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STUDY OBJECTIVES: To examine the association between multiple measures of socioeconomic status (SES) and objectively measured obstructive sleep apnea (OSA) in a Canadian pediatric population. METHODS: This was a cross-sectional study of 188 children (4–17 years, mean age 9.3 ± 3.5 years) prospectively recruited from two hospital sleep clinics in Canada, using multivariable-adjusted linear and logistic regression of five measures of SES including parental education, income, social class, geographic location, and perceived SES based on the MacArthur Scale of Subjective Social Status, assessed in relation to four polysomnographic OSA variables including apnea-hypopnea index, apnea index, mean oxygen saturation level, and oxygen desaturation index. RESULTS: Overall, low household-level SES appeared to be associated with both frequency (apnea index ≥ 1 events/h) and severity (apnea-hypopnea index ≥ 5 events/h) of OSA in children, with maternal education showing the most consistent and significant associations. Specifically, children with mothers reporting less than high school education had nearly three times the odds of having OSA after controlling factors including body mass index (odds ratio 2.96 [95% confidence interval, 1.05–8.37]), compared to university-educated participants. Consistent associations were also observed for geographic location with less frequency and severity of OSA among nonurban children. Perceived SES was minimally inversely associated with our outcomes. CONCLUSIONS: This cross-sectional, multicenter study demonstrated that SES factors are linked to the occurrence and severity of OSA in children. Results indicated the need to incorporate the screening of SES in the diagnostic process of pediatric OSA to provide more targeted intervention and patient-centered care. CITATION: Park JW, Hamoda MM, Almeida FR, et al. Socioeconomic inequalities in pediatric obstructive sleep apnea. J Clin Sleep Med. 2022;18(2):637–645.

Intergenerational trauma increases lifetime susceptibility to depression and other psychiatric disorders. Whether intergenerational trauma transmission is a consequence of in-utero neurodevelopmental disruptions versus early-life mother–infant interaction is unknown. Here, we demonstrate that trauma exposure during pregnancy induces in mouse offspring social deficits and depressive-like behavior. Normal pups raised by traumatized mothers exhibited similar behavioral deficits to those induced in pups raised by their biological traumatized mothers. Good caregiving by normal mothers did not reverse prenatal trauma-induced behaviors, indicating a two-hit stress mechanism comprising both in-utero abnormalities and early-life poor parenting. The behavioral deficits were associated with profound changes in the brain metabotranscriptome. Striking increases in the mitochondrial hypoxia marker and epigenetic modifier 2-hydroxyglutaric acid in the brains of neonates and adults exposed prenatally to trauma indicated mitochondrial dysfunction and epigenetic mechanisms. Bioinformatic analyses revealed stress- and hypoxia-response metabolic pathways in the neonates, which produced long-lasting alterations in mitochondrial energy metabolism and epigenetic processes (DNA and chromatin modifications). Most strikingly, early pharmacological interventions with acetyl-L-carnitine (ALCAR) supplementation produced long-lasting protection against intergenerational trauma-induced depression., Sammy Alhassen, Siwei Chen, et al. use mouse models to examine the effects of prenatal and postnatal stress on metabolomic and transcriptomic pathways in the brain. Their results suggest that altered mitochondrial metabolism may underlie trauma-induced behavioral deficits, and that correcting metabolism with ALCAR supplementation may protect against intergenerational transmission of traumatic stress.

Background: Esophageal squamous cell carcinoma (ESCC) is a high recurrence rate of upper-digestive cancer with a low 5-year survival rate. Therefore, there is an urgent need for effective chemopreventive drugs that can extend the survival rate of patients. Through screening of FDA-approved drugs, dasabuvir was found to suppress ESCC proliferation. Methods: Cell number count assay was used to screen for drugs with inhibitory effect on ESCC cells and detect the inhibitory effect of dasabuvir on proliferation of ESCC cells KYSE150 and KYE450. Phosphoproteomics and proteomics were used to investigate the mechanism of dasabuvir inhibiting ESCC. In vitro kinase assay was used to verify the inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) activation by ROCK1 by dasabuvir. The PDX model was used to test the inhibitory effect of dasabuvir on ESCC in vivo.Results: In this study, we found that dasabuvir is a novel inhibitor of Rho-associated protein kinase 1 (ROCK1). Dasabuvir inhibited the growth of the KYSE150 and KYSE450 ESCC cell lines in a time and dose-dependent manner and arrested cell cycle at the G0/G1 phase. The antitumor activity was validated in vivo using a patient-derived xenograft tumor model in mice. Dasabuvir inhibited the activation of ERK1/2 by ROCK1 and downregulated cyclin-dependent kinase 4 (CDK4) and cyclin D1 expression. Conclusions: These results provide the first evidence that dasabuvir serves as a ROCK1 inhibitor, suppresses ESCC growth in vivo and in vitro, and arrests the cell cycle through the ROCK1/ERK signaling pathway.

