Publications by authors named "Xin Ni"

319 Publications

Hepatic macrophages: key players in the development and progression of liver fibrosis.

Liver Int 2021 May 9. Epub 2021 May 9.

National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China.

Hepatic fibrosis is a common pathological process involving persistent liver injury with various etiologies and subsequent inflammatory responses that occur in chronic liver diseases. If left untreated, liver fibrosis can progress to liver cirrhosis, hepatocellular carcinoma, and eventually, liver failure. Unfortunately, to date, there is no effective treatment for liver fibrosis, with the exception of liver transplantation. Although the pathophysiology of liver fibrosis is multifactorial and includes the activation of hepatic stellate cells, which are known to drive liver fibrogenesis, hepatic macrophages have emerged as central players in the development of liver fibrosis and regression. Hepatic macrophages, which consist of resident macrophages (Kupffer cells) and monocyte-derived macrophages, have been shown to play an intricate role in the initiation of inflammatory responses to liver injury, progression of fibrosis, and promotion of fibrosis resolution. These features have made hepatic macrophages uniquely attractive therapeutic targets in the fight against hepatic fibrosis. In this review, we synthesized the literature to highlight the functions and regulation of heterogeneity in hepatic macrophages. Furthermore, using the existing findings, we attempt to offer insights into the molecular mechanisms underlying the phenotypic switch from fibrogenic macrophages to restorative macrophages, the regulation of heterogeneity, and modes of action for hepatic macrophages. A better understanding of these mechanisms may guide the development of novel anti-fibrotic therapies (e.g., macrophage subset-targeted treatments) to combat liver fibrosis in the future.
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http://dx.doi.org/10.1111/liv.14940DOI Listing
May 2021

A somatic mutation in PIK3CD unravels a novel candidate gene for lymphatic malformation.

Orphanet J Rare Dis 2021 May 8;16(1):208. Epub 2021 May 8.

Department of Otolaryngology-Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.

Background: Lymphatic malformations (LMs) are benign congenital malformations that stem from the abnormal development of the lymphatic vessels during early embryogenesis. Somatic PIK3CA gene mutations are conventional cause leading to LMs. Both macrocystic and microcystic LMs arise due to lymphatic endothelial cell-autonomous defects, depending on the time in development at which PIK3CA gene mutation occurs. Recent study finds a PIK3CA mutation in 79% of LMs. However, discovering new genetic events in this disease is crucial to identify the molecular mechanism of the pathogenesis and further develop new targeted therapies.

Results: Here, we initially performed whole-exome sequencing in six children with LMs to find a new causal gene. Somatic mutations in PIK3CA (c.1633G > A [p. E545K] and PIK3CD (c.1997T > C [p.L666P]) were discovered in two different individuals. In vitro functional studies were conducted to demonstrate the pathogenicity of the novel mutation c.1997T > C in PIK3CD. We found that L666P promoted the cell proliferation and migration of human umbilical vein endothelial cells (HUVECs) and induced hyperactivation of the mTOR pathway. These findings indicate that the PIK3CD mutation affects downstream signalling in endothelial cells, which may impair normal lymphangiogenesis.

Conclusions: This study reveals a novel candidate gene associated with the development of LMs, which is consistent with previous researches. These findings in our study may offer a novel gene target for developing therapies, which acts in tight interaction with the previously known PIK3CA.
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http://dx.doi.org/10.1186/s13023-021-01782-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106842PMC
May 2021

Urocortins exhibit differential effects on PGE2 and PGF2α output via CRHR2 in human myometrium.

Reproduction 2021 Apr 1. Epub 2021 Apr 1.

X Ni, Research Centre for Molecular Metabolomics, Xiangya Hospital Central South University, Changsha, China.

Urocortins (UCNs), belonging to corticotropin-releasing hormone (CRH) family, exert their function via CRH receptor type 1(CRHR1) and 2 (CRHR2). Our previous studies have demonstrated that CRH acts on CRHR1 to potentiate prostaglandin (PG) output induced by inflammatory stimuli in myometrial cells. In the present study, we sought to investigate the effects of UCNs on prostaglandin (PG) output via CRHR2 in cultured human uterine smooth muscle cells (HUSMCs) from human term myometrium. We found that UCN and UCN3 treatment promoted PGE2 and PGF2α secretion in a dose-dependent manner. In contrast, UCN2 dose-dependently inhibited PGE2 and PGF2α secretion. Their effects could be reversed by CRHR2 antagonist and CRHR2 siRNA. Mechanically, we showed that UCN and UCN3 suppressed cAMP production and led to Gi activation, while UCN2 promoted cAMP production and activated Gs signaling. Further, UCN and UCN3 could activate NF-κB and MAPK signaling pathways. These effects were dependent on Gi signaling. In contrast, UCN did not activate MAPK and NF-κB signaling. UCN and UCN3 stimulation of PG secretion was dependent on Gi/adenylyl cyclase (AC)/cAMP, NF-κB and MAPK signaling pathways, while UCN2 suppression of PG output was through Gs/AC/cAMP signaling pathways. Our data suggest that UCN, UCN2 and UCN3 can finely regulate the secretion of PGs via CRHR2, which facilities the functional status of uterus during pregnancy.
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http://dx.doi.org/10.1530/REP-20-0659DOI Listing
April 2021

Effects of obstructive sleep apnoea severity on neurocognitive and brain white matter alterations in children according to sex: a tract-based spatial statistics study.

Sleep Med 2020 Aug 28;82:134-143. Epub 2020 Aug 28.

Department of Otolaryngology, Head and Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China. Electronic address:

Objectives: To investigate alterations in neurocognitive, attention, paediatric sleep questionnaire (PSQ) scores and whole brain white matter (WM) integrity between children with mild and severe obstructive sleep apnoea (OSA) according to sex and whether these changes are associated with OSA severity.

Methods: Fifty-seven children (36 males and 21 females) diagnosed with OSA were recruited for this study. Children of both sexes were divided into mild (male-MG, female-MG) and severe (male-SG, female-SG) groups according to OSA severity. Polysomnography (PSG), neurocognitive, attention and PSQ tests were compared between groups by one-way samples analysis of variance (ANOVA) F test. Diffusion tensor imaging (DTI) was scanned using a 3T GE MRI scanner and analysed by Tract-based Spatial Statistics (TBSS). Spearman correlation was calculated between DTI Eigenvalues and clinical characteristics.

