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Background: Papillary thyroid carcinoma (PTC) is one of the most common endocrine malignancies and has a favorable prognosis. However, optimal treatments and prognostic markers have not been clearly identified. Methods: Gene expression data from primary PTC were downloaded from the Gene Expression Omnibus database and subjected to two analyses of differentially expressed genes (DEGs), followed by intersecting individual and integrated DEGs analyses as well as gene set enrichment analysis. Analysis of data from Sequence Read Archive and The Cancer Genome Atlas, immunohistochemistry and qRT-PCR of TFF3 were performed to validate the results. Finally, the relationship between gene expression and disease-free survival as well as immune cell infiltration were investigated. Results: Six critical DEGs and several tumor-enriched signaling pathways were identified. Immunohistochemistry and qRT-PCR validated the low expression of TFF3 in PTC. TFF3 and FCGBP are coexpressed in PTC, and patients with lower gene expression had worse disease-free survival but higher immune cell infiltration. Conclusion: TFF3 was significantly underexpressed and may function with FCGBP synergistically in PTC.

Diabetic nephropathy (DN) is still on the rise worldwide, and millions of patients have to be treated through dialysis or transplant because of kidney failure caused by DN. Recent reports have highlighted circRNAs in the treatment of DN. Herein, we aimed to investigate the mechanism by which high glucose‐induced exo‐circ_0125310 promotes diabetic nephropathy progression. circ_0125310 is highly expressed in diabetic nephropathy and exosomes isolated from high glucose‐induced mesangial cells (MCs). High glucose‐induced exosomes promote the proliferation and fibrosis of MCs. However, results showed that the effects of exosomes on MCs can be reversed by the knockdown of circ_0125310. miR‐422a, which targets IGF1R, was the direct target of circ_0125310. circ_0125310 regulated IGF1R/p38 axis by sponging miR‐422a. Exo‐circ_0125310 increased the luciferase activity of the WT‐IGF1R reporter in the dual‐luciferase reporter gene assays and upregulated the expression level of IGF1R and p38. Finally, in vivo research indicated that the overexpression of circ_0125310 promoted the diabetic nephropathy progression. Above results demonstrated that the high glucose‐induced exo‐circ_0125310 promoted cell proliferation and fibrosis in diabetic nephropathy via sponging miR‐422a and targeting the IGF1R/p38 axis.

Lin Mei,1,* Xiaodan Li,1,* Shengcai Wang,1,* Run Si,2 Tingting Ji,1 Zhifei Xu,3 Yun Peng,4 Yue Liu,4 Hongbin Li,1 Jie Zhang,1 Yongli Guo,5 Jinghong Tian,6 Guifei Zhou,2 Huifang Huang,2 Jun Tai,1,7,* Jiangang Liu,8,9 Xin Ni1 1Department of Otolaryngology, Head and Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 2School of Computer and Information Technology, Beijing Jiaotong University, Beijing, People’s Republic of China; 3Department of Respiration, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, Beijing, People’s Republic of China; 4Department of Radiology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 5Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, People’s Republic of China; 6Department of Neurorehabilitation, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 7Department of Otorhinolaryngology, Children’s Hospital, Capital Institute of Pediatrics, Beijing, People’s Republic of China; 8Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, People’s Republic of China; 9Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology of the People’s Republic of China, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiangang LiuBeijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing, 100191, People’s Republic of ChinaEmail jgliu@buaa.edu.cnXin NiDepartment of Otolaryngology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, No. 56 Nanlishilu, Beijing, People’s Republic of ChinaTel +86-139-1011-1999Email nixin@bch.com.cnObjective: To investigate the impacts of obstructive sleep apnea (OSA) on white matter (WM) integrity and cognitive functions of pediatric patients with different levels of OSA severity.Methods: Fifty-eight children with OSA and thirty-four healthy controls (HC) were recruited. All participants underwent diffusion tensor imaging (DTI) examination, polysomnography (PSG), and neurocognitive assessments. Patients were divided into mild OSA (MG) and moderate-severe OSA (SG) groups. WM integrity, PSG data, and neurocognitive assessment scores were compared among those groups.Results: For apnea hypopnea index (AHI), obstructive apnea hypopnea index (OAHI), arousal index, SpO2 nadir, and attention, SG was worse than both MG and HC with MG worse than HC. For baseline SpO2 and intelligence, SG was worse than both MG and HC with no significant difference between MG and HC. Impaired WM integrity was observed in bilateral anterior thalamic radiation, bilateral inferior fronto-occipital fasciculus, bilateral inferior longitudinal fasciculus, right superior longitudinal fasciculus, right hippocampus, left cingulate gyrus, right uncinate fasciculus, callosum forceps major, and callosum forceps minor only for SG than for HC. WM integrity was significantly correlated with OSA severity and neurocognitive assessment scores only for SG, but not for MG.Conclusion: Decreased baseline SpO2, WM impairment, and intelligence decline were all observed only for SG, but not for MG, implying an associated relationship among decreased SpO2, WM impairment and WM impairment. Thus, for SG, additional assessments of brain damage and cognitive function decline are needed for prognostic evaluation of OSA.Keywords: diffusion tensor imaging, obstructive sleep apnoea, children, tract-based spatial statistics, white matter

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.

