistance ability of the three VMAs on rebar increased in the following order: HEC< HPMC< PAM. Furthermore, the inhibition effect of PAM, HPMC and HEC on the cathodic corrosion process of rebar was stronger than that of the anodic process. Among them, PAM and HPMC were cathode type rust inhibitors, while HEC was a mixed type rust inhibitor that mainly suppressed the cathode.

Severe bronchopulmonary dysplasia (BPD) is a chronic lung disorder that primarily affects premature babies with extremely low birth weight and involves in multiple organ system; no effective pharmacotherapy for this disease exists, and mortality remains high. Based on the evidence from previous preclinical studies and phase I clinical trials, this study aims to test the safety of intravenous application of a single dose of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in patients with severe BPD. The Mesenchymal Stem cells for Bronchopulmonary Dysplasia Treatment (MSBDT) trial is a single center, open-label, dose-escalation phase I clinical trial. Severe BPD patients were enrolled in Children Hospital of Chongqing Medical University, Chongqing, China. The first six patients were treated with low-dose hUC-MSCs (1 × 106 cells/kg) and the next seven patients were treated with high-dose hUC-MSCs (5 × 106 cells/kg). This study is registered with ClinicalTrials.gov, number NCT03558334. No prespecified infusion-associated adverse events, immediate complication, respiratory or cardiovascular compromise were observed during infusion and 24 h after infusion. No significant changes in safety laboratory values were observed. One death event occurred in the low-dose group on study day 10, and one death event occurred in the high-dose group on study day 24, while, after review in detail, the two cases are not believed to be infusion-associated events. In conclusion, intravenous application of a single dose of hUC-MSCs was tolerated in thirteen patients with severe BPD.

Aiming at the problems of large statistical error and the poor real-time performance of catch weight in the ocean fishing tuna industry, an algorithm based on improved YOLOv8-Pose for albacore tuna (Thunnus alalunga) fork length extraction and weight estimation is proposed, with reference to the human body’s pose estimation algorithm. Firstly, a lightweight module constructed using a heavy parameterization technique is used to replace the backbone network, and secondly, a weighted bidirectional feature pyramid network BIFPN is utilized. Finally, the upper and lower jaw and tail feature points of the albacore tuna (Thunnus alalunga) were extracted using the key point detection algorithm, and the weight of the albacore tuna (Thunnus alalunga) was estimated based on the fitted relationship between fork length and weight. The experimental results show that the improved YOLOv8-Pose algorithm reduces the number of model parameters by 13.63% and the number of floating-point operations by 14.03% compared with the baseline model without decreasing the accuracy of the target detection and key point detection and improves the model inference speed by 374%. At the same time, it reduces the drift of the key point detection, and the error of the comparison with the actual albacore tuna (Thunnus alalunga) body weight is not more than 10%. The improved key point detection algorithm has high detection accuracy and inference speed, which provides accurate yield data for pelagic fishing and is expected to solve the existing statistical problems and improve the accuracy and real-time performance of data in the fishing industry.

RUNX3 is a transcription factor and tumor suppressor that is silenced or inactivated in diverse tumors. The effect of RUNX3 on the epithelial–mesenchymal transition in clear-cell renal cell carcinoma (CCRCC) remains unclear. We determined the expression of RUNX3 and E-cadherin in tumor tissues and adjacent normal tissues of 30 CCRCC patients; established cultured CCRCC cells with the overexpression of RUNX3; and examined the in vivo tumorigenic function of RUNX3 in a nude mouse xenograft model of CCRCC. RUNX3 and E-cadherin were downregulated in human CCRCC samples. Cell lines with RUNX3 overexpression had reduced cell proliferation, invasion, and migration, a prolonged cell cycle, increased apoptosis, and increased expression of E-cadherin. In the nude mouse xenograft model of CCRCC, tumors with the overexpression of RUNX3 had smaller volumes and weights and had increased expression of E-cadherin. In conclusion, RUNX3 overexpression increased the level of E-cadherin and inhibited the proliferation, invasion, and migration of CCRCC in vitro and in vivo. RUNX3 has potential use as a biomarker for prognostic monitoring of CCRCC and as a therapeutic target for the treatment of this cancer.