Results: Compared to mild OSA patients, severe OSA patients presented greater severity of obstructive apnoea hypopnea index (OAHI), neurocognition, PSQ and attention tests in both male and female patients. Brain WM integrity in the male-SG, compared to the male-MG, demonstrated significantly reduced fractional anisotropy (FA) values in the right middle frontal gyrus and the right frontal sub-gyral regions and increased axial diffusivity (AD) values in the right inferior frontal gyrus, left parietal angular gyrus and sub-gyral regions, while no differences were found between the female-MG and female-SG. Alterations in male-SG brain regions were observably correlated with severity in male OSA patients.

Conclusions: The integrity of WM, which regulates autonomic, cognitive, and attention functions, is impaired in male, but not female, children with severe OSA.
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http://dx.doi.org/10.1016/j.sleep.2020.08.026DOI Listing
August 2020

Furin is involved in uterine activation for labor.

FASEB J 2021 May;35(5):e21565

Department of Gynecology and Obstetrics, Research Center for Molecular Metabolomics, Xiangya Hospital Central South University, Changsha, China.

The uterus undergoes distinct molecular and functional changes during pregnancy and parturition. These processes are associated with the dramatic changes in various proteins. Given that the maturation and activation of many proteins require proteolytic processing by proprotein convertases (PCs), we sought to explore the role of PCs in uterine activation for labor. First, we found that furin was the most dramatically increased PC member in myometrial tissues from the pregnant women after onset of labor at term. Using the model of cultured human myometrial smooth muscle cells (HMSMCs), we showed that furin inhibitor CMK, D6R treatment and furin siRNA transfection suppressed contractility. Inhibition of furin activity or interfering furin expression decreased connexin 43 (CX43), prostaglandin (PG) endoperoxide synthase-2 (COX-2) and PGF2α receptor (FP) expression and NF-κB activation. In mouse model, administration of furin inhibitors prolonged gestational length. However, D6R treatment did not affect RU38486- and lipopolysaccharides (LPS)-induced preterm birth. Furthermore, D6R and furin siRNA treatment reduced the release of soluble form of tumor necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK), while furin overexpression led to an increase in soluble TWEAK release in cultured HMSMCs. D6R treatment decreased TWEAK level in blood of pregnant mice. TWEAK treatment promoted contractility and NF-κB activation, while TWEAK receptor fibroblast growth factor-inducible 14 (FN14) antagonist treatment inhibited contractility and NF-κB activation in HMSMCs. In pregnant mice, administration of FN14 antagonist prolonged gestational length. Our data suggest that furin can act as a stimulator for uterine activation for labor at term. TWEAK is one of the potential substrates which mediate furin regulation of parturition initiation.
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http://dx.doi.org/10.1096/fj.202002128RRDOI Listing
May 2021

Spatial learning and memory deficits induced by prenatal glucocorticoid exposure depend on hippocampal CRHR1 and CXCL5 signaling in rats.

J Neuroinflammation 2021 Apr 2;18(1):85. Epub 2021 Apr 2.

Department of Gynecology and Obstetrics and Research Center for Molecular Metabolomics, Xiangya Hospital Central South University, Changsha, 410008, China.

Background: Prenatal synthetic glucocorticoid (sGC) exposure increases the susceptibility to cognitive and affective disorders in postnatal life. We previously demonstrated that prenatal sGC exposure results in an increase in corticotropin-releasing hormone (CRH) receptor type 1 (CRHR1) expression in the hippocampus of rats, and CRHR1 is involved in synapse formation via regulation of C-X-C chemokine ligand 5 (CXCL5) in hippocampus. We sought to investigate that the roles of CRHR1 and CXCL5 in learning and memory impairment caused by prenatal sGC exposure.

Methods: Pregnant rats were administered with saline or dexamethasone (DEX) from gestational day (GD) 14 to GD21. DEX offspring at 2-day old were treated with saline and CRHR1 antagonists (antalarmin and CP154526) for 7 days. Some DEX offspring received intra-hippocampal injection of AAV9 carrying CXCL5 gene. Spatial learning and memory was assessed by Morris water maze test. Immunofluorescence analysis was applied to show synapsin I and PSD95 signals in hippocampus. Synapsin I and PSD95 protein level and CXCL5 concentration were determined by western blotting and ELISA, respectively. Organotypic hippocampal slice cultures were used to investigate the effect of DEX on CXCL5 production in vitro.

Results: Both male and female DEX offspring displayed impairment of spatial learning and memory in adulthood. Synapsin I and PSD95 signals and CXCL5 levels were decreased in DEX offspring. DEX offspring with antalarmin and CP154526 treatment showed improved spatial learning and memory. Antalarmin and CP154526 treatment increased synapsin I and PSD95 signals and CXCL5 concentration in hippocampus. Bilaterally hippocampal injection of AAV9 carrying CXCL5 gene improved the spatial learning and memory and increased CXCL5 concentration and synapsin I and PSD95 levels in hippocampus. DEX dose-dependently suppressed CXCL5 production in cultured hippocammpal slices, which was prevented by antalarmin treatment.

Conclusion: CRHR1 and CXCL5 signaling in the hippocampus are involved in spatial learning and memory deficits caused by prenatal DEX exposure. CRHR1 activation contributes to decreased CXCL5 production in hippocampus induced by prenatal DEX treatment. Our study provides a molecular basis of prenatal GC exposure programming spatial learning and memory.
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http://dx.doi.org/10.1186/s12974-021-02129-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019183PMC
April 2021

Disease characteristics and neuropathological changes associated with cognitive dysfunction in obstructive sleep apnea.

Pediatr Investig 2021 Mar 22;5(1):52-57. Epub 2021 Mar 22.

Department of Otolaryngology, Head and Neck Surgery Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.

Obstructive sleep apnea (OSA) is a common sleep-disordered breathing disease that often leads to many comorbidities (e.g., cognitive dysfunction), which adversely affect the quality of life for patients with OSA. Thus far, the underlying mechanisms of this dysfunction remain unclear. Many studies have focused on OSA-related characteristics, including intermittent hypoxemia and sleep fragmentation. There is increasing emphasis on neuroimaging studies to explore underlying relationships between neuropathological changes and cognitive dysfunction. This article reviews recent research progress concerning cognitive dysfunction associated with OSA to reveal potential mechanisms that contribute to this dysfunction.
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http://dx.doi.org/10.1002/ped4.12247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984002PMC
March 2021

A novel role of kallikrein-related peptidase 8 in the pathogenesis of diabetic cardiac fibrosis.

