Tonsil microbiome in pediatric patients with post tonsillectomy hemorrhage for tonsillar hypertrophy.

OBJECTIVE: This study aimed to compare the tonsillar microbiota between post tonsillectomy patients with bleeding and without bleeding, and to investigate the potential role of tonsillar microbiota in the development of post-tonsillectomy hemorrhage (PTH). METHODS: Nineteen tonsillar tissues from PTH patients and 21 tissues from control patients were collected. Metagenomic sequencing was used to compare the microbiota in PTH and control groups. Alpha diversity indices were used to compare the richness and evenness of the microbiota between the two groups. PCoA and NMDS analyses were used to evaluate beta diversity. LDA analysis was conducted to identify significantly abundant genera. RESULTS: No significant difference in alpha diversity indices was found between PTH and control patients. The dominant bacteria in the tonsillar microbiota were Haemophilus, Streptococcus, and Fusobacterium. PCoA and NMDS analyses showed significant differences in beta diversity between PTH and control patients. PTH patients had a significantly higher relative abundance of Neisseria, Capnocytophaga, and Veillonella. Capnocytophaga was also identified as a significantly abundant genus by LDA analysis. CONCLUSION: This study demonstrates that there is a difference in the tonsillar microbiota between PTH and control patients. The results suggest that Neisseria, Capnocytophaga, and Veillonella may be associated with the development of PTH. These findings provide new insights into the potential role of the tonsillar microbiota in the development of PTH, and may help to develop new strategies for preventing and treating this potentially life-threatening complication.

An integrative analysis of the tumor suppressors and oncogenes from sexual dimorphism and gene expression alteration features in thyroid cancer.

BACKGROUND: The incidence of thyroid cancer has risen rapidly over the last decades. Although mortality rates are relatively low compared to other cancers, the rate of new cases started to increase in the early 2000s. While tumor suppressors and oncogenes were recently identified in thyroid cancer, the potential roles of these genes in thyroid cancer remain unclear. OBJECTIVE: Analyze the roles and functions of tumor suppressors and oncogenes in thyroid cancer. METHODS: Thyroid cancer data were collected from public databases, such as the UCSC Xena database of TCGA thyroid cancer, TISIDB, and UALCAN. The genes frequently associated with unfavorable thyroid cancer were examined and validated. The association of these target genes with thyroid tumorigenesis, stages, subtypes, and survival rates were analyzed. Additionally, the genes aberrantly expressed in thyroid cancer and significantly involved in thyroid tumorigenesis, stages, subtypes, and survival rates were identified. RESULTS: Female sex was identified as a risk factor for thyroid cancer. The expression of PAPSS2, PDLIM3, COPZ2, ALDH1B1, ANTXR1, GUF1, and SENP6 negatively correlated with thyroid cancer prognosis. CONCLUSION: Female sex was a risk factor for thyroid cancer. In addition, our analysis suggested that PAPSS2, PDLIM3, COPZ2, ALDH1B1, ANTXR1, GUF1, and SENP6 are negatively correlated with the prognosis of thyroid cancer. The expression of ANTXR1, GUF1, and PDLIM3 was weakly associated with thyroid cancer's immune and molecular subtypes.

Deep learning for the screening of primary ciliary dyskinesia based on cranial computed tomography.

Objective: To analyze the cranial computed tomography (CT) imaging features of patients with primary ciliary dyskinesia (PCD) who have exudative otitis media (OME) and sinusitis using a deep learning model for early intervention in PCD. Methods: Thirty-two children with PCD diagnosed at the Children's Hospital of Fudan University, Shanghai, China, between January 2010 and January 2021 who had undergone cranial CT were retrospectively analyzed. Thirty-two children with OME and sinusitis diagnosed using cranial CT formed the control group. Multiple deep learning neural network training models based on PyTorch were built, and the optimal model was trained and selected to observe the differences between the cranial CT images of patients with PCD and those of general patients and to screen patients with PCD. Results: The Swin-Transformer, ConvNeXt, and GoogLeNet training models had optimal results, with an accuracy of approximately 0.94; VGG11, VGG16, VGG19, ResNet 34, and ResNet 50, which are neural network models with fewer layers, achieved relatively strong results; and Transformer and other neural networks with more layers or neural network models with larger receptive fields exhibited a relatively weak performance. A heat map revealed the differences in the sinus, middle ear mastoid, and fourth ventricle between the patients with PCD and the control group. Transfer learning can improve the modeling effect of neural networks. Conclusion: Deep learning-based CT imaging models can accurately screen for PCD and identify differences between the cranial CT images.

