[Clinical characteristics of plastic bronchitis and risk factors for recurrence in children]. / å„¿ç«¥å¡‘åž‹æ€§æ”¯æ°”ç®¡ç‚Žä¸´åºŠç‰¹å¾åŠå¤å‘å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To study the clinical characteristics of plastic bronchitis (PB) in children and investigate the the risk factors for recurrence of PB. METHODS: This was a retrospective analysis of medical data of children with PB who were hospitalized in Children's Hospital of Chongqing Medical University from January 2012 to July 2022. The children were divided into a single occurrence of PB group and a recurrent PB group and the risk factors for recurrence of PB were analyzed. RESULTS: A total of 107 children with PB were included, including 61 males (57.0%) and 46 females (43.0%), with a median age of 5.0 years, and 78 cases (72.9%) were over 3 years old. All the children had cough, 96 children (89.7%) had fever, with high fever in 90 children. Seventy-three children (68.2%) had shortness of breath, and 64 children (59.8%) had respiratory failure. Sixty-six children (61.7%) had atelectasis and 52 children (48.6%) had pleural effusion. Forty-seven children (43.9%) had Mycoplasma pneumoniae infection, 28 children (26.2%) had adenovirus infection, and 17 children (15.9%) had influenza virus infection. Seventy-one children (66.4%) had a single occurrence of PB, and 36 cases (33.6%) had recurrent occurrence of PB (≥2 times). Multivariate logistic regression analysis showed that involvement of ≥2 lung lobes (OR=3.376) under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts (OR=3.275), and concomitant multi-organ dysfunction outside the lungs (OR=2.906) were independent risk factors for recurrent occurrence of PB (P<0.05). CONCLUSIONS: Children with pneumonia accompanied by persistent high fever, shortness of breath, respiratory failure, atelectasis or pleural effusion should be highly suspected with PB. Involvement of ≥2 lung lobes under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts, and concomitant multi-organ dysfunction outside the lungs may be risk factors for recurrent occurrence of PB.

Vancomycin efficiency and safety of a dosage of 40-60 mg/kg/d and corresponding trough concentrations in children with Gram-positive bacterial sepsis.

Background: Optimal vancomycin trough concentrations and dosages remain controversial in sepsis children. We aim to investigate vancomycin treatment outcomes with a dosage of 40-60 mg/kg/d and corresponding trough concentrations in children with Gram-positive bacterial sepsis from a clinical perspective. Methods: Children diagnosed with Gram-positive bacterial sepsis and received intravenous vancomycin therapy between January 2017 and June 2020 were enrolled retrospectively. Patients were categorized as success and failure groups according to treatment outcomes. Laboratory, microbiological, and clinical data were collected. The risk factors for treatment failure were analyzed by logistic regression. Results: In total, 186 children were included, of whom 167 (89.8%) were enrolled in the success group and 19 (10.2%) in the failure group. The initial and mean vancomycin daily doses in failure group were significantly higher than those in success group [56.9 (IQR =42.1-60.0) vs. 40.5 (IQR =40.0-57.1), P=0.016; 57.0 (IQR =45.8-60.0) vs. 50.0 (IQR =40.0-57.6) mg/kg/d, P=0.012, respectively] and median vancomycin trough concentrations were similar between two groups [6.9 (4.0-12.1) vs.7.3 (4.5-10.6) mg/L, P=0.568)]. Moreover, there was no significant differences in treatment success rate between vancomycin trough concentrations ≤15 mg/L and >15 mg/L (91.2% vs. 75.0%, P=0.064). No vancomycin-related nephrotoxicity adverse effects occurred among all enrolled patients. Multivariate analysis revealed that a PRISM III score ≥10 (OR =15.011; 95% CI: 3.937-57.230; P<0.001) was the only independent clinical factor associated with increased incidence of treatment failure. Conclusions: Vancomycin dosages of 40-60 mg/kg/d are effective and have no vancomycin-related nephrotoxicity adverse effects in children with Gram-positive bacterial sepsis. Vancomycin trough concentrations >15 mg/L are not an essential target for these Gram-positive bacterial sepsis patients. PRISM III scores ≥10 may serve as an independent risk factor for vancomycin treatment failure in these patients.

