Real-time detection of laryngopharyngeal cancer using an artificial intelligence-assisted system with multimodal data.

BACKGROUND: Laryngopharyngeal cancer (LPC) includes laryngeal and hypopharyngeal cancer, whose early diagnosis can significantly improve the prognosis and quality of life of patients. Pathological biopsy of suspicious cancerous tissue under the guidance of laryngoscopy is the gold standard for diagnosing LPC. However, this subjective examination largely depends on the skills and experience of laryngologists, which increases the possibility of missed diagnoses and repeated unnecessary biopsies. We aimed to develop and validate a deep convolutional neural network-based Laryngopharyngeal Artificial Intelligence Diagnostic System (LPAIDS) for real-time automatically identifying LPC in both laryngoscopy white-light imaging (WLI) and narrow-band imaging (NBI) images to improve the diagnostic accuracy of LPC by reducing diagnostic variation among on-expert laryngologists. METHODS: All 31,543 laryngoscopic images from 2382 patients were categorised into training, verification, and test sets to develop, validate, and internal test LPAIDS. Another 25,063 images from five other hospitals were used as external tests. Overall, 551 videos were used to evaluate the real-time performance of the system, and 200 randomly selected videos were used to compare the diagnostic performance of the LPAIDS with that of laryngologists. Two deep-learning models using either WLI (model W) or NBI (model N) images were constructed to compare with LPAIDS. RESULTS: LPAIDS had a higher diagnostic performance than models W and N, with accuracies of 0·956 and 0·949 in the internal image and video tests, respectively. The robustness and stability of LPAIDS were validated in external sets with the area under the receiver operating characteristic curve values of 0·965-0·987. In the laryngologist-machine competition, LPAIDS achieved an accuracy of 0·940, which was comparable to expert laryngologists and outperformed other laryngologists with varying qualifications. CONCLUSIONS: LPAIDS provided high accuracy and stability in detecting LPC in real-time, which showed great potential for using LPAIDS to improve the diagnostic accuracy of LPC by reducing diagnostic variation among on-expert laryngologists.

[Clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation: a multicenter retrospective analysis].

OBJECTIVE: To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation. METHODS: A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation (n=1 184), tracheal intubation (n=166), and extensive cardiopulmonary resuscitation (ECPR; n=116). The three groups were compared in terms of general information and clinical outcomes. RESULTS: Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid (P < 0.05). As the intensity of resuscitation increased, the Apgar scores at 1 minute and 5 minutes gradually decreased (P < 0.05), and the proportion of infants with Apgar scores of 0 to 3 at 1 minute and 5 minutes gradually increased (P < 0.05). Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly higher mortality rate and incidence rates of moderate-severe bronchopulmonary dysplasia and serious complications (P < 0.05). The incidence rates of grade Ⅲ-Ⅳ intracranial hemorrhage and retinopathy of prematurity (stage Ⅲ or above) in the tracheal intubation group were significantly higher than those in the non-tracheal intubation group (P < 0.05). CONCLUSIONS: For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.

Dose-dependent effect of human milk on Bronchopulmonary dysplasia in very low birth weight infants.