Background: Esophageal squamous cell carcinoma (ESCC) is among one of the leading causes of cancer death worldwide owing to late detection and low survival rate. The clinical outcome of ESCC remains dismal. To date, the disease lacks available targeted therapies. Recently, drugs approved by the Food and Drug Administration have been reported to have potential as cancer chemoprevention agents. Methods: Benzydamine, available as a hydrochloride salt, a locally acting non-steroidal anti-inflammatory drug, was screened out among FDA-approved drugs owing to its effective cytotoxic effect on KYSE450 cells, which remained unexplored. Mass spectrometry, kinase prediction and Swiss Target Prediction were used to verify the potential target(s) of benzydamine. Patient-derived oesophageal xenograft mouse model were used to investigate the effect of benzydamine on tumor growth in vivo.Results: We found that benzydamine inhibited anchorage-dependent and -independent growth of ESCC cells. Kyoto Encyclopedia of Genes and Genomes pathway enrichment revealed that benzydamine attenuated five signaling pathways, including the DNA replication pathway. We further found that benzydamine could bind to CDK2 in its ATP-binding site. Inhibition of the activity of CDK2 suppressed the growth of ESCC cells and led to a G1/S cell cycle arrest. Additionally, knocking-down CDK2 decreased the sensitivity of ESCC cells to benzydamine hydrochloride. Notably, benzydamine suppressed tumour growth in a patient-derived oesophageal xenograft mouse model of ESCC in vivo.Conclusions: We have identified CDK2 as a potential target of benzydamine for the treatment and prevention of ESCC. Benzydamine suppressed the growth of ESCC cells by inhibiting the activity of CDK2.

Microcarriers are beads with a diameter of 60-250 µm and a large specific surface area, which are commonly used as carriers for large-scale cell cultures. Microcarrier culture technology has become one of the main techniques in cytological research and is commonly used in the field of large-scale cell expansion. Microcarriers have also been shown to play an increasingly important role in in vitro tissue engineering construction and clinical drug screening. Current methods for preparing microcarriers include microfluidic chips and inkjet printing, which often rely on complex flow channel design, an incompatible two-phase interface, and a fixed nozzle shape. These methods face the challenges of complex nozzle processing, inconvenient nozzle changes, and excessive extrusion forces when applied to multiple bioink. In this study, a 3D printing technique, called alternating viscous-inertial force jetting, was applied to enable the construction of hydrogel microcarriers with a diameter of 100-300 µm. Cells were subsequently seeded on microcarriers to form tissue engineering modules. Compared to existing methods, this method offers a free nozzle tip diameter, flexible nozzle switching, free control of printing parameters, and mild printing conditions for a wide range of bioactive materials.

Intergenerational stress increases lifetime susceptibility to depression and other psychiatric disorders. Whether intergenerational stress transmission is a consequence of in utero neurodevelopmental disruptions vs early-life mother-infant interaction is largely unknown. Here, we demonstrated that exposure to traumatic stress in mice during pregnancy, through predator scent exposure, induces in the offspring social deficits and depressive-like behavior. We found, through cross-fostering experiments, that raising of normal pups by traumatized mothers produced a similar behavioral phenotype to that induced in pups raised by their biological traumatized mothers. Good caregiving (by non-traumatized mothers), however, did not completely protect against the prenatal trauma-induced behavioral deficits. These findings support a two-hit stress mechanism of both in utero and early-life parenting (poor caregiving by the traumatized mothers) environments. Associated with the behavioral deficits, we found profound changes in brain metabolomics and transcriptomic (metabotranscriptome). Striking increases in the mitochondrial hypoxia marker and epigenetic modifier 2-hydroxyglutaric acid, in the brains of neonatal and adult pups whose mothers were exposed to stress during pregnancy, indicated mitochondrial metabolism dysfunctions and epigenetic mechanisms. Bioinformatic analyses revealed mechanisms involving stress- and hypoxia-response metabolic pathways in the brains of the neonatal mice, which appear to lead to long-lasting alterations in mitochondrial-energy metabolism, and epigenetic processes pertaining to DNA and chromatin modifications. Most strikingly, we demonstrated that an early pharmacological intervention that can correct mitochondria metabolism - lipid metabolism and epigenetic modifications with acetyl-L-carnitine (ALCAR) supplementation - produces long-lasting protection against the behavioral deficits associated with intergenerational transmission of traumatic stress.

