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The heat generation problem of axle box bearing during churning phase leads to abnormal temperature rise and temperature alarm, which affects the normal operation of high-speed train. Aiming at this problem, the temperature characteristics of bearing initial lubrication phase is studied, and the multi-speed grade cycle running schemes are used in tests to run multiple bearings for multiple times. The temperature data and friction data in tests are collected by using non-destructive testing method, and characteristic extraction is carried out. Under the premise of not destroying the internal structure and lubrication state of the bearing, the lubrication state inside the bearing is reflected by the change of the characteristic values. A 118 min scheme is proposed, and the bearing using this scheme to run on the test rig is used in the actual operation. The results show that the temperature of the bearing with running-in test is lower than that of the bearing without running-in test, which indicates the effectiveness of the proposed temperature control strategy. [ABSTRACT FROM AUTHOR]

The article highlights the significance of family-centered care (FCC) in the Neonatal Intensive Care Unit (NICU) setting, emphasizing its role in reducing parental stress and improving long-term outcomes for both parents and infants. Topics include the development and growth of an FCC program in a safety net hospital, the composition and roles of the FCC team, and strategies employed to enrich the family experience during NICU stays.

Increasing evidence supports a central role of the immune system in lung diseases. Understanding how immunological alterations between lung diseases provide opportunities for immunotherapy. Exhausted T cells play a key role of immune suppression in lung cancer and chronic obstructive pulmonary disease was proved in our previous study. The present study aims to furthermore define molecular landscapes and heterogeneity of systemic immune cell target proteomic and transcriptomic profiles and interactions between circulating immune cells and lung residential cells in various lung diseases. We firstly measured target proteomic profiles of circulating immune cells from healthy volunteers and patients with stable pneumonia, stable asthma, acute asthma, acute exacerbation of chronic obstructive pulmonary disease, chronic obstructive pulmonary disease and lung cancer, using single‐cell analysis by cytometry by time‐of‐flight with 42 antibodies. The nine immune cells landscape was mapped among those respiratory system diseases, including CD4+ T cells, CD8+ T cells, dendritic cells, B cells, eosinophil, γδT cells, monocytes, neutrophil and natural killer cells. The double‐negative T cells and exhausted CD4+ central memory T cells subset were identified in patients with acute pneumonia. This T subset expressed higher levels of T‐cell immunoglobulin and mucin domain‐containing protein 3 (Tim3) and T‐cell immunoreceptor with Ig and ITIM domains (TIGIT) in patients with acute pneumonia and stable pneumonia. Biological processes and pathways of immune cells including immune response activation, regulation of cell cycle and pathways in cancer in peripheral blood immune cells were defined by bulk RNA sequencing (RNA‐seq). The heterogeneity among immune cells including CD4+, CD8+ T cells and NK T cells by single immune cell RNA‐seq with significant difference was found by single‐cell sequencing. The effect of interstitial telocytes on the immune cell types and immune function was finally studied and the expressions of CD8a and chemokine C–C motif receptor 7 (CCR7) were increased significantly in co‐cultured groups. Our data indicate that proteomic and transcriptomic profiles and heterogeneity of circulating immune cells provides new insights for understanding new molecular mechanisms of immune cell function, interaction and modulation as a source to identify and develop biomarkers and targets for lung diseases. [ABSTRACT FROM AUTHOR]

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a major public health issue. In the study, mass cytometry is used with extensive antibody panels to perform in‐depth immune profiling of samples from patients with AECOPD, acute lung infection(AI) and healthy controls. Immune composition of 11 populations including CD4/CD8 T cells, B cells, NK cells, and others is identified. Significantly, 7 T cell subsets are changed among the three groups. Then RNA sequencing at single cell level is further processed to provide a detailed peripheral T cell immunity of AECOPD. Combined analysis suggests that dysfunctional effector T cells in AECOPD are characterized with suppressed mitochondria, dampened mTOR activity, and IFN‐γ production. Furthermore, targeting mTOR pathway synergized the PD‐1 blockade therapy promotes T cell glycolysis and IFN‐γ production. The study presents an in‐depth immunometabolic atlas of AECOPD. [ABSTRACT FROM AUTHOR]

Background: Cell proliferation and death are key components of wound healing and tissue repair. Telocytes (TCs) represent a newly discovered cell type that can protect tissue from acute injury via cell-cell communication with adjacent cells. The aim of this study was to use a mouse model of skin wound healing and lipopolysaccharide (LPS)-induced cell injury to evaluate the effects of TCs on skin wound healing in vivo and in vitro.Material/methods: Immunohistochemical staining was performed to evaluate the alteration of TCs in tissues from normal and chronic wound patients. Then, a male C57BL/6 mouse wound model of the back was established. The mice were divided randomly into three groups, and wound healing was estimated according to the wound healing rate and histology. An LPS-induced co-culture model of a mouse lung telocyte cell line (TCs) with human keratinocyte (HaCaT), human dermal microvascular endothelial cell (HDMEC) or murine fibroblast (L929) cell lines was established to analyse the effects of TCs on constitutive cell types of the skin. Cell proliferation, migration and apoptosis were examined, and reactive oxygen species (ROS) and inflammatory factors in HaCaT cells, HDMECs, and L929 cells were detected to study the mechanisms involved in TC protection in skin wounds.Results: TCs were significantly increased in tissues from chronic wound patients compared with healthy controls. Wound healing was significantly improved in wound mouse models treated with exogenous TCs compared with LPS-induced models. TCs reversed the LPS-induced inhibition of HaCaT cells and HDMECs and reduced the LPS-induced apoptosis of HaCaT cells and the death ratios of HDMECs and L929 cells. TCs reversed LPS-induced ROS in HDMECs and L929 cells and decreased inflammatory factor mRNA levels in HaCaT cells, HDMECs and L929 cells.Conclusions: TCs reduce wound healing delay, and inflammatory responses caused by LPS might be mediated by inflammatory inhibition, thus restricting apoptosis and promoting migration of the main component cell types in the skin. [ABSTRACT FROM AUTHOR]

Background: Telocytes (TCs) have the capacity of cell-cell communication with adjacent cells within the tissue, contributing to tissue repair and recovery from injury. The present study aims at investigating the molecular mechanisms by which the TGFβ1-ITGB1-PI3K signal pathways regulate TC cycle and proliferation.Methods: Gene expression of integrin (ITG) family were measured in mouse primary TCs to compare with other cells. TC proliferation, movement, cell cycle, and PI3K isoform protein genes were assayed in ITGB1-negative or positive mouse lung TCs treated with the inhibition of PI3Kp110α, PI3Kα/δ, PKCβ, or GSK3, followed by TGFβ1 treatment.Results: We found the characters and interactions of ITG or PKC family member networks in primary mouse lung TCs, different from other cells in the lung tissue. The deletion of ITGB1 changed TCs sensitivity to treatment with multifunctional cytokines or signal pathway inhibitors. The compensatory mechanisms occur among TGFβ1-induced PI3Kp110α, PI3Kα/δ, PKCβ, or GSK3 when ITGB1 gene was deleted, leading to alterations of TC cell cycle and proliferation. Of those PI3K isoform protein genes, mRNA expression of PIK3CG altered with ITGB1-negative TC cycle and proliferation.Conclusion: TCs have strong capacity of proliferation through the compensatory signaling mechanisms and contribute to the development of drug resistance due to alterations of TC sensitivity. [ABSTRACT FROM AUTHOR]

Anti-apoptotic and anti-inflammatory treatments are imperative for skeletal muscle regeneration following injury. Baicalin is well known and has previously been investigated for its role in the treatment of injury and inflammatory diseases. Therefore, the present study aimed to investigate the effects of baicalin in inhibiting apoptosis of C2C12 myoblasts and preventing skeletal muscle injury. A cell counting kit-8 (CCK-8) assay and Annexin V/PI staining were initially performed to measure cell viability and apoptosis under conditions of H2O2 exposure with or without baicalin. Subsequently, oxidative activity, mitochondrial function, mitochondrial apoptogenic factors and caspase proteins were analyzed to examine the mechanism underlying the effect of baicalin on inhibiting apoptosis in C2C12 myoblasts. Furthermore, BALB/C mice with skeletal muscle injuries were established, and the potential application of baicalin for anti-apoptotic and anti-inflammatory effects was examined via small animal β-2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) imaging and pathological examination. The CCK-8 assay and Annexin V/PI staining revealed cell death in the C2C12 myoblasts induced by H2O2, which was apoptotic, and this was effectively reversed by treatment with baicalin. H2O2 increased the reactive oxygen species and malondialdehyde levels in C2C12 myoblasts, which was caused by mitochondrial dysfunction, decreased expression of cytochrome c and apoptosis-inducing factor from cytosolic and mitochondrial fractions, and activated expression of caspase-3 and caspase-9; however, treatment with baicalin reversed these effects. In addition, small animal PET imaging revealed that treatment with baicalin decreased the accumulation of FDG by ~65.9% in the injured skeletal muscle induced by H2O2. These pathological results also confirmed the protective effect of baicalin on injured skeletal muscle. Taken together, the results of the present study indicated that baicalin effectively inhibited the apoptosis of C2C12 myoblasts and protected skeletal muscle from injury, which may have potential therapeutic benefits for patients in a clinical setting. [ABSTRACT FROM AUTHOR]