Theranostics 2021 20;11(9):4207-4231. Epub 2021 Feb 20.

Department of Physiology, Navy Medical University, Shanghai, China.

Among all the diabetic complications, diabetic cardiomyopathy, which is characterized by myocyte loss and myocardial fibrosis, is the leading cause of mortality and morbidity in diabetic patients. Tissue kallikrein-related peptidases (KLKs) are secreted serine proteases, that have distinct and overlapping roles in the pathogenesis of cardiovascular diseases. However, whether KLKs are involved in the development of diabetic cardiomyopathy remains unknown.The present study aimed to determine the role of a specific KLK in the initiation of endothelial-to-mesenchymal transition (EndMT) during the pathogenesis of diabetic cardiomyopathy. By screening gene expression profiles of KLKs, it was found that KLK8 was highly induced in the myocardium of mice with streptozotocin-induced diabetes. KLK8 deficiency attenuated diabetic cardiac fibrosis, and rescued the impaired cardiac function in diabetic mice. Small interfering RNA (siRNA)-mediated KLK8 knockdown significantly attenuated high glucose-induced endothelial damage and EndMT in human coronary artery endothelial cells (HCAECs). Diabetes-induced endothelial injury and cardiac EndMT were significantly alleviated in KLK8-deficient mice. In addition, transgenic overexpression of KLK8 led to interstitial and perivascular cardiac fibrosis, endothelial injury and EndMT in the heart. Adenovirus-mediated overexpression of KLK8 (Ad-KLK8) resulted in increases in endothelial cell damage, permeability and transforming growth factor (TGF)-β1 release in HCAECs. KLK8 overexpression also induced EndMT in HCAECs, which was alleviated by a TGF-β1-neutralizing antibody. A specificity protein-1 (Sp-1) consensus site was identified in the human KLK8 promoter and was found to mediate the high glucose-induced KLK8 expression. Mechanistically, it was identified that the vascular endothelial (VE)-cadherin/plakoglobin complex may associate with KLK8 in HCAECs. KLK8 cleaved the VE-cadherin extracellular domain, thus promoting plakoglobin nuclear translocation. Plakoglobin was required for KLK8-induced EndMT by cooperating with p53. KLK8 overexpression led to plakoglobin-dependent association of p53 with hypoxia inducible factor (HIF)-1α, which further enhanced the transactivation effect of HIF-1α on the TGF-β1 promoter. KLK8 also induced the binding of p53 with Smad3, subsequently promoting pro-EndMT reprogramming via the TGF-β1/Smad signaling pathway in HCAECs. The and findings further demonstrated that high glucose may promote plakoglobin-dependent cooperation of p53 with HIF-1α and Smad3, subsequently increasing the expression of TGF-β1 and the pro-EndMT target genes of the TGF-β1/Smad signaling pathway in a KLK8-dependent manner. The present findings uncovered a novel pro-EndMT mechanism during the pathogenesis of diabetic cardiac fibrosis via the upregulation of KLK8, and may contribute to the development of future KLK8-based therapeutic strategies for diabetic cardiomyopathy.
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http://dx.doi.org/10.7150/thno.48530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977470PMC
February 2021

Narrow-linewidth self-injection locked diode laser with a high-Q fiber Fabry-Perot resonator.

Opt Lett 2021 Mar;46(6):1397-1400

Narrow-linewidth lasers are essential for various applications, but are limited by their size, weight, power, and cost requirements. Here we demonstrate a self-injection locked diode laser fabricated with a high quality factor fiber Fabry-Perot resonator, with a 145 Hz free-running linewidth. The locking scheme is all-fiber for plug-and-play operation. White frequency noise of 50/ is measured with over 42 dB reduction from the low-cost TO-can distributed feedback laser diode, and shows its wide applications in a compact and cost-effective way.
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http://dx.doi.org/10.1364/OL.415859DOI Listing
March 2021

Serum TSH is not a risk factor for malignancy of pediatric thyroid nodules.

Endocr Relat Cancer 2021 Apr;28(4):247-255

Department of Otorhinolaryngology, Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, Beijing, China.

It is uncertain whether serum TSH concentration is an independent risk factor for the malignancy of pediatric thyroid nodules. We sought the association of serum TSH concentration with the malignancy of pediatric thyroid nodules and with the characteristics of pediatric thyroid cancer. A total of 219 pediatric thyroid nodule patients were collected retrospectively for 5 consecutive years. The medical records collected included sex, age, serum TSH concentration, thyroid autoantibody status, thyroid ultra-sonography parameters, histological type, and pathological TNM stages. The serum TSH concentrations were compared between benign and malignant nodules or corresponding subgroups. Binary logistic regression analysis was used to evaluate the correlation of TSH concentration with the malignancy of thyroid nodules and with the characteristics of pediatric thyroid cancer. There was no significant difference in TSH concentration between benign nodule and thyroid cancer in total subjects and various subgroups. The serum TSH level was not correlated with the malignancy of thyroid nodules in univariate analysis, but negatively correlated with the malignancy of thyroid nodules (odds ratio = 0.856, P = 0.013) after adjusting for the patients' sex, age, thyroid autoantibody status, and nodule size. The serum TSH level was not correlated with the tumor characteristics in pediatric thyroid cancer patients. In conclusion, the serum TSH concentration seems not to be a carcinogenic factor in pediatric thyroid nodule patients, nor to be an independent risk factor for characteristics of pre-existing pediatric thyroid cancers.
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http://dx.doi.org/10.1530/ERC-20-0508DOI Listing
April 2021

Brain Function in Children with Obstructive Sleep Apnea: A Resting-State fMRI Study.

Sleep 2021 Mar 1. Epub 2021 Mar 1.

Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing, People's Republic of China.

Objective: To explore the neural difference between children with obstructive sleep apnea (OSA) and healthy controls, together with the relation between this difference and cognitive dysfunction of children with OSA.