Background Multiple sclerosis (MS) is an inflammatory demyelinating disease featured with neuroinflammation, demyelination, and the loss of oligodendrocytes. Cognitive impairment and depression are common neuropsychiatric symptoms in MS that are poorly managed with the present interventions. Objective This study aimed to investigate the effects of low field magnetic stimulation (LFMS), a novel non-invasive neuromodulation technology, on cognitive impairment and depressive symptoms associated with MS using a mouse model of demyelination. Methods C57BL female mice were fed with a 0.2% cuprizone diet for twelve weeks to induce a chronic demyelinating model followed by four weeks of cuprizone withdrawal with either sham or LFMS treatment. Results Improved cognition and depression-like behavior and restored weight gain were observed in mice with LFMS treatment. Immunohistochemical and immunoblotting data showed enhanced myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein expressions (MOG) in the prefrontal cortex of mice with LFMS treatment, supporting that myelin repair was promoted. LFMS also increased the protein expressions of mature oligodendrocyte biomarker glutathione-S-transferase (GST-π).In addition, expression of TGF-β and associated receptors were elevated with LFMS treatment, implicating this pathway in the response. Conclusion Results from the present study revealed LFMS to have neuroprotective effects, suggesting that LFMS has potential therapeutic value for treating cognitive impairment and depression related to demyelination disorders.

Compute First Networking (CFN) recently is proposed as an in-network computing paradigm for well balancing between the networking and computation resource scheduling. Thanks to the proliferation of network functions virtualization, the virtualized network functions can coexist with the computing services on a shared platform like edge computing environment. Thus, one critical issue incurred by CFN is how to manage and schedule the resources among various services from different over-the-top service provider (OSP) with different resource requirements, i.e., network slicing. In this paper, we first formulate the network slicing problem as a Stackelberg game problem and prove that there exists a Nash equilibrium beneficial to both the Network Slice Broker (NSB) and OSP. Furthermore, we propose a cooperative game model on the networking and computation resource allocation within each slice and invent a Nash bargaining solution to resolve the intra-slice resource competition for slice performance promotion. Simulation results are provided to validate the effectiveness and high efficiency of the our proposed game based network slicing and resource scheduling algorithm.

Longitudinal trajectories of vital signs and biomarkers during hospital admission of patients with COVID-19 remain poorly characterized despite their potential to provide critical insights about disease progression. We studied 1884 patients with severe acute respiratory syndrome coronavirus 2 infection from April 3, 2020, to June 25, 2020, within 1 Maryland hospital system and used a retrospective longitudinal framework with linear mixed-effects models to investigate relevant biomarker trajectories leading up to 3 critical outcomes: mechanical ventilation, discharge, and death. Trajectories of 4 vital signs (respiratory rate, ratio of oxygen saturation (Spo2) to fraction of inspired oxygen (Fio2), pulse, and temperature) and 4 laboratory values (C-reactive protein (CRP), absolute lymphocyte count (ALC), estimated glomerular filtration rate, and D-dimer) clearly distinguished the trajectories of patients with COVID-19. Before any ventilation, log(CRP), log(ALC), respiratory rate, and Spo2-to-Fio2 ratio trajectories diverge approximately 8–10 days before discharge or death. After ventilation, log(CRP), log(ALC), respiratory rate, Spo2-to-Fio2 ratio, and estimated glomerular filtration rate trajectories again diverge 10–20 days before death or discharge. Trajectories improved until discharge and remained unchanged or worsened until death. Our approach characterizes the distribution of biomarker trajectories leading up to competing outcomes of discharge versus death. Moving forward, this model can contribute to quantifying the joint probability of biomarkers and outcomes when provided clinical data up to a given moment.