Slope kinematics is normally used to evaluate the temporal and spatial evolution of landslides. The inverse velocity method (INV) is an important tool for predicting the initiation of landslide, but its correlation with the physical and mechanical mechanisms of multiple physical fields inside the landslide need to be further clarified. In this paper, the slope deformation and geological characteristics of the Lijie Beishan landslide in Zhouqu, Gansu Province was investigated. The inverse velocity method, velocity threshold method and numerical simulation based on unsaturated soil theory were used to study the kinematic characteristic of slope. The results showed that after the lowest value of the inverse velocity on June 3, 2021, a stable stage lasted for approximately 60 days and then suddenly accelerated on September 20. The velocity became more than 200 mm/d over 20 days, and the deformation did not converged. There was an obvious acceleration point in the time-dependent inverse velocity curve. The end of the landslide life cycle was obtained by extending the straight line after the onset of the acceleration point. The prediction period was within 8 days compared to the actual instability startup, and the landslide was predicted 130 days in advance. According to the post analysis of the whole time-dependent velocity curve, the multi-level speed thresholds of v1=20 mm/d, v2=60 mm/d, and v3=100 mm/d were set up. Because there were two peaks of velocity, the prediction of landslide triggering was lagging compared to the inverse velocity method. The coupling of slope stresses, deformation and pore water transportation was simulated. The results showed that the inflection point of the time-dependent deformation curve was correlated with the increase in precipitation intensity, and the cumulative precipitation was negatively exponentially correlated with the safety factor. The cumulative deformation obtained by numerical simulation was 2 250 mm, the velocity of deformation was 10-35 mm/d, and the inverse velocity was 0.03-0.12 d/mm, which were close to the actual monitoring data. However, there was still a deviation between the prediction of the inflection point of slope deformation and the actual situation.

Abstract Objective The therapeutic effect of umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in combination with pirfenidone (PFD) on pulmonary fibrosis in mice and its possible mechanism were investigated. Methods C57BL/6 mice were randomly divided into six groups: control group, model group, P10 group, P30 group, P100 group, and P300 group. Modeled by tracheal intubation with 3 mg/kg bleomycin drip, each dose of PFD was administered daily by gavage from day 7 onwards. The mice were observed continuously for 21 days and survival was recorded. Lung tissues were collected on day 21, and hematoxylin–eosin (HE) and Masson staining were performed to assess morphological changes and collagen deposition in the lungs. Collagen content was measured by the Sircol method, and fibrosis marker levels were detected by PCR and Western blot. Another batch of C57BL/6 mice was then randomly divided into five groups: hUC-MSC control group, model group, P100 group, hUC-MSC treatment group, and hUC-MSCs + P30 group. On day 7, 5 × 105 hUC-MSCs were injected into the tail vein, the mice were administered PFD gavage daily from day 7 onwards, and their survival was recorded. Lung tissues were collected on day 21 to detect pathological changes, the collagen content, and the expression of regulator of G protein signaling 2 (RGS2). Pulmonary myofibroblasts (MFBs) were divided into an MFB group and an MFB + hUC-MSCs group; different doses of PFD were administered to each group, and the levels of RGS2, intracellular Ca2+, and fibrosis markers were recorded for each group. Results Compared with other PFD group doses, the P100 group had significantly improved mouse survival and lung pathology and significantly reduced collagen and fibrosis marker levels (p

Abstract Background A healthy alveolar epithelium is critical to the gas exchange function of the lungs. As the major cell type of alveolar epithelium, alveolar type 2 (AT2) cells play a critical role in maintaining pulmonary homeostasis by serving as alveolar progenitors during lung injury, inflammation, and repair. Dysregulation of AT2 cells may lead to the development of acute and chronic lung diseases and cancer. The lack of clinically relevant AT2 cell models hampers our ability to understand pulmonary diseases. Here, we sought to establish reversibly immortalized mouse pulmonary alveolar type 2 cells (imPAC2) and investigate their potential in forming alveolar organoids to model pulmonary diseases. Methods Primary mouse pulmonary alveolar cells (mPACs) were isolated and immortalized with a retroviral expression of SV40 Large T antigen (LTA). Cell proliferation and survival was assessed by crystal violet staining and WST-1 assays. Marker gene expression was assessed by qPCR, Western blotting, and/or immunostaining. Alveolar organoids were generated by using matrigel. Ad-TGF-β1 was used to transiently express TGF-β1. Stable silencing β-catenin or overexpression of mutant KRAS and TP53 was accomplished by using retroviral vectors. Subcutaneous cell implantations were carried out in athymic nude mice. The retrieved tissue masses were subjected to H & E histologic evaluation. Results We immortalized primary mPACs with SV40 LTA to yield the imPACs that were non-tumorigenic and maintained long-term proliferative activity that was reversible by FLP-mediated removal of SV40 LTA. The EpCAM+ AT2-enriched subpopulation (i.e., imPAC2) was sorted out from the imPACs, and was shown to express AT2 markers and form alveolar organoids. Functionally, silencing β-catenin decreased the expression of AT2 markers in imPAC2 cells, while TGF-β1 induced fibrosis-like response by regulating the expression of epithelial-mesenchymal transition markers in the imPAC2 cells. Lastly, concurrent expression of oncogenic KRAS and mutant TP53 rendered the imPAC2 cells a tumor-like phenotype and activated lung cancer-associated pathways. Collectively, our results suggest that the imPAC2 cells may faithfully represent AT2 populations that can be further explored to model pulmonary diseases.