• Understood the role of genome regulation at the biological level by defining the overall profile of chromosomal organization. • HNRNPU plays important role in 3D genome organization by high-throughput assays. • The disruption of this protein not only results in compartment switching on of the genome. The complexity of higher eukaryote genomes is far from being explained by linear information. There is a need to understand roles of genome regulation at the organism level through defining a comprehensive profile of chromosomal organization. Chromosome conformation capture (3C)-based studies reveal that higher-order of chromatin include not only long-range chromatin loops, but also compartments and topologically associating domains as the basis of genome structure and functions. However, the molecular machinery how the genome is spatially organized is still inadequate. Exciting progress has been made with the development of today's technology, we find that heterogeneous nuclear ribonucleoprotein U, initially identified as a structural nuclear protein, plays important role in three-dimensional (3D) genome organization by high-throughput assays. The disruption of this protein not only results in compartment switching on of the genome, it also reduces of TAD boundary strengths at borders between two types of compartments, and regulates chromatin loop by decrease its intensities. In addition, HNRNPU mainly binds to active chromatin. Most of HNRNPU peaks is consistent with CTCF or RAD21.It also plays an irreplaceable role in the processes of mitosis. This review aims to discuss the role of HNRNPU in maintaining the 3D chromatin architecture, as well as the recent development and human diseases involved in this nuclear matrix (NM)-associated protein. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of patterned, frequency-modulated oro-somatosensory stimulation on time to full oral feeds in preterm infants born 26–30 weeks gestation. Study design: This is a multicenter randomized controlled trial. The experimental group (n = 109) received patterned, frequency-modulated oral stimulation via the NTrainer system through a pulsatile pacifier and the control group (n = 101) received a non-pulsatile pacifier. Intent-to-treat analysis (n = 210) was performed to compare the experimental and control groups and the outcomes were analyzed using generalized estimating equations. Time-to-event analyses for time to reach full oral feeds and length of hospital stay were conducted using Cox proportional hazards models. Results: The experimental group had reduction in time to full oral feeds compared to the control group (-4.1 days, HR 1.37 (1.03, 1.82) p = 0.03). In the 29–30 weeks subgroup, infants in the experimental group had a significant reduction in time to discharge (-10 days, HR 1.87 (1.23, 2.84) p < 0.01). This difference was not observed in the 26–28 weeks subgroup. There was no difference in growth, mortality or morbidities between the two groups. Conclusions: Patterned, frequency-modulated oro-somatosensory stimulation improves feeding development in premature infants and reduces their length of hospitalization. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Copper(II) ion (Cu2+) is the essential element for numerous pathophysiological processes in vivo. Copper transporter 1 (CTR1) is mainly responsible for maintaining Cu2+ accumulation in cells, which has been found to be over-expressed in inflammatory tissues. Therefore, we explored the potential application of 64CuCl2 for PET imaging of inflammation through targeting CTR1. The animal models of H2O2 induced muscle inflammation and lipopolysaccaharide induced lung inflammation were successfully established, then imaged by small animal PET (PET/CT) post-injection of 64CuCl2, and PET images were quantitatively analyzed. H&E and immunohistochemical (IHC) staining and western blot experiments were performed for evaluating CTR1 levels in the inflammatory and control tissues. Both inflammatory muscle and lungs can be clearly imaged by PET. PET image quantitative analysis revealed that the inflammatory muscle and lungs showed significantly higher 64Cu accumulation than the controls, respectively (p < 0.05). Furthermore, IHC staining and western blot analysis demonstrated that compared with the controls, CTR1 expression was increased in both the inflammatory muscle and lungs, which was consistent with the levels of 64Cu2+ accumulation in these tissues. 64CuCl2 can be used as a novel, simple, and highly promising PET tracer for CTR1 targeted imaging of inflammation. [ABSTRACT FROM AUTHOR]

• A full generalization of Gini index is proposed for sparse quantification. • Fully generalized Gini indices are theoretically proven to be sparsity measures. • Two key performances of fully generalized Gini indices are investigated. • Fully generalized Gini indices exhibit excellent performance in characterizing repetitive transients. • Fully generalized Gini indices can effectively achieve bearing condition monitoring and fault diagnosis. The classic Gini index (GI) is generalized recently by using nonlinear weight sequences as sparsity measures for sparse quantification and machine condition monitoring. The generalized GIs with different weight parameters are more robust to random transients. However, they show insufficient performance in discriminating repetitive transients under noise contamination. To overcome this shortage, this paper proposes a two-parameter generalization method to tune not only the weight parameter but also the norm order, allowing for a full generalization of the classic GI to quantify transient features and leading to new statistical indicators which are named fully generalized GIs (FGGIs). Mathematical derivations show that FGGIs satisfy at least four of the six typical attributes of sparsity measures and that those with weight parameter equal to one satisfy at least five sparse attributes, proving that they are a new family of sparsity measures. Numerical simulations demonstrate that FGGIs can monotonically evaluate the sparseness of the signals and that the FGGIs with appropriate parameters exhibit improved performance in resisting random transient interferences and discriminating noise-contaminated repetitive transients compared to traditional sparsity measures. The performance of FGGIs in the condition monitoring of rolling element bearings is validated using two different run-to-failure experiment datasets, including a gradual failure and a sudden failure. The results show that increasing the norm order can improve the capability of FGGIs to characterize transient fault features, allowing more accurate trending of bearing health conditions, and therefore achieving better condition monitoring performance than the traditional sparsity measures. [ABSTRACT FROM AUTHOR]

Background: Delayed cord clamping (DCC, ≥30s) increases blood volume in newborns and is associated with fewer blood transfusions and short-term neonatal complications. The optimal timing of cord clamping for very preterm infants should maximize placental transfusion without interfering with stabilization and resuscitation. Aim: We compared the effect of different durations of DCC, 30-45s vs. 60-75s, on delivery room (DR) and neonatal outcomes in preterm infants <32 weeks gestational age (GA). Methods: This is a single-center prospective observational study. Data were collected prospectively from eligible infants from two groups: 30-45s DCC group (January 2008 to February 2011, n = 187) and 60-75s DCC group (March 2011 to April 2014, n = 166). Results: The 60-75s DCC group compared to the 30-45s DCC group had higher hematocrits at <2 hours (49.2% vs. 47.4%, p = 0.02). In infants <28 weeks GA, the 12–36 hours hematocrit was higher in the 60-75s DCC group compared to the 30-45s DCC group (47.9% vs. 42.1%, p = 0.002). The 60-75s DCC group had reductions in DR intubation (11% vs. 22%, p = 0.004), hypothermia on admission (1% vs. 5%, p = 0.01), surfactant therapy (13% vs. 28%, p = 0.001), intubation in the first 24 hours (20% vs. 34%, p = 0.004), any intubation (27% vs. 40%, p = 0.007), and any red blood cell transfusion (20% vs. 33%, p = 0.008) during the hospitalization compared to the 30-45s DCC group. These reductions remained significant after adjusting for GA, gender and >48 hours of antenatal steroid exposure. There was no difference between the two groups in neonatal death, intraventricular hemorrhage, chronic lung disease, late onset sepsis, necrotizing enterocolitis and severe retinopathy of prematurity. Conclusion: In this study cohort increasing DCC duration from 30-45s to 60-75s is associated with decreased hypothermia on admission, neonatal respiratory interventions and red blood cell transfusions without increase in neonatal mortality and morbidities. [ABSTRACT FROM AUTHOR]

OPLS-DA score plots were used for the pairwise difference polar metabolites analysis among adult CRC, senior CRC and HC groups. The expression of 5-aminovaleric acid and d-allose in adult CRC patients was higher than that of HC and senior CRC patients (Figure 1J,L). Blood samples from CRC patients and healthy control (HC) groups were collected and identified by LC-MS and GC-MS and used for trans-omics analysis (A). Dear Editor, Colorectal cancer (CRC) is third most frequently diagnosed malignancy with the second highest mortality rate among all cancers.[[1], [3]] As CRC survival is highly dependent upon early diagnosis and treatment, novel sensitive and non-invasive detective approaches f are urgently required.[5] CRC is characterized by metabolic reprogramming.[[6]] In present study, using plasma metabolome analysis, a large scale trans-omic network was constructed by connecting polar metabolite data, lipid data, clinical phenoms and survival outcomes of CRC patients. [Extracted from the article]

Abstract: The aim of the present paper is to study the damage mechanism of the TSG19-type pantographs. Firstly, a rigid-flexible coupled dynamics model is established to predict the pantograph–catenary contact forces with different values of stiffness and damping. A three-dimensional finite element model of a pantograph is then built up to investigate the time history of the stress in a critical section of the pantograph. Dynamics simulations provide the contact forces for the finite element analysis, which the authors needed to extract the stress amplitude and the stress cycles for different values of stiffness and damping. Finally, a reliability model based on the Miner cumulative damage theory is proposed for the TSG19-type pantograph in which the stiffness and damping characteristics degenerate with time. The proposal also takes into account the pantograph life under a given reliability. The results show that the stress amplitude and stress cycles increase when so does the stiffness characteristic and damping decreases. In such way, the stiffness and the damping of the pantograph sets the operating life and the reliability of the component. Therefore, the reliability model appears as a useful tool in the design process of the TSG19-type pantograph since its parameters change with time. [Copyright &y& Elsevier]