SARS-CoV-2 infection induces severe disease in a subpopulation of patients, but the underlying mechanisms remain unclear. We demonstrate robust IgM autoantibodies that recognize angiotensin converting enzyme-2 (ACE2) in 18/66 (27%) patients with severe COVID-19, which are rare (2/52; 3.8%) in hospitalized patients who are not ventilated. The antibodies do not undergo class-switching to IgG, suggesting a T-independent antibody response. Purified IgM from anti-ACE2 patients activates complement. Pathological analysis of lung obtained at autopsy shows endothelial cell staining for IgM in blood vessels in some patients. We propose that vascular endothelial ACE2 expression focuses the pathogenic effects of these autoantibodies on blood vessels, and contributes to the angiocentric pathology observed in some severe COVID-19 patients. These findings may have predictive and therapeutic implications.One-sentence summaryACE2 autoantibodies in severe COVID-19 have features of a T-independent immune response, and may mediate vascular damage.

Cervical cancer induced by human papillomavirus (HPV) causes severe morbidity worldwide. Although cervical conization has been widely accepted as the most conventional surgery against cervical cancer, tissue defects and high recurrence rates have a significant negative impact on women's mental and physical health. Herein we developed an implantable, personalized cervical implant with drug release function using 3D printing technology. The cervical implant was designed in cone-shape with hieratical porous structures according to the clinical data, 3D-printed using polyurethane by low-temperature deposition manufacturing (LDM), and finished by lyophilization. Anti-HPV protein was loaded into the porous structure under negative pressure afterwards. Elastic biomedical polyurethane and the porous structure ensured that these cervical implants were equipped with tailored mechanical properties comparable to physiological cervix tissue. Cytotoxicity and cytocompatibility tests indicated that these 3D-printed cervical implants supported cell adhesion and growth. More importantly, the cervical implants with regulated pores could help to quantitatively control the loading and release of anti-HPV protein to inhibit dissociative viruses near the cervix validly. As a result, the 3D-printed cervical implants in the present study showed considerable potential for use as functional tissue implants against HPV infection after cervical conization.

The activation of the renin-angiotensin system (RAS) induced by increased angiotensin II (AngII) levels has been implicated in muscle atrophy, which is involved in the pathogenesis of congestive heart failure. Although peroxisome proliferator-activated receptor gamma (PPARγ) activation can suppress RAS, the exact role of PPARγ in AngII-induced muscle atrophy is unclear. Here we identified PPARγ as a negative regulator of miR-29b, a microRNA that is able to promote multiple types of muscle atrophy. Suppression of miR-29b could prevent AngII-induced muscle atrophy both in vitro and in vivo. IGF1, PI3K(p85α), and Yin Yang 1 (YY1) were identified as target genes of miR-29b, and overexpression of these targets could rescue AngII-induced muscle atrophy. Importantly, inhibition of PPARγ was sufficient to induce muscle atrophy, while PPARγ overexpression could attenuate that. These data indicate that the PPARγ/miR-29b axis mediates AngII-induced muscle atrophy, and increasing PPARγ or inhibiting miR-29b represents a promising approach to counteract AngII-induced muscle atrophy., Graphical Abstract, Xiao and colleagues report that the PPARγ/miR-29b axis mediates Ang II-induced muscle atrophy via inhibition of the target genes IGF1, PI3K(p85α), and Yin Yang 1 (YY1) and the AKT/FOXO3A/mTOR pathway. Their work implies that overexpression of PPARγ and inhibition of miR-29b are novel approaches to counteract AngII-induced muscle atrophy.

BACKGROUND It has been reported that there are more circulating tumor cells (CTCs) in the pulmonary vein (PV) than in the peripheral blood; however, it is unclear whether the CTC count changes in the PV after resection of a lung lobe. METHODS Thirty-three lung cancer patients were recruited for the study, including 17 who underwent lobectomy via video-assisted thoracoscopic surgery and 16 via open thoracotomy. Sixty-six blood specimens were sampled from the PV before the PV was interrupted and after lobectomy. The CTCs were quantified using the oHSV1-hTERT-GFP method. RESULTS Before PV interruption, the CTC (pre-CTC) detection rate was 79.0% (26/33), the mean number of CTCs was 3.36 (median 2, range: 0-18), and there was no significant relationship between the pre-CTC count and clinical factors, such as histologic findings and pathological T stage (P > 0.05). After lobectomy, the CTC (post-CTC) detection rate was 100% (33/33), the average number of CTCs was 14.88 (median 11, range: 1-69), and the post-CTC count was significantly higher in patients in whom the PV was interrupted prior to the pulmonary artery (PA) than in patients in whom the PA was interrupted before the PV (P = 0.016). Overall, the CTC count was significantly higher following surgery (P < 0.001). CONCLUSION Post-CTC counts were significantly higher than pre-CTC counts, suggesting that surgical manipulation may potentially dislodge tumor cells into the PV. Interrupting the PV prior to the PA during lobectomy may prevent partial CTC entry into the circulation.