Abstract Background Primary ciliary dyskinesia (PCD) is a rare, inherited disorder of the motile cilia that exhibits genetic and clinical heterogeneity among different populations. PCD diagnosis remains challenging owing to the heterogeneity of associated clinical features and lack of a gold standard diagnostic test. Objective The aim of this study was to analyze the clinical and genetic characteristics of a group of children with clinically suspected PCD in one region of China, with the goal of providing a more robust knowledge base regarding the genetic stratification underlying this disease in Chinese populations. Methods We retrospectively analyzed the data from 38 patients with clinically suspected PCD who had undergone next-generation sequencing (NGS) between November 2016 and March 2021 in the respiratory department of a tertiary Children‘s hospital in Western China. The genetic features of the confirmed cases were summarized by reviewing data associated with other cohorts of Chinese children. Results Overall, 16 patients were ultimately diagnosed with PCD with a median age of 8.5 years. All patients presented with a chronic wet cough, 93.75% exhibited chronic or recurrent sinusitis/rhinitis, 43.75% experienced recurrent wheezing, 56.25% reported respiratory symptoms present since infancy, 31.25% had a history of neonatal respiratory distress (NRD), and 25% exhibited otitis media. Only 18.75% of these patients exhibited laterality defects. High frequencies of DNAH11 mutations were detected by integrating data from PCD patient cohorts in China. Conclusion The high frequency of DNAH11 mutations may limit the utility of transmission electron microscopy (TEM) as a first-line approach to diagnosing PCD in China in the absence of other indicators.

BackgroundMultinational studies have reported that the implementation of nonpharmaceutical interventions (NPIs) to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission coincided with the decline of other respiratory viruses, such as influenza viruses and respiratory syncytial virus.ObjectiveTo investigate the prevalence of common respiratory viruses during the coronavirus disease 2019 (COVID-19) pandemic.MethodsRespiratory specimens of children with lower respiratory tract infections (LRTIs) hospitalized at the Children’s Hospital of Chongqing Medical University from January 1, 2018 to December 31, 2021 were collected. Seven common pathogens, including respiratory syncytial virus (RSV), adenovirus (ADV), influenza virus A and B (Flu A, Flu B), and parainfluenza virus types 1–3 (PIV1–3), were detected by a multiplex direct immunofluorescence assay (DFA). Demographic data and laboratory test results were analyzed.Results1) A total of 31,113 children with LRTIs were enrolled, including 8141 in 2018, 8681 in 2019, 6252 in 2020, and 8059 in 2021.The overall detection rates decreased in 2020 and 2021 (P < 0.001). The detection rates of RSV, ADV, Flu A, PIV-1, and PIV-3 decreased when NPIs were active from February to August 2020, with Flu A decreasing most predominantly, from 2.7% to 0.3% (P < 0.05). The detection rates of RSV and PIV-1 resurged and even surpassed the historical level of 2018–2019, while Flu A continued decreasing when NPIs were lifted (P < 0.05). 2) Seasonal patterns of Flu A completely disappeared in 2020 and 2021. The Flu B epidemic was observed until October 2021 after a long period of low detection in 2020. RSV decreased sharply after January 2020 and stayed in a nearly dormant state during the next seven months. Nevertheless, the detection rates of RSV were abnormally higher than 10% in the summer of 2021. PIV-3 decreased significantly after the COVID-19 pandemic; however, it atypically surged from August to November 2020.ConclusionThe NPIs implemented during the COVID-19 pandemic affected the prevalence and seasonal patterns of certain viruses such as RSV, PIV-3, and influenza viruses. We recommend continuous surveillance of the epidemiological and evolutionary dynamics of multiple respiratory pathogens, especially when NPIs are no longer necessary.

The overall failure mode of a tower-shaped unstable rock mass associated with bottom compression-induced fracturing frequently occurs on the steep-high slope with a gentle dip angle in the karst regions, and its damage-catastrophe mechanism belongs to a key issue in the mountainous disaster discipline. Taking a collapse case of Zengziyan unstable rock mass #W12 in Nanchuan District of Chongqing, China, for example, a damage-catastrophe geomechanical model considering the load and the water- weakening effect was built. A damage constitutive equation and a total damage degree evolution equation were derived based on the strain equivalence principle, and the water-weakening function was developed into a cubic function in one unknown for the softening coefficient. Then, the geomechanical model was simplified into an equivalent spring model and the damage-fold catastrophe model was established by the energy balance theory. Finally, the failure criterion and eigenvalue expression of critical displacement mutation for the tower-shaped unstable rock mass were obtained. The results show that when the unstable rock mass #W12 fails, the control variant determining the stability of a fold catastrophe model is –0.003 251, which is less than zero, demonstrating that the system turns into an unstable state. The initial calculated value of the theoretical displacement mutation of 148.70 mm is smaller than the first inflection point of the measured value of 154.34 mm, and the relative error is about 3.65% which tends to be safer. The theoretical damage constitutive curve and evolution curve are consistent with the numerical results obtained in the literature, suggesting that the theoretical model has a good applicability. The research outcome can be applied to predicting the damage evolution process and the eigenvalue of critical displacement mutation for the compression-induced fracturing and failure of a tower-shaped unstable rock mass. It also provides a theoretical basis for monitoring and early-warning of the steep-high unstable rock mass collapse and disaster prevention and mitigation in limestone area.