Rolling contact fatigue (RCF) of high-speed train wheels is detrimental to reliability and entails huge maintenance costs. Accurate prediction of RCF damage is important for train operators, however, physics-based methods are not suitable for practical applications. Based on accumulated RCF data, this paper develops a physics-based data-driven method for the interpretation and prediction of RCF damage risk. First, based on RCF mechanism, it is found that many relevant parameters can be used for RCF prediction. Then, eight predictors are extracted from RCF-related data through dimensionality reduction methods, including linear discriminant analysis and kernel Fisher discriminant analysis. It shows that greater wheel out-of-roundness or smaller wheel diameters leads to higher RCF risks; previously defective wheels are more likely to reencounter RCF damage; the RCF risk varies in different seasons; the effect of wear on RCF damage is significantly nonlinear. Afterwards, a predictive model is established based on logistic regression. Validation results yield an average accuracy of 75% and also demonstrate its easy interpretability, fast computational speed and stable performance. Further, test result shows an accuracy of 85% to distinguish high-risk wheelsets prior to RCF inspections. The proposed method can be applied to the risk-based maintenance of high-speed train wheels. • The proposed method bridges the gap between RCF mechanism and RCF data. • Eight RCF predictors are extracted through dimensionality reduction. • The predictive model has accurate, interpretable, fast and stable performance. • High-risk wheelsets can be effectively distinguished prior to inspections. • The proposed method can be applied to risk-based maintenance. [ABSTRACT FROM AUTHOR]

The operating temperature and thermal stress play key roles in overall performance of a cylindrical roller bearing used in high-speed train traction motor. The cylindrical roller bearing studied in this paper is in the housing of the traction motor. Due to the heating of each component of the traction motor, a thermal environment is formed in the housing that changes the temperature and stress of the traction motor bearing. In this paper, a thermal-mechanical coupled model of bearing considering the stator, rotor, and shaft was established to study the temperature and thermal stress of traction motor bearing. Experiments were conducted on a service high-speed train to validate the proposed bearing thermal analysis model, meanwhile, the temperature of the measurement point was revised by the theory of heat transfer. The revised experiment results show that the established thermal-mechanical coupled model is reasonable and effective. The results show that the heating of the stator and rotor of the traction motor has a great influence on the temperature and stress of the cylindrical roller bearing of the traction motor. When the heating of the stator and rotor is considered, the temperature of inner ring near the traction motor is higher than that of far away from the traction motor, and the overall temperature of each component of the bearing also increases. As for the stress, when the traction motor stator and rotor is considered, the maximum stress increases by 66.9%. Therefore, the heating of the stator of the traction motor must be considered when the thermal characteristics analysis and reliability analysis are carried out on the cylindrical roller bearing. [ABSTRACT FROM AUTHOR]

• A new MHPO is proposed to enhance impulse feature extraction. • A new time-varying SE design strategy is proposed for morphological filtering. • An ATVMF method is proposed for adaptive extraction of bearing fault features. • An ATVMF-DSS method is developed to enhance bearing fault diagnosis. • ATVMF-DSS exhibits excellent bearing fault diagnosis performance. Fault feature extraction and broadband noise elimination are the keys to weak bearing fault diagnosis. Morphological filtering is a typical fault feature extraction method. However, the parameter selection of structural element (SE) has an important influence on the filtering result. To solve this problem, an adaptive time-varying morphological filtering (ATVMF) is proposed. ATVMF adaptively determines the shape and scale of SE according to the inherent characteristics of vibration signal, effectively improving the fault feature extraction capability and computational efficiency. To solve broadband noise pollution, the diagonal slice spectrum (DSS) is applied to the resulting signal of ATVMF to further eliminate the fault-unrelated components. Finally, a weak bearing fault diagnosis method combining ATVMF and DSS is developed. Simulation and experimental results verify that the proposed method can effectively enhance fault-related impulse features and diagnose weak bearing faults. The comparison with several existing methods demonstrates the advantages of the proposed method. [ABSTRACT FROM AUTHOR]

Bearings of rail vehicles bear various dynamic forces. Any fault of the bearing seriously threatens running safety. For fault diagnosis, vibration and temperature measured from the bogie and acoustic signals measured from trackside are often used. However, installing additional sensing devices on the bogie increases manufacturing cost while trackside monitoring is susceptible to ambient noise. For other application, structural displacement based on computer vision is widely applied for deflection measurement and damage identification of bridges. This article proposes to monitor the health condition of the rail vehicle bearings by detecting the displacement of bolts on the end cap of the bearing box. This study is performed based on an experimental platform of bearing systems. The displacement is monitored by computer vision, which can image real-time displacement of the bolts. The health condition of bearings is reflected by the amplitude of the detected displacement by phase correlation method which is separately studied by simulation. To improve the calculation rate, the computer vision only locally focuses on three bolts rather than the whole image. The displacement amplitudes of the bearing system in the vertical direction are derived by comparing the correlations of the image's gray-level co-occurrence matrix (GLCM). For verification, the measured displacement is checked against the measurement from laser displacement sensors, which shows that the displacement accuracy is 0.05 mm while improving calculation rate by 68%. This study also found that the displacement of the bearing system increases with the increase in rotational speed while decreasing with static load. [ABSTRACT FROM AUTHOR]

The axle box bearing of bogie is one of the key components of the rail transit train, which can ensure the rotary motion of wheelsets and make the wheelsets adapt to the conditions of uneven railways. At the same time, the axle box bearing also exposes most of the load of the car body. Long-time high-speed rotation and heavy load make the axle box bearing prone to failure. If the bearing failure occurs, it will greatly affect the safety of the train. Therefore, it is extremely important to monitor the health status of the axle box bearing. At present, the health status of the axle box bearing is mainly monitored by vibration information and temperature information. Compared with the temperature data, the vibration data can more easily detect the early fault of the bearing, and early warning of the bearing state can avoid the occurrence of serious fault in time. Therefore, this paper is based on the vibration data of the axle box bearing to carry out adaptive fault diagnosis of bearing. First, the AR model predictive filter is used to denoise the vibration signal of the bearing, and then the signal is whitened in the frequency domain. Finally, the characteristic value of vibration data is extracted by energy operator demodulation, and the fault type is determined by comparing with the theoretical value. Through the analysis of the constructed simulation signal data, the characteristic parameters of the data can be effectively extracted. The experimental data collected from the bearing testbed of high-speed train are analyzed and verified, which further proves the effectiveness of the feature extraction method proposed in this paper. Compared with other axle box bearing fault diagnosis methods, the innovation of the proposed method is that the signal is denoised twice by using AR filter and spectrum whitening, and the adaptive extraction of fault features is realized by using energy operator. At the same time, the steps of setting parameters in the process of feature extraction are avoided in other feature extraction methods, which improves the diagnostic efficiency and is conducive to use in online monitoring system. [ABSTRACT FROM AUTHOR]

Wear modelling of train wheels has long been an important research topic; both physics-based and data-based methods have some weaknesses. To bridge the gap between them and take their advantages, this paper proposes a new physics-based data-driven guideline for wheel wear modelling and prediction. First, based on wear mechanism analysis, the basic model of tread wear and flange wear are designed considering their correlation; wear models are established separately for different wheel positions considering the uncertainty in a wear process, and further trained mathematically with wear data. Second, wheel reprofiling is closely related to wheel wear and is modelled based on theoretical analysis and reprofiling data. Then, the numerical method for predicting wheel degradation is proposed based on the closed-loop alternation between wear and reprofiling; the remaining useful life (RUL) of wheels is further evaluated through point estimation and interval estimation. Finally, the good agreement between trained models and wear data validates the wear models; the proposed guideline is verified by measurement data to produce accurate prediction of wheel degradation and effective evaluation of wheel RUL. The proposed guideline has been applied to the prognostics and health management of wheels for various train types. • Physics-based methods and data-based methods are combined for wear modelling and prediction. • Tread wear is influenced by wheel diameter, while flange wear is influenced by wheel diameter and flange thickness. • Wear models are built separately for different wheel positions, and the uncertainty is modelled and simulated mathematically. • The alternation of wear and reprofiling forms a closed-loop wheel degradation process for numerical wear prediction. • Evaluation of remaining useful life is valuable for prognostics and health management of train wheels. [ABSTRACT FROM AUTHOR]

An axle box bearing is one of the most important components of high-speed EMUs (electric multiple units), which runs at a very fast speed, suffers a heavy load, and operates under various complex working conditions. Once a bearing fault occurs, it not only has an enormous impact on the railway system, but also poses a threat to personal safety. Therefore, there is significant value in studying a real-time fault early warning of a high-speed EMU axle box bearing. However, to our best knowledge, there are three obvious defects in the existing fault early warning methods used for high-speed EMU axle box bearings: (1) these methods based on vibration are extremely mature, but there are no vibration sensors installed in high-speed EMU axle box because it will greatly increase the manufacturing cost; (2) a TADS (trackside acoustic device system) can effectively detect early failures, but only a portion of railways are equipped with such a facility; and (3) an EMU-ODS (electric multiple unit onboard detection system) has reported numerous untimely warnings, along with warnings of frequent occurrence being missed. Whereupon, a method is proposed to realize the fault early warning of an axle box bearing without installing a vibration sensor on the high-speed EMU in service, namely a MLSTM-iForest (multilayer long short-term memory–isolation forest). First, the time-series data of the temperature-related variables of the axle box bearing is used as the input of MLSTM to predict the axle box bearing temperature in the future. Then, the deviation index of the predicted axle box bearing temperature is calculated. Finally, the deviation index is input into an iForest algorithm for unsupervised classification to realize the fault early warning of an axle box bearing. Experimental results on high-speed EMU operation data sets demonstrated the availability and feasibility of the presented method toward achieving early fault warnings of a high-speed EMU axle box bearing. [ABSTRACT FROM AUTHOR]