Jin Lou,1,2 Junjie Huang,1 Zitong Wang,3 Bingbing Wen,1 Chuanqing Tu,4 Wangxiang Huang,5 Zhimin Zhai,2 Xin Du1 1Department of Hematology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, China; 2Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China; 3School of Medicine, University of Sydney, Sydney, NSW, Australia; 4Department of Hematology, People’s Hospital of Baoan District, Shenzhen 518101, China; 5Department of Hematology, Longgang District Central Hospital of Shenzhen, Shenzhen 518116, China Background: Treatment-free remission (TFR) is becoming an essential goal for chronic myeloid leukemia (CML) patients in clinical practice. Few studies have emphasized patient attitudes or preferences about discontinuing tyrosine kinase inhibitors treatment. This study aimed to evaluate the characteristics of Chinese CML patients and their views and perspectives on TFR. Methods: A total of 329 CML patients participated in this multicenter, questionnaire-based, standardized, semi-structured, interview-guided, open-ended, cross-sectional study. Information about demographics, diagnosis information, treatment history, quality of life (QoL), and TFR preference was collected. Results: The adherence rate was 50% (N=163) and sex dependent (males, OR=2.24, 95% CI=1.40–3.58). Physical activity, symptom burden, mood impact, and daily impact were found to be better among adherent patients. Thirty-four percent of the patients were willing to attempt TFR positively. The reasons for preferring TFR were due to side effects (56%) followed by high cost (52%), inconvenience (42%), and pregnancy need (41%). Multivariate analysis indicated that patients who were younger (OR=0.96, 95% CI=0.94–0.99) with shorter disease duration (OR=0.90, 95% CI=0.82–0.98) and higher disease symptom burden (OR=1.08, 95% CI=0.98–1.21) were more likely positive about TFR. Conclusion: Patients who were younger with shorter disease duration and higher disease symptom burden were more likely to try TFR. They expressed several perceived noncost factors of TFR. Our data may help promote the management of CML and designing of clinical trials for TFR in some developed regions of China. Keywords: CML, TKI, TFR, preference, perception

This work systematically analyzed the application of LEDs in underwater white lighting. The characteristics of a RGB-LED and a phosphor-converted LED (PC-LED) have been compared in different water types. The green light shows the smallest attenuation, while the red light has the greatest attenuation coefficient. Such different attenuation effects at different wavelengths lead to the different spectra, CIE coordinates and color rendering index (CRI) of the two kinds of LEDs. With increasing distance, the illuminance of the PC-LED decreases much more rapidly than the RGB-LED due to the stronger attenuation of the wide phosphor-based yellow spectrum. However, the CIE coordinates calculated from the spectra of the PC-LED vary little due to the wider yellow spectrum. On the contrary, the CIE coordinates shift is very clear for the RGB-LED. What's more, the CRI of the RGB-LED increases at distances from 0 to 1.5 m, and then decreases at longer distances, but the CRI of the PC-LED keeps decreasing at all distances, which can be explained by the variation of the R values of the color samples due to wavelength dependent light attenuation. This work will benefit the applications and designs of LED-based underwater lighting.

Due to the many influencing factors of the risk of ground subsidence in goaf, the degree of influence of each factor is different, the relationship between factors is complex and the uncertainty is strong. Therefore, how to construct the evaluation model reasonably is the focus of this paper. The undetermined measure theory can well solve many uncertain problems affecting the ground collapse of the goaf. Therefore, based on the actual situation, this paper determines 15 influencing factors, uses entropy weight method and analytic hierarchy process to determine the combined weight, introduces the principle of confidence, establishes the risk assessment model of ground collapse in goaf based on the theory of certainty, and applies the model. In the Zhangjiatun Coal Mine Area I, the evaluation results are consistent with the actual situation.