Gastric cancer is the fifth most common malignancy and the third most deadly tumor in the world. Zinc finger protein 479 (ZNF479) has been demonstrated to play crucial roles in hepatocellular carcinoma. However, the function of ZNF479 in gastric cancer remains to be clarified. The current study aimed to investigate the role of ZNF479 in gastric cancer progression and elucidate the potential molecular mechanism. In this study, Cell Count Kit‐8 and colony formation assays demonstrated that knockdown of ZNF479 inhibited cell proliferation in AGS and SGC‐7901 cells. Of note, knockdown of ZNF479 hinders tumor growth of xenograft tumor mice. What is more, knockdown of ZNF479 inhibited glucose uptake, lactate production, adenosine triphosphate level, and extracellular acidification ratio; increased oxygen consumption ratio in gastric cancer cells; and decreased the expression of glycolytic proteins both in vitro and in vivo. Furthermore, analysis mechanism suggests that ZNF479 participated in the regulation of gastric cancer progression through affecting the β‐catenin/c‐Myc signaling pathway. Collectively, ZNF479 plays a role as an oncogene through modulating β‐catenin/c‐Myc signaling pathway in the development of gastric cancer, which provides a new research target for future studies.

Risk and resilience assessments have been both widely, but separately, used as tools for guiding policymakers to formulate disaster-risk reduction policies. On the one hand, risk assessment is utilized to estimate the risk associated with disasters in terms of operational metrics such as monetary or casualties’ loss; on the other hand, most resilience analysis assesses and represent community resilience as an index, without a specific unit metric, to gauge levels of disparity in community’s post-disaster recovery capability among the areas of interest. Although disaster-risk reduction policies should be best informed by both risk and resilience assessments, an informative integrated assessment approach accounting for both seems to be lacked in current research, insofar as the difficulty in properly integrating their distinct measurement metrics. This paper commences with a literature review of risk assessment and community resilience. It then proposes an integrated framework that can comprehensively assess both seismic risk and resilience, by taking into account the casualties and economic losses associated with earthquakes resulted from a risk assessment, and the infrastructure-system resilience and community socioeconomic–demographic resilience resulted from a resilience assessment. More specifically, an integrated tool, risk-based resilience-concentration curve, is proposed for assessing the inequality of given types of risk in the community’s infrastructure-system resilience, and socioeconomic–demographic resilience, respectively. A case study is presented using the data from a city in Israel: the first phase of the case study focused on the concentration of casualties’ risk in community’s infrastructure-system resilience, and the second on the concentration of economic risk in community’s socioeconomic–demographic resilience. The results show that unevenly distributed risk and community resilience can cause inequality of risk in resilience capacity in certain administrative tracts of the city. Based on these findings, the paper recommends a range of risk-reduction strategies for different administrative tracts based on their risk-based resilience concentration curves.

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., Obstructive sleep apnea (OSA) often leads to cognitive dysfunction, however, the underlying mechanisms of this damage remain unclear. In previous studies, a various of researches have been showed that cognitive dysfunction was associated with OSA‐related characteristics and specific neuropathological changes, thus, these findings may provide specific insight into exploring the potential mechanisms.

Graphical abstract, Excessive inflammation and the pyroptosis of vascular endothelial cells caused by estrogen deficiency is one cause of atherosclerosis in post-menopausal women. Because autophagy is highly regulated by estrogen, we hypothesized that estrogen can reduce vascular endothelial cell pyroptosis through estrogen receptor alpha (ERα)-mediated activation of autophagy to improve atherosclerosis in post-menopausal stage. Aortic samples from pro-menopausal and post-menopausal women with ascending aortic arteriosclerosis were analyzed, and bilateral ovariectomized (OVX) female ApoE-/- mice and homocysteine (Hcy)-treated HUVECs were used to analyze the effect of estrogen supplementation therapy. The aortic endothelium showed a decrease in ERα expression and autophagy, but presented an increase in inflammation and pyroptosis in female post-menopausal patients. Estrogen treatment accelerated autophagy and ameliorated cell pyroptosis in the cardiac aortas of OVX ApoE-/- mice and Hcy-treated HUVECs. Estrogen had therapeutic effect on atherosclerosis and improved the symptoms associated with lipid metabolism disorders in OVX ApoE-/- mice. Inhibition and silencing of ERα led to a reduction in the autophagy promoting ability of estrogen and aggravated pyroptosis. Moreover, the inhibition of autophagy promoted pyroptosis and abolished the protective effect of estrogen, but had no influence on ERα expression. Thus, the results of the present study demonstrated that post-menopausal women present decreased autophagy and ERα expression and excessive damage to the ascending aorta. In addition, in vitro and in vivo assay results demonstrated that estrogen prevents atherosclerosis by upregulating ERα expression and subsequently induces autophagy to reduce inflammation and pyroptosis.