BACKGROUND AND AIM: Human milk has potential protective effects against bronchopulmonary dysplasia (BPD). However, studies on the association between the dose of human milk and BPD in China are limited. This study aimed to evaluate the dose-dependent effects of human milk on BPD and other neonatal morbidities in very low birth weight (VLBW) infants. METHODS: This retrospective cohort study of preterm infants was conducted on preterm infants of gestational age ≤ 34 weeks and birth weight < 1500 g admitted to the multicenter clinical research database for breastfeeding quality improvement in Jiangsu province. The multivariate analysis was performed to compare the effect outcomes of daily graded doses [1-24 mL/(kg · day), 25-49 mL/(kg · day), and ≥ 50 mL/(kg · day) of body weight] of human milk on neonatal outcomes throughout the first 4 weeks of life versus a reference group receiving no human milk. The models were adjusted for potential confounding variables. RESULTS: Of 964 included infants, 279 (28.9%) received exclusive preterm formula, 128 (13.3%) received 1-24 ml/(kg · day), 139 (14.4%) received 25-49 ml/(kg · day), and 418 (43.4%) received ≥50 ml/(kg · day) human milk for the first 4 weeks of life. Compared with infants receiving exclusive formula, those receiving the highest volume of human milk daily [≥50 mL/(kg · day)] had lower incidences of BPD [27.5% in ≥50 mL/(kg · day) vs 40.1% in 0 mL/(kg · day) human milk, P = 0.001)], moderate and severe BPD [8.9% in ≥50 mL/(kg · day) vs 16.1% in 0 mL/(kg · day), P = 0.004], necrotizing enterocolitis [NEC; 3.8% in ≥50 mL/(kg · day) vs 10.8% in 0 mL/(kg · day), P = 0.001], late-onset sepsis [LOS; 9.3% in ≥50 mL/(kg · day) vs 19.7% in 0 mL/(kg · day), P <0.01], and extrauterine growth retardation [EUGR; 38.5% in ≥50 mL/(kg · day) vs 57.6% in 0 mL/(kg · day), P <0.01)]. The logistic regression indicated that those receiving ≥50 ml/kg · day human milk had lower odds of BPD [adjusted odds ratio (AOR) 0.453; 95% confidence interval (CI): 0.309, 0.666], moderate and severe BPD (AOR 0.430; 95% CI: 0.249, 0.742), NEC (AOR 0.314; 95% CI: 0.162, 0. 607), LOS (AOR 0.420; 95% CI: 0.263, 0.673), and EUGR (AOR 0.685; 95% CI: 0.479, 0.979). CONCLUSIONS: A daily threshold amount of ≥50 ml/(kg · day) human milk in the first 4 weeks of life was associated with lower incidence of BPD as well as NEC, LOS, and EUGR in VLBW infants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03453502 . Registration date: March 5, 2018. This study was retrospectively registered.

Phosphonate-Substituted Ruthenium(II) Bipyridyl Derivative as a Photoelectrochemical Probe for Sensitive and Selective Detection of Mercury(II) in Biofluids.

A ruthenium(II) bipyridyl derivative photoelectrochemical probe, Ru-1, is synthesized and coupled with TiO2 nanoparticles (Ru-1/TiO2) for the specific recognition and highly sensitive photoelectrochemical (PEC) detection of Hg2+ in a series of biofluids. The probe is designed with a chromophore, a thiocyanate recognition unit, a π-conjugated photoelectron-transfer pathway, and a phosphonate anchor. TiO2 nanoparticles with strong affinity to phosphonate and suitable conduction band energy are used as intermediate layers to increase the Ru-1 adsorption amount and amplify the photocurrent response. Under irradiation, the Ru-1/TiO2/fluorine-doped tin oxide (FTO), with strong visible light-harvesting capacity, aqueous stability, and efficient photoelectron transfer, shows a high and stable photocurrent response. In the presence of Hg2+, however, the specific Hg2+ and NCS coordination changes the photophysical properties of Ru-1, imposing the probe with a wider band gap, a weaker absorbance, and a poorer photoelectron and hole separation efficiency, thus resulting in a significant photocurrent decrease. On the basis of the Hg2+-induced photocurrent change, the Ru-1/TiO2/FTO shows good selectivity and high sensitivity toward the PEC detection of Hg2+, with wide linear ranges from 10-12 to 10-7 and 10-7 to 10-3 g/mL, and a low limit of detection of 0.63 pg/mL. The PEC probe is recyclable and accurate for selective detection of Hg2+ in urine, serum, and cell extracts. The whole analysis can be completed within 15 min. These good analytical performances indicate that the PEC method might have great potential for the onsite detection of small molecules in biosystems.

Circulating LncRNAs as Novel, Non-Invasive Biomarkers for Prenatal Detection of Fetal Congenital Heart Defects.