Abstract Background Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs. Result The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints. Conclusions In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs.

Objective. Skin cutaneous melanoma (SKCM) is a highly lethal malignancy that poses a significant threat to human health. Recent research has shown that competing endogenous RNA (ceRNA) regulatory networks play a critical role in the development and progression of various types of cancer, including SKCM. The objective of this study is to investigate the ceRNA regulatory network associated with the transmembrane protein semaphorin 6A (SEMA6A) and identify the underlying molecular mechanisms involved in SKCM. Methods. Expression profiles of four RNAs, including pseudogenes, long non-coding RNAs, microRNAs, and mRNAs were obtained from The Cancer Genome Atlas database. The analysis was completed by bioinformatics methods, and the expression levels of the selected genes were verified by cell experiments. Results. Bioinformatics analysis revealed that the LINC00511–hsa-miR-625-5p–SEMA6A ceRNA network was associated with SKCM prognosis. Furthermore, immune infiltration analysis indicated that the LINC00511–hsa-miR-625-5p–SEMA6A axis may have an impact on changes in the tumor immune microenvironment of SKCM. Conclusion. The LINC00511–hsa-miR-625-5p–SEMA6A axis could be a promising therapeutic target and a prognostic biomarker for SKCM.

Tyrosine kinase inhibitors (TKIs), as an important tumor therapy, can induce severe proteinuria that significantly affects anti-tumor therapy. Existing therapies against proteinuria induced by other etiologies are currently ineffective for TKI-induced proteinuria. It has been shown that various types of proteinuria are related to podocyte damage caused by changes in the RelA signaling pathway. Our experiments confirmed that TKIs activate the renal RelA signaling pathway, and induce death of podocytes and destruction of the glomerular filtration barrier. Here we found that Liuwei Dihuang Pill (LDP) attenuated the inflammatory injury of podocytes through inhibiting activation of RelA, and subsequently relieved TKI-related proteinuria and prevented the progression of TMA and FSGS. Our finding indicated that LDP may be effective for the treatment of TKI-induced proteinuria, which is clinically significant.

BackgroundPrevious limited studies have identified that Bordetella pertussis (B. pertussis) isolates circulating in China possess distinct molecular features and high rates of erythromycin-resistance (ER). Their evolution and potential impact on the prevention and control of global pertussis are worthy of attention.MethodsThe present cross-sectional study involved 311 non-duplicate and unrelated B. pertussis strains isolated from Chinese children from 2017 to 2019. Their antimicrobial susceptibilities were assessed using both E-test strips and Kirby-Bauer (KB) disk diffusion methods. Seven virulence-related genes (ptxA, ptxC, ptxP, prn, fim2, fim3, and tcfA2) and the A2047G mutation in the 23S rRNA gene were detected by PCR. Based on the susceptibilities and genotypes, 50 isolates were selected for multi-locus variable-number tandem-repeat analysis (MLVA) typing and whole-genome sequencing.ResultsA total of 311 B. pertussis strains were isolated from children with a median age of 4 months (interquartile range: 2–9 months). Strains carrying the ptxP1 allele were more frequent (84.9%, 264/311), were always ER (except for one strain), and were mainly related to ptxA1/ptxC1/prn1 alleles (99.6%, 263/264). The remaining 47 (15.1%) strains carried the ptxP3 allele, mainly harboring the ptxA1/ptxC2/prn2 alleles (93.6%, 44/47), and were sensitive to erythromycin (except for two strains). The two ER-ptxP3 isolates were first identified in China, belonged to MT27 and MT28 according to MLVA, and were classified into sub-lineage IVd by phylogenetic analysis of their genome sequences. This sub-lineage also includes many strains carrying the ptxP3 allele spreading in developed countries. For each tested antimicrobial, the susceptibilities judged by KB disks were consistent with those determined by E-test strips.ConclusionThe present results reveal that B. pertussis strains with the ptxP1-ER profile still dominate in China, and a few strains carrying the ptxP3 allele have acquired the A2047G mutation in the 23S rRNA gene and the ER phenotype. The surveillance of the drug susceptibility of B. pertussis is necessary for all countries, and the KB disk method can be adopted as a screening test.