Objectives: The objectives of this study were to explore the clinical heterogeneity of differentiated thyroid cancer (DTC) between prepubertal children and adolescents and guide clinical treatment. Methods: A retrospective study included patients with DTC aged ≤19 years in Beijing Children’s Hospital from June 2014 to June 2019. All patients were enrolled and divided into 2 subgroups based on the threshold age of 10 years, namely the childhood group (CG) (≤10 years old); and the adolescent group (AG) (between 10 and 19 years old). The χ2 test and Fisher’s exact test were used to estimate the effect of risk factors in the 2 age groups. Multivariate binary logistic regression models were conducted to assess the recurrent risk factors. Results: Seventy cases of DTC were included with an average age of 9.94 ± 2.88 years, including 35 in CG and 35 in AG. The most common clinical manifestation was a painless mass in the neck, accounting for 77.1% (54/70) of patients. Compared with the AG, the CG was more likely to have lymph node metastasis (p = 0.022) and distant metastasis (p = 0.041). The CG was more likely to have extrathyroidal extension (p = 0.012) and had a significantly higher recurrence rate than the AG (p = 0.040). Age was an independent variable predictive of recurrence (p = 0.0347). Conclusion: Regional invasiveness, cervical lymph node metastasis, and distant metastasis of DTC were more likely to occur in children ≤10 years old. Meanwhile, children ≤10 years old with DTC were more likely to have recurrence than adolescent’s postsurgical treatment. Thus, children younger than 10 years of age with DTC should be treated more aggressively.

Childhood obstructive sleep apnea (OSA) is a common chronic sleep-related breathing disorder in children, which leads to growth retardation, neurocognitive impairments, and serious complications. Considering the previous studies about brain structural abnormalities in OSA, in the present study, we aimed to explore the altered spontaneous brain activity among OSA patients, using amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) methods based on resting-state functional magnetic resonance imaging (MRI). Thirty-one untreated OSA children and 33 age-and gender-matched healthy children (HC) were included in this study. Compared with controls, the OSA group showed significant lower ALFF in the right lingual gyrus, decreased fALFF in the left middle frontal gyrus (MFG), but increased fALFF in the left precuneus. Decreased ReHo was found in the left inferior frontal gyrus (orbital part) and left middle frontal gyrus. Notably, the mean fALFF value of left MFG was not only significantly related to multiple sleep parameters but also demonstrated the best performance in ROC curve analysis. These findings revealed OSA children were associated with dysfunctions in the default mode network, the frontal lobe, and the lingual gyrus, which may implicate the underlying neurophysiological mechanisms of intrinsic brain activity. The correlation between the altered spontaneous neuronal activity and the clinical index provides early useful diagnostic biomarkers for OSA children as well.

This letter proposes a simple and effective method to remove haze from a single input foggy or underwater image. The algorithm is originated from the physically valid description of the transmission of the scattering light during the volumetric scattering medium, interpreting the formation of the haze with the layered transmission model. We establish the explicit expression of the transmittance with respect to statistics of the back scattered light in front of the scene. The parameters for the evaluation of the transmittance can be estimated by the second order statistics of the back scattered light both with and without the scene. Since the transmittance map is evaluated for each RGB channel respectively, the color recovery by the proposed method is wavelength dependent and physically valid. Experimental results on both terrestrial and underwater images are given, which show the effectiveness and advantage of the proposed method.

The definition of large-volume pathologic N1 metastases has been changed in the 2017 version 2 of the National Comprehensive Cancer Network guidelines, leading to a controversy over the optimal surgical approach selection for patients with biopsy-proven papillary thyroid carcinoma (PTC). The aim of this study was to investigate the therapeutic efficacy of total thyroidectomy (TT) and thyroid lobectomy (TL) for these patients.Retrospective population-based database analysis.A total of 906 consecutive PTC patients with pathologic N1 metastases (5 involved nodes with metastases ≤5 mm in the largest dimension) were retrieved from the Surveillance, Epidemiology, and End Results database, and divided into two groups (≤2 mm,2-5 mm) based on the size of the extent of disease. Overall survival (OS) was then compared between patients treated with TT and TL, followed by Cox proportional hazards regression analysis to explore multiple prognostic factors.OS favored TT compared with TL in patients with more than five involved nodes and metastases2 to 5 mm in the largest dimension (P .05). Cox analysis showed that the TL was not an independent factor associated with poorer OS than TT in these patients (P .05).TT showed better survival than TL for patients with more than five involved nodes and metastases2 to 5 mm in the largest dimension. For patients with more than five involved nodes and metastases ≤2 mm in the largest dimension, either TT or TL can be recommended because there was no difference in survival.NA Laryngoscope, 130:269-273, 2020.