Temporospatial Expression of Neuropeptide Substance P in Dental Pulp Stem Cells During Odontoblastic Differentiation in Vitro and Reparative Dentinogenesis in Vivo.

INTRODUCTION: Substance P (SP) is a neuropeptide released from the nervous fibers in response to injury. In addition to its association with pain and reactions to anxiety and stress, SP exerts various physiological functions by binding to the neurokinin-1 receptor (NK1R). However, the expression and role of SP in reparative dentinogenesis remain elusive. Here, we explored whether SP is involved in odontoblastic differentiation during reparative dentinogenesis. METHODS: Dental pulp stem cells (DPSCs) were isolated from healthy human dental pulp tissues and subjected to odontoblastic differentiation. The expression of SP and NK1R during odontoblastic differentiation was investigated in vitro. The effects of SP on odontoblastic differentiation of DPSCs were evaluated using alizarin red staining, alkaline phosphatase staining, and real-time polymerase chain reaction. After direct pulp capping with mineral trioxide aggregate, the expression of SP and NK1R during reparative dentin formation in rats were identified using histological and immunohistochemical staining. RESULTS: SP and NK1R expression increased during the odontoblastic differentiation of DPSCs. SP translocated to the nucleus when DPSCs were exposed to differentiation medium. NK1R was always present in the nuclei of DPSCs and odontoblast-like cells. Additionally, we discovered that 10-8 M SP marginally enhanced the odontoblastic differentiation of DPSCs, and that these effects could be impaired by the NK1R antagonist. Furthermore, SP and NK1R were expressed in odontoblast-like and dental pulp cells during reparative dentin formation in vivo. CONCLUSIONS: SP contributes to odontoblastic differentiation during reparative dentin formation by binding to the NK1R.

Auditory and Speech Outcomes of Cochlear Implantation in Children With Auditory Neuropathy Spectrum Disorder: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this meta-analysis was to critically assess the effect of cochlear implantation on auditory and speech performance outcomes of children with auditory neuropathy spectrum disorder (ANSD). MATERIAL AND METHODS: A systematic literature search was conducted on PubMed, EMbase, and Web of Science. The outcomes included speech recognition score, Categories of Auditory Performance (CAP), Speech Intelligibility Rating (SIR) score, and open-set speech perception. Results were expressed as standardized mean difference (SMD) or risk ratio (RR) with a 95% confidence interval (95% CI). RESULTS: A total of 15 studies was included in this meta-analysis. Pooled data showed that, there were no significant differences between ANSD and sensorineural hearing loss (SNHL) groups in terms of speech recognition score (SMD = 0.01, 95% CI: -0.45, 0.47; P = .959),CAP (SMD = 0.71, 95% CI: -0.13, 1.54; P = .098), SIR score (SMD = -0.09, 95% CI: -0.49, 0.32; P = .667), and open-set speech perception (RR = 0.85, 95% CI: 0.69, 1.05; P = .142). Sensitivity analysis by removing individual studies one at a time showed that the overall estimate and level of heterogeneity did not change substantially. CONCLUSION: The current evidence suggested that children with ANSD who underwent cochlear implants achieved comparable effects in auditory and speech performance as children with non-ANSD SNHL.

The role of different macrophages-derived conditioned media in dental pulp tissue regeneration.