Abstract Background Glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL) plays an important role in tumors, autoimmunity and inflammation. However, GITRL is not known to modulate the pathogenesis of allergic asthma. In this study, we investigated whether regulating GITRL expressed on dendritic cells (DCs) can prevent asthma and to elucidate its mechanism of action. Methods In vivo, the role of GITRL in modulating house dust mite (HDM)-induced asthma was assessed in adeno-associated virus (AAV)-shGITRL mice. In vitro, the role of GITRL expression by DCs was evaluated in LV-shGITRL bone marrow dendritic cells (BMDCs) under HDM stimulation. And the direct effect of GITRL was observed by stimulating splenocytes with GITRL protein. The effect of regulating GITRL on CD4+ T cell differentiation was detected. Further, GITRL mRNA in the peripheral blood of asthmatic children was tested. Results GITRL was significantly increased in HDM-challenged mice. In GITRL knockdown mice, allergen-induced airway inflammation, serum total IgE levels and airway hyperresponsiveness (AHR) were reduced. In vitro, GITRL expression on BMDCs was increased after HDM stimulation. Further, knocking down GITRL on DCs partially restored the balance of Th1/Th2 and Th17/Treg cells. Moreover, GITRL stimulation in vitro inhibited Treg cell differentiation and promoted Th2 and Th17 cell differentiation. Similarly, GITRL mRNA expression was increased in the peripheral blood from asthmatic children. Conclusions This study identified a novel role for GITRL expressed by DCs as a positive regulator of CD4+ T cells responses in asthma, which implicates that GITRL inhibitors may be a potential immunotherapy for asthma.

Objectives: Linezolid (LNZ) has recently been listed by the World Health Organization (WHO) as a Group A agent for the treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in longer regimens (18–20 months). However, little is known about the safety of LNZ in longer TB treatment regimens in children. Methods: Here we report 31 children who received LNZ treatment for drug-resistant tuberculosis (DR-TB) and extensive tuberculosis in the Children’s Hospital of Chongqing Medical University, China, during September 2016 to March 2019. The mean duration of LNZ treatment was 8.56 months (range, 1–24 months). Results: Of the 31 patients, 13 (42%) had suspected or confirmed adverse events (AEs) related to LNZ treatment, including digestive symptoms, haematological toxicity, neuropathy and lactic acidosis. Haematological toxicity was the most frequent AE, presenting as leukopenia (9/13) and anaemia (5/13). No hepatotoxicity or nephrotoxicity was observed. Two patients suffered from life-threatening lactic acidosis when the LNZ dose was increased to 1.2 g daily, however they recovered following LNZ withdrawal. Conclusion: A high rate of AEs of LNZ treatment was observed in children receiving a longer regimen, which might relate to the treatment course and dose. Haematological toxicity was the most frequent AE in children. It is necessary to regularly monitor the blood chemistry and lactic acid concentration during LNZ treatment.

Abstract The outbreak of 2019 novel coronavirus disease (COVID-19) worldwide is becoming rapidly a major concern. The number of severe cases has increased dramatically worldwide, while specific treatment options are scarce. The main pathologic features of severe or critical COVID-19 were consistent with acute lung injure (ALI)/acute respiratory distress syndrome (ARDS), characterized by cellular fibromyxoid exudates, extensive pulmonary inflammation, pulmonary edema, and hyaline membrane formation. Mesenchymal stem cells (MSCs) can balance the inflammatory response and has been mentioned to be effective on ALI/ARDS from both infectious and noninfectious causes previously, presenting an important opportunity to be applied to COVID-19. In this commentary, we summarize the clinical trials of MSCs treatments on ALI/ARDS and raise MSCs as a hopefully alternative therapy for severe or critical COVID-19.

Abstract Background Bronchopulmonary dysplasia (BPD) is a complex lung pathological lesion secondary to multiple factors and one of the most common chronic lung diseases. It has a poor prognosis, especially in preterm infants. However, effective therapies for this disease are lacking. Stem-cell therapy is a promising way to improve lung injury and abnormal alveolarization, and the human umbilical cord (hUC) is a good source of mesenchymal stem cells (MSCs), which have demonstrated efficacy in other diseases. We hypothesized that intravenously administered allogeneic hUC-MSCs are safe and effective for severe BPD. Methods The MSC-BPD trial is a randomized, single-center, open-label, dose-escalation, phase-II trial designed to investigate the safety and efficacy of hUC-MSCs in children with severe BPD. In this study, 72 patients will be enrolled and randomly divided into two intervention groups and one control group. Patients in the intervention groups will receive a low dose of hUC-MSCs (n = 24; 2.5 million cells/kg) or a high dose of hUC-MSCs (n = 24; 5 million cells/kg) in combination with traditional supportive treatments for BPD. The patients in the control group (n = 24) will be treated with traditional supportive treatments alone without hUC-MSCs. The primary outcome measures will be cumulative duration of oxygen therapy. Follow-up assessments will be performed at 1, 3, 6, 12, and 24 months post intervention, and the key outcome during follow-up will be changes on chest radiography. Statistical analyses will evaluate the efficacy of the hUC-MSC treatment. Discussion This will be the first randomized controlled trial to evaluate the safety and efficacy of intravenously administered hUC-MSCs in children with severe BPD. Its results should provide a new evidence-based therapy for severe BPD. Trial registration ClinicalTrials.gov, ID: NCT03601416 . Registered on 26 July 2018.