Three-dimensional (3D) printing technology has received great attention in the past decades in both academia and industry because of its advantages such as customized fabrication, low manufacturing cost, unprecedented capability for complex geometry, and short fabrication period. 3D printing of metals with controllable structures represents a state-of-the-art technology that enables the development of metallic implants for biomedical applications. This review discusses currently existing 3D printing techniques and their applications in developing metallic medical implants and devices. Perspective about the current challenges and future directions for development of this technology is also presented. Keywords: 3D printing, Biometals, Biocompatibility, Medical devices, Clinical application

// Junjie Huang 1, * , Min Sun 2, * , Zitong Wang 3, * , Qiaoxia Zhang 1 , Jin Lou 1 , Yun Cai 1 , Weihong Chen 1 , Xin Du 1 1 Shenzhen Bone Marrow Transplantation Public Service Platform, Department of Hematology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, China 2 Department of General Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China 3 The University of Sydney Medical School, Sydney, NSW 2006, Australia * These authors have contributed equally to this work Correspondence to: Xin Du, email: duxingz@medmail.com.cn Keywords: induction treatment, acute promyelocytic leukemia, network meta-analysis Received: May 03, 2016 Accepted: September 28, 2016 Published: October 04, 2016 ABSTRACT Background: 9 treatments for acute promyelocytic leukemia (APL) have been compared in many randomized controlled trials (RCT). The conclusions have been inconsistent and the purpose of this study is to conduct a network meta-analysis. Results: Rankings of event-free survival are ATRA+RIF (81.2%), ATRA+ATO (69.6%), ATO (50.6%). Rankings of complete remission are ATRA+RIF (79.3%), ATRA+ATO (64.8%), RIF (60.3%), ATO (55.9%). Rankings of avoiding differentiation syndromes are CT (84.3%), ATO (80.3%), RIF (71.6%), ATRA+RIF (49%), ATRA+ATO (40.8%). Methods: A total of 1,666 patients from 12 RCTs were enrolled. The frequentist method was used. Relative risks with 95% confidence intervals were calculated. We produced a network plot, a contribution plot, and a forest plot predictive intervals. The inconsistency factor, the surface under the cumulative ranking curve and the publication bias were evaluated. Conclusions: ATRA+ATO is eligible to be the first-line treatment for APL. ATRA+RIF is a prospective alternative to the first-line treatment. RIF or ATO should be reconsidered as another option for de novo APL.

Background Lung carcinoid tumors are rare, low-grade, malignant neoplasms with some unclear features. The aim of this study was to analyze clinicopathological features and long-term survival in patients with primary lung carcinoid tumors. Methods Patients who underwent surgery in our clinic and were diagnosed with carcinoid tumors, between August 1997 and July 2012, were included in the study. Patient characteristics and clinicopathological factors were retrospectively evaluated. Results Bronchial carcinoids comprised only 1.0% of lung cancer cases treated by resection. They are classified into two distinct categories: typical carcinoid (TC) and atypical carcinoid (AC) tumors. AC tumors occurred more frequently in younger patients and in smokers, and had a poorer prognosis than TC tumors. Overall three and five-year survival rates for TC and AC were 92.6% and 81.1%, respectively. Univariate analysis showed that tumor size ( P = 0.012) and histological type ( P = 0.013) are prognostic factors. Multivariate analysis revealed that only tumor size ( P = 0.044) was an independent prognostic factor. Conclusions The prognosis for bronchial carcinoid tumors was better than other types of lung cancer and TC was significantly better than AC. Radical lymph node dissection was the best treatment, with complete removal of the tumor. Tumor size was an independent prognostic factor for bronchial carcinoid tumors.

A stabilized finite element algorithm potential for wind-structure interaction (WSI) problem is presented in this paper. Streamline upwind Petrov-Galerkin (SUPG) scheme of the large eddy simulation (LES) of dynamic sub-grid scale (DSGS) is developed under the framework of arbitrary Lagrangian-Eulerian (ALE) description to solve the governing equations. High stabilization is achieved by a three-step technique in the temporal discretization. On the other hand, the partitioned procedure is employed for the consideration of the coupled WSI problem. Newmark integral method is introduced for the computation of structure domain, while spring analogy method is used for the grid update of the mesh domain. The developed computational codes are applied to the analysis of wind-induced effect of a spatial latticed structure. The numerical predictions of the three-dimensional wind flow features, the wind pressures and the wind-induced effect of spatial structures are given. Comparisons are made between the effects of rigid structure in view of the WSI.