Methods: Twenty children with OSA (7.2 ± 3.1 years, apnea hypopnea index (AHI): 16.5 ± 16.6 events/h) and 29 healthy controls (7.7 ± 2.8 years, AHI: 1.7 ± 1.2 events/h) were recruited and matched with age, gender, and handedness. All children underwent resting-state fMRI (rs-fMRI) and T1-wighted imaging. Some children were sedated for MRI scanning. We compared amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo) of children with OSA with those of healthy controls. During resting-state, the former reflects the intensity of the spontaneous neural activities, whereas the latter reflects temporal similarity of the spontaneous neural activities within a local brain region. Pearson correlation analysis was performed between these features of rs-fMRI and cognitive scores among children with OSA.

Results: Compared with controls, children with OSA showed decreased ALFF in the left angular gyrus but increased ALFF in the right insula, and decreased ReHo in the left medial superior frontal gyrus, right lingual gyrus and left precuneus. Additionally, among children with OSA, the ReHo value in the right lingual gyrus was negatively correlated with FIQ and VIQ, whereas that in the left medial superior frontal gyrus was positively correlated with VIQ.

Conclusions: Children with OSA presented abnormal neural activities in some brain regions and impaired cognitive functions with the former possibly being the neural mechanism of the latter.
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http://dx.doi.org/10.1093/sleep/zsab047DOI Listing
March 2021

[Research advances of natural killer cells at the maternal-fetal interface].

Authors:
Ya-Li Shan Xin Ni

Sheng Li Xue Bao 2021 Feb;73(1):103-114

Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Changsha 410008, China.

Natural killer (NK) cells are the main immune cells at the maternal-fetal interface and accumulate in the uterine decidua in early pregnancy. Many studies have shown that NK cells at the maternal-fetal interface have unique phenotypes and play critical roles in various processes, including immune tolerance during pregnancy, decidualization, invasion of trophoblasts, remodeling of the uterine spiral artery, formation of the placenta and growth of embryo. However, specific functions of NK cells and their mechanism remain to be fully elucidated. This review summarizes the research progress of NK cells at the maternal-fetal interface and their roles in the pregnancy-related disorders in recent years. The aims of this review are to gain deep insight of the function of NK cells at the maternal-fetal interface and provide new ideas for intervention of pregnancy-related diseases.
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February 2021

Hydrogen Sulfide Is a Regulator of Hemoglobin Oxygen-Carrying Capacity via Controlling 2,3-BPG Production in Erythrocytes.

Oxid Med Cell Longev 2021 13;2021:8877691. Epub 2021 Feb 13.

National Clinical Research Center for Geriatric Disorders and National International Joint Research Center for Medical Metabolomics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China.

Hydrogen sulfide (HS) is naturally synthesized in a wide range of mammalian tissues. Whether HS is involved in the regulation of erythrocyte functions remains unknown. Using mice with a genetic deficiency in a HS natural synthesis enzyme cystathionine--lyase (CSE) and high-throughput metabolomic profiling, we found that levels of erythrocyte 2,3-bisphosphoglycerate (2,3-BPG), an erythroid-specific metabolite negatively regulating hemoglobin- (Hb-) oxygen (O) binding affinity, were increased in CSE knockout () mice under normoxia. Consistently, the 50% oxygen saturation (P50) value was increased in erythrocytes of mice. These effects were reversed by treatment with HS donor GYY4137. In the models of cultured mouse and human erythrocytes, we found that HS directly acts on erythrocytes to decrease 2,3-BPG production, thereby enhancing Hb-O binding affinity. Mouse genetic studies showed that HS produced by peripheral tissues has a tonic inhibitory effect on 2,3-BPG production and consequently maintains Hb-O binding affinity in erythrocytes. We further revealed that HS promotes Hb release from the membrane to the cytosol and consequently enhances bisphosphoglycerate mutase (BPGM) anchoring to the membrane. These processes might be associated with S-sulfhydration of Hb. Moreover, hypoxia decreased the circulatory HS level and increased the erythrocyte 2,3-BPG content in mice, which could be reversed by GYY4137 treatment. Altogether, our study revealed a novel signaling pathway that regulates oxygen-carrying capacity in erythrocytes and highlights a previously unrecognized role of HS in erythrocyte 2,3-BPG production.
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http://dx.doi.org/10.1155/2021/8877691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896853PMC
February 2021

Summary of the Experience in the Diagnosis and Treatment of Complex Preauricular Fistulas in 78 Children.

Front Surg 2020 1;7:609852. Epub 2021 Feb 1.

Department of Otorhinolaryngology Head and Neck Surgery Henan Children's Hospital, Department of Otorhinolaryngology Head and Neck Surgery, Zhengzhou Children's Hospital, Zhengzhou, China.

This study aimed to investigate the application of mini-incisions in complex preauricular fistula resection in children. A total of 78 children who were diagnosed with preauricular fistula infection between January 2017 and December 2019 were included in the study. Their clinical data were analyzed retrospectively, and surgical treatment with mini-incisions based on plastic surgery principles and techniques was provided. All the patients achieved healing following the first application of the treatment. The patients were followed up for 6-42 months, and no recurrence or local auricular deformation occurred. The application of mini-incisions and plastic surgery techniques in complex preauricular fistula resection in children can achieve a good effect and improve the satisfaction of the children and their parents.
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http://dx.doi.org/10.3389/fsurg.2020.609852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882734PMC
February 2021

Clinical and Genetic Spectrum of Children With Primary Ciliary Dyskinesia in China.

Chest 2021 May 10;159(5):1768-1781. Epub 2021 Feb 10.

Department of Otolaryngology Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Background: Primary ciliary dyskinesia (PCD) is a heterogeneous disease with a diverse clinical and genetic spectrum among populations worldwide. Few cases of pediatric PCD have been reported from China.

Research Question: What are the clinical and genotypic characteristics of children with PCD in China?

Study Design And Methods: Clinical characteristics, laboratory findings, and genetic results obtained for 75 patients with PCD were reviewed retrospectively at a single center in China. Genetic sequencing was conducted using whole-exome screening.

Results: Patient median age at diagnosis was 7.0 years (range, 2 months-14 years). Of 75 patients, 88% (66/75) had chronic wet cough, 77% (58/75) had recurrent sinusitis, 76% (57/75) had bronchiectasis, 40% (30/75) had neonatal respiratory distress, and 28% (21/75) had coexistent asthma. Notably, postinfectious bronchiolitis obliterans (PIBO) as first presentation was found in 8% of children (6/75). Genes with the highest incidence of mutations were DNAH11 (15/51), followed by DNAH5 (9/51), CCDC39 (5/51), DNAH1 (4/51), and CCNO (3/51). Four genes (DNAI1, HEATR2, RSPH9, and DNAAF3) each were respectively found in two patients, and seven genes (CCDC40, LRRC6, SPAG1, RSPH4A, ARMC4, CCDC114, and DNAH14, a novel gene) each were mutated once. No differences in classical clinical features were observed among patients with commonly observed PCD-associated genotypes. However, three of six PIBO patients carried DNAH1 mutations.