Although it is known that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) alleviate hyperoxic lung injury of bronchopulmonary dysplasia (BPD) in animal models, the role of microvesicles (MVs) derived from hUCMSCs in BPD is poorly defined. Furthermore, antenatal inflammation has been linked to high risk of BPD in preterm infants. The purpose of this study was to explore whether MVs derived from hUCMSCs can preserve lung structure and function in an antenatal lipopolysaccharide- (LPS-) induced BPD rat model and to clarify the underlying mechanism. We demonstrate that antenatal LPS induced alveolar simplification, altered lung function, and dysregulated pulmonary vasculature, which restored by hUCMSCs and MVs treatment. Furthermore, MVs were large vesicles with a diameter of 100-900 nanometers and mostly uptaken by alveolar epithelial type II cells (AT2) and macrophages. Compared with the LPS-exposed group, MVs restored the AT2 cell number and SP-C expression in vivo and promoted the proliferation of AT2 cells in vitro. MVs also restored the level of IL-6 and IL-10 in lung homogenate. Additionally, PTEN/AKT and MAPK pathways were associated with the protection of MVs. Taken together, this study suggests MVs derived from hUCMSCs improve lung architecture and function in an antenatal LPS-induced BPD rat model by promoting AT2 cell proliferation and attenuating lung inflammation; thus, MVs provide a promising therapeutic vehicle for BPD treatment.

Extracellular vesicles (EVs) are nano-sized membrane vesicles secreted by cells. EVs serve as a mediator for cell-to-cell communication by regulating the exchange of genetic materials and proteins between the donor and surrounding cells. Current studies have explored the therapeutic value of mesenchymal stem cells-derived EVs (MSC-EVs) for the treatment of infectious diseases extensively. MSC-EVs can eliminate the pathogen, regulate immunity, and repair tissue injury in contagious diseases through the secretion of antimicrobial factors, inhibiting the replication of pathogens and activating the phagocytic function of macrophages. MSC-EVs can also repair tissue damage associated with the infection by upregulating the levels of anti-inflammatory factors, downregulating the pro-inflammatory factors, and participating in the regulation of cellular biological behaviors. The purpose of this mini-review is to discuss in detail the various mechanisms of MSC-EV treatment for infectious diseases including respiratory infections, sepsis, and intestinal infections, as well as challenges for implementing MSC-EVs from bench to bedside.

Objective: Pertussis is a highly contagious respiratory illness mainly caused by the Gram-negative bacterium Bordetella pertussis. The infection of B. pertussis has been increasing and the current diagnosis of pertussis in children is challenging; little is known of B. pertussis infection in Chongqing. Methods: There were 25,441 children (14,863 male and 10,578 female) with suspected pertussis enrolled in our retrospective study from December 2012 to November 2018. Then 800 children with suspected B. pertussis infection were randomly chosen to be evaluated by simultaneous amplification and testing in this prospective study. Results: Infants younger than 12 months had the greatest burden of pertussis, and the incidence of pertussis in Chongqing appeared to have a periodic pattern. The problem of vaccine quality in China was more serious than previously reported based on the fluctuation of infection rates from 2012 to 2018. Simultaneous amplification and testing to detect B. pertussis RNA (Area Under Curve: 0.900 and Kappa value: 0.831) had better diagnostic performance than real-time PCR for B. pertussis DNA (Area Under Curve: 0.869 and Kappa value: 0.690). Conclusions: We revealed the characteristics of B. pertussis infection and vaccine issues in Chongqing. Simultaneous amplification and testing could be a potential novel assay for measuring B. pertussis infection in the future. Keywords: Pertussis, Epidemiology, Vaccine, Simultaneous amplification and testing