Spatial transcriptomics is considered as an important part of spatiotemporal molecular images to bridge molecular information with clinical images. Of those potentials and opportunities, the excellent quality of human sample preparation and handling will ensure the precise and reliable information generated from clinical spatial transcriptome. The present study aims at defining potential factors that might influence the quality of spatial transcriptomics in lung cancer, para‐cancer, or normal tissues, pathological images of sections and the RNA integrity before spatial transcriptome sequencing. We categorised potential influencing factors from clinical aspects, including patient selection, pathological definition, surgical types, sample harvest, temporary preservation conditions and solutions, frozen approaches, transport and storage conditions and duration. We emphasis on the relationship between the combination of histological scores with RNA integrity number (RIN) and the unique molecular identifier (UMI), which is determines the quality of of spatial transcriptomics; however, we did not find significantly relevance between them. Our results showed that isolated times and dry conditions of sample are critical for the UMI and the quality of spatial transcriptomic samples. Thus, clinical procedures of sample preparation should be furthermore optimised and standardised as new standards of operation performance for clinical spatial transcriptome. Our data suggested that the temporary preservation time and condition of samples at operation room should be within 30 min and in 'dry' status. The direct cryo‐preservation within OCT media for human lung sample is recommended. Thus, we believe that clinical spatial transcriptome will be a decisive approach and bridge in the development of spatiotemporal molecular images and provide new insights for understanding molecular mechanisms of diseases at multi‐orientations. [ABSTRACT FROM AUTHOR]

Telocytes (TCs) are a new type of interstitial cell identified in multiple tissues of mammals, including the human lung, and mediate homocellular or heterocellular cell‐cell communication. Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia respiratory failure and combined with direct and indirect lung injury, which is induced by pneumonia, sepsis, burns, etc. Pulmonary fibrosis is a progressive lung disease that occurs due to increased fibrosis of lung tissue in response to chronic injury of the epithelium and gets more and more attention as a well‐recognized sequela of ARDS or mechanical ventilation. However, the existing intervention measures could not prevent the progression of pulmonary fibrosis. Although the protective effect of TCs in acute lung injury had been demonstrated in both cellular and animal models in previous studies by our or other researchers, the roles of TCs mediated cell‐cell communication in fibroproliferative ARDS is unclear. This review is aimed at integrating our understanding of TC‐mediated cell–cell communication in lung diseases with pulmonary fibrosis after ARDS. [ABSTRACT FROM AUTHOR]

Background: Telocyte (TC) is a recently defined renewed cell and its dominant intercommunication with other cells displays multiple functions in tissue homeostasis and diseases. Alveolar epithelial cells and immune cells were in the lung cancer heterogeneity, progression, and metastasis, and further associated with antitumor therapeutic strategies. However, few studies focus on the roles of TCs in lung cancer. Methods: In this article, we used the public scRNA‐Seq data (including healthy control, chronic obstructive pulmonary disease, non–small cell lung cancer, lymph node metastases from non–small cell lung cancer, and systemic sclerosis–associated interstitial lung disease patients) to analyze the cellular dynamics in human lung and distinct types of TCs and their communication networks with the variety of cell types. Results: Six subclusters of TCs were identified by expression of specific biological function markers, which demonstrated the diversity of TCs subsets in lung tissue. Further results showed TCs had communication with epithelial cells or immune cells subsets by the ligand–receptor interaction, including TIMP metallopeptidase inhibitor 1CD63, fibulin 1integrin subunit beta 1, vimentinCD44, macrophage migration inhibitory factorCD74, and amyloid beta precursor proteinCD74. Ligand–receptor interaction heterogeneity was revealed in lung tissue of healthy or diseases. Enhanced specific signals in ligandreceptor interaction were revealed, including integrin beta 1 and CD44 were appraised in the communication of TCs with epithelial cells, NK cells, NKT cells, CD4+ exhausted T cells, CD4+ memory/effector T cells, CD4+ naïve T cells, CD8+ exhausted T cells, CD8+ memory/effector T cells, and CD8+ naïve T cells. CD63, a marker identified in TCs exosomes was emphasized in our current analysis which is closely related to communication of TCs with other cell types. Conclusion: These results will provide us with new insight into the mechanisms of TCs‐dominated communication and promise therapy of TC exosomes in lung diseases. [ABSTRACT FROM AUTHOR]

Background: Telocytes play key roles in maintenance of organ/tissue function and prevention of organ injury. However, there are great challenges to investigate telocytes functions using primary telocytes, due to the difficulties of isolation, identification, and stability. The present study aims at constructing continuous cell strain of mouse lung telocyte cell line with stable characters by gene modification and investigating biological behaviors and responses of gene-modified telocytes to inflammation.Methods: Mouse primary lung telocytes were isolated and identified using immune-labeling markers and immunoelectron microscopy. Primary telocytes were transformed with Simian vacuolating virus 40 small and large T antigen (SV40). Biological characters, behaviors morphology, and proliferation of those gene-modified telocytes were defined and monitored dynamically for 50 generations, as compared with primary lung telocytes. Cell cycle of mouse primary lung telocytes or gene-modified telocytes was detected by flow cytometry.Results: Gene modified telocytes of generations 5, 10, 30 and 50 were observed with telopodes and also showed CD34 and ckit positive. Multiple cellular morphology were also observed on telocyte cell-line under monitor of celliq and enhanced cell proliferation were showed. SV40 transduction was also reduced apoptosis and increased the ratio of S and G2 phases in telocyte cell-line.Conclusion: We successfully constructed mouse lung telocyte cell-line which maintained the biological properties and behaviors as primary telocytes and could responses to inflammation induced by LPS. Thus, gene-modified lung telocytes, Telocyte Line, would provide a cell tool for researchers exploring the roles and applications of telocytes involved in physiological and pathological states in future. [ABSTRACT FROM AUTHOR]

Background: Interferon gamma (IFNγ) plays an important role in the development of chronic lung diseases via the production of inflammatory mediators, although the exact mechanism remains unclear. The present study aimed at investigating the potential mechanisms by which IFNγ induced over-production of interleukins through the interaction between carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway.Methods: IFN-γ induced over-production of interleukin (IL) 6 and IL8, and RNA expression of CEACAM1 and its subtypes or PI3K and its subtypes in human bronchial epithelial cells (HBE). The production of IL6 and IL8 or cell proliferation and movement were also evaluated in cellCEACAM1- or cellCEACAM1+ after the induction of IFN-γ. Roles of PI3K subtype proteins, e.g. PI3Kp110α/δ, Akt, p110α/γ/δ/β/mTOR, PI3Kp110α/δ/β, PI3Kp110δ, or pan-PI3K in IFN-γ-induced CEACAM1 subtype alterations were furthermore validated using those proteins of PI3K subtypes.Results: CEACAM1, especially CEACAM1-S isoforms, was significantly up-regulated in HBE cells after treatment with IFN-γ. CEACAM1 played roles in expression of IL-6 and IL-8, and facilitated cellular proliferation and migration. IFN-γ up-regulated the expression of CEACAM1 in airway epithelial cells, especially CEACAM1-S isoforms, promoting cellular proliferation, migration, and the production of inflammatory factors. PI3K (p110δ)/Akt/mTOR pathway was involved in the process of IFN-γ-upregulated CEACAM1, especially CEACAM1-S. On the other hand, CEACAM1 could promote the activation of PI3K/Akt/mTOR pathway.Conclusion: IFN-γ could induce inflammatory responses, cellular growth and proliferation through the interaction of CEACAM1 (especially CEACAM1-S isoforms) and PI3K(p110δ)/Akt/mTOR in airway epithelial cells, which might be new alternative of future therapies against epithelial transition from inflammation to cancer. [ABSTRACT FROM AUTHOR]

Prenatal maternal psychological distress (PMPD) is a known risk factor for adverse birth outcomes. N6-methyladenosine RNA (m6A) methylation is crucial in moderating RNA biology. This study aimed to evaluate the relationships between PMPD, birth outcomes, and placental m6A methylation. This was a prospective cohort study. PMPD exposure was assessed by questionnaires about prenatal stress, depression, and anxiety. Placental m6A methylation was measured using a colorimetric assay. The relationships between PMPD, m6A methylation, gestational age (GA), and birth weight (BW) were analyzed using structural equation models (SEMs). Maternal weight gain during pregnancy and infant sex were included as covariables. The study included 209 mother-infant dyads. In an adjusted SEM, PMPD was associated with BW (B = −26.034; 95 % CI: −47.123, −4.868) and GA (B = −0.603; 95 % CI: −1.102, −0.154). M6A methylation was associated with PMPD (B = 0.055; 95 % CI: 0.040,0.073) and BW (B = −305.799; 95 % CI: −520.164, −86.460) but not GA. The effect of PMPD on BW was partially mediated by m6A methylation (B = −16.817; 95 % CI: −31.348, −4.638) and GA (B = −12.280; 95 % CI: −23.612, −3.079). Maternal weight gain was associated with BW (B = 5.113; 95 % CI: 0.229,10.438). The study sample size was small, and the specific mechanism of m6A methylation on birth outcomes needs to be further explored. In this study, PMPD exposure negatively affected BW and GA. Placental m6A methylation was associated with PMPD and BW and partially mediated the effect of PMPD on BW. Our findings highlight the importance of perinatal psychological evaluation and intervention. • Maternal depression, anxiety, and stress were integrated to describe Prenatal maternal psychological distress. • SEMs were used to evaluate relationships between prenatal maternal psychological distress and birth outcomes. • Placental m6A methylation was associated with maternal psychological distress and mediated the effects on birth weight. [ABSTRACT FROM AUTHOR]