This cross-sectional study assesses the recent epidemiological trend of pulmonary tuberculosis in mainland China based on national surveillance data., Key Points Question Have the incidence and epidemiological characteristics of pulmonary tuberculosis (PTB) changed in China from 2005 to 2016? Findings In this cross-sectional study of the Chinese population, a total of 10 582 903 patients with PTB were reported from 2005 to 2016. The annual incidence ranged from 72.95 per 100 000 population in 2005 to 52.18 per 100 000 population in 2016, with a mean incidence of 66.61 per 100 000 population; the median patient age was 46 years, and 70.1% were farmers and herders. Meaning These findings suggest that preventive measures for PTB should be based on the results of epidemiological investigation., Importance The World Health Organization End TB (Tuberculosis) Strategy aims to decrease the global incidence and mortality of TB by 90% and 95%, respectively, as of 2035. Objective To characterize the recent epidemiological trend of pulmonary TB (PTB) in mainland China based on the national surveillance data. Design, Setting, and Participants This cross-sectional study collected demographic and clinical data of all patients reported in the national Tuberculosis Information Management System of China from January 1, 2005, to November 21, 2016. Data were analyzed from December 1, 2019, to July 31, 2020. Exposures Pulmonary TB was defined as bacteriologically confirmed or clinically diagnosed TB in the lung parenchyma or the tracheobronchial tree. Main Outcomes and Measures Temporal and spatial variation of annual incidence and demographic features of PTB in mainland China. Results In total, 10 582 903 patients with PTB were reported in mainland China from 2005 to 2016. The median age of patients with PTB was 46 (interquartile range [IQR], 30-61) years, and 28.53% were 60 years or older. Most patients with PTB were male (69.8%) and farmers or herders (70.0%). The mean (SD) incidence of PTB was 66.61 (8.09) per 100 000 population. The annual incidence decreased from 72.95 per 100 000 population in 2005 to 52.18 per 100 000 population in 2016, and the reduction was greater in the eastern and central regions (31.6%; from 69.43 to 47.48 per 100 000 population) than in the western region (21.0%; from 82.06 to 64.82 per 100 000 population). Xinjiang Uygur Autonomous Region (135.03 per 100 000 population), Guizhou Province (115.98 per 100 000 population), and the Tibet Autonomous Region (101.98 per 100 000 population) had the highest mean annual incidences. The median time from onset of illness to diagnosis decreased from 36 (IQR, 16-92) days from 2005 to 2007 to 31 (IQR, 15-63) days in 2008 and later (P

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease. Although numerous reports have demonstrated a correlation between epithelial-mesenchymal transition (EMT) and renal fibrosis, how these processes lead to tubular dysfunction remains unclear. Here, we show that FOXO3a protects kidneys from injury in type II DN by increasing Sirt6 expression, which deacetylates Smad3 and inhibits its transcriptional activity. The results showed that progressive EMT in the kidneys from db/db mice is associated with Sirt6 downregulation and involved in tubular injury and dysfunction. The reduction of Sirt6 levels in db/db mice resulted in progressive kidney injury, indicating the protective role of Sirt6. Furthermore, Sirt6 was shown to directly bind to Smad3, a key downstream mediator of TGF-β, and could deacetylate it to inhibit its nuclear accumulation and transcriptional activity in HK2 cells. Besides, we demonstrate that FOXO3a activates Sirt6 expression by binding to its promoter. shRNA-induced FOXO3a knockdown in the kidneys of db/db mice exacerbated tubular injury and renal function loss. Mechanistically, FOXO3a protects against kidney injury in type II DN through the Sirt6/Smad3 axis. Thus, the pharmacological targeting of FOXO3a-mediated Sirt6/Smad3 signaling pathways may provide a novel strategy for treating type II DN.