Interpretation: Besides typical clinical features, PIBO was observed as the first presentation of pediatric PCD in China. An association of the novel gene DNAH14 with PCD was observed, expanding the PCD genotypic spectrum.
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http://dx.doi.org/10.1016/j.chest.2021.02.006DOI Listing
May 2021

Efficacy of Initial Sirolimus Therapy for 27 Patients with Intractable Lymphatic Malformations.

Laryngoscope 2021 Feb 11. Epub 2021 Feb 11.

Department of Otolaryngology, Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, China.

Objective/hypothesis: To evaluate the efficacy of initial sirolimus therapy in the treatment of intractable head and neck lymphatic malformations (LMs) in children.

Study Design: Prospective open-label study.

Methods: In this study, Twenty-seven children diagnosed with LMs were given oral sirolimus as primary treatment over a minimum 6-month trial. The major parameter to evaluate therapeutic outcome was percentage of lesion volume change compared with baseline. Average serum sirolimus concentrations, and adverse side effects, were monitored throughout the study period.

Results: Fifteen girls and twelve boys, average age 27 months (16 days-171 months), constitute the study group. Treatment was deemed effective for twenty-three participants, judged as fair in seven, good in nine, and excellent in seven. Two patients had minimal improvement, and two had increased volume to some degree. Effectiveness differed among LMs subtypes with responsiveness of macrocystic LMs exceeding that of microcystic LMs (P < .05). Adverse drug reactions totaled 27 events in ten patients, the majority being mild with upper respiratory infections being most common.

Conclusions: Sirolimus as initial therapy is effective in decreasing lesion volume in intractable LMs in head and neck region, especially in macrocystic subtypes. Although most cases cannot be completely cured, side effects are few and tolerable.

Level Of Evidence: IV Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29419DOI Listing
February 2021

Application of Gastroscopy in the Diagnosis of Congenital Pyriform Sinus Fistula in Children.

Front Pediatr 2020 25;8:541249. Epub 2021 Jan 25.

Department of Otolaryngology, Head and Neck Surgery, National Center for Children's Health (NCCH), Beijing Children's Hospital, Capital Medical University, Beijing, China.

The aim of this study was to explore the diagnostic value of gastroscopy under local anesthesia for congenital pyriform sinus fistula (CPSF). This research was a diagnostic study. Patients received gastroscopy under local anesthesia to diagnose CPSF, and suspension laryngoscopy under general anesthesia was performed 2 days after gastroscopy. Various conditions of the internal opening of CPSF were then recorded. Patients were grouped according to lesion sides, age, time after the inflammation subsided, and history of previous surgery. The sensitivity, specificity, area under the receiver operating characteristic curve (AUC), accuracy, and positive and negative predictive values of gastroscopy were compared between the groups. A total of 48 patients were recruited in this study, and no patients had severe gastroscopy-related complications. The diagnostic values of gastroscopy in 41 cases (85.4%) were consistent with suspension laryngoscopy. The sensitivity of gastroscopy was 86.4%, the specificity was 75%, the AUC was 0.807, the positive prediction rate was 97.4%, the negative prediction rate was 33.3%, the accuracy rate was 85.4%, and the diagnostic odds ratio (DOR) was 2.1. The kappa consistency test results had statistical significance ( = 0.0026, kappa = 0.3913). The diagnostic value of gastroscopy was better for the patients with inflammation subsiding for more than 4 weeks ( < 0.0001). Gastroscopy under local anesthesia is a safe, effective, reliable and novel diagnostic method for CPSF, and it is especially recommended as a diagnostic method for the patients with inflammation subsiding for more than 4 weeks.
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http://dx.doi.org/10.3389/fped.2020.541249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868526PMC
January 2021

The Traditional Chinese Medicine Fuyou Formula Alleviates Precocious Puberty by Inhibiting GPR54/GnRH in the Hypothalamus.

Front Pharmacol 2020 21;11:596525. Epub 2021 Jan 21.

Clinical Research Center, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China.

The purpose of this study was to explore the effect of the traditional Chinese medicine Fuyou formula on precocious puberty (PP). The Fy formula may exert an effect in female rats with PP and GT-7 cells through the GPR54/GnRH signaling pathway. To confirm the effect of the Fy formula on PP through the GPR54/GnRH signaling pathway, we first treated GT1-7 cells with the Fy formula and observed changes in the expression of related genes and proteins and in GnRH secretion. Then, we randomly divided young female Sprague-Dawley rats into the control group, model group, leuprorelin group and the Fy formula group. A PP model was established by injection of danazol on postnatal day 5, and the Fy formula was administered on PND15. The time of vaginal opening, the wet weights of the ovary and uterus, serum hormone levels and the expression of hypothalamic-related genes were observed. We found that the Fy formula delayed vaginal opening, decreased the wet weights and coefficients of the ovary and uterus, decreased the levels of serum hormones (E2, follicle-stimulating hormone and luteinizing hormone) and the cellular GnRH level, and downregulated the gene expression of Kiss1, GPR54 and GnRH in the hypothalamus and the gene and protein expression of GPR54 and GnRH in GT1-7 cells. In conclusion, the Fy formula may alleviate PP via the GPR54/GnRH signaling pathway.
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http://dx.doi.org/10.3389/fphar.2020.596525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859969PMC
January 2021

Optical-Relayed Entanglement Distribution Using Drones as Mobile Nodes.

Phys Rev Lett 2021 Jan;126(2):020503

National Laboratory of Solid State Microstructures, School of Electronic Science and Engineering, School of Physics, College of Engineering and Applied Sciences, and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China.

Entanglement distribution has been accomplished using a flying drone, and this mobile platform can be generalized for multiple mobile nodes with optical relay among them. Here we develop the first optical relay to reshape the wave front of photons for their low diffraction loss in free-space transmission. Using two drones, where one distributes the entangled photons and the other serves as relay node, we achieve entanglement distribution with Clauser-Horne-Shimony-Holt S parameter of 2.59±0.11 at 1 km distance. Key components for entangled source, tracking, and relay are developed with high performance and are lightweight, constructing a scalable airborne system for multinode connectio and toward mobile quantum networks.
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http://dx.doi.org/10.1103/PhysRevLett.126.020503DOI Listing
January 2021

Developmental performance between pediatric cochlear implantation candidates with and without large vestibular aqueduct syndrome.