OBJECTIVES: To explore the clinical value of circulating long non-coding RNAs (lncRNAs) as biomarkers to predict fetal congenital heart defects (CHD) in pregnant women. METHODS: Differential expression of lncRNAs isolated from the plasma of pregnant women with typical fetal CHD or healthy controls was analyzed by microarray. Gene ontology (GO), pathway and network analysis were performed to study the function of the lncRNAs. Differentially expressed lncRNAs were validated in plasma samples from 62 pregnant women with typical CHD and 62 matched controls by RT-PCR. The sensitivity and specificity of each lncRNA in the diagnosis of fetal CHD was determined by ROC curve analysis. RESULTS: Microarray analysis identified 3694 up-regulated and 3919 down-regulated (fold change ≥2.0) lncRNAs. The top ten significantly differentially expressed, CHD-associated lncRNAs were validated by RT-PCR. Five significantly up-regulated or down-regulated lncRNAs were identified: ENST00000436681, ENST00000422826, AA584040, AA709223 and BX478947 with the AUC of ROC curves calculated as 0.892, 0.817, 0.755, 0.882 and 0.886, respectively. CONCLUSIONS: Specific lncRNAs aberrantly expressed in the plasma of pregnant women with typical fetal CHD may play a key role in the development of CHD and may be used as novel biomarkers for prenatal diagnosis of fetal CHD.

Therapeutic effect of human umbilical cord mesenchymal stem cells on neonatal rat hypoxic-ischemic encephalopathy.

The therapeutic potential of umbilical cord blood mesenchymal stem cells has been studied in several diseases. However, the possibility that human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hUCMSCs) can be used to treat neonatal hypoxic-ischemic encephalopathy (HIE) has not yet been investigated. This study focuses on the potential therapeutic effect of hUCMSC transplantation in a rat model of HIE. Dermal fibroblasts served as cell controls. HIE was induced in neonatal rats aged 7 days. hUCMSCs labeled with Dil were then transplanted into the models 24 hr or 72 hr post-HIE through the peritoneal cavity or the jugular vein. Behavioral testing revealed that hUCMSC transplantation but not the dermal fibroblast improved significantly the locomotor function vs. vehicle controls. Animals receiving cell grafts 24 hr after surgery showed a more significant improvement than at 72 hr. More hUCMSCs homed to the ischemic frontal cortex following intravenous administration than after intraperitoneal injection. Differentiation of engrafted cells into neurons was observed in and around the infarct region. Gliosis in ischemic regions was significantly reduced after hUCMSC transplantation. Administration of ganglioside (GM1) enhanced the behavioral recovery on the base of hUCMSC treatment. These results demonstrate that intravenous transplantation of hUCMSCs at an early stage after HIE can improve the behavior of hypoxic-ischemic rats and decrease gliosis. Ganglioside treatment further enhanced the recovery of neurological function following hUCMSC transplantation.

[Altered patterns of functional connectivity of posterior cingulate cortex on resting-state magnetic resonance imaging in children with attention-deficit or hyperactivity disorder].

OBJECTIVE: To explore the pathophysiological changes in the functional connectivity of posterior cingulate cortex (PCC) with other brain regions in children with attention-deficit or hyperactivity disorder (ADHD) on resting-state functional magnetic resonance imaging(fMRI) and explore the neural mechanisms of ADHD at the point of relationships between brain regions. METHODS: Thirty children with ADHD from the Third Affiliated Hospital of Soochow University from June 2008 to April 2010 and another 30 age-and-gender-matched controls from a normal primary school over the same period underwent resting-state fMRI scans. And blood oxygenation level dependent (BOLD) signal was acquired to calculate the functional connectivity of PCC with other brain regions controls. Significant differences of connectivity between groups were analyzed with REST software. RESULTS: The pattern of functional connectivity of PCC for the ADHD group was similar to that of the control group. Significant positive functional connectivity with PCC was observed in the default mode of network (DMN) while negative functional connectivity was present in dorsolateral prefrontal cortex, anterior cingulate, parietal cortex and basal ganglia(all P < 0.05, corrected). Compared to the controls, the ADHD group exhibited decreased positive connectivity with PCC in bilateral medial prefrontal cortex (0.07 ± 0.20 vs 0.33 ± 0.23, t = -5.47), right posterior cingulate gyrus(0.25 ± 0.28 vs 0.48 ± 0.30, t = -3.44), right inferior temporal gyrus (-0.05 ± 0.19 vs 0.22 ± 0.22, t = -4.61) and cerebellar posterior lobe (-0.04 ± 0.21 vs 0.17 ± 0.16, t = -3.99), while decreased negative functional connectivity with PCC was observed in left insula (-0.10 ± 0.26 vs -0.30 ± 0.19, t = 3.71), right inferior parietal lobule (0.02 ± 0.18 vs -0.23 ± 0.17, t = 5.20), left postcentral gyrus (0.08 ± 0.26 vs -0.17 ± 0.25, t = 4.06), left superior temporal gyrus (-0.04 ± 0.25 vs -0.27 ± 0.17, t = 4.27), right superior temporal gyrus (-0.08 ± 0.25 vs -0.31 ± 0.21, t = 3.80) and left fusiform gyrus (-0.01 ± 0.25 vs -0.18 ± 0.17, t = 3.57)(all P < 0.05, corrected). CONCLUSIONS: The connectivity of DMN between brain regions is abnormal in ADHD group. And the strengthen of negative relationship between DMN and task activated network becomes reduced. It is surmised that the decreased internal synchronization of default network and disrupted balance between DMN and prefrontal-parietal attentional networks may be important neural mechanisms of ADHD.