Jianbin Wu,1,* Juntao Zhang,1,* Mei Jiang,1 Tianhui Zhang,2 Yue Wang,1 Ziyu Wang,1 Yaodong Miao,1 Zitong Wang,2 Weiying Li1 1Department of Cellular and Molecular Biology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Tumor Surgery, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China *These authors contributed equally to this work Background: Patient-derived tumor xenografts (PDX) are considered as a more reliable experiment model for screening chemotherapeutic drugs. However, the tumorigenic rate differs depending on mouse strains, which generates the experimental variability. Materials and methods: In this study, we built PDX models of human non-small-cell lung cancer (NSCLC) in NOD/SCID mice in comparison with BALB/c mice. Results: The result showed that the tumorigenesis rate of NOD/SCID mice (46.2%, 18/39) was higher than that of BALB/c mice (17.39%, 4/23). Latent times of tumorigenesis of NOD/SCID mice (41±18 days) were shorter than these of BALB/c mice (53±17 days). Times of tumorigenesis of NOD/SCID mice (85±25 days) were shorter than that of BALB/c mice (104±14 days). In addition, squamous carcinoma tissues were more likely to form tumors than adenocarcinoma tissues in NOD/SCID mice (P=0.008) and BALB/c mice (P=0.09). Also tumors could retain patients’ tumor characteristics in NOD/SCID mice and BALB/c mice xenograft models.Conclusion: It is worth mentioning that the result of the drug experiment in the PDX models was consistent with the effect of clinical chemotherapy. As a result, NOD/SCID mice have advantages in a higher rate of tumorigenesis, shorter latent times of tumorigenesis and times of tumorigenesis over BALB/c mice in PDX models. It can provide a more reliable model of drug screening. Keywords: NOD/SCID mice, BALB/c mice, PDX models, chemotherapeutic drugs, NSCLC

Lei Shen,1,* Xiaoguang Wu,2,* Jinjing Tan,1 Meng Gu,1 Yu Teng,1 Zitong Wang,3 Wentao Yue1,4 1Department of Cellular and Molecular Biology, Beijing Tuberculosis and Thoracic Tumor Research Institute, 2Department of Ward 2, 3Department of Thoracic Surgery, Beijing Chest Hospital, Beijing, 4Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Chaoyang, Beijing, People’s Republic of China *These authors contributed equally tothis work Purpose: This study aims to identify the clinical significance of serum autoantibodies against dickkopf-1 (DKK1) and evaluate their feasibility in the immunodiagnosis and prognosis of non-small cell lung cancer (NSCLC).Experimental design: Epitope mapping by peptide microarray-based serum screening of NSCLC patients (n=72) and healthy controls (n=16) was performed. Indirect ELISA with peptides was used to measure the serum levels of autoantibodies in 206 NSCLC patients and 99 healthy controls. A 3-year follow-up was monitored to evaluate the correlation between serological levels of autoantibodies and overall survival (OS) and progression-free survival (PFS).Results: Four highly reactive epitopes were identified, which included peptides 67–84 (PepA), 37–54 (Pep B), 145–156 (Pep C) and 247–261 (Pep D). The autoantibodies levels were considerably higher in sera of NSCLC patients compared with controls (P

Personalized medicine has become essential in the treatment of lung cancer. However, the lung cancer-related gene expression profiles in non-small cell lung cancer (NSCLC) patients have not been elucidated. In this study, the correlation between gene expression profiles and clinicopathological characteristics was investigated in NSCLC patients. A total of 95 patients were enrolled in this study. The mRNA expression levels of 14 genes were assessed by multiplex branched DNA liquidchip (MBL) technology and data on 9 clinicopathological characteristics of patients were collected simultaneously. The correlation between gene expression and clinicopathological characteristics was investigated. Out of the 9 clinicopathological parameters, 6 were associated with several of the 14 genes analyzed. Patient gender was associated with TYMS and TOP2A. Clinical stage was associated with VEGFR2, KIT and HER2. There was weak correlation between primary tumor size of ≤3 cm and the expression level of KIT. The mRNA expression levels of VEGFR2 and HER2 correlated with distant metastasis. BRCA1, TYMS, TOP2A and HER2 were associated with histological type. Smoking correlated with higher expression levels of BRCA1, TYMS and TOP2A and lower expression levels of PDGFRβ. The results were suggestive of correlation between the clinicopathological parameters of the NSCLC patients and the mRNA expression levels of certain lung cancer-related genes, including BRCA1, TYMS, TOP2A, PDGFRβ, VEGFR2, KIT and HER2.