Macrophages have been reported to play important roles in tissue repair and regeneration. While it is known that macrophages are present in the dental pulp, their role in dental pulp regeneration is not fully understood. In the present study, we investigated the effects of different phenotype macrophages conditioned medium on the cellular behaviors of hDPSCs and their extracellular matrix (cell sheets) in vitro. Moreover, twenty-four root fragments inserted with cell sheets cultured with different conditioned media were placed into the back subcutaneous space of 6-8-week-old male BALB/c nude mouse. The regenerated tissues in the root fragments were assessed via histologic analysis after 8 weeks of transplantation. M2 macrophages could promote the proliferation, migration, and osteogenic differentiation of hDPSCs. Dental pulp-like tissue with an odontoblast-like layer lining the dentinal surface and well-arranged collagen fibers was harvested in root fragment combined with M2 conditioned medium cultured cell sheet, whereas a large amount of calcium salt deposition and disorganization of collagen fibers were observed in root fragments combined with M1 conditioned medium cultured cell sheet. Therefore, promoting the transformation of M1 into M2 macrophage in dental pulp tissue regeneration may be a potential way for dental pulp regeneration via functional healing.

An in-depth discussion of cholesteatoma, middle ear Inflammation, and langerhans cell histiocytosis of the temporal bone, based on diagnostic results.

Objective: This study aimed to conduct an in-depth investigation of the learning framework used for deriving diagnostic results of temporal bone diseases, including cholesteatoma and Langerhans cell histiocytosis (LCH). In addition, middle ear inflammation (MEI) was diagnosed by CT scanning of the temporal bone in pediatric patients. Design: A total of 119 patients were included in this retrospective study; among them, 40 patients had MEI, 38 patients had histology-proven cholesteatoma, and 41 patients had histology-proven LCH of the temporal bone. Each of the 119 patients was matched with one-third of the disease labels. The study included otologists and radiologists, and the reference criteria were histopathology results (70% of cases for training and 30% of cases for validation). A multilayer perceptron artificial neural network (VGG16_BN) was employed and classified, based on radiometrics. This framework structure was compared and analyzed by clinical experts according to CT images and performance. Results: The deep learning framework results vs. a physician's diagnosis, respectively, in multiclassification tasks, were as follows. Receiver operating characteristic (ROC) (cholesteatoma): (0.98 vs. 0.91), LCH (0.99 vs. 0.98), and MEI (0.99 vs. 0.85). Accuracy (cholesteatoma): (0.99 vs. 0.89), LCH (0.99 vs. 0.97), and MEI (0.99 vs. 0.89). Sensitivity (cholesteatoma): (0.96 vs. 0.97), LCH (0.99 vs. 0.98), and MEI (1 vs. 0.69). Specificity (cholesteatoma): (1 vs. 0.89), LCH (0.99 vs. 0.97), and MEI (0.99 vs. 0.89). Conclusion: This article presents a research and learning framework for the diagnosis of cholesteatoma, MEI, and temporal bone LCH in children, based on CT scans. The research framework performed better than the clinical experts.

Apparent homozygosity for a novel splicing variant in EPS8 causes congenital profound hearing loss.

Autosomal recessive deafness-102 (DFNB102), a new profound prelingual non-syndromic hearing loss, is caused by mutations in the EPS8 gene. To date, only three such consanguineous families with three different homozygous variants in EPS8 have been reported. Here, we report the fourth case from a non-consanguineous Chinese family, an 11-month-old male infant presented with congenital profound non-syndromic hearing loss. Trio whole-exome sequencing initially identified the patient with a novel seemingly homozygous splicing variant NM_004447.5: c.1435-2A > T in intron 14 of the EPS8 gene and was inherited from his father; further CNVs analysis identified a novel 65.9 kb intragenic deletion and was inherited from his mother. The deletion is covering intron 14 that could account for the apparent homozygosity of the patient. In vitro splicing assay showed the variant c.1435-2A > T creates a new donor site at position c.1443, which is predicted to produce a stop codon after 14 additional amino acids (p.His479Cysfs*14). Furthermore, quantitative allele-specific expression assay showed that relative EPS8 gene expression in the patient significantly decreased (0-fold for the wild-type transcript and 0.25-0.27-fold for the mutant transcript) compared to the control (P < 0.05), indicating the pathogenicity of the identified variants. Overall, our study provides additional evidence that EPS8 is a causative gene for DFNB102 and highlights the clinical utility of simultaneous analysis of CNVs and SNVs to avoid potential errors in the diagnosis and interpretation of patients with apparent homozygosity.