Diabetic kidney disease (DKD) is closely associated with the high risk of cardiovascular disease and mortality. Exosomal circRNAs can exert significant roles in the pathology of various diseases. Nevertheless, the role of exosomal circRNAs in DKD progression remains barely known. Circular RNA DLGAP4 has been reported to be in involved in acute ischemic stroke. In our study, we found exosomal circ_DLGAP4 was increased in the exosomes isolated from HG-treated mesangial cells (MCs), DKD patients, and DKD rat models compared with the corresponding normal subjects. Then, we observed that exo-circ_DLGAP4 significantly promoted proliferation and fibrosis of MCs cells. Moreover, to study the underlying mechanism of circ_DLGAP4 in regulating DKD, bioinformatics method was consulted and miR-143 was predicted as its target. The direct correlation between miR-143 and circ_DLGAP4 was validated in MCs. MCs proliferation and fibrosis were increased by circ_DLGAP4, which could be decreased by mimic-miR-143. Next, elevated expression of Erb-b2 receptor tyrosine kinase 3 (ERBB3) is involved in various diseases. However, the function of ERBB3 in DKD development remains poorly known. Next, ERBB3 was predicted as the downstream target for miR-143. It was displayed that circ_DLGAP4 promoted proliferation and fibrosis of MCs by sponging miR-143 and regulating ERBB3/NF-κB/MMP-2 axis. Meanwhile, the loss of exo-circ_DLGAP4 induced miR-143 and repressed ERBB3/NF-κB/MMP-2 expression in MCs. Subsequently, in vivo assays were performed and it was proved that overexpression of circ_DLGAP4 markedly promoted DKD progression in vivo via modulating miR-143/ERBB3/NF-κB/MMP-2. In conclusion, we indicated that exosomal circ_DLGAP4 could prove a novel insight for DKD development.

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.

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.

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 SpO2, 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.

Background Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Although dysfunction of renal tubule, also exhibited as epithelial-mesenchymal transition (EMT) and fibrosis, is closely associated with DN, the mechanism underlying renal tubule dysfunction still remains obscure. Methods Here, we identify that miR-199b-3p protect renal tubule from diabetic- induced injury by repressing KDM6A, a histone lysine demethylase reinforcing diabetic renal tubule dysfunction through regulating E-cadherin expression. We investigated the relationship between KDM6A, E-cadherin and miR-199b-3p with a series of gain- and loss- function assay in different cell models and animal models. The expression of KDM6A, E-cadherin and miR-199b-3p was tested by qPCR, western bolt or IHC. The EMT was measured by wound healing assay. The dysfunction of renal tubule were observed through HE and PAS stain and the kidney functions were monitored through several pathological signs detection assay, such as albumin to creatinine ratio (ACR), blood urea nitrogen (BUN), creatinine (Cr), proteinuria. Results Lower expression of E-cadherin was related to a higher level of KDM6A, while E-cadherin was increased with KDM6A-inhibitor GSK-J4 treatment both in HG-induced HK-2 cells and STZ-induced kidney. However, the variable expression of E-cadherin caused by overexpression or silence RNA was failed to alter the KDM6A expression. The target prediction and dual-luciferase assay results showed miR-199b-3p is a new miRNA targeting KDM6A. Overexpression of miR-199b-3p increased E-cadherin expression and prevented EMT through repressing KDM6A expression in HG-induced HK-2 cells, whereas miR-199b-3p knockdown by inhibitor displayed opposite results with lower E-cadherin and worse EMT accompanying with higher level of KDM6A. In addition, the miR-199b-3p knockout mice exhibited more dysfunctional renal tubule and more serious damage in kidney tissue treated with STZ. Conclusions These results demonstrate that miR-199b-3p improve E-cadherin expression and prevent the progression of DN through targeting KDM6A. MiR-199b-3p could be a potential biomarker or target for the diagnosis and treatment of diabetic nephropathy in the future.

A new methodology is presented for 3-D automated mapping of joints that are exposed primarily as traces in a rock face as opposed to planar facets. The method identifies 3-D points in a photogrammetry or a LiDAR derived point cloud that corresponds to the traces of the joints as observed in image data. First, the 2-D trace texture is extracted from image data using a hybrid global and local threshold method and integrating a series of image-processing algorithms. Second, data matching links the pixel locations corresponding to the identified traces in an image to the 3-D coordinates in the point cloud. This matching is accomplished by a coordinate transformation between the image coordinates and point cloud coordinates. Finally, a 3-D discontinuity trace map is acquired by analysing the 3-D spatial features of the traces. A case study of a rock slope along a highway is presented using the proposed method. The results demonstrate that the fusion of image data and point cloud data improves the mapping of discontinuities that primarily appear as traces in outcrops versus that achieved by existing methods that rely only on point cloud data.