[Mathematical cognitive function in children with attention deficit hyperactivity disorder: a behavior and event-related potential study].

OBJECTIVE: To explore the mathematics cognitive function of children with attention deficit hyperactivity disorder and explore neural mechanisms with event-related potential(ERP) and behaviors. METHODS: Behavior data and ERP elicited by performing mental calculation tasks were recorded in 27 children with ADHD and 29 normal controls from July to October 2012 at Third Affiliated Hospital of Soochow University.The differences of behaviors and N2 component of ERP were compared and analyzed. RESULTS: The reaction time of the children with ADHD were longer than the control group in addition, subtraction and multiplication ((949 ± 144) vs (829 ± 166) ms, (981 ± 129) vs (856 ± 170) ms, (944 ± 136) vs (825 ± 172) ms, all P < 0.05). While the correct rate were less than normal control in all three arithmetic operations (0.80% (0.72%, 0.88%) vs 0.90% (0.85%,0.96%), 0.78% (0.64%,0.85%) vs 0.90% (0.84%,0.93%), 0.86% (0.74%,0.92%) vs 0.93%(0.90%,0.98%), all P < 0.05). N2 component could be elicited by all subjects in forehead. The amplitude of N2 of children with ADHD were significantly lower than control group in all three arithmetic operations at left frontal (F3: (-3.5 ± 5.2) vs (-6.7 ± 3.5)µV, (-3.8 ± 4.0) vs (-7.4 ± 4.5)µV, -5.8 (-7.6,1.6) vs -6.4(-10.3, -4.9) µV, all P < 0.05) and Fz ((-4.3 ± 6.4) vs ( -7.4 ± 4.2) µV, (-5.0 ± 5.4) vs (-7.9 ± 4.6)µV, -5.2(-9.7, -0.6) vs -7.9 (-10.5, -5.1)µV, all P < 0.05), the latency of ADHD group were prolonger than controls in subtraction operations at right and left frontal ((328 ± 36) vs (307 ± 27)ms, 325 (307,354)vs 309 (280, 330)ms) and frontal electrodes ((331 ± 35) vs (311 ± 30) ms, all P < 0.05). In addition and multiplication operations, there was no significant difference in latency (all P > 0.05). CONCLUSIONS: The children with ADHD have weak capacities of inhibition irrelevant information and paying attention to control. Their deficits in mental arithmetics may be due to the difficulties of selecting the best strategy during cognitive tasks.

Promotion of liver fibrosis by Y-box binding protein 1 via the attenuation of transforming growth factor-beta 3 transcription.