A novel epithelial-mesenchymal transition (EMT)-related gene signature of predictive value for the survival outcomes in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a remarkably heterogeneous and aggressive disease with dismal prognosis of patients. The identification of promising prognostic biomarkers might enable effective diagnosis and treatment of LUAD. Aberrant activation of epithelial-mesenchymal transition (EMT) is required for LUAD initiation, progression and metastasis. With the purpose of identifying a robust EMT-related gene signature (E-signature) to monitor the survival outcomes of LUAD patients. In The Cancer Genome Atlas (TCGA) database, least absolute shrinkage and selection operator (LASSO) analysis and cox regression analysis were conducted to acquire prognostic and EMT-related genes. A 4 EMT-related and prognostic gene signature, comprising dickkopf-like protein 1 (DKK1), lysyl oxidase-like 2 (LOXL2), matrix Gla protein (MGP) and slit guidance ligand 3 (SLIT3), was identified. By the usage of datum derived from TCGA database and Western blotting analysis, compared with adjacent tissue samples, DKK1 and LOXL2 protein expression in LUAD tissue samples were significantly higher, whereas the trend of MGP and SLIT3 expression were opposite. Concurrent with upregulation of epithelial markers and downregulation of mesenchymal markers, knockdown of DKK1 and LOXL2 impeded the migration and invasion of LUAD cells. Simultaneously, MGP and SLIT3 silencing promoted metastasis and induce EMT of LUAD cells. In the TCGA-LUAD set, receiver operating characteristic (ROC) analysis indicated that our risk model based on the identified E-signature was superior to those reported in literatures. Additionally, the E-signature carried robust prognostic significance. The validity of prediction in the E-signature was validated by the three independent datasets obtained from Gene Expression Omnibus (GEO) database. The probabilistic nomogram including the E-signature, pathological T stage and N stage was constructed and the nomogram demonstrated satisfactory discrimination and calibration. In LUAD patients, the E-signature risk score was associated with T stage, N stage, M stage and TNM stage. GSEA (gene set enrichment analysis) analysis indicated that the E-signature might be linked to the pathways including GLYCOLYSIS, MYC TARGETS, DNA REPAIR and so on. In conclusion, our study explored an innovative EMT based prognostic signature that might serve as a potential target for personalized and precision medicine.

TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA.

Tripartite motif-containing 44 (TRIM44) has recently been implicated in various pathological processes in numerous cancers, including lung adenocarcinoma (LUAD); however, its functional roles in chemoresistance are poorly understood. Herein, TRIM44 knockdown sensitized LUAD cells to cisplatin and enhanced cisplatin-induced apoptosis. Microarray analysis indicated that the "Role of BRCA1 in DNA damage" and the BRCA1 gene expression were positively regulated by TRIM44, which was further verified by immunofluorescence, qRT-PCR, and Western blotting. BRCA1 depletion effectively abolished TRIM44-modulated cisplatin resistance and regulation of homologous recombination (HR) repair. Interestingly, TRIM44 interacted with FLNA, an upstream regulator of BRCA1 as specified by STRING V 11.5, and facilitated its stability and deubiquitination. FLNA was also found to be required for the functions of TRIM44 in drug resistance. Using animal models, overexpression of TRIM44 was shown to confer resistance to cisplatin in a BRCA1- and FLNA-dependent manner. TRIM44 expression levels in tissues from cisplatin-resistant LUAD patients were significantly higher than those in tissues from cisplatin-sensitive LUAD patients. Collectively, our study results demonstrate that the TRIM44/FLNA/BRCA1 axis is involved in cisplatin chemoresistance, providing potential therapeutic targets for LUAD patients with cisplatin resistance.

A novel EHD1/CD44/Hippo/SP1 positive feedback loop potentiates stemness and metastasis in lung adenocarcinoma.