Background: Lung epithelial cells play important roles in lung inflammation and injury, although mechanisms remain unclear. Osteopontin (OPN) has essential roles in epithelial damage and repair and in lung cancer biological behaviours. Telocyte (TC) is a type of interstitial cell that interacts with epithelial cells to alleviate acute inflammation and lung injury. The present studies aim at exploring potential mechanisms by which OPN regulates the epithelial origin lung inflammation and the interaction of epithelial cells with TCs in acute and chronic lung injury. Methods: The lung disease specificity of OPN and epithelial inflammation were defined by bioinformatics. We evaluated the regulatory roles of OPN in OPN‐knockdown or over‐expressed bronchial epithelia (HBEs) challenged with cigarette smoke extracts (CSE) or in animals with genome OPN knockout (gKO) or lung conditional OPN knockout (cKO). Acute lung injury and chronic obstructive pulmonary disease (COPD) were induced by smoking or lipopolysaccharide (LPS). Effects of OPN on PI3K subunits and ERK were assessed using the inhibitors. Spatialization and distribution of OPN, OPN‐positive epithelial subtypes, and TCs were defined by spatial transcriptomics. The interaction between HBEs and TCs was assayed by the co‐culture system. Results: Levels of OPN expression increased in smokers, smokers with COPD, and smokers with COPD and lung cancer, as compared with healthy nonsmokers. LPS and/or CSE induced over‐production of cytokines from HBEs, dependent upon the dysfunction of OPN. The severity of lung inflammation and injury was significantly lower in OPN‐gKO or OPN‐cKO mice. HBEs transferred with OPN enhanced the expression of phosphoinositide 3‐kinase (PI3K)CA/p110α, PIK3CB/p110β, PIK3CD/p110δ, PIK3CG/p110γ, PIK3R1, PIK3R2 or PIK3R3. Spatial locations of OPN and OPN‐positive epithelial subtypes showed the tight contact of airway epithelia and TCs. Epithelial OPN regulated the epithelial communication with TCs, and the down‐regulation of OPN induced more alterations in transcriptomic profiles than the up‐regulation. Conclusion: Our data evidenced that OPN regulated lung epithelial inflammation, injury, and cell communication between epithelium and TCs in acute and chronic lung injury. The conditional control of lung epithelial OPN may be an alternative for preventing and treating epithelial‐origin lung inflammation and injury. [ABSTRACT FROM AUTHOR]

Targeted therapies are suggested as an effective alternative for patients with cancer that harbor mutations, but treatment outcomes are frequently limited by primary or acquired drug resistance. The present review describes potential mechanisms of primary or acquired drug resistances to provide a resource for considering how to be overcome. We focus on strategies of targeted drug combinations to minimize the development of drug resistance within the context how resistance develops. Strategies benefit from the combined use of “omics” technologies, i.e., high-throughput functional genomics data, pharmacogenomics, or genome-wide CRISPR-Cas9 screening, to analyze and design targeted drug combinations for mutation-driven drug resistance. We also introduce new insights towards pathway-centric combined therapies as an alternative to overcome the heterogeneity and benefit patient prognoses. [ABSTRACT FROM AUTHOR]

Lung cancer is a widespread malignancy with a high death rate and disorder of lipid metabolism. Lysophosphatidylcholine (lysoPC) has anti‐tumour effects, although the underlying mechanism is not entirely known. The purpose of this study aims at defining changes in lysoPC in lung cancer patients, the effects of lysoPC on lung cancer cells and molecular mechanisms. Lung cancer cell sensitivity to lysoPC was evaluated and decisive roles of long‐chain acyl‐coenzyme A synthase 5 (ACSL5) in lysoPC regulation were defined by comprehensively evaluating transcriptomic changes of ACSL5‐downregulated epithelia. ACSL5 over‐expressed in ciliated, club and Goblet cells in lung cancer patients, different from other lung diseases. LysoPC inhibited lung cancer cell proliferation, by inducing mitochondrial dysfunction, altering lipid metabolisms, increasing fatty acid oxidation and reprograming ACSL5/phosphoinositide 3‐kinase/extracellular signal‐regulated kinase‐regulated triacylglycerol‐lysoPC balance. Thus, this study provides a general new basis for the discovery of reprogramming metabolisms and metabolites as a new strategy of lung cancer precision medicine. [ABSTRACT FROM AUTHOR]

Background: The incidence of depression is twice higher in women than in men, and gender differences in the prevalence rates first emerge around puberty. Prenatal stress (PS) induces gender-dependent depressive-like behavior in adolescent offspring, but the neuro-physiological mechanisms remain unclear. Our study aimed to investigate the possible neuro-physiological mechanisms of gender-dependent depressive-like behavior in PS adolescent offspring and further explored the possibility of treating depression in adolescent female rats. Methods: The pregnant rats were exposed to restraint stress in the third trimester for 7 days. The depressive-like behavior and the expression of N-cadherin and AMPARs in the hippocampus of adolescent offspring rats were assessed. 10 mg/kg AMPAR antagonist CNQX and 10 mg/kg N-cadherin antagonist ADH-1 were intraperitoneally injected into female adolescent offspring, respectively; 0.2 µg AMPAR agonist CX546 was administered to the dentate gyrus of male adolescent offspring to determine the role of N-cadherin-AMPARs in depressive-like behavior of the offspring following PS. Results: We found that PS increased N-cadherin expression, which upregulated GluA1 expression in the dentate gyrus, mediating depressive-like behavior in adolescent female rat offspring by reducing PSD-95. In addition, ADH-1 and CNQX improved depressive-like behavior in adolescent female offspring following PS. Furthermore, injection of the CX546 into the dentate gyrus induced depressive-like behavior in PS male offspring. Conclusion: The gender-dependent expression of N-cadherin-GluA1 pathway in adolescent offspring in the dentate gyrus was the key factor in gender differences of depressive-like behavior following PS. [ABSTRACT FROM AUTHOR]

The communication between endoplasmic reticulum (ER) and mitochondria (Mt) plays important roles in maintenance of intra‐ and extra‐cellular microenvironment, metabolisms, signaling activities and cell‐cell communication. The present review aims to overview the advanced understanding about roles of ER‐Mt structural contacts, molecular interactions and chemical exchanges, signal transmissions and inter‐organelle regulations in ER‐Mt communication. We address how the ER‐Mt communication contributes to the regulation of lipid, amino acid and glucose metabolisms by enzymes, transporters and regulators in the process of biosynthesis. We specially emphasize the importance of deep understanding about molecular mechanisms of ER‐Mt communication for identification and development of biology‐specific, disease‐specific and metabolism‐specific biomarkers and therapeutic targets for human diseases. The inhibitors and modulators of the ER‐Mt communication are categorized according to therapeutic targets. Rapid development of biotechnologies will provide new insights for spatiotemporally understanding the molecular mechanisms of ER‐Mt communication. [ABSTRACT FROM AUTHOR]

Dysfunction of basal forebrain cholinergic neurons (BFCNs) is an early pathological hallmark of Alzheimer's disease (AD). Numerous studies have indicated that nerve growth factor (NGF) supports survival and phenotypic differentiation of BFCNs. Consistent with a potential link toADpathogenesis, TrkA, aNGFreceptor, is expressed in cholinergic forebrain neuronal populations including those in BF and striatum, and is markedly reduced in individuals with mild cognitive impairment (MCI) without dementia and early-stage AD. To investigate the role of TrkA in the development, connectivity, and function of the BF cholinergic system and its contribution to AD pathology, we have generated a forebrain-specific conditional TrkA knock-out mouse line. Our findings show a key role for TrkA signaling in establishing the BF cholinergic circuitry through the ERK pathway, and demonstrate that the normal developmental increase of choline acetyltransferase expression becomes critically dependent on TrkA signaling before neuronal connections are established. Moreover, the anatomical and physiological deficits caused by lack of TrkA signaling in BFCNs have selective impact on cognitive activity. These data demonstrate that TrkA loss results in cholinergic BF dysfunction and cognitive decline that is reminiscent of MCI and early AD. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction contributes to the imbalance of cellular homeostasis and the development of diseases, which is regulated by mitochondria‐associated factors. The present review aims to explore the process of the mitochondrial quality control system as a new source of the potential diagnostic biomarkers and/or therapeutic targets for diseases, including mitophagy, mitochondrial dynamics, interactions between mitochondria and other organelles (lipid droplets, endoplasmic reticulum, endosomes, and lysosomes), as well as the regulation and posttranscriptional modifications of mitochondrial DNA/RNA (mtDNA/mtRNA). The direct and indirect influencing factors were especially illustrated in understanding the interactions among regulators of mitochondrial dynamics. In addition, mtDNA/mtRNAs and proteomic profiles of mitochondria in various lung diseases were also discussed as an example. Thus, alternations of mitochondria‐associated regulators can be a new category of biomarkers and targets for disease diagnosis and therapy. [ABSTRACT FROM AUTHOR]