Background: Spurred by the seriousness of liver fibrosis, we evaluated the correlation between Y-box binding protein 1 (YB-1) and transforming growth factor-beta 3 (TGF-ß3) expression levels in the signaling pathways of the disease. Methods: Based on a mouse model of carbon tetrachloride-induced liver fibrosis, YB-1 overexpression lentivirus was used to explore the effect of YB-1 on liver fibrosis in vivo. In addition, a hepatic stellate cell (HSC) activation model in the HSC line LX-2 was developed using TGF-ß1. Western blot assays were used to investigate the effects of YB-1 overexpression and knockdown on liver fibrosis. Finally, chromatin immunoprecipitation and luciferase reporter assays were used to elucidate the relationship between YB-1 and its downstream signaling pathways. Results: YB-1 was overexpressed in fibrotic liver tissue, which enhanced both fibrosis and the relative protein expressions of the TGF-ß pathway. Moreover, YB-1 overexpression promoted HSC activation in response to TGF-ß1 stimulation, but its knockdown inhibited liver fibrosis in vitro. Both in vitro and in vivo experiments indicated the expression of TGF-ß3 in the YB-1 overexpression group to be suppressed, and liver fibrosis was more obvious in the YB-1-overexpression group than in the YB-1-inhibition group. YB-1 attenuated TGF-ß3 transcription by binding to its promoter, which is involved in the effect of YB-1 on liver fibrosis. Conclusions: YB-1 overexpression in HSCs promoted liver fibrosis by attenuating TGF-ß3 transcription.

A sustainable and low pollutive strategy for the recycling of waste hot-gas filter bags: The development of filter reinforced epoxy composites.

The fast accumulation of waste hot-gas filter bags has become a growing public concern considering its difficulty in degradation, severe pollution elicited by landfill and incineration, high energy consumption during burning or complicated recycling and low margin of regenerative products. Herein, we provide a new feasible recycling strategy by directly employing the cleaned polyphenylene sulfide (PPS) /polytetrafluoroethylene (PTFE) waste filters in their fabric state as the reinforcement of epoxy composites. Merely two layers of filters could produce composites with flexural strength and modulus sufficient for many applications and the additional carbon fiber fabric (CFF) covering could further strengthen the composites (295 to 1010 % increments). The filters also showed a bonding promotion function between CFF and polymethacrylimide foam in lightweight composites. After hydrothermal treatment, the composites reinforced by the recycled filters displayed 97.2 % and 90.9 % retention rate for flexural strength and modulus, respectively. Compared to the pure epoxy, the composites could achieve a limiting oxygen index of 27.6 %, and display 24 % decline in thermal energy release and 20.0 to 31.0 % reduction in the generation rate of combustion products, indicating strengthened flame-retardancy. With shortened processes and elevated properties of composites, the approach established for recycling waste filters in this work showed far-reaching implications in carbon emission reduction, environmental pollution diminishing and commercialization potential.

Predictive value of electroencephalogram, event-related potential, and general movements quality assessment in neurodevelopmental outcome of high-risk infants.

OBJECTIVE: The objective of the study is to investigate the predictive value of electroencephalogram (EEG), event-related potential (ERP), and general movements (GMs) quality assessment in the neurodevelopmental outcome of high-risk infants at one year old. METHODS: EEG and ERP were performed in high-risk infants at four weeks old, and GMs quality was evaluated once at 4 weeks and once at 12 weeks. The Gesell score was used to assess neurodevelopment outcome at one year old. A comparative analysis of the effects of EEG, GMs, EEG + ERP, and EEG + ERP + GMs was used to predict high-risk neonatal neurodevelopmental outcome. RESULTS: Of 71 high-risk infants at the age of one year, 3 (4.23%) had cerebral palsy, 14 (19.72%) had psychomotor retardation, and 54 (76.05%) were normal. The sensitivity, specificity, positive predictive value, and negative predictive value of EEG + ERP + GMs method were 90.00%, 95.08%, 75.00%, and 98.31%, respectively, and these indexes were the highest among the four methods (EEG, GMs, EEG + ERP, and EEG + ERP + GMs). The kappa statistic for the reliability of predicting neurodevelopmental outcome of high risk newborns by the EEG + ERP + GMs method was substantial at 0.785, while the other three methods obtained relatively low Kappa values (0.599, 0.586, and 0.712, respectively). CONCLUSIONS: The combination of EEG, ERP, and GMs quality assessment can greatly improve the prediction of neurodevelopmental outcome of high-risk newborns.