BACKGROUND: There is growing evidence that endocytosis plays a pivotal role in cancer metastasis. In this study, we first identified endocytic and metastasis-associated genes (EMGs) and then investigated the biological functions and mechanisms of EMGs. METHODS: Cancer stem cells (CSCs)-like characteristics were evaluated by tumour limiting dilution assays, three-dimensional (3D) spheroid cancer models. Microarray analysis was used to identify the pathways significantly regulated by mammalian Eps15 homology domain protein 1 (EHD1) knockdown. Mass spectrometry (MS) was performed to identify EHD1-interacting proteins. The function of EHD1 as a regulator of cluster of differentiation 44 (CD44) endocytic recycling and lysosomal degradation was determined by CD44 biotinylation and recycling assays. RESULTS: EHD1 was identified as a significant EMG. Knockdown of EHD1 suppressed CSCs-like characteristics, epithelial-mesenchymal transition (EMT), migration and invasion of lung adenocarcinoma (LUAD) cells by increasing Hippo kinase cascade activation. Conversely, EHD1 overexpression inhibited the Hippo pathway to promote cancer stemness and metastasis. Notably, utilising MS analysis, the CD44 protein was identified as a potential binding partner of EHD1. Furthermore, EHD1 enhanced CD44 recycling and stability. Indeed, silencing of CD44 or disruption of the EHD1/CD44 interaction enhanced Hippo pathway activity and reduced CSCs-like traits, EMT and metastasis. Interestingly, specificity protein 1 (SP1), a known downstream target gene of the Hippo-TEA-domain family members 1 (TEAD1) pathway, was found to directly bind to the EHD1 promoter region and induce its expression. Among clinical specimens, the EHD1 expression level in LUAD tissues of metastatic patients was higher than that of non-metastatic patients. CONCLUSIONS: Our findings emphasise that EHD1 might be a potent anti-metastatic target and present a novel regulatory mechanism by which the EHD1/CD44/Hippo/SP1 positive feedback circuit plays pivotal roles in coupling modules of CSCs-like properties and EMT in LUAD. Targeting this loop may serve as a remedy for patients with advanced metastatic LUAD.

[The Effect of Interventional Treatment with Bronchoscopy in 10 Children with Acquired Subglottic Stenosis].

OBJECTIVE: To explore the effects of interventional therapy with bronchoscopy in children with acquired subglottic stenosis (SGS). METHODS: The clinical data of ten pediatric inpatients with acquired SGS who were admitted to Children's Hospital of Chongqing Medical University, as well as their follow-up information obtained 1 week, 1 month, 3 months and 6 months after the procedure was done.were retrospectively analyzed to examine the effect of interventional bronchoscopic therapies, including balloon dilatation, holmium laser, and cryotherapy, in pediatric patients with acquired SGS. RESULTS: Among the 10 patients with acquired SGS, there were 5 boys and 5 girls aged between 1 month and 6 years and 5 months, with a median age of 11 months and 1 day. Among the 5 patients with acute acquired SGS, two were treated with balloon dilatation only, with one cured and one showing clinical improvement, while three received comprehensive interventional therapy combining balloon dilatation, holmium laser, and cryotherapy, with two cured and one showing improvement. Among the 5 patients with chronic acquired SGS, four cases were cured with comprehensive interventional therapy, while one case suffered from aggravated upper airway obstruction 4 + hours after balloon dilatation. The patient was subsequently put on invasive mechanical ventilation for 4 days, but was unable to be extubated. The parents signed do-not-resuscitate order and the patient died afterwards. Bronchoscopy performed 1 week, 1 month and 3 months after the procedure was done showed that the SGS was improved to varying degrees. CONCLUSION: Bronchoscopy intervention is an effective therapy for acquired SGS in children.

Founder Effects Contribute to the Population Genetic Structure of the Major Dermatophytosis Pathogen Trichophyton rubrum on Hainan Island, China.