Inflammatory Factors as Potential Markers of Early Neurological Deterioration in Acute Ischemic Stroke Patients Receiving Endovascular Therapy - The AISRNA Study.

BACKGROUND AND PURPOSE: This study aimed to explore several peripheral blood-based markers related to the inflammatory response in a total of 210 patients with acute ischemic stroke (AIS) caused by large artery occlusion in the anterior circulation who received endovascular therapy (EVT) from an observational study of clinical significance of circulating non-coding RNA in acute ischemic stroke (AISRNA). METHODS: We collected baseline characteristics of 210 AIS patients participating in an observational acute stroke cohort: the AISRNA study. The following inflammatory factors were measured in these participants: interleukin-2 [IL-2], IL-4, IL-6, IL-10, tumor necrosis factor-α [TNF-α], and interferon-γ [IFN-γ]. The National Institute of Health Stroke Scale score increase of ≥4 within 24 hours after EVT defined as early neurological deterioration (END). RESULTS: Compared with patients without END, patients with END had a higher incidence of atrial fibrillation (P=0.012), and also had higher levels of IL-6 and IL-10 (P<0.01). Furthermore, we found that the area under the curves (AUCs) of IL-6 and IL-10 for predicting END were 0.768 (0.697-0.829), and 0.647 (0.570-0.719), respectively. Adjusting for age, sex, and atrial fibrillation, the odds ratios (ORs; 95% confidence interval) for incident END for IL-6 and IL-10 were 1.98 (1.05-6.69) and 1.18 (1.04-1.33), respectively. Additionally, we found significant changes over time in the expression levels of IL-4, IL-6, and IL-10 in patients with END compared with patients without END (P<0.05). CONCLUSION: IL-6 and IL-10 levels at admission may be potential markers of END after EVT, and the time course of IL-4, IL-6, and IL-10 is correlated with stroke progression. Further larger studies are needed to confirm the current findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04175691. Registered November 21, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04175691.

Clinical significance of stroke nurse in patients with acute ischemic stroke receiving intravenous thrombolysis.

BACKGROUND: Reports have proven that shorter door-to-needle time (DTN time) indicates better outcomes in AIS patients received intravenous thrombolysis. Efforts have been made by hospitals and centers to minimize DTN time in many ways including introducing a stroke nurse. However, there are few studies to discuss the specific effect of stroke nurse on patients' prognosis. This study aimed to compare consecutive AIS patients before and after the intervention to analyze the effect of stroke nurse on clinical outcome of AIS patients. METHODS: In this retrospective study, we observed 1003 patients from November 2016 to December 2020 dividing in two groups, collected and analyzed AIS patients' medical history, clinical assessment information, important timelines, 90 mRS score, etc. Comparative analysis and mediation analysis were also used in this study. RESULTS: A total of 418 patients was included in this study, and 199 patients were enrolled in the stroke nurse group and 219 was in the preintervention group. Baseline characteristics of patients showed no significant difference except there seems more patients with previous ischemic stroke history in the group of stroke nurse. (p = 0.008). The median DTN time significantly decreased in the stroke nurse group (25 min versus 36 min, p < 0.001) and multivariate logistic regression analysis showed the 90-day mRS clinical outcome significantly improved in the stroke nurse group (p = 0.001). Mediation analysis indicated the reduction of DTN time plays a partial role on the 90 days mRS score and the stroke nurse has some direct effect on the improvement of clinical outcome (p = 0.006). CONCLUSIONS: The introduction of stroke nurse is beneficial to clinical outcome of AIS patients and can be use of reference in other hospitals or centers.