The three-dimensional Flipped Classroom teaching website can be constructed by the innovating of the theory and practice as well as the teacher's improvement of the way to teach.Combining the digitization with the heuristic teaching and in virtue of the multimedia courseware,the classroom teaching can be deepened.This article also raise the TBP teaching mode,and build a concept based on the harmonious unification of teaching researching and learning and the training of the students' creative ability. The Flipped Classroom raised by Jon Bergmann and Jon Bergmann was start to try out in part of the U.S which got the prominent effects.However,these research did not analyze the essence of the Flipped Classroom deeply but only stopped in the way to carry out. Therefore,Professor Robert Talbert took some experiments during his teaching time and has got good effects. He has summarized the teaching model of the Flipped Classroom according to the several-year experience.Although the model summarized the main process,it ignored the other important facts which can influence the Flipped Classroom.Thus,the Flipped Classroom need to be improved further especially in the lessons of information technology. When referring to the construction of the lessons' innovation, the teachers are meant to pay attention to how to impart the knowledge to students based on mastering the theoretical lessons as the 《Principles of Computer Composition》is a professional and less-well understood course. Traditional ways for teaching mainly focus on the teachers,and the students have to take lessons passively.As the less teaching period ,the stronger theoretical property ,the wider scope of knowledge,the more contents and the faster speed of updating of the《Principles of Computer Composition》 increase the difficulty of teachers and students,how to realize the harmonious unification between teaching and learning becomes to be a difficulty for all the educators.The authors has accumulated some experience during the eight-year teaching and practicing.Here are

With the rapid development of Web 2.0 and interactive technologies, learning resources are proliferating online. Confronting such large volume of educational data, users require effective and efficient methodologies to organize and manage them, which reveals the importance of clustering. In this paper, we first propose a method to estimate the data density, and then apply it to merge learning resources. The proposed algorithm estimates the confidence of any two learning resources to be a pair of neighbors, and conducts clustering by combining the above confidence with the similarities among resources. Experiments are designed to evaluate the performance of our algorithm using the standard clustering datasets. We also demonstrate how to employ the proposed algorithm in educational applications, including e-learner grouping, resource recommendation and usage patterns discovery.

Aiming at the problem that clinical hemolysis is difficult to be observed and judged, a method of Adaboost learning classification based on SVM is proposed. The method firstly extracts the basic features of the target area of the blood sample, such as the average of the gray level, the standard deviation of the gray level and the appearance frequency of the particles, as the input eigenvectors of the learning, and carries out SVM weak learner learning. Subsequently, Adaboost algorithm is used to measure the weak learner Set linear weighting, so as to enhance the strong learning device; Finally, online testing, calculation of test sample hemolytic degree and classification. The Adaboost learning classification test based on SVM is compared with the macroscopic and red blood cell counting methods. The experimental results show that the learning-based classification testing method achieves higher detection accuracy without subjective factors and has the highest detection efficiency.

BACKGROUND: The diagnosis of pleural tuberculosis (TB) remains to be difficult. Interferon-gamma release assay (IGRA) is a promising method for diagnosing TB in low TB burden countries. The release of interferon-gamma (IFN-γ) by T lymphocytes increases at a localized site of infection with Mycobacterium tuberculosis antigen. This study aimed to examine the clinical accuracy of T-SPOT.TB on pleural fluid and peripheral blood for the diagnosis of pleural TB in high TB burden country. METHODS: 168 subjects with pleural effusion were enrolled prospectively and examined with T-SPOT.TB on pleural fluid and peripheral blood samples simultaneously. RESULTS: The receiver operating characteristic (ROC) curve and cut-off value of pleural fluid T-SPOT.TB was established according to spot forming cells (SFC) between culture/biopsy-confirmed pleural TB group and no pleural TB group. The sensitivity of pleural fluid T-SPOT.TB and peripheral blood T-SPOT.TB was similar (96.3% and 92.7%, respectively) (P= 0.691). In contrast, the specificity of pleural fluid T-SPOT.TB (94.5%) was significantly higher than that of peripheral blood T-SPOT.TB (76.1%) (P=0.002). 2% (2/98) of pleural fluid T-SPOT.TB results were indeterminate. CONCLUSION: The diagnostic accuracy of peripheral blood T-SPOT.TB is low in high TB burden countries due to latent tuberculosis infection. Pleural fluid T-SPOT.TB is a relatively useful and supplementary test to explore pleural TB in high TB burden countries, but its diagnostic accuracy needs to be validated in further large scale research.

Without traditional mechanical differentials, electric vehicles need electric differentials to avoid slipping. This paper proposed a novel electric differential control strategy to solve the problem. According to the given speed and road conditions, target slip ratios can be calculated. Based on the closed-loop control, this strategy regulates torques of the driving wheels to follow the required slip ratios strictly. The simulation results indicate that it could realize differential for the two driving wheels. Meanwhile, compared with traditional mechanical differentials, the slip ratios of driving wheels and the risk of slipping are minimized.