Abstract Dexamethasone (Dex) are widely used for the treatment of asthma. However, they may cause apoptosis of bronchial epithelial cells and delay the recovery of asthma. Therefore, it is an urgent problem to find effective drugs to reduce this side effects. Panax notoginseng saponins R1 (PNS-R1) is known to exhibit anti-oxidative and anti-apoptotic properties in many diseases. We aim to investigate whether PNS-R1 can reduce Dex-induced apoptosis in bronchial epithelial cells. In this study, the anti-apoptotic effects of PNS-R1 were investigated by conducting in vitro and in vivo. Annexin V-FITC/PI staining flow cytometry analysis and TUNEL assay were conducted to detect apoptotic cells. Mitochondrial membrane potential was detected by JC-1 analysis. Western blotting and immunohistochemical analysis were conducted to measure caspase3, Bcl-2, Bax, Cyt-c, Apaf-1, cleaved-caspase3 and cleaved-caspase9 levels in lung tissues and 16HBE cells. Our findings demonstrated that Dex could induce apoptosis of bronchial epithelial cells and upregulate caspase3 expression of lung tissues. Western blot showed that Dex increased Bax, Cyt-c, Apaf-1, cleaved-caspase9, cleaved-caspase3 expression and decreased Bcl-2 expression. PNS-R1 could suppress Dex-induced apoptosis of bronchial epithelial cells by inhibiting Bax, Cyt-c, Apaf-1, cleaved-caspase9, cleaved-caspase3 expression and upregulating Bcl-2 expression. Flow cytometry analysis showed PNS-R1 alleviated JC-1 positive cells induced by Dex in 16HBE cells. These results showed that PNS-R1 alleviated Dex-induced apoptosis in bronchial epithelial cells by inhibition of mitochondrial apoptosis pathway. Furthermore, our findings highlighted the potential use of PNS-R1 as an adjuvant drug to treat asthma.

The mechanism(s) underlying endotoxin tolerance in asthma remain elusive. As the endotoxin lipopolysaccharide (LPS) affects the expression of the regulatory T-cell (Treg)-suppressive glucocorticoid-induced tumor necrosis factor receptor ligand (GITRL) on antigen-presenting dendritic cells (DCs), we hypothesized that LPS-induced changes in DC GITRL expression may impact Treg-mediated T-helper (Th) cell suppression and the induction of endotoxin tolerance. Here, we propose a novel mechanism by which low-dose LPS inhalation in neonatal mice induces endotoxin tolerance, thereby offering protection from later asthma development. Three-day old wild-type and Toll-like receptor 4 (TLR4)-deficient neonatal mice were exposed to low-dose LPS (1 μg) intranasally for 10 consecutive days prior to ovalbumin (OVA)-induced asthma to better understand the tolerogenic mechanism(s) of low-dose LPS pre-exposure. In vivo findings were validated using in vitro co-culturing studies of primary CD11c+ DCs and CD4+ T-cells with or without low-dose LPS pre-exposure before OVA stimulation. Low-dose LPS pre-exposure upregulated the Treg response and downregulated pathogenic Th2 and Th17 responses through promoting apoptosis of Th2 and Th17 cells. Low-dose LPS pre-exposure downregulated DC GITRL expression and T-cell GITR expression. Artificial DC GITRL expression abrogated the tolerogenic Treg-skewing effect of low-dose LPS pre-exposure. Low-dose LPS pre-exposure inhibited TRIF/IRF3/IFNβ signaling and upregulated expression of tolerogenic TRIF/IRF3/IFNβ negative regulators in a TLR4-dependent manner. This tolerogenic DC GITRL downregulation was attributable to TRIF/IRF3/IFNβ signaling inhibition. Low-dose LPS pre-exposure produces tolerogenic Treg skewing in neonatal asthmatic mice, a phenomenon attributable to TLR4-dependent TRIF/IRF3/IFNβ-mediated DC GITRL downregulation.

Background/Aims: Previous studies have shown that lipopolysaccharide (LPS) exposure may have a protective effect on asthma by reducing airway hyper-responsiveness, airway inflammation and serum IgE levels. However, there are few studies investigating the effect of LPS on mucous secretion in asthma. In this study, we evaluate the relationship between LPS pre-treatment in infant mice and airway mucus hypersecretion in an OVA (ovalbumin)-induced asthma model, and further explore the mechanisms behind this effect. Methods: Mice were pre-treated with LPS by intranasal instillation (i.n.) from the 3rd day of life for 10 consecutive days before the OVA-induced asthma model was established. In order to detect mucus secretion, periodic acid-Schiff (PAS) staining was carried out, and the expression of Muc5ac was detected. The IL-13 levels in Bronchoalveolar lavage fluid (BALF) and lung tissue were also detected. In vitro, the expression of Muc5ac mRNA and protein was quantified in IL-13-stimulated 16HBE cells with or without LPS pre-treatment. In addition, proteins in the JAK2/STAT6 pathway, transcription factors (forkhead box transcription factor A2 (FOXA2), activation protein-1(AP-1), NF-κB), and the levels of reactive oxygen species (ROS) were also measured in vivo and in vitro. Results: LPS pre-treatment reduced mucus secretion, as demonstrated by decreased PAS staining and muc5ac expression. Further exploration of the underlying mechanisms of this phenomenon revealed that LPS pre-treatment decreased the production of IL-13, IL-13 induced ROS synthesis was reduced, and the JAK2/STAT6 pathway was inhibited. Decreased stat6 increased transcription factor FOXA2, and the relatively increased FOXA2 further decreased the level of Muc5ac and mucous hypersecretion in OVA-induced asthma. Conclusions: LPS pre-treatment ameliorated mucus hypersecretion in an OVA-induced asthma model by inhibition of IL-13 production and by further inhibiting the JAK2/STAT6 pathway and ROS activity, and up-regulating expression of FOXA2.