• Six kinds of periodicity detection techniques are introduced and compared. • The PDTs-assisted MCKD, MOMEDA and CYCBD are proposed for feature enhancement. • BD assisted by AF, PMIF and CKF can adaptively enhance bearing fault features. • Simulations and experiments demonstrate the effectiveness of proposed methods. Maximum correlated kurtosis deconvolution (MCKD), multipoint optimal minimum entropy deconvolution adjusted (MOMEDA) and maximum second-order cyclostationarity blind deconvolution (CYCBD) have remarkable performances in extracting periodic impulses. However, these deconvolution methods highly rely on the prior period of measured signal and can only enhance the specific periodic impulses. Aiming at these limitations, six kinds of periodicity detection techniques (PDTs) are introduced to adaptively identify the period of repetitive impulses. Further, PDTs-assisted MCKD, MOMEDA and CYCBD are proposed for bearing fault feature enhancement. The improved deconvolution methods have two characteristics: first, the fault period is automatically identified by PDTs according to the characteristics of the measured signal; second, the impulses of different faults can be enhanced adaptively. The analysis results of simulated and experimental datasets demonstrated the better capability of the proposed methods in enhancing bearing fault features with respect to original deconvolution methods and the fast kurtogram method. [ABSTRACT FROM AUTHOR]

Objective: To compare the effect of delayed cord clamping on cord blood gas values in vaginally delivered, healthy, term singletons.Data Source: We used MEDLINE, CINAHL, CENTRAL, EMBASE, and ClinicalTrials.gov databases.Methods Of Study Selection: Eligible studies included randomized controlled trials (RCTs) comparing cord blood gas values obtained from early compared with delayed cord clamping groups and observational studies using serial cord blood gas from the same umbilical cord. We described the difference in means of cord blood gas parameters and comparative descriptive statistics when a difference in means was not available. We used a domain-based risk bias tool to extract methodologic details and assess potential risk of bias.Tabulation, Integration, and Results: This review included two RCTs and three observational studies. These studies included a total of 234 newborns with early cord clamping and 218 newborns with delayed cord clamping. The observational studies showed that 45-90 seconds delayed cord clamping was associated with mean decreases in umbilical arterial pH (0.02-0.03), HCO3 (0.3-0.8 mmol/L) and increases in base deficit (0.3-1.3 mmol/L) compared with early cord clamping. One observational study showed that delayed cord clamping was associated with decreases in umbilical venous pH (0.01) and HCO3 (0.2 mmol/L) and increase in venous base deficit (0.1-0.3 mmol/L) compared with early cord clamping. These changes were not observed in the two RCTs.Conclusion: Delayed cord clamping up to 120 seconds has either no effect or only a small effect on cord blood acid-base balance; overall, the magnitude of these changes is not clinically significant in vaginally delivered, healthy, term singletons.Systematic Review Registration: PROSPERO, CRD42019135779. [ABSTRACT FROM AUTHOR]

Background: Telocytes (TCs) are newly identified interstitial cells that participate in tissue protection and repair. The present study investigated the mechanisms underlying the protective effect of TCs in a mouse model of respiratory distress.Methods: The mouse model of acute respiratory distress syndrome (ARDS) was established by intratracheal instillation of lipopolysaccharide (LPS). After instillation of TCs culture medium, lung injury was assessed, and angiogenesis markers, including CD31 and endothelial nitric oxide synthase (eNOS), were detected by immunofluorescence. Bioinformatics analysis was used to screen significantly differentially expressed microRNAs (miRNAs) in cultured TCs stimulated with LPS, and the regulation of downstream angiogenesis genes by these miRNAs was analysed and verified. PI3K subunits and pathways were evaluated by using a PI3K p110α inhibitor to study the involved mechanisms.Results: In ARDS mice, instillation of TCs culture medium ameliorated LPS-induced inflammation and lung injury and increased the protein levels of CD31 and eNOS in the injured lungs. A total of 7 miRNAs and 1899 mRNAs were differentially regulated in TCs stimulated with LPS. Functional prediction analysis showed that the differentially expressed mRNAs were enriched in angiogenesis-related processes, which were highly correlated with miR-21a-3p. Culture medium from TCs with miR-21a-3p inhibition failed to promote angiogenesis in mouse models of LPS-induced ARDS. In cultured TCs, LPS stimulation upregulated the expression of miR-21a-3p, which further targeted the transcription factor E2F8 and decreased Notch2 protein expression. TCs culture medium enhanced hemangioendothelioma endothelial cells (EOMA cells) proliferation, which was blocked by the miR-21a-3p inhibitor. The PI3K p110α inhibitor decreased vascular endothelial growth factor levels in LPS-stimulated TCs and reversed the enhancing effect of TCs culture medium on EOMA cells proliferation.Conclusions: TCs exerted protective effects under inflammatory conditions by promoting angiogenesis via miR-21a-3p. The PI3K p110α subunit and transcriptional factor E2F8 could be involved in this process. [ABSTRACT FROM AUTHOR]

Background: The morbidity and mortality of patients with critical illnesses remain high in pulmonary critical care units and a poorly understood correlation between alterations of lipid elements and clinical phenomes remain unelucidated.Methods: In the present study, we investigated plasma lipidomic profiles of 30 patients with severe acute pneumonia (SAP), acute pulmonary embolism (APE), and acute exacerbation of chronic pulmonary diseases (AECOPD) or 15 healthy with the aim to compare disease specificity of lipidomic patterns. We defined the specificity of lipidomic profiles in SAP by comparing it to both APE and AECOPD. Analysis of the correlation between altered lipid elements and clinical phenotypes using the lipid-QTL model was then carried out.Results: We integrated lipidomic profiles with clinical phenomes measured by score values from the digital evaluation score system and found phenome-associated lipid elements to identify disease-specific lipidomic profiling. The present study demonstrates that lipidomic profiles of patients with acute lung diseases are different from healthy lungs, and there are also disease-specific portions of lipidomics among SAP, APE, or AECOPD. The comprehensive profiles of clinical phenomes or lipidomics are valuable in describing the disease specificity of patient phenomes and lipid elements. The combination of clinical phenomes with lipidomic profiles provides more detailed disease-specific information on panels of lipid elements When compared to the use of each separately.Conclusions: Integrating biological functions with disease specificity, we believe that clinical lipidomics may create a new alternative way to understand lipid-associated mechanisms of critical illnesses and develop a new category of disease-specific biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

Background and Objective: The emergence of the nonnutritive suck (NNS) pattern in preterm infants reflects the integrity of the brain and is used by clinicians in the neonatal intensive care unit (NICU) to assess feeding readiness and oromotor development. A critical need exists for an integrated software platform that provides NNS signal preprocessing, adaptive waveform discrimination, feature detection, and batch processing of big data sets across multiple NICU sites. Thus, the goal was to develop and describe a cross-platform graphical user interface (GUI) and terminal application known as NeoNNS for single and batch file time series and frequency-domain analyses of NNS compression pressure waveforms using analysis parameters derived from previous research on NNS dynamics. Methods. NeoNNS was implemented with Python and the Tkinter GUI package. The NNS signal-processing pipeline included a low-pass filter, asymmetric regression baseline correction, NNS peak detection, and NNS burst classification. Data visualizations and parametric analyses included time- and frequency-domain view, NNS spatiotemporal index view, and feature cluster analysis to model oral feeding readiness. Results. 568 suck assessment files sampled from 30 extremely preterm infants were processed in the batch mode (<50 minutes) to generate time- and frequency-domain analyses of infant NNS pressure waveform data. NNS cycle discrimination and NNS burst classification yield quantification of NNS waveform features as a function of postmenstrual age. Hierarchical cluster analysis (based on the Tsfresh python package and NeoNNS) revealed the capability to label NNS records for feeding readiness. Conclusions. NeoNNS provides a versatile software platform to rapidly quantify the dynamics of NNS development in time and frequency domains at cribside over repeated sessions for an individual baby or among large numbers of preterm infants at multiple hospital sites to support big data analytics. The hierarchical cluster feature analysis facilitates modeling of feeding readiness based on quantitative features of the NNS compression pressure waveform. [ABSTRACT FROM AUTHOR]

Introduction. Avoiding intubation and promoting noninvasive modes of ventilator support including continuous positive airway pressure (CPAP) in preterm infants minimizes lung injury and optimizes neonatal outcomes. Discharge home on oxygen is an expensive morbidity in very preterm infants (VPI) with lung disease. In 2007 a standardized bundle was introduced for VPI admitted to the neonatal care unit (NICU) which included delayed cord clamping (DCC) at birth and noninvasive ventilation as first-line cardiorespiratory support in the delivery room (DR), followed by bubble CPAP upon NICU admission. Objective. Our goal was to evaluate the risk of (1) intubation and (2) discharge home on oxygen after adopting this standardized DR bundle in VPI born at a regional perinatal center and treated in the NICU over a ten-year period (2008-2017). Materials and Methods. We compared maternal and neonatal demographics, respiratory care processes and outcomes, as well as neonatal mortality and morbidity in VPI (< 33 weeks gestation) and extremely low birth weight (ELBW, < 1000 g) subgroup for three consecutive epochs: 2008-2010, 2011-2013, and 2014-2017. Results. Of 640 consecutive inborn VPI, 55% were < 1500 g at birth and 23% were ELBW. Constant through all three epochs, DCC occurred in 83% of VPI at birth. There was progressive increase in maternal magnesium during the three epochs and decrease in maternal antibiotics during the last epoch. Over the three epochs, VPI had less risk of DR intubation (23% versus 15% versus 5%), NICU intubation (39% versus 31% versus 18%), and invasive ventilation (37% versus 30% versus 17%), as did ELBW infants. Decrease in postnatal steroid use, antibiotic exposure, and increase in early colostrum exposure occurred over the three epochs both in VPI and in ELBW infants. There was a sustained decrease in surfactant use in the second and third epochs. There was no significant change in mortality or any morbidity in VPI; however, there was a significant decrease in pneumothorax (17% versus 0%) and increase in survival without major morbidity (15% versus 41%) in ELBW infants between 2008-2010 and 2014-2017. Benchmarked risk-adjusted rate for oxygen at discharge in a subgroup of inborn VPI (401-1500 g or 22-31 weeks of gestation) is 2.5% (2013-2017) in our NICU compared with > 8% in all California NICUs and > 10% in all California regional NICUs (2014-2016). Conclusion. Noninvasive strategies in DR and NICU minimize risk of intubation in VPI without adversely affecting other neonatal or respiratory outcomes. Risk-adjusted rates for discharge home on oxygen remained significantly lower for inborn VPI compared with rates at regional NICUs in California. Reducing intubation risk in ELBW infants may confer an advantage for survival without major morbidity. Prenatal magnesium may reduce intubation risk in ELBW infants. [ABSTRACT FROM AUTHOR]