BACKGROUND: Founder events have been observed among numerous plants and animal species living on oceanic islands due to the geographic separation of these islands and the small amount of original life they harbor. However, there has been little research on the ecological characteristics of pathogenic microorganisms on islands. Trichophyton rubrum ranks the most common isolated dermatophyte causing dermatophytosis in clinic and has become an epidemic strain worldwide in recent decades. OBJECTIVE: To study the phylogenetic characteristics and the distribution pattern of genetic polymorphism of T. rubrum in China, which further provide theoretical basis for the prevention and control of T. rubrum. METHODS: In the present study, we sequenced and analyzed the genetic characteristics of 204 T. rubrum isolates from Hainan Island and other sites in China. Phylogenetic analysis and genetic polymorphisms were studied based on a total of 41,409 high-quality whole-genome SNPs. RESULTS: The majority of the isolates from Hainan Island clustered together. Mixed T. rubrum population differentiation was observed among the strains of different geographical origins. In addition, the genetic diversity (π) of the Hainan isolates was low and showed no significant difference from that of isolates from other sites. CONCLUSION: This study is the first to discuss general ecological and evolutionary principles related to pathogenic fungi. Our findings reveal a founder effect during the origination of T. rubrum on Hainan Island and provide guidance regarding prevention and treatment strategies.

Identification of Differentially Expressed Circular RNAs as miRNA Sponges in Lung Adenocarcinoma.

BACKGROUND: Circular RNAs (circRNAs) may function as the decoys for microRNAs (miRNAs) or proteins, the templates for translation, and the sources of pseudogene generation. The purpose of this study is to determine the diagnostic circRNAs, which are related to lung adenocarcinoma (LUAD), that adsorb miRNAs on the basis of the competing endogenous RNA (ceRNA) hypothesis. METHODS: The differentially expressed circRNAs (DEcircRNAs) in LUAD were revealed by the microarray data (GSE101586 and GSE101684) that were obtained from the Gene Expression Omnibus (GEO) database. The miRNAs that were targeted by the DEcircRNAs were predicted with the CircInteractome, and the target mRNAs of the miRNAs were found by the miRDB and the TargetScan. The ceRNA network was built by the Cytoscape. The potential biological roles and the regulatory mechanisms of the circRNAs were investigated by the Gene Ontology (GO) enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The expression of the host genes of circRNAs was examined by the Ualcan. The survival analysis was performed by the Kaplan-Meier plotter. RESULTS: In comparison with normal lung tissues, LUAD tissues contained 7 overlapping cancer-specific DEcircRNAs with 294 miRNA response elements (MREs). Among the 7 DEcircRNAs, 3 circRNAs (hsa_circ_0072088, hsa_circ_0003528, and hsa_circ_0008274) were upregulated and 4 circRNAs (hsa_circ_0003162, hsa_circ_0029426, hsa_circ_0049271, and hsa_circ_0043256) were downregulated. A circRNA-miRNA-mRNA regulatory network, which included 33 differentially expressed miRNAs (DEmiRNAs) and 2007 differentially expressed mRNAs (DEmRNAs), was constructed. These mRNAs were enriched in the biological function of cell-cell adhesion, response to hypoxia, and stem cell differentiation and were involved in the PI3K-Akt signaling, HIF-1 signaling, and cAMP signaling pathways. CONCLUSION: Our results indicated that 7 DEcircRNAs could have diagnostic value for LUAD. Additionally, the circRNAs-mediated ceRNA network might provide a novel perspective into unraveling the pathogenesis and progression of LUAD.

LINC02678 as a Novel Prognostic Marker Promotes Aggressive Non-small-cell Lung Cancer.