Alveolar epithelial cells (AECs) injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis (PF). Nevertheless, the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear. SMARCA4 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF, which is essential for kidney and heart fibrosis. We investigates SMARCA4 function in lung fibrosis by establishing PF mice model with bleomycin firstly and found that the expression of SMARCA4 was mainly enhanced in alveolar type II (ATII) cells. Moreover, we established an alveolar epithelium-specific SMARCA4-deleted SP-C-rtTA/(tetO)7-Cre/SMARCA4f/f mice (SOSM4Δ/Δ) model, as well as a new SMARCA4-deleted alveolar type II (ATII)-like mle-12 cell line. We found that the bleomycin-induced PF was more aggressive in SOSM4Δ/Δ mice. Also, the proliferation of ATII cells was decreased with the loss of SMARCA4 in vivo and in vitro. In addition, we observed increased proliferation of ATII cells accompanied by abnormally high expression of SMARCA4 in human PF lung sections. These data uncovered the indispensable role of SMARCA4 in the proliferation of ATII cells, which might affect the progression of PF.

Abstract Background Asthma is characterized by chronic airway inflammation, airway hyperresponsiveness (AHR), and airway remodeling. While exposure of house dust mites (HDM) is a common cause of asthma, the pathogenesis of the HDM-induced asthma is not fully understood. Bronchopulmonary C-fibers (PCFs) contribute to the neurogenic inflammation, viral infection induced-persistent AHR, and ovalbumin induced collagen deposition largely via releasing neuropeptides, such as substance P (SP). However, PCF roles in the pathogenesis of the HDM-induced asthma remain unexplored. The goal of this study was to determine what role PCFs played in generating these characteristics. Methods We compared the following variables among the PCF-intact and -degenerated BALB/c mice with and without chronic HDM exposure (four groups): 1) AHR and pulmonary SP; 2) airway smooth muscle (ASM) mass; 3) pulmonary inflammatory cells; and 4) epithelium thickening and mucus secretion. Results We found that HDM evoked AHR associated with upregulation of pulmonary SP and inflammation, ASM mass increase, epithelium thickenings, and mucus hypersecretion. PCF degeneration decreased the HDM-induced changes in AHR, pulmonary SP and inflammation, and ASM mass, but failed to significantly affect the epithelium thickening and mucus hypersecretion. Conclusion Our data suggest an involvement of PCFs in the mechanisms by which HDM induces allergic asthma via airway inflammation, AHR, and airway remodeling.

Background MicroRNA (miR)-145-5p is a respiratory disease biomarker, and is upregulated in asthma pathogenesis. However, its underlying mechanisms were unclear, so were investigated in the present study. Methods A mouse model of asthma was established by challenge with house dust mite (HDM) extract. An miR-145-5p antagomir was administered nasally and expression of kinesin family member 3A (KIF3A) and miR-145-5p was measured by immunohistochemistry, PCR, and western blot. Eosinophils in lavage fluid and levels of interleukin (IL)-4, IL-5, and IL-13 were quantified. Airway hyper-responsiveness was measured and KIF3A expression was tested following miR-145-5p overexpression or interference in the 16HBE14o- airway epithelial cell line. The effects of miR-145-5p and KIF3A co-transfection in 16HBE14o- cells were examined on cytokine release, epithelial barrier dysfunction, and epithelial repair in HDM-exposed cells. Results KIF3A downregulation and miR-145-5p upregulation were noted in airway epithelial cells of HDM-exposed asthmatic mice, while miR-145-5p antagonism significantly improved symptoms. MiR-145-5p promoted the HDM-induced release of chemokines and inflammatory factors and epithelial barrier dysfunction, and suppressed epithelial repair by directly targeting KIF3A. Conclusion miR-145-5p influenced HDM-induced epithelial cytokine release and epithelial barrier dysfunction via regulating KIF3 expression. It also affected epithelial repair, exacerbating the HDM-induced T helper 2-type immune response in mice.

Introduction. Double aortic arch is a congenital vascular abnormality in which the connected segments and their branches course between and compress the trachea and esophagus, often resulting in invariable airway compression. Case Presentation. A 4-year-old boy with a history of recurrent wheezing was admitted to our hospital for evaluation of asthma based on his past medical history, persistent cough, wheezing, and airway hyperresponsiveness by lung function test. Double aortic arch was diagnosed with computed tomography angiogram. After surgery, the respiratory infection improved strikingly. Early diagnosis and treatment may prevent chronic, irreversible complications. Conclusion. We present a case of double aortic arch masquerading as asthma.