Correction: Evaluation of auditory perception development in neonates by quantitative electroencephalography and auditory event-related potentials.

[This corrects the article DOI: 10.1371/journal.pone.0183728.].

Sialylated human milk oligosaccharides prevent intestinal inflammation by inhibiting toll like receptor 4/NLRP3 inflammasome pathway in necrotizing enterocolitis rats.

BACKGROUND: Necrotizing enterocolitis (NEC) remains a fatal gastrointestinal disorder in neonates and has very limited therapeutic options. Sialylated human milk oligosaccharides (SHMOs) improve pathological changes in experimental NEC models. The objectives of this study were to investigate the involvement of NLRP3 inflammasome in NEC pathology and to explore the effects of SHMOs on toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB)/NLRP3 inflammatory pathway in experimental NEC. METHODS: The intestinal-tissue segments were collected from NEC infants, NLRP3 and caspase-1 positive cell were examined by immunohistochemistry. Newborn rats were hand-fed with formula containing or non-containing SHMOs (1500 mg/L) and exposed to hypoxia/cold stress to induce experimental NEC. The NEC pathological scores were evaluated; ileum protein expression of membrane TLR4 (mTLR4), inhibitor κB-α (IκB-α), NF-κB p65 subunit and phospho-NF-κB p65, as well as NLRP3 and caspase-1 were analyzed; ileum concentrations of interleukin-1ß, interleukin-6, tumor necrosis factor-α (TNF-α) were also measured. Human colon epithelial Caco-2 cells were pre-treated with or without SHMOs and stimulated with TLR4 activator, lipopolysaccharide. Cell viabilities, mitochondrial membrane potential and supernatant matrix metalloprotease 2 (MMP-2) activities were analyzed. RESULTS: Increased frequencies of NLRP3 and caspase-1 positive cells were found in the lamina propria of damaged intestinal area of NEC neonates. SHMOs supplementation reduced NEC incidence and pathological damage scores of rats challenged with hypoxia/cold stress. Accumulation of interleukin-1ß, interleukin-6 and TNF-α in NEC group were attenuated in SHMOs + NEC group. Protein expression of mTLR4, NLRP3 and caspase-1 were elevated, cytoplasmic IκB-α were reduced, nuclear phospho-NF-κB p65 were increased in the ileum of NEC rats. SHMOs supplementation ameliorated the elevation of mTLR4, NLRP3 and caspase-1, restored IκB-α in the cytoplasmic fraction and reduced phospho-NF-κB p65 in the nuclear fraction in the ileum of NEC rats. SHMOs pre-treatment improved Caco-2 cell viability, mitigated loss of mitochondrial membrane potential and modulated MMP-2 activities in the presence of lipopolysaccharide in-vitro. CONCLUSIONS: This study provided clinical evidence of involvement of NLRP3 inflammasome in NEC pathology, and demonstrated the protective actions of SHMOs might be owing to the suppression of TLR4/NF-κB/NLRP3-mediated inflammation in NEC.

Influence of Exercise on Exhausted and Senescent T Cells: A Systematic Review.

The impaired effector function of exhausted and senescent T cells is implicated in cancer progression and inadequate vaccine responses. Exercise has been shown to improve cancer therapy and vaccine efficacy, most likely by improving immune function. However, given inconsistent terminology and definitions, the interactions between exercise and exhausted and senescent T cells remain unclear. We therefore performed a systematic review to investigate the effect of exercise on senescent and exhausted CD8+ T cell populations clearly defined by protein surface markers. Thirty articles were included, with the majority (n = 24) reporting senescent T cell populations defined according to a variety of surface markers. Repeated exercise was shown to be beneficial through limiting the accumulation of senescent and exhausted CD8+ T cells. This outcome is likely related to exercise-induced preferential mobilization of senescent T cells promoting apoptosis in the peripheral blood compartment. Future studies need to determine the clinical relevance of this effect in cancer prevention and vaccine efficacy. Data regarding exercise and exhausted T cells are limited due to a lack of available high-quality studies. Future studies require the control of confounding variables such as sex and cytomegalovirus (CMV) status, and consistent definitions of exhausted and senescent T cell populations to improve comparisons between studies and interventions.