Acta Otolaryngol 2021 Mar 27;141(3):250-255. Epub 2021 Jan 27.

Department of Otorhinolaryngology Head and Neck Surgery, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China.

Background: We are inclined to pay special care and attention to children with large vestibular aqueduct syndrome (LVAS). However, it is not clear whether children with LVAS have more developmental delays than children without LVAS.

Objectives: To compare the developmental performance between pediatric cochlear implantation (CI) candidates with and without LVAS.

Materials And Methods: Medical records of pediatric CI candidates were reviewed. Through propensity score matching analysis, 70 children with LVAS and 70 gender-, age-, and auditory-matched children were recruited as the LVAS and non-LVAS group, respectively. Developmental performances were compared between the two groups.

Results: Compared with normal developmental metrics, both LVAS and non-LVAS groups had developmental delay in multiple domains (both  .001). Although some differences in motor developments between children with LVAS and without LVAS, they demonstrated overall equal developmental levels in both verbal and nonverbal aspects (all  .05). Age of intervention was the primary risk factor for developmental performance of LVAS children ( 0 .05) with an obvious delay starting at 1 year of age.

Conclusion: Pediatric CI candidates with LVAS had both verbal and nonverbal developmental delays. However, they exhibited similar overall developmental performances to those without LVAS.
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http://dx.doi.org/10.1080/00016489.2020.1862909DOI Listing
March 2021

Surgical Experiences of Pediatric Cervical Bronchogenic Cysts: A Case Series of 6 Patients.

Ear Nose Throat J 2021 Jan 25:145561320982194. Epub 2021 Jan 25.

Department of Otolaryngology, Head and Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Xicheng, Beijing, People's Republic of China.

Objectives: Bronchogenic cyst is a rare congenital disease which occurs especially in the neck region. This report presents 6 cases of bronchogenic cysts and discusses the diagnosis and surgical experience of this anomaly.

Methods: A retrospective study of 6 pediatric patients with cervical bronchogenic cysts treated in our hospital during 2016 to 2019 was performed. We recorded and analyzed the clinical data of the patients, including age, symptoms, imaging findings, surgical procedure, and complications.

Results: All patients underwent surgical excision. The chondroid tissues were found at the base of cysts which clung to the trachea in 5 patients and completely removed by surgery without recurrence. One patient showed recurrence due to residual cartilage after the first surgery, and the second surgery was required to resect the remaining cartilage. During the surgery, the recurrent laryngeal nerve (RLN) detector was used, which confirmed that all the RLNs clung to the side wall of cysts. All cases were cured without complications.

Conclusions: Although rare, bronchogenic cysts should be considered in the differential diagnosis of peritracheal masses in children. Complete resection of the bronchogenic cysts, including the cartilages at the base, is vital in preventing recurrence. The RLN must be protected during the surgery.
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http://dx.doi.org/10.1177/0145561320982194DOI Listing
January 2021

The efficacy and safety of montelukast in children with obstructive sleep apnea: a systematic review and meta-analysis.

Sleep Med 2021 Feb 10;78:193-201. Epub 2020 Nov 10.

Department of Respiratory Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, PR China. Electronic address:

Objective: The efficacy and safety of montelukast in children with obstructive sleep apnea (OSA) remain controversial. Therefore, the aims of this systemic review and meta-analysis are to verify this issue and further provide reference for clinical practice.

Methods: Seven databases were searched for randomized controlled trials (RCTs) up to September 30, 2019. The literature screening and data extraction were performed by two independent researchers. Adverse reactions from trials were also recorded. Meta-analysis was performed and analyzed heterogeneity. Methodological and evidence quality were followed by to evaluate according to Cochrane handbook.

Results: A total of 4 RCTs including 305 children with mild to moderate OSA were involved. Compared with placebo, we found that oral montelukast (OM) significantly improved polysomnography (PSG) monitoring parameters, typical and relevant symptoms including snoring and mouth breathing, and adenoid morphology in children with OSA. When compared with routine drugs, not only PSG monitoring parameters and adenoid morphology, but also sleep-disordered breathing (SDB)-related questionnaire scores were improved in patients with OSA treated by combination of OM and routine drugs. In addition, compared with single nasal spray of mometasone furoate, the present study also showed that OM combined with nasal spray of mometasone furoate significantly improved PSG monitoring parameters, symptoms of snoring and mouth breathing and reduced tonsil morphology in pediatric OSA. In terms of treatment safety, one study reported adverse reactions of OM such as headache, nausea and vomiting, while no adverse events were reported after OM treatment in another study.

Conclusion: As a classic leukotriene receptor antagonist, montelukast can be used to treat children with mild to moderate OSA in the short term and improve clinical characteristics. The promotion and application of OM in clinic is considered to be a noninvasive option to avoid surgical treatment.
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http://dx.doi.org/10.1016/j.sleep.2020.11.009DOI Listing
February 2021

Downregulated NORAD in neuroblastoma promotes cell proliferation via chromosomal instability and predicts poor prognosis.

Acta Biochim Pol 2020 Dec;67(4):595-603

Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing 100045, China; 2Department of Otolaryngology, Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing 100045, China.

Increasing evidence suggests that long non-coding RNAs (lncRNAs) are involved in neuroblastoma (NB) pathogenesis. The aim of this study was to elucidate the roles and underlying mechanism of non-coding RNA activated by DNA damage (NORAD) in childhood NB. Both public data and clinical specimens were used to determine NORAD expression. Colony formation, cell proliferation and wound healing assays were performed to evaluate NORAD effects on proliferation and migration of SH-SY5Y and SK-N-BE(2) cells. Flow cytometry was used to examine the cell cycle changes. The expression of genes and proteins involved in chromosomal instability was determined by qRT-PCR and western blotting, respectively. Our results showed that low NORAD expression correlated with advanced tumor stage, high risk and MYCN amplification in both public data and clinical samples. Kaplan-Meier analysis indicated that patients with low NORAD expression had poor survival outcomes. Functional research showed that NORAD knockdown promoted cell proliferation and migration, and arrested the cell cycle at the G2/M phase. Moreover, the expression of the DNA damage sensor, PARP1, increased after NORAD knockdown, indicating a potential contribution of NORAD to DNA damage repair. NORAD silencing also affected the expression of genes and proteins related to sister chromatid cohesion and segregation, which are involved in chromosomal instability and consequent aneuploidy. These results suggest that NORAD may serve as a tumor suppressor in NB pathogenesis and progression. Thus, NORAD is a potential therapeutic target and a promising prognostic marker for NB patients.
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http://dx.doi.org/10.18388/abp.2020_5454DOI Listing
December 2020

Interactions of iron-based nanoparticles with soil dissolved organic matter: adsorption, aging, and effects on hexavalent chromium removal.