The survival benefits of sorafenib treatment for patients with hepatocellular carcinoma (HCC) are limited due to drug resistance and side effects. Therefore, combinations of sorafenib with other low toxicity drugs, including arsenic trioxide (As2O3) require investigation. The present study aimed to evaluate the potency of apoptosis‑induction by As2O3/sorafenib treatment in HCC cell lines, Huh7, 97H and freshly‑isolated HCC cells, and also to elucidate the underlying mechanism. A total of 10 patients with HCC were enrolled in the present study. Freshly‑isolated HCC cells were purified from HCC tissues collected at surgery. HCC‑cell apoptosis was measured by flow cytometry using proprium iodide/Annexin‑V staining. The impacts of As2O3 and/or sorafenib on Huh7, 97H and fresh‑isolated HCC‑cell proliferation were evaluated by Cell Counting Kit‑8 assay. The expression of TNF‑related apoptosis‑inducing ligand (TRAIL) was determined by reverse transcription‑quantitative polymerase chain reaction and western blotting. The downregulation of TRAIL protein expression was achieved using small interfering RNA. The combination of As2O3 and sorafenib had anti‑proliferative and pro‑apoptotic effects in the liver cancer cell line, Huh7, via increased expression of TRAIL, but not in 97H cells. TRAIL‑knockdown increased the drug‑resistance of Huh7 cells. Freshly‑isolated HCC cells were more sensitive to the As2O3 and sorafenib combination than the single drug treatments. Overall, the combination of As2O3 and sorafenib demonstrated potent anti‑tumor activity in Huh7 and freshly‑isolated HCC cells via a TRAIL‑dependent pathway. This may be a potential therapeutic approach for advanced HCC treatment. [ABSTRACT FROM AUTHOR]

• Generalized envelopes and generalized envelope spectra are proposed for signal demodulation. • The performance of generalized envelope spectra in rolling bearing fault diagnosis is revealed using simulations and experiments. • The product envelope spectrum is proposed as an enhanced spectral analysis tool. • Product Envelope Spectrum Optimization-gram (PESOgram) is developed for rolling bearing fault diagnosis. • PESOgram shows excellent capability in identifying bearing fault characteristic frequencies. The vibration signal of a faulty rolling bearing exhibits typical non-stationarity – often in the form of cyclostationarity. The spectrum tools often used to characterize cyclostationarity mainly include envelope spectrum, squared envelope spectrum and log-envelope spectrum. In this paper, new detection methods of cyclostationarity are developed for obtaining a larger family of envelope analysis and their effectiveness in rolling bearing fault diagnosis is evaluated rigorously. Firstly, based on the simplified Box-Cox transformation, the generalized envelope signals are constructed from the analytic signal for demodulation purposes, and then a spectrum family named generalized envelope spectra (GESs) is proposed to reveal cyclostationarity. Especially, GESs with different transformation parameters exhibit different performance advantages against the random impulse noise and Gaussian background noise which are commonly present in rolling bearing vibration signals. Subsequently, a novel spectrum tool that combines the performance advantages of different GESs, called product envelope spectrum (PES), is developed to strengthen the capability to detect cyclostationarity. Finally, an enhanced envelope analysis named Product Envelope Spectral Optimization-gram (PESOgram) is proposed to improve the accuracy and robustness of PES for rolling bearing fault diagnosis in the presence of different fault-unrelated interference noises. The performance of the PESOgram method is validated on numerically generated signal and experimental signals collected from two railway axle bearing test rigs and compared with several state-of-the-art envelope analysis methods. The results demonstrate the effectiveness of the proposed method for fault diagnosis of rolling bearings and its advantages over other state-of-the-art methods. [ABSTRACT FROM AUTHOR]

Maternal prenatal depression is a significant public health issue associated with mental disorders of offspring. This study aimed to determine if maternal prenatal depressive symptoms are associated with changes in neonatal behaviors and brain function at the resting state. A total of 204 pregnant women were recruited during the third trimester and were evaluated by Edinburgh Postpartum Depression Scale (EPDS). The mother-infant pairs were divided into the depressed group (n = 75) and control group (n = 129) based on the EPDS, using a cut-off value of 10. Cortisol levels in the cord blood and maternal blood collected on admission for delivery were measured. On day three of life, all study newborns were evaluated by the Neonatal Behavior Assessment Scale (NBAS) and 165 infants were evaluated by resting-state functional near-infrared spectroscopy (rs-fNIRS). To minimize the influences of potential bias on the rs-fNIRS results, we used a binary logistic regression model to carry out propensity score matching between the depressed group and the control group. Rs-fNIRS data from 21 pairs of propensity score-matched newborns were used for analysis. The associations between maternal EPDS scores, neonatal NBAS scores, and cortisol levels were analyzed using linear regressions and the mediation analysis models. Compared to the control group, the newborns in the depressed group had lower scores in the social-interaction and autonomic system dimensions of NBAS (P < 0.01). Maternal and umbilical cord plasma cortisol levels in the depressed group were higher (P < 0.01) than in the control group. However, only umbilical cord plasma cortisol played a negative mediating role in the relationship between maternal EPDS and NBAS in the social-interaction and autonomic system (β med = −0.054 [−0.115,−0.018] and −0.052 [−0.105,−0.019]. Proportional mediation was 13.57 % and 12.33 for social-interaction and autonomic systems, respectively. The newborns in the depressed group showed decreases in the strength of rs-fNIRS functional connections, primarily the connectivity of the left frontal-parietal and temporal-parietal regions. However, infants in the depressed and control groups showed no differences in topological characteristics of the brain network, including standardized clustering coefficient, characteristic path length, small-world property, global efficiency, and local efficiency (P > 0.05). The social-interaction Z-scores had positive correlations with functional connectivity strength of left prefrontal cortex-left parietal lobe (r = 0.57, p < 0.01)，prefrontal cortex-left parietal lobe - left temporal lobe (r = 0.593, p < 0.01) and left parietal lobe - left temporal lobe (r = 0.498, p < 0.01). Autonomic system Z-scores were also significantly positive correlation with prefrontal cortex-left parietal lobe (r = 0.509, p < 0.01)，prefrontal cortex-left parietal lobe - left temporal lobe (r = 0.464, p < 0.01), left parietal lobe - left temporal lobe (r = 0.381, p < 0.05), and right temporal lobe and left temporal lobe (r = 0.310, p < 0.05). This study shows that maternal prenatal depression may affect the development of neonatal social-interaction and autonomic system and the strength of neonatal brain functional connectivity. The fetal cortisol may play a role in behavioral development in infants exposed to maternal prenatal depression. Our findings highlight the importance of prenatal screening for maternal depression and early postnatal behavioral evaluation that provide the opportunity for early diagnosis and intervention to improve neurodevelopmental outcomes. • Maternal prenatal depression may influence neonatal social-interaction and autonomic system development. • Fetal cortisol played partial mediation on neonatal behavioral development after prenatal depression. • Maternal depression in pregnancy may be associated with changes of neonatal functional connectivity strength, primarily with fronto-parietal connectivity and temporo-parietal connectivity [ABSTRACT FROM AUTHOR]

• The concept of generalized combined morphological operators is proposed. • Typical combined morphological operators are investigated and compared. • MHCCO is proposed for extracting bearing fault-induced repetitive transients. • An enhanced morphological filtering method is proposed for bearing diagnostics. • The proposed method exhibits excellent bearing fault diagnosis performance. Morphological filtering adopting the combined morphological operators (CMOs) has been widely used to extract bearing fault features from vibration signals. However, few studies focus on the comprehensive performance of various CMOs under different interferences. In this paper, several new CMOs for feature extraction are proposed firstly, and then the impulse extraction performance of fourteen typical CMOs in the presence of harmonic interference, random impulses and background noise is investigated through simulations. To enhance the capability of impulse extraction and noise elimination, the morphological hat cross-correlation operator (MHCCO) is constructed through the cross-correlation of two CMOs with excellent performance. Additionally, an improved strategy is proposed to adaptively determine the optimal length of the structural element for MHCCO. Simulations, experiments and comparisons demonstrate the effectiveness and superiority of the proposed method. This paper provides important guidance for selecting CMO for feature extraction and an effective method for bearing fault diagnosis. [ABSTRACT FROM AUTHOR]