Identification of key genes in allergic rhinitis by bioinformatics analysis.

OBJECTIVE: This study aimed to explore the potential molecular mechanism of allergic rhinitis (AR) and identify gene signatures by analyzing microarray data using bioinformatics methods. METHODS: The dataset GSE19187 was used to screen differentially expressed genes (DEGs) between samples from patients with AR and healthy controls. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied for the DEGs. Subsequently, a protein-protein interaction (PPI) network was constructed to identify hub genes. GSE44037 and GSE43523 datasets were screened to validate critical genes. RESULTS: A total of 156 DEGs were identified. GO analysis verified that the DEGs were enriched in antigen processing and presentation, the immune response, and antigen binding. KEGG analysis demonstrated that the DEGs were enriched in Staphylococcus aureus infection, rheumatoid arthritis, and allograft rejection. PPI network and module analysis predicted seven hub genes, of which six (CD44, HLA-DPA1, HLA-DRB1, HLA-DRB5, MUC5B, and CD274) were identified in the validation dataset. CONCLUSIONS: Our findings suggest that hub genes play important roles in the development of AR.

Recessive LOXHD1 variants cause a prelingual down-sloping hearing loss: genotype-phenotype correlation and three additional children with novel variants.

BACKGROUND: Biallelic mutations in LOXHD1 have been identified as the cause of DFNB77 (deafness, autosomal recessive 77). It is a new progressive, severe-to-profound, and late-onset nonsyndromic sensorineural hearing loss (NSHL), and is highly heterogeneous genetically and phenotypically. This study aimed to provide an additional three cases of DFNB77. METHODS: We presented three unrelated children diagnosed with prelingual mild-to-severe NSHL, and their audiograms showed mild hearing loss at 250 Hz before downsloping to a moderate-to-severe degree. Trio whole-exome sequencing (WES) was conducted to identify the pathogenic variants. Additionally, we reviewed the literature to further analyze the relationships between the genotype and audiology phenotype of LOXHD1. RESULTS: Six novel possible pathogenic LOXHD1 variants were identified, including three missense, one nonsense, and two splicing variants. The literature review showed that 68.5% of patients with DFNB77 onset before five years old; Most variants (62%) were associated with a down-sloping audiogram of mild-to-moderate hearing loss at low frequencies (200Hz, 500Hz), particularly variants in the protein domain of PLAT 9. We found that compared with homozygous LOXHD1 variants, individuals with heterozygous compound variants had a significantly milder phenotype, especially individuals carrying one missense and one splicing or bi-allelic missense variants (P < 0.05). Audiometric analysis at different ages showed that the hearing loss degree was aggravated at all frequencies by increasing age. CONCLUSIONS: We report three children with prelingual NSHL carrying six novel LOXHD1 variants. Furthermore, our work indicates that DFNB77 may be milder than previously reported and recommends considering the genotype combination and mutation location of LOXHD1 and race-specificity in DFNB77 molecular diagnoses and management.

The Role of Small Extracellular Vesicles Derived from Lipopolysaccharide-preconditioned Human Dental Pulp Stem Cells in Dental Pulp Regeneration.