Acute kidney injury (AKI) is a complex renal disease. Long non-coding RNAs (lncRNAs) have frequently been associated with AKI. In the present study, we aimed to investigate the molecular mechanism(s) of LINC00052 in AKI. We found that LINC00052 expression was significantly decreased in AKI patient serum. In addition, in a hypoxic AKI cell model, LINC00052 expression was strongly elevated. In an I/R-triggered AKI rat model, the expression of TNF-α, IL-6 and IL-1β mRNA was strongly elevated. Moreover, we predicted miR-532-3p to be targeted by LINC00052 in AKI. Overexpression of LINC00052 increased hypoxia-induced inhibition of NRK-52E cell proliferation and reversed hypoxia-triggered apoptosis. Furthermore, we found that induction of TNF-α, IL-6 and IL-1β was repressed by overexpression of LINC00052. LINC00052 decreased hypoxia-induced ROS and MDA accumulation in vitro and increased SOD activity. Decreased levels of c-myc and cyclin D1 were observed in renal tissues of AKI rats. Lastly, Wnt/β-catenin signaling was inactivated in NRK-52E cells experiencing hypoxia, and LINC00052 upregulation reactivated Wnt/β-catenin signaling by sponging miR-532-3p. Taken together, these results suggest that LINC00052 ameliorates AKI by sponging miR-532-3p and activating Wnt signaling.

Acute kidney injury (AKI) is a common kidney disease that markedly affects public health. To date, the roles of long noncoding RNA XIST in AKI are poorly understood. Here, we investigated the biological functions of XIST in AKI. We observed that XIST expression increased in patients with AKI and HK-2 cells stimulated by CoCl2 . In addition, a rat AKI model induced by ischemia-reperfusion was established. Tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2 messenger RNA expression were induced in vivo; moreover, XIST expression was upregulated. Knockdown of XIST significantly repressed CoCl2 -triggered injury in HK-2 cells. However, microRNA (miR)-142-5p, a downstream target of XIST, was downregulated in AKI. miR-142-5p was repressed by XIST and miR-142-5p could inhibit CoCl2 -induced injury in HK-2 cells. Moreover, PDCD4 expression was significantly increased in AKI. PDCD4 was predicted to be the target of miR-142-5p. Subsequently, loss of PDCD4 was able to retard injury in HK-2 cells exposed to CoCl2. Thus, we suggest that XIST regulates miR-142-5p and PDCD4, and it has the potential to function as a biomarker in therapeutic strategies for AKI.

PURPOSE The purpose of this study was to explore the potential early diagnostic value of serum microRNA-381(miRNA-381) in patients with gastric cancer (GC). MATERIALS AND METHODS Patients with advanced gastric cancer (AGC) and early gastric cancer (EGC), as well as healthy individuals, were enrolled in this study. Expression of miRNA-381 in serum was detected using real-time quantitative PCR. Electrochemiluminescence analysis was used to investigate the expression of classic tumor markers, including carbohydrate antigen (CA) 199, CA724, and carcinoembryonic antigen. Finally, receiver operating characteristic curve and Kaplan-Meier analysis were used to determine the value of miRNA-381 in clinical diagnosis of GC. RESULTS miRNA-381 was differentially expressed among the study groups. AUC analysis showed that the sensitivity and specificity of serum miRNA-381 in the diagnosis of GC were superior to those of other tumor markers. Furthermore, low levels of miRNA-381 expression were positively correlated with lymph node metastasis and AGC. Finally, Kaplan-Meier survival analysis showed that down-regulation of miRNA-381 was associated with lymph node metastasis and the development of GC. CONCLUSION miRNA381, which was down-regulated in GC, might be a novel early diagnosis marker for patients with GC.

Underwater image processing technologies have always been challenging tasks due to the complex underwater environment. Images captured under water are not only affected by the water itself, but also by the diverse suspended particles that increase the effect of absorption and scattering. Moreover, these particles themselves are usually imaged on the picture, causing the spot noise signal to interfere with the target objects. To address this issue, we propose a novel deep neural network for removing the spot noise from underwater images. Its main idea is to train a generative adversarial network (GAN) to transform the noisy image to clean image. Based on the deep encoder and decoder framework, the skip connections are introduced to combine the features of low-level and high-level to help recover the original image. Meanwhile, the self-attention mechanism is employed to the generative network to capture global dependencies in the feature maps, which can generate the image with fine details at every location. Furthermore, we apply the spectral normalization to both the generative and discriminative networks to stabilize the training process. Experiments evaluated on synthetic and real-world images show that the proposed method outperforms many recent state-of-the-art methods in terms of quantitative and visual quality. Besides, the results also demonstrate that the proposed method has the good ability to remove the spot noise from underwater images while preserving sharp edge and fine details.