Background: Telocytes (TCs) are suggested as a new type of interstitial cells with specific telopodes. Our previous study evidenced that TCs differed from fibroblasts and stem cells at the aspect of gene expression profiles. The present study aims to search the characters and patterns of chromosome X genes of TC-specific or TC-dominated gene profiles and fingerprints, investigate the network of principle genes, and explore potential functional association.Methods: We compared gene expression profiles in chromosome X of pulmonary TCs with mesenchymal stem cells (MSC), fibroblasts (Fb), alveolar type II cells (ATII), airway basal cells (ABC), proximal airway cells (PAC), CD8(+) T cells come from bronchial lymph nodes (T-BL), or CD8(+) T cells from lungs (T-L) by global analyses, and selected the genes which were consistently up or down regulated (>1 fold) in TCs compared to other cells as TC-specific genes. The functional and characteristic networks were identified and compared by bioinformatics tools.Results: We selected 31 chromosome X genes as the TC-specific or dominated genes, among which 8 up-regulated (Flna, Msn, Cfp, Col4a5, Mum1l1, Rnf128, Syn1, and Srpx2) and 23 down-regulated (Abcb7, Atf1, Ddx26b, Drp2, Fam122b, Gyk, Irak1, Lamp2, Mecp2, Ndufb11, Ogt, Pdha1, Pola1, Rab9, Rbmx2, Rhox9, Thoc2, Vbp1, Dkc1, Nkrf, Piga, Tmlhe and Tsr2), as compared with other cells.Conclusions: Our data suggested that gene expressions of chromosome X in TCs are different with those in other cells in the lung tissue. According to the selected TC-specific genes, we infer that pulmonary TCs function as modulators which may enhance cellular growth and migration, resist senescence, protect cells from external stress, regulate immune responses, participate in tissue remodeling and repair, regulate neural function, and promote vessel formation. [ABSTRACT FROM AUTHOR]

Background: Erythropoietin is neuroprotective in animal models of neonatal hypoxic-ischemic encephalopathy. We previously reported a phase I safety and pharmacokinetic study of erythropoietin in neonates. This article presents the neurodevelopmental follow-up of infants who were enrolled in the phase I clinical trial.Methods: We enrolled 24 newborns with hypoxic-ischemic encephalopathy in a dose-escalation study. Patients received up to six doses of erythropoietin in addition to hypothermia. All infants underwent neonatal brain magnetic resonance imaging (MRI) reviewed by a single neuroradiologist. Moderate-to-severe neurodevelopmental disability was defined as cerebral palsy with Gross Motor Function Classification System levels III-V or cognitive impairment based on Bayley Scales of Infant Development II mental developmental index or Bayley III cognitive composite score.Results: Outcomes were available for 22 of 24 infants, at mean age 22 months (range, 8-34 months). There were no deaths. Eight (36%) had moderate-to-severe brain injury on neonatal MRI. Moderate-to-severe disability occurred in one child (4.5%), in the setting of moderate-to-severe basal ganglia and/or thalamic injury. Seven infants with moderate-to-severe watershed injury exhibited the following outcomes: normal (three), mild language delay (two), mild hemiplegic cerebral palsy (one), and epilepsy (one). All 11 patients with a normal brain MRI had a normal outcome.Conclusions: This study is the first to describe neurodevelopmental outcomes in infants who received high doses of erythropoietin and hypothermia during the neonatal period. The findings suggest that future studies are warranted to assess the efficacy of this new potential neuroprotective therapy. [ABSTRACT FROM AUTHOR]

Background & Aims Thrombocytopaenia is a frequent feature in patients with HBV-related liver disease. Its underlying mechanism is not fully understood. Multiple factors might contribute to the development of thrombocytopaenia. In this study, we investigated the reticulated platelets ( RP), glycocalicin ( GC), serum thrombopoietin ( TPO) and platelet glycoprotein ( GP) in different stages of the disease. Methods One hundred and fourteen patients with HBV-related liver disease (30 with chronic hepatitis B ( CHB), 20 patients in Child A without thrombocytopaenia, 19 patients in Child A with thrombocytopaenia, 45 in Child B/C with thrombocytopaenia) and 25 normal controls ( NC) were enrolled. Liver cirrhosis ( LC) was classified according to modified Child-Turcotte-Pugh ( CTP) score. Serum TPO levels and GC were measured by ELISA. RP and platelet glycoprotein ( GP) expression were detected by flow cytometry. Results The TPO levels of patients with LC were significantly lower than that of controls, even in patients of Child A without thrombocytopaenia group. Serum TPO level was positively correlated ( r = 0.65, p < 0.01) with serum albumin in Child B/C group. Both the RP percentages and the glycocalicin index ( GCI) levels were significantly higher in patients groups including CHB and Child A without thrombocytopaenia than that of normal controls. A negative correlation existed in HBV DNA copies and the GPs% in patients with CHB and Child A without thrombocytopaenia. Conclusion Abnormal platelet production, destruction and platelet-specific glycoproteins levels were detected before the occurrence of thrombocytopaenia in HBV-related liver disease, indicating that multiple mechanisms might play roles in thrombocytopaenia in HBV-infected patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Skeletal myoblast (SkM) transplantation combined with vascular endothelial growth factor (VEGF) gene delivery has been proposed as a promising therapy for cardiac repair. Nevertheless, the defective gene vectors and unregulable VEGF expression in vivo hinder its application. Therefore, the search for an economical, effective, controllable gene delivery system is quite necessary. Methods: In our study, hyperbranched polyamidoamine (h-PAMAM) dendrimer was synthesized as a novel gene delivery vector using a modified method. And hypoxia-regulated human VEGF-165 plasmids (pHRE-hVEGF165) were constructed for controllable VEGF gene expression. The efficiency and feasibility of h-PAMAM-HRE-hVEGF165 gene delivery system manipulated SkM transplantation for cardiac repair were investigated in myocardial infarction models. Results: The h-PAMAM encapsulated pHRE-hVEGF165 could resist nuclease digestion for over 120min. In primary SkMs, h-PAMAM-pHRE-hVEGF165 gene delivery system showed high transfection efficiency (43.47±2.22%) and minor cytotoxicity (cell viability=91.38±0.48%). And the transfected SkMs could express hVEGF165 for 18days under hypoxia in vitro. For myocardial infarction models, intramyocardial transplantation of the transfected SkMs could result in reduction of apoptotic myocardiocytes, improvement of grafted cell survival, decrease of infarct size and interstitial fibrosis, and increase of blood vessel density, which inhibited left ventricle remodeling and improved heart function at the late phase following infarction. Conclusions: These results indicate that h-PAMAM based pHRE-hVEGF165 gene delivery into SkMs is feasible and effective, and may serve as a novel and promising gene therapy strategy in ischemic heart disease. [Copyright &y& Elsevier]

Abstract: The Escherichia coli homolog of GroEL, a 60 kDa heat shock protein (HSP), is a dominant protein produced not only in response to heat stress but also under in vitro growth condition. Beside its traditional cytoplasmic location, the surface exposures of GroEL have been observed in many pathogenic bacteria. To investigate the role of the surface-associated GroEL in the binding of E. coli to macrophages, we constructed a new strain of E. coli displaying GroEL on the outer membrane. We found that surface-associated GroEL increases the clearance ratio of E. coli by macrophages. It has been previously demonstrated that lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the receptor for Hsp60 from different species. Our present results showed that GroEL on E. coli was recognized by LOX-1 on macrophages, leading to the phagocytosis of pathogen by macrophages. In addition, surface-associated GroEL made mice more susceptible to E. coli-induced peritonitis. These findings add to the research that clarifies the factors mediating bacterial adherence to host cells. Our results suggest that GroEL is a novel therapeutic target for modulating the immune response in infectious and inflammatory conditions. [Copyright &y& Elsevier]

Background: B cells expressing CD5 are potentially capable of producing interleukin 10 (IL-10) which contributes to the regulatory function of B cells. This study was aimed at exploring the alteration of numbers of CD5 B cells and their ability of producing IL-10 in patients with immune thrombocytopenia (ITP), and the effects of pulsed high-dose dexamethasone (HD-DXM) therapy on CD5 B cells. Methods: Peripheral blood mononuclear cells from 25 adult ITP patients were stained with PE-CD5/FITC-CD19 antibodies for flow cytometry analyses before and after HD-DXM therapy. The expression of IL-10 mRNA was measured by RT-PCR. After 24 h culture with or without dexamethasone in the presence of PMA, ionomycin and Brefeldin A, cells were permeabilized and stained with APC-IL-10 antibody to investigate intracellular IL-10 expression. Supernatant IL-10 concentration was detected by ELISA. Results: The number of CD5 B cells was elevated in patients with ITP. Expression of IL-10 mRNA, percentage of IL-10 cells and intracellular IL-10 in CD5 B cells from untreated patients were significantly higher than that in controls. In contrast, ITP patients showed lower IL-10 concentration in supernatants than controls. After HD-DXM therapy, the number of CD5 B cells decreased to normal level, while intracellular IL-10 expression in CD5 B cells was further enhanced and IL-10 concentration in supernatants was also increased. Similar results were observed when dexamethasone was administrated in vitro. Conclusions: Increased number of CD5 B cells in which IL-10 is accumulated with decreased IL-10 concentration in supernatants suggests that the ability of CD5 B cells to secret IL-10 is impaired in ITP patients. Both the aberrant number and ability of IL-10 secretion of CD5 B cells could be corrected by HD-DXM. [ABSTRACT FROM AUTHOR]