INTRODUCTION: Regenerative endodontics has created a desirable shift in the treatment paradigm despite current limitations of regenerative outcomes. Mesenchymal stem cells (MSCs) facilitate tissue regeneration and repair in a mild inflammatory environment. Small extracellular vesicles (sEVs) derived from MSCs play an imperative role in the paracrine modulation of regenerative responses modulated by MSCs. However, it remains unknown whether MSCs enhance dental pulp regeneration or whether this enhancement is mediated by sEVs in a mild inflammatory environment. The present study aimed to elucidate the effects of sEVs originated from lipopolysaccharide (LPS)-preconditioned human dental pulp stem cells (hDPSCs) on dental pulp regeneration. METHODS: All sEVs were isolated from hDPSCs cultured with or without LPS (ie, N-sEVs and L-sEVs, respectively). The effect of N-sEVs and L-sEVs on proliferation, migration, angiogenesis, and differentiation of rat bone marrow MSCs was identified in vitro. Moreover, N-sEVs or L-sEVs were implanted into rat pulpless root canal models, and the regenerated tissue in root canals was assessed via hematoxylin-eosin staining, Masson staining, and immunohistochemistry after 30 days of transplantation. RESULTS: Both N-sEVs and L-sEVs could modulate BMSC proliferation, migration, angiogenesis, and differentiation. Both kinds of sEVs enhanced the structure of the regenerated tissue closer to that of a normal dental pulp in vivo. L-sEVs had a more significant effect than N-sEVs. CONCLUSIONS: sEVs released by hDPSCs in a mild inflammatory microenvironment are capable of facilitating the regeneration of dental pulp through functional healing instead of scar healing, which has potential applications in regenerative endodontics.

Nonalcoholic Fatty Liver Disease-Associated Liver Fibrosis Is Linked with the Severity of Coronary Artery Disease Mediated by Systemic Inflammation.

METHODS AND RESULTS: We conducted a retrospective study of 531 patients with ultrasonogram-confirmed NAFLD who underwent percutaneous coronary intervention (PCI). Then, all patients were separated into four categories by Gensini score (0, 0-9, 9-48, and ≥48) for use in ordinal logistic regression analysis to determine whether NAFLD fibrosis was associated with increased Gensini scores. Mediation analysis was used to investigate whether systemic inflammation is a mediating factor in the association between NAFLD fibrosis and CAD severity. FIB - 4 > 2.67 (OR = 5.67, 95% CI 2.59-12.38) and APRI > 1.5 (OR = 14.8, 95% CI 3.24-67.60) remained to be independent risk factors for the severity of CAD after adjusting for conventional risk factors, whereas among the inflammation markers, only neutrophils and neutrophil-to-lymphocyte ratio (NLR) were independently associated with CAD. Multivariable ordinal regression analysis suggested that increasing Gensini score (0, 0-9, 9-48, and ≥48) was associated with advanced NAFLD fibrosis. ROC curve showed that either fibrosis markers or inflammation markers, integrating with traditional risk factors, could increase the predictive capacity for determining CAD. Inflammation markers, especially neutrophils and NLR, were mediators of the relationship between NAFLD fibrosis and CAD severity. CONCLUSIONS: NAFLD patients with advanced fibrosis are at a high risk of severe coronary artery stenosis, and inflammation might mediate the association between NAFLD fibrosis and CAD severity.

Microvesicles derived from human umbilical cord mesenchymal stem cells ameliorate renal ischemia-reperfusion injury via delivery of miR-21.

Microvesicles (MVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs-MVs) and miR-21 were demonstrated to ameliorate renal ischemia-reperfusion injury (IRI). Since hUC-MSC-MVs contained a substantial quantity of miR-21, we speculated that miR-21 might account for a part of the therapeutic effects of hUC-MSCs-MVs. The human tubule epithelial (HK-2) cells were cultured under low oxygen (LO) condition to mimic a cellular IRI model. A rat model of unilateral renal IRI was established. A co-culture model of HK-2 cells and MSC-MVs was utilized to examine the therapeutic role of MSC-MVs in HK-2 cell apoptosis and mechanism. The results showed that hUC-MSCs-MVs inhibited LO-induced HK-2 cell apoptosis through transferring miR-21 to HK-2 cells. Mechanistically, miR-21 directly targeted and negatively regulated programmed cell death protein 4 (PDCD4) in HK-2 cells. Moreover, PDCD4 overexpression in HK-2 cells abrogated the hUC-MSCs-MVs-inhibited HK-2 cell apoptosis under LO condition. Additionally, the beneficial effect of MSC-MVs on rat renal IRI was partly eliminated when miR-21 was knocked down in MSCs. Taken together, MSC-MVs inhibit tubular epithelial cell apoptosis and ameliorate renal IRI, at least partially, via delivery of miR-21.