Recently, microRNAs have been recognized as crucial regulators of diabetic nephropathy (DN) development. Epithelial-to-mesenchymal transition (EMT) can play a significant role in tubulointerstitial fibrosis, and it is a hallmark of diabetic nephropathy progression. Nevertheless, the function of miR-98-5p in the modulation of EMT and renal fibrosis during DN remains barely investigated. Hence, identifying the mechanisms of miR-98-5p in regulating EMT and fibrosis is of huge significance. In our present research, decreased miR-98-5p was demonstrated in db/db mice and mice mesangial cells treated with the high dose of glucose. Meanwhile, activated EMT and increased fibrosis was accompanied with the decrease of miR-98-5p in vitro and in vivo. Additionally, to further find out the roles of miR-98-5p in DN development, overexpression of miR-98-5p was applied. Firstly, in vivo investigation exhibited that elevation of miR-98-5p restrained proteinuria, serum creatinine, BUN, the EMT process, and fibrosis. Furthermore, high glucose was able to promote mice mesangial cell proliferation, EMT process, and induced renal fibrosis, which could be prevented by overexpression of miR-98-5p. Moreover, high mobility group A (HMGA2) can exhibit an important role in diverse biological processes. Here, HMGA2 was investigated as a target of miR-98-5p currently. Luciferase reporter assay was conducted and the correlation of miR-98-5p and HMGA2 was validated. Moreover, it was displayed that HMGA2 was remarkably elevated in db/db mice and mice mesangial cells. Furthermore, miR-98-5p strongly depressed HMGA2 protein and mRNA levels in mice mesangial cells. Overall, these revealed miR-98-5p could suppress the EMT process and renal fibrosis through targeting HMGA2 in DN.

AIM Vaspin is an adipokine separated from visceral fat tissues of obese diabetic rats. This study was to investigate the association between vaspin rs2236242 gene polymorphism and type 2 diabetes mellitus (T2DM) or obesity in a Chinese population. MATERIALS AND METHODS T2DM patients and nondiabetic controls were recruited from Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University (Shanghai, China) from May 1, 2015 to June 30, 2017. Clinicopathologic characteristics were recorded and their blood samples were collected. Serum vaspin levels were detected by enzyme-linked immunosorbent assay and vaspin rs2236242 genotypes by tetra-amplification refractory mutation system-polymerase chain reaction. RESULTS Two hundred and ninety-nine patients with T2DM and 311 controls were recruited at last. The vaspin genotypes of diabetic patients were distinct from nondiabetic controls (χ 2 = 54.611, p

Diabetic nephropathy (DN) is serious diabetic complication with capillary injury. Podocyte injury exerts a crucial effect on DN pathogenesis. MicroRNA-503 (miR-503) has been reported in various diseases including DN. Here, we investigated the detailed mechanism of miR-503 in the podocyte injury of DN. The functional role of miR-503 was investigated in cultured podocytes and diabetic rats. Podocyte injury was evaluated by migration and apoptosis experiments in podocytes and we observed that high glucose elevated miR-503 in a time and dose-dependent manner. Meanwhile, E2F transcription factor 3 (E2F3), as a crucial regulator in multiple diseases, was predicted as a potential target of miR-503 here. It was shown that E2F3 was greatly decreased in podocytes incubated with high glucose and miR-503 modulated its expression negatively. In addition, downregulation of E2F3 contributed to podocyte injury, which was reversed by miR-503 inhibitors in vitro. Furthermore, we proved that increase of miR-503 resulted in an unfavorable renal function in diabetic rats via targeting E2F3. These revealed for the first time that the overexpression of miR-503 promoted podocyte injury via targeting E2F3 in diabetic nephropathy and miR-503/E2F3 axis might represent a pathological mechanism of diabetic nephropathy progression.

Underwater imaging posts a challenge due to the degradation by the absorption and scattering occurred during light propagation as well as poor lighting conditions in water medium. Although image filtering techniques are utilized to improve image quality effectively, problems of the distortion of image details and the bias of color correction still exist in output images due to the complexity of image texture distribution. This paper proposes a new underwater image enhancement method based on image structural decomposition. By introducing a curvature factor into the Mumford_Shah_G decomposition algorithm, image details and structure components are better preserved without the gradient effect. Thus, histogram equalization and Retinex algorithms are applied in the decomposed structure component for global image enhancement and non-uniform brightness correction for gray level and the color images, then the optical absorption spectrum in water medium is incorporate to improve the color correction. Finally, the enhanced structure and preserved detail component are recomposed to generate the output. Experiments with real underwater images verify the image improvement by the proposed method in image contrast, brightness and color fidelity.

Carvedilol is a non-selective β-blocker used in the treatment of cardiovascular disease, including myocardial ischemia. The aim of the present study was to investigate the molecular mechanisms underlying the effects of carvedilol on simulated ischemia/reperfusion (SI/R)-induced cardiomyocyte apoptosis in vitro. H9c2 cardiomyocytes were incubated with either a vehicle or an ischemic buffer during hypoxia followed by reoxygenation with or without carvedilol. In two additional groups, toll-like receptor 4 (TLR4) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) were inhibited by a TLR4 antibody and pyrrolidine dithiocarbamate, respectively. The results revealed that carvedilol markedly decreased SI/R-induced apoptosis in a concentration-dependent manner, as demonstrated by flow-cytometric analysis. This effect was shown to be associated with an increase in the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X (Bax) protein ratio and concurrent reductions in the expression levels of TLR4 and NF-κB. These results suggest that carvedilol provides significant cardioprotection against SI/R-induced injury in H9c2 cardiomyocytes, an effect likely to be mediated through the TLR4/NF-κB signaling pathway.