Non-small-cell lung carcinoma (NSCLC) is considered to be a fatal disease and characterized by a poor prognosis. Long non-coding RNAs (lncRNAs) have been reported to act as biomarkers and therapeutic targets in solid tumors. However, the expression of lncRNAs and their clinical relevance in NSCLC remain undetermined. The gene expression data profiled in The Cancer Genome Atlas and Gene Expression Omnibus (GSE81089) were employed to screen differentially expressed lncRNAs in NSCLC. LINC02678 was found to be upregulated in NSCLC and exhibited hypomethylation of the promoter region in NSCLC tissues. LINC02678 (also called RP11-336A10.5) was associated with poorer overall survival and relapse-free survival in NSCLC patients. In vitro models of gain- and loss-of-function demonstrated that LINC02678 promotes NSCLC progression by promoting NSCLC cell proliferation and cell cycle progression, as well as inducing NSCLC cell migration, invasion and epithelial-mesenchymal transition. LINC02678 was primarily located in the nucleus and could bind with the enhancer of zeste homolog 2 (EZH2). Moreover, we found that LINC02678 knockdown impaired the occupancy capacity of EZH2 and trimethylation of lysine 27 on histone 3 (H3K27me3) at the promoter region of cyclin dependent kinase inhibitor 1B (CDKN1B) and E-cadherin, as confirmed by ChIP-qPCR. A mouse transplantation model further demonstrated that LINC02678 could promote the tumorigenic and metastatic capacities of NSCLC cells. We identified LINC02678 as a tumor promoter in NSCLC, which enhanced the growth and metastasis of NSCLC cells by binding with EZH2, indicating that LINC02678 may serve as a potential biomarker for cancer diagnosis and treatment.

Diagnosis and management of protracted bacterial bronchitis: a survey of Chinese pediatricians.

BACKGROUND: Protracted bacterial bronchitis (PBB) is a common cause of chronic wet cough in children. However, it is often misdiagnosed and inappropriately treated in clinical practices. This study aims to investigate the current diagnosis and management of PBB among Chinese pediatricians. METHODS: An electronic questionnaire designed to assess the diagnosis and management of PBB was sent to pediatricians in China. RESULTS: A total of 1,022 pediatricians completed the questionnaire. Most (68.8%) of the pediatricians diagnosed PBB in compliance with the guidelines, 44.3% and 24.5% of them followed microbiology-based and clinical-based diagnosis criteria, respectively. Only 40.4% of the pediatricians chose amoxicillin-clavulanate as the first-line antibiotic for PBB treatment, 23.7% and 23.5% of them chose third-generation cephalosporins and macrolides, respectively. The majority of pediatricians (75.4%) reported 2-4 weeks of antibiotics course, 19.3% of them prescribed a shorter course and 5% of them selected a longer course. Only 26.3% of the pediatricians performed combined investigations of chest high-resolution computed tomography scan (c-HRCT), bronchoscopy, and immunological tests for recurrences of PBB. Compared with general pediatricians (GP), pediatric pulmonologists (PP) preferred microbiology-based diagnosis criteria, prescribed more amoxicillin-clavulanate, and performed more investigations for recurrent patients (P<0.05). CONCLUSIONS: The majority of Chinese pediatricians diagnosed PBB in compliance with guidelines. However, the reasonable antibiotics applications and the investigations for recurrent PBB need to be improved.

Identification of Differentially Expressed and Prognostic lncRNAs for the Construction of ceRNA Networks in Lung Adenocarcinoma.