Novel heterozygous GATA3 and SLC34A3 variants in a 6-year-old boy with Barakat syndrome and hypercalciuria.

BACKGROUND: Barakat syndrome is an autosomal dominant disorder characterized by the triad of hypoparathyroidism, sensorineural deafness, and renal anomalies and is caused by mutations in GATA3 gene. SLC34A3 is the cause gene of hypophosphatemic rickets with hypercalciuria, and heterozygous carriers may have milder clinical symptoms. The aim of this study was to identify the underlying genetic cause of a patient who initially presented with renal failure, hypercalciuria, kidney stone, and bilateral sensorineural deafness. METHODS: A 6-year-old boy with complex clinical presentations was investigated. Comprehensive medical evaluations were performed including auditory function tests, endocrine function tests, metabolic studies, and imaging examinations. Molecular diagnoses were analyzed by trio whole-exome sequencing. RESULTS: One novel de novo deleterious variant (c. 324del) of the GATA3 gene was identified in the patient. The patient can be diagnosed with Barakat syndrome. In addition, one novel variant (c. 589A>G) of the SLC34A3 gene was detected, which was inherited from the father. This heterozygous variant can explain the hypercalciuria and kidney stone that occurred in both the patient and his father. CONCLUSION: This study provides a special case which is phenotype-driven dual diagnoses, and the two novel variants can parsimoniously explain the complex clinical presentations of this patient.

Microvesicles derived from human Wharton's jelly mesenchymal stem cells enhance autophagy and ameliorate acute lung injury via delivery of miR-100.

OBJECTIVES: Microvesicles (MVs) derived from human Wharton's jelly mesenchymal stem cells (MSC-MVs) were demonstrated to ameliorate acute lung injury (ALI). We have previously found that MSC-MV-transferred hepatocyte growth factor was partly involved in their therapeutic effects. Since MSC-MVs also contained a substantial quantity of miR-100, which plays an important role in lung cancer and injury, we speculated that miR-100 might similarly account for a part of the therapeutic effects of MSC-MVs. METHODS: MSCs were transfected with miR-100 inhibitor to downregulate miR-100 in MSC-MVs. A rat model of ALI and cell injury in rat type II alveolar epithelial cell line (L2) was induced by bleomycin (BLM). A co-culture model of alveolar epithelial cells and MSC-MVs was utilized to examine the therapeutic role of MSC-MVs and mechanism. RESULTS: MSC-MV treatment attenuated BLM-induced apoptosis and inflammation in BLM-treated L2 cells and ameliorated BLM-induced lung apoptosis, inflammation, and fibrosis in BLM-induced ALI rats. The beneficial effect of MSC-MVs was partly eliminated when miR-100 was knocked down in MSCs. Moreover, MSC-MV-transferred miR-100 mediated the therapeutic effect of MSC-MVs in ALI through enhancing autophagy by targeting mTOR. CONCLUSION: MSC-MVs enhance autophagy and ameliorate ALI partially via delivery of miR-100.

Quality of Root Filling after Obturation with Gutta-percha and 3 Different Sealers of Minimally Instrumented Root canals of the Maxillary First Molar.