Thermal history can affect organisms' thermal resistance, however, effects of thermal history on thermal resistance and roles of heat shock protein 70 (Hsp70) in sea cucumber Apostichopus japonicus are not well understood. In the present study, the lethal thermal limits and expressions of Hsp70 of sea cucumbers that were acclimated at different temperatures (22 °C or 12 °C) for 30 days were studied. The upper lethal temperatures (ULTs 50 ) for sea cucumbers acclimated at 22 and 12 °C were 31.8 °C (31.5–32.1 °C) and 30.9 °C (30.6–31.3 °C), respectively. In heat shock experiments, sea cucumbers acclimated at different temperatures (22 °C or 12 °C) were exposed to several high temperatures (25, 27, 29, 31 and 32 °C) for 2 h, followed by 2 h recovery at 17 °C, and the levels of hsp70 were measured using semi-quantitative RT-PCR and western blotting. The maximum induction temperatures for sea cucumbers in 22 °C and 12 °C acclimation treatments were 31 °C and 29 °C, respectively. These results showed that the temperature acclimation could affect sea cucumbers' upper thermal limit, which was related to the changed expression pattern of Hsp70 in the sea cucumber. In practice, sea cucumbers that overwinter in southern China could acquire higher thermal resistance than those reared in the north.

Understanding the nature of rail transit dwell time has potential benefits for both the users and the operators. Crowded passenger trains cause longer dwell times and may prevent some passengers from boarding the first available train that arrives. Actual dwell time and the process of passenger alighting and boarding are interdependent through the sequence of train stops and propagated delays. A comprehensive and feasible dwell time simulation model was developed and optimized to address the problems associated with scheduled timetables. The paper introduces the factors that affect dwell time in urban rail transit systems, including train headway, the process and number of passengers alighting and boarding the train, and the inability of train doors to properly close the first time because of overcrowded vehicles. Finally, based on a time-driven micro-simulation system, Shanghai rail transit Line 8 is used as an example to quantify the feasibility of scheduled dwell times for different stations, directions of travel and time periods, and a proposed dwell time during peak hours in several crowded stations is presented according to the simulation results.

Underwater imaging system has been widely applied in varieties and it is desired to recover underwater image using image processing techniques. In this paper, we proposed a fourth order P_Laplace underwater image restoration method based on MSG. Although the fourth order P_Laplace method has been proved that it could effectively reduce the gradient effect, the bright spot effect and color distortion still exist in the restored image especially when iterations increase. However, MSG model can be applied to solve this issue. The structure image is restored by the fourth order P_Laplace approach to recover the detailed information embedded in the blurred structure image. Then the texture and the restored structure image are recomposed to output the recovered image.

Heterogeneity is one of the key indicators to evaluate the quality of a rail transit timetable; it not only affects the station's capacity and operational processes, but also affects the continuation of rolling stock use and the efficiency of station equipment, network reliability, and the service level of passengers. First, this paper gives the arriving, departing, and whole timetable heterogeneity index based on the deviation of the actual interval and the average intervals in stations, and then gives an assessment of a model and solution method. Finally, taking Shanghai rail transit lines 3 and 4 as an example, the corresponding optimization recommendation is proposed by a different scheduling methodology.

We used forebrain-specific conditional presenilin 1 (PS1) and presenilin 2 (PS2) double knockout mice (dKO mice), which exhibit neurodegenerative disease-like symptoms, including inflammation of the brain and periphery, to investigate whether periodontal and salivary tissues display alterations. Mandibles were dissected for alveolar bone height analysis. Maxillae were fixed and decalcified for histological observation and osteoclast detection. Submandibular glands were fixed for histological observation. The submandibular gland and the gingiva of the mandibular incisor teeth were used to assay inflammatory mediators. At 9 months, the number of osteoclasts had significantly increased in the periodontal ligament and the periodontal tissues exhibited obvious histomorphological abnormalities in the dKO mice compared to the control mice at the same age. Alveolar bone loss in dKO mice increased with age. The salivary tissues in dKO mice exhibited obvious age-dependent histomorphological abnormalities. The levels of the inflammatory mediators IL-1β, TNF-α, and GM-CSF in the submandibular gland and gingiva also increased in an age-dependent manner. These findings suggest that inflammation in the dKO brain could expand to the periphery, including the oral tissue, which could ultimately induce abnormalities in the periodontal and salivary tissues.