Short-term effects of single-dose chloral hydrate on neonatal auditory perception: An auditory event-related potential study.

OBJECTIVE: To study the short-term effects of a single-dose chloral hydrate on neonatal auditory perception by measuring auditory event-related potentials (aERPs). METHODS: Thirty-nine full-term neonates, aged 2-28 days and weighing 2980-4350 g, were divided into two groups including a chloral hydrate group (CH group, n = 17) and a non-chloral hydrate control group (non-CH group, n = 22). The CH group was given single-dose chloral hydrate (30 mg/kg) orally before aERPs measurement. An auditory oddball paradigm was used to elicit aERPs. P2 and N2 components of the ERP were recorded from electrodes at the Fz and Cz locations, and the areas under their curves (P2 and N2 areas) were calculated for the comparison between two groups. RESULTS: Significant differences was found in the P2 area between the two groups at Fz and Cz (Fz: F (1,37) = 487.75, P < 0.05; Cz: F (1,37) = 1465.94, P < 0.05). Similarly, significant difference was also in the N2 area between the two groups at both locations (Fz: F(1,37) = 153.38, P < 0.05; Cz: F(1,37) = 798.42, P < 0.05). CONCLUSION: A single-dose of chloral hydrate impacts neonatal auditory perception in the short-term. Long-term effects will also be studied in future.

Chrysophanol alleviates myocardial injury in diabetic db/db mice by regulating the SIRT1/HMGB1/NF-κB signaling pathway.

Myocardial injury induced by diabetes has become an increasing health problem. Chrysophanol (CHR) has been widely studied as a potential treatment for many diseases due to its anti-inflammatory effects, but has not been investigated in regard to diabetes-induced myocardial injury. The present study evaluated the myocardial protective effects of CHR in C57BL/KsJ-db/db diabetic mice. C57BL/KsJ-db/db and C57BLKS/J mice were treated with vehicle, metformin (100 mg/kg/day) or CHR (50 or 100 mg/kg/day) for 28 days. An oral glucose tolerance test was performed to detect blood glucose levels. Blood lipids, triglycerides, total cholesterol, myocardial function-associated enzymes, namely creatine kinase (CK) and lactate dehydrogenase (LDH), and insulin levels were analyzed. TNF-α, interleukin (IL)-1ß and IL-6 inflammatory cytokine levels in serum and myocardial tissues were determined by ELISA. Expression of silent information regulator l (SIRT1) and high mobility group box 1/NF-κB pathway-associated proteins in myocardial tissues were measured by western blot analysis and immunohistochemistry. CHR treatment at both concentrations markedly decreased blood lipid and serum insulin levels, and inhibited the myocardial enzymes CK and LDH. CHR also significantly ameliorated the cardiac pathological changes in diabetic mice. The inflammatory cytokine levels that were increased in C57BL/KsJ-db/db diabetic mice were downregulated by CHR treatment. CHR also increased SIRT1 protein expression and inhibited activation of the HMGB1/NF-κB pathway. In conclusion, the present study indicates that CHR effectively protected against diabetic myocardial injury via regulation of SIRT1 and the HMGB1/NF-κB signaling pathway.

Resting-state network complexity and magnitude changes in neonates with severe hypoxic ischemic encephalopathy.