INTRODUCTION: The aim of this study was to compare the quality of root fillings completed by a modified single-cone (MSC) technique with 3 different sealers after minimal instrumentation and multisonic cleaning of root canals of maxillary first molars. METHODS: Root canals of 18 maxillary first molars were instrumented to size 15/.04 taper using rotary files. Sodium hypochlorite 5.25% was used during instrumentation; the final cleaning was performed by the GentleWave System (Sonendo Inc, Laguna Hills, CA). The specimens were allocated into 3 groups and root filled by the MSC technique using a size fitted gutta-percha master cone and GuttaFlow Bioseal (Coltene Whaledent GmBH + Co KG, Langenau, Switzerland), GuttaFlow 2 (Coltene Whaledent GmBH + Co KG), and MTA Fillapex (Angelus Industria de Produtos Odontológicos S/A, Londrina, PR, Brazil) sealers. Micro-computed tomographic scans were obtained before and after instrumentation, post-GentleWave, and after obturation. Reconstructed images were analyzed for the volumetric percentage of filling materials. Mesiobuccal roots of the selected teeth were sectioned at 0.5-mm increments starting at the apex of the root. The cross sections were further examined using a light microscope. RESULTS: The 3 groups had 90%-99% of the canal space filled with the root filling material. The mean volume of the filling material was higher in the GuttaFlow Bioseal and GuttaFlow 2 groups than in the MTA Fillapex group (P < .05). There was no significant difference among the apical, middle, and coronal thirds. The cross-sectional images showed no obvious gaps or voids in the GuttaFlow groups. After instrumentation, 49 of the 189 canal thirds (25.9%) had hard tissue debris in the root canal system. After GentleWave cleaning, only 4 of 63 canals (6.3%) and 4 of the 189 canal thirds (2.1%) still had debris. CONCLUSIONS: The MSC method with GuttaFlow 2 and GuttaFlow Bioseal sealers after multisonic cleaning of minimally instrumented molar canals resulted in high-quality root fillings. Multisonic cleaning of minimally instrumented molars seems to be effective in debris removal.

Mediation in the second-order synaptic emulator with conductive atomic force microscopy.

Memristors have been extensively studied for synaptic simulation and neuromorphic computation. Instead of focusing on implementing specific synaptic learning rules by carefully engineering external programming parameters, researchers recently have paid more attention to taking advantage of the second-order memristor that is more analogous to biologic synapses and modulated not only by external inputs but also by internal mechanisms. However, experimental evidence is still scarce. Here, we explore a BiMnO3 memristor by applying simple spike forms. The filament evolution dynamics, including processes of forming and spontaneous decay, were directly observed by the conductive atomic force microscopy (c-AFM) technique. We propose that the unique conductance state of the BMO memristor is regulated by the oxygen vacancy (VO) dynamic process. We believe this primary result is helpful to improve understanding of the internal mechanisms of the second-order oxide memristor, which exhibits promising application in building selectors, memories and neuromorphic-computing systems.

Measurement of Thresholds Using Auditory Steady-State Response and Cochlear Microphonics in Children with Auditory Neuropathy.

BACKGROUND: The detection of precise hearing thresholds in infants and children with auditory neuropathy (AN) is challenging with current objective methods, especially in those younger than six months of age. PURPOSE: The aim of this study was to compare the thresholds using auditory steady-state response (ASSR) and cochlear microphonics (CM) in children with AN and children with normal hearing. RESEARCH DESIGN: The thresholds of CM, ASSR, and visual reinforcement audiometry (VRA) tests were recorded; the ASSR and VRA frequencies used were 250, 500, 1000, 2000, and 4000 Hz. STUDY SAMPLE: The participants in this study were 15 children with AN (27 ears) (1-7.6 years, median age 4.1 years) and ten children with normal hearing (20 ears) (1-8 years, median age four years). DATA COLLECTION AND ANALYSIS: The thresholds of the three methods were compared, and histograms were used to represent frequency distributions of threshold differences obtained from the three methods. RESULTS: In children with normal hearing, the average CM thresholds (84.5 dB) were significantly higher than the VRA thresholds (10.0-10.8 dB); in children with AN, both CM and VRA responses were seen at high signal levels (88.9 dB and 70.6-103.4 dB, respectively). In normal children, the difference between mean VRA and ASSR thresholds ranged from 17.5 to 30.3 dB, which was significantly smaller than the difference seen between the mean CM and VRA thresholds (71.5-72.3 dB). The correlation between VRA and ASSR in children with normal hearing ranged from 0.38 to 0.48, whereas no such correlation was seen in children with AN at any frequency (0.03-0.19). CONCLUSIONS: Our results indicated that ASSR and CM were poor predictors of the conventional behavioral threshold in children with AN.