J Hazard Mater 2021 Mar 28;406:124650. Epub 2020 Nov 28.

Institute of Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

The interactions and mechanisms between soil dissolved organic matter (DOM) and three types of iron-based nanoparticles (NPs), i.e., nanoscale zero-valent iron (nZVI) particles, FeO NPs, and FeO NPs, were investigated in short-term exposure experiments. The adsorption results showed that soil DOM was rapidly adsorbed on the surface of the iron-based NPs with the adsorption rate varying according to FeO > FeO > nZVI. Spectral analysis results revealed that aromatic DOM fractions with high-molecular-weights were preferentially adsorbed. The binding mechanism was determined as hydrogen bonding and ligand exchange via Fourier transform infrared spectroscopy (FT-IR) analysis. Scanning electron microscopy, FT-IR, X-ray photoelectron spectroscopy, and X-ray diffraction were used to identify the corrosion products of the three iron-based NPs at the adsorption equilibrium. The results suggest that FeO and/or γ-FeO and α-FeOOH were the main corrosion products of nZVIs and α-FeOOH was obtained as an aged product of FeO NPs. Results of Cr(VI) removal tests suggest that the aged nZVI achieved 79.87% of Cr(VI) removal and the Cr(VI) removal efficiency was significantly improved by coating DOM onto FeO NPs. The overall data indicate the fate and transformation of iron-based NPs and the enhancement for Cr(VI) removal after interactions between DOM and NPs.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124650DOI Listing
March 2021

Surgical Treatment of Cervicothoracic Junction Lesions in Children: A Series of 18 Cases.

J Invest Surg 2020 Dec 7:1-5. Epub 2020 Dec 7.

Department of Otolaryngology, Head and Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, P.R. China.

Purpose: The cervicothoracic junction (CTJ) lesions in children is rare. Surgical treatment for lesions at the cervicothoracic junction is challenging due to the presence of the great vessels and other thoracic structures. There are no criteria that help select a surgical approach to manage cervicothoracic lesions in children so far. This study focuses on the cervicothoracic junction lesions in children(C7-T4) and provides experience for the appropriate surgical approach for them.

Methods: This retrospective study enrolled 18 children with cervicothoracic junction lesions who underwent surgical treatment in our Hospital from January 2015 to September 2019. They were evaluated with preoperative CT or MR imaging and diagnosed postoperatively by pathological examination.

Results: This study included 2 patients with congenital lesions, 4 patients with benign lesions, and 12 patients with malignant lesions. Lesions with a margin below C7-T3, including benign and malignant tumors could be resected using a simple low anterior cervical approach (LACA). Congenital lesions and benign lesions with a margin below T4 could also be treated with this approach. Two-thirds of the malignant lesions below T4 were resected through the LACA combined with video-assisted thoracoscopic surgery (VATS). 1 patient with malignant lesion extending to T4 was removed by the LACA combined with posterolateral thoracotomy.

Conclusions: The lesions at the cervicothoracic junction (C7-T4) in children may be managed with the simple LACA used in most patients. For malignancies extending to the T4 level, LACA and VATS could be performed in combination to resect lesions completely and invasively.
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http://dx.doi.org/10.1080/08941939.2020.1839821DOI Listing
December 2020

Tim-3 is a potential regulator that inhibits monocyte inflammation in response to intermittent hypoxia in children with obstructive sleep apnea syndrome.

Clin Immunol 2021 Jan 30;222:108641. Epub 2020 Nov 30.

Department of Otolaryngology, Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. Electronic address:

The mechanism of the characteristic intermittent hypoxia (IH) of obstructive sleep apnea syndrome (OSAS) on monocyte remain unclear. Our study found that OSAS children had a significantly upregulated expression in circulating proinflammatory cytokines IL-6 and IL-12, and endothelial injury markers VEGF and ICAM1. Association analysis revealed that the plasma TNFα, IL-1β, IL-6, IL-10 and IL-12 concentration were negatively associated with the minimal SpO, a negative index for disease severity. OSAS monocytes presented an inflammatory phenotype with higher mRNA levels of inflammatory cytokines. Importantly, we noted a significant decrease in T-cell immunoglobulin and mucin domain (Tim)-3 expression in OSAS monocytes with the increase of the plasma proinflammatory cytokines. In vitro assay demonstrated that IH induced THP-1 cell overactivation via NF-κB dependent pathway was inhibited by the Tim-3 signal. Our results indicated that activation of monocyte inflammatory responses is closely related to OSAS-induced IH, and negatively mediated by a Tim-3 signaling pathway.
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http://dx.doi.org/10.1016/j.clim.2020.108641DOI Listing
January 2021

Prothrombotic Factors in Obstructive Sleep Apnea: A Systematic Review With Meta-Analysis.

Ear Nose Throat J 2020 Nov 9:145561320965208. Epub 2020 Nov 9.

Department of Otolaryngology-Head and Neck Surgery, 117984Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Background: Previous studies revealed that the prothrombotic factors in patients with obstructive sleep apnea (OSA) remain controversial.

Aim/objective: The aim of the systematic review is to elucidate the relationship between prothrombotic factors and OSA.

Materials And Methods: This systematic review was performed under the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The literature we investigated was extracted from 4 main medical databases (PubMed, Web of Science, Cochrane Library, and Chinese databases) as of February 2020. We used significant weighted mean differences (SMDs) with 95% CIs from random-effects model.

Results: A total of 15 studies comprising 2190 patients were available for the meta-analysis. The pooled results showed that the levels of fibrinogen (SMD = 0.95, 95% CI = 0.26 to 1.65, = .000), vascular endothelial growth factor (SMD = 0.37, 95% CI = -0.90 to 1.63, = .000), and plasminogen activator inhibitor 1 (SMD = 0.61, 95% CI = 0.29 to 0.92, = .040) increased in patients with OSA. There were no statistical differences between groups in terms of d-dimer ( = .108) and platelet counts ( = .233). Subgroup analyses demonstrated that specimen types and age could account for the heterogeneity.