BACKGROUND: Long noncoding RNAs (lncRNAs) could function as competitive endogenous RNAs (ceRNAs) to competitively adsorb microRNAs (miRNAs), thereby regulating the expression of their target protein-coding mRNAs. In this study, we aim to identify more effective diagnostic and prognostic markers for lung adenocarcinoma (LUAD). METHODS: We obtained differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) for LUAD by using The Cancer Genomes Atlas (TCGA) portal. Weighted gene coexpression network analysis (WGCNA) was performed to unveil core gene modules associated with LUAD. The Cox proportional hazards model was performed to determine the prognostic significance of DElncRNAs. The diagnostic and prognostic significance of DElncRNAs was further verified based on the receiver operating characteristic curve (ROC). Cytoscape was used to construct the ceRNA networks comprising the lncRNAs-miRNAs-mRNAs axis based on the correlation obtained from the miRcode, miRDB, and TargetScan. RESULTS: Compared with normal lung tissues, 2355 DElncRNAs, 820 DEmiRNAs, and 17289 DEmRNAs were identified in LUAD tissues. We generated 8 WGCNA core modules in the lncRNAs coexpression network, 5 modules in the miRNAs, and 12 modules in the mRNAs coexpression network, respectively. One lncRNA module (blue) consisting of 441 lncRNAs, two miRNA modules (blue and turquoise) containing 563 miRNAs, and one mRNA module (turquoise), which consisted of 15162 mRNAs, were mostly significantly related to LUAD status. Furthermore, 67 DEmRNAs were found to be tumor-associated as well as the target genes of the DElncRNAs-DEmiRNAs axis. Survival analyses showed that 6 lncRNAs (LINC01447, WWC2-AS2, OGFRP1, LINC00942, LINC01168, and AC005863.1) were significantly correlated with the prognosis of LUAD patients. Ultimately, the potential ceRNA networks including 6 DElncRNAs, 4 DEmiRNAs, and 22 DEmRNAs were constructed. CONCLUSION: Our study indicated that 6 DElncRNAs had the possibilities as diagnostic and prognostic biomarkers for LUAD. The lncRNA-mediated ceRNA networks might provide novel insights into the molecular mechanisms of LUAD progression.

PHLPP2 as a novel metastatic and prognostic biomarker in non-small cell lung cancer patients.

BACKGROUND: PH domain and leucine-rich repeat protein phosphatase 2 (PHLPP2) has been reported to be a potent tumor suppressor in many human cancers. However, PHLPP2 has not been fully researched as a putative clinical prognostic biomarker of lung cancer. METHODS: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases including data on 1383 non-small cell lung cancer (NSCLC) patients were used to determine PHLPP2 expression. PHLPP2 expression was then examined by immunohistochemistry, and its clinical significance analyzed in 134 NSCLC patients, including 73 patients with adenocarcinoma and 81 with squamous cell carcinoma. RESULTS: We found PHLPP2 expression to be less pronounced in NSCLC tissue samples than that in nontumoral lung tissues according to data taken from TCGA and GEO datasets; this outcome was further validated by immunohistochemistry assay. The low PHLPP2 expression level was found to be associated with the presence of lymph node metastasis (P = 0.003). Importantly, PHLPP2 was found to be an independent indicator of prognosis for overall (hazard ratio [HR] = 0.520, 95% confidence interval [Cl] = 0.327-0.827; P = 0.006) and disease-free survival (HR = 0.489, 95% Cl = 0.308-0.775; P = 0.002) in patients with surgically-resected NSCLC by multivariate analysis. CONCLUSION: Taken together, our findings show that PHLPP2 is a robust clinical marker for NSCLC survival and could serve as a potential therapeutic target.

Design of Robust Thermal and Anion Dual-Responsive Membranes with Switchable Response Temperature.

In this study, poly(ionic liquids/ N-isopropylacrylamide) (PIL/NIPAM) modified poly(ether sulfone) microporous membranes were prepared using a pore-filling method. Due to the anion-sensitive wettability of the PIL and the thermal-sensitive phase transformation of PNIPAM, the permeability of the modified membranes showed robust anion and thermal dual-responsive behaviors. In addition, the response temperature of the membranes could be adjusted precisely from 30 to 55 °C by anion exchange, which was attributed to the cooperative interaction of the PIL and PNIPAM. The switchable response temperature and the dual-responsive performances of the membranes were demonstrated by measuring the water fluxes under various conditions. The results indicated that the membrane permeabilities increased when exchanging the counteranions (CAs) from hydrophilic to hydrophobic ones; the thermal response behaviors were also obvious, and the sensitivity increased when increasing the hydrophobicity of the CA (the fluxes could be adjusted from 0 to 3800 mL/m2 mmHgh by controlling the temperature and CAs). At last, filtration tests were designed with the membranes, and the results indicated that by controlling the temperature and/or CA species, three different poly(ethylene glycol) molecules could be easily separated according to their molecule sizes in a single step.