Conclusions And Significance: This meta-analysis indicated the relationship between prothrombotic factors in OSA hypopnea. Obstructive sleep apnea-related effects may underline the importance of considering the dysfunction of the hemostatic system. The prothrombotic factors in OSA can influence making a choice of appropriate therapy.
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http://dx.doi.org/10.1177/0145561320965208DOI Listing
November 2020

Analysis of the impact of allergic rhinitis on the children with sleep disordered breathing.

Int J Pediatr Otorhinolaryngol 2020 Nov 12;138:110380. Epub 2020 Sep 12.

Department of Otolaryngology, Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, People's Republic of China. Electronic address:

Objectives: We assessed the influence of allergic rhinitis (AR) on sleep disordered breathing (SDB) in children with adenotonsillar hypertrophy (ATH), and compared sleep quality and polysomnographic data in habitually snoring children with or without AR.

Methods: Children with snoring resulting from adenoid/tonsils hypertrophy were recruited between Jan 1st, 2018 and Jun 30th, 2018. The exclusion criteria were congenital disorders, metabolic disorders, neurological disorders and pulmonary diseases, such as, asthma etc. Overnight polysomnography (PSG) and Sleep Questionnaire (SQ) were assessed on each participant to identify children with obstructive sleep apnea (OSA). Cross-sectional study design was used to examine PSG and SQ data. The diagnosis of AR was based upon history of allergies and positive clinical examinations, then confirmed by allergen test. Participants were categorized into four groups (AR and Non-OSA group; AR and OSA group; Non-AR and Non-OSA group; Non-AR and OSA group). Non-parametric rank sum test was used for statistical analysis.

Results: Six hundred and sixty children (age between 3yrs and 14yrs) with SDB were enrolled in the study (mean age 6.7 ± 2.1yrs, 67.4% male). The number of children diagnosed with OSA was 495 (74.3%). The prevalence of AR among all participating SDB children was 25.8%, and AR with OSA was19.4%. The behavioral problems scores in SQ showed significant difference among SDB children with AR (P<.0001). No difference was observed in the OAHI (obstructive apnea-hypopnea index) and AHI (apnea-hypopnea index) between the groups of children with and without AR regardless whether OSA was coexisting. The percentage of time spent in the rapid eye movement (REM) sleep stage was shortened among children with AR without OSA (P = 0.031), however, the percentage of time spent in the REM sleep stage was not different among children with OSA (P = 0.98). The total sleep time was shorter among children with AR (OSA P = 0.02; without OSA P = 0.03).

Conclusions: Despite the high prevalence of AR in patients with SDB, AR is not an aggravating factor for the severity of AHI. High risk behavioral problems link to SDB with AR. AR is associated with shortened REM sleep stage in children with SDB without sleep apnea, and shortened total sleep time in children with SDB.
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http://dx.doi.org/10.1016/j.ijporl.2020.110380DOI Listing
November 2020

Treatment and outcomes of 1041 pediatric patients with neuroblastoma who received multidisciplinary care in China.

Pediatr Investig 2020 Sep 27;4(3):157-167. Epub 2020 Sep 27.

Department of Otorhinolaryngology Head and Neck Surgery Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.

Importance: Neuroblastoma is the most common extracranial malignant solid tumor in children. Multidisciplinary care is critical to improving the survival of pediatric patients with neuroblastoma.

Objective: To systematically summarize the clinical characteristics of children with neuroblastoma and evaluate their prognosis with multidisciplinary care provided in a single center.

Methods: This retrospective study analyzed the clinical data of 1041 patients with neuroblastoma who were diagnosed, treated, and followed-up in the Hematology-Oncology Center of Beijing Children's Hospital from 2007 to 2019.

Results: The median age at diagnosis was 34 months; 80.8% of the patients were younger than 5 years of age. Notably, 243 patients (23.3%) were classified as low-risk, 249 patients (23.9%) were classified as intermediate-risk, and 549 (52.7%) were classified as high-risk. Furthermore, 956 patients underwent surgical resections; 986 (94.7%) patients received chemotherapy; and 176 patients with high-risk neuroblastoma received hematopoietic stem cell transplantation. The 5-year event-free survival (EFS) rate was 91.3% and 5-year overall survival (OS) rate was 97.5% in low-risk group; in the intermediate-risk group, these rates were 85.1% and 96.7%, respectively, while they were 37.7% and 48.9% in the high-risk group ( 0.001 for both). The 5-year EFS and OS rates were significantly higher in patients diagnosed between 2015 and 2019 than in patients diagnosed between 2007 and 2014 ( 0.001). In total, 278 patients (26.7%) exhibited tumor relapse or progression; the median interval until relapse or progression was 14 months. Of the 233 patients who died, 83% died of relapse or progression of neuroblastoma and 4.3% died of therapy-related complications.

Interpretation: The 5-year OS rate was low in high-risk patients, compared with low-and intermediate-risk patients. Multidisciplinary care is critical for improvement of survival in pediatric patients with neuroblastoma. Additional treatment strategies should be sought to improve the prognosis of patients with high-risk neuroblastoma.
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http://dx.doi.org/10.1002/ped4.12214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520112PMC
September 2020

Photonic Flywheel in a Monolithic Fiber Resonator.

Phys Rev Lett 2020 Oct;125(14):143902

Department of Electrical, Computer and Energy Engineering, University of Colorado Boulder, Boulder, Colorado 80309, USA.

We demonstrate the first compact photonic flywheel with sub-fs time jitter (averaging times up to 10  μs) at the quantum-noise limit of a monolithic fiber resonator. Such quantum-limited performance is accessed through novel two-step pumping scheme for dissipative Kerr soliton generation. Controllable interaction between stimulated Brillouin lasing and Kerr nonlinearity enhances the DKS coherence and mitigates the thermal instability challenge, achieving a remarkable 22-Hz intrinsic comb linewidth and an unprecedented phase noise of -180  dBc/Hz at 945-MHz carrier at free running. The scheme can be generalized to various device platforms for field-deployable precision metrology.
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http://dx.doi.org/10.1103/PhysRevLett.125.143902DOI Listing
October 2020