Resting-state functional magnetic resonance imaging has revealed disrupted brain network connectivity in adults and teenagers with cerebral palsy. However, the specific brain networks implicated in neonatal cases remain poorly understood. In this study, we recruited 14 term-born infants with mild hypoxic ischemic encephalopathy and 14 term-born infants with severe hypoxic ischemic encephalopathy from Changzhou Children's Hospital, China. Resting-state functional magnetic resonance imaging data showed efficient small-world organization in whole-brain networks in both the mild and severe hypoxic ischemic encephalopathy groups. However, compared with the mild hypoxic ischemic encephalopathy group, the severe hypoxic ischemic encephalopathy group exhibited decreased local efficiency and a low clustering coefficient. The distribution of hub regions in the functional networks had fewer nodes in the severe hypoxic ischemic encephalopathy group compared with the mild hypoxic ischemic encephalopathy group. Moreover, nodal efficiency was reduced in the left rolandic operculum, left supramarginal gyrus, bilateral superior temporal gyrus, and right middle temporal gyrus. These results suggest that the topological structure of the resting state functional network in children with severe hypoxic ischemic encephalopathy is clearly distinct from that in children with mild hypoxic ischemic encephalopathy, and may be associated with impaired language, motion, and cognition. These data indicate that it may be possible to make early predictions regarding brain development in children with severe hypoxic ischemic encephalopathy, enabling early interventions targeting brain function. This study was approved by the Regional Ethics Review Boards of the Changzhou Children's Hospital (approval No. 2013-001) on January 31, 2013. Informed consent was obtained from the family members of the children. The trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800016409) and the protocol version is 1.0.

Lysine-Specific Histone Demethylase 1A Regulates Macrophage Polarization and Checkpoint Molecules in the Tumor Microenvironment of Triple-Negative Breast Cancer.

Macrophages play an important role in regulating the tumor microenvironment (TME). Here we show that classical (M1) macrophage polarization reduced expression of LSD1, nuclear REST corepressor 1 (CoREST), and the zinc finger protein SNAIL. The LSD1 inhibitor phenelzine targeted both the flavin adenine dinucleotide (FAD) and CoREST binding domains of LSD1, unlike the LSD1 inhibitor GSK2879552, which only targeted the FAD domain. Phenelzine treatment reduced nuclear demethylase activity and increased transcription and expression of M1-like signatures both in vitro and in a murine triple-negative breast cancer model. Overall, the LSD1 inhibitors phenelzine and GSK2879552 are useful tools for dissecting the contribution of LSD1 demethylase activity and the nuclear LSD1-CoREST complex to switching macrophage polarization programs. These findings suggest that inhibitors must have dual FAD and CoREST targeting abilities to successfully initiate or prime macrophages toward an anti-tumor M1-like phenotype in triple-negative breast cancer.

Altered patterns of resting-state functional connectivity between the caudate and other brain regions in medication-naïve children with attention deficit hyperactivity disorder.

BACKGROUND: Structural and functional alterations occur in the caudate of patients with attention-deficit/hyperactivity disorder (ADHD). Here we aimed to investigate the functional connectivity between the dorsal caudate and other brain regions in ADHD children. METHODS: Resting-state functional connectivity from 30 ADHD and 33 age- and gender-matched "normal" children were measured by functional Magnetic Resonance Imaging. RESULTS: Positive connectivity with dorsal caudate was observed in the prefrontal areas, cingulate cortex and temporal lobe. Negative functional connectivity was observed in the precuneus, occipital cortices and cerebellum. The connectivity of left dorsal caudate to left inferior frontal gyrus was correlated with severity of ADHD. CONCLUSIONS: Connectivity of dorsal caudate with several brain regions was identified in ADHD children.

Evaluation of auditory perception development in neonates by quantitative electroencephalography and auditory event-related potentials.

OBJECTIVE: The present study was performed to investigate neonatal auditory perception function by quantitative electroencephalography (QEEG) and auditory event-related potentials (aERPs) and identify the characteristics of auditory perception development in newborns. METHODS: Fifty-three normal full-term neonates were divided into three groups according their age in days. An auditory oddball paradigm was used. QEEG (resting state and task state) and aERPs were performed. EEG δ power in the resting and task states and at different ages was respectively analyzed. The N2 area and latency of aERPs at different ages were also compared. RESULTS: The four main findings of this study are as follows. First, the increase in the EEG δ power was significantly greater in the task than resting state in Group 3 at the Fz lead (t = -3.371, P = 0.004) and in Groups 2 and 3 at the Cz lead (Group 2: t = -3.149, P = 0.005; Group 3: t = -3.609, P = 0.002). Second, the δ power gradually increased from 1 to 10 days of age (Group 1), peaked at 11 to 20 days (Group 2), and gradually decreased from 21 to 28 days (Group 3). The data in the Fz lead during the task state and in the Cz lead during the resting and task states were statistically significant (F = 5.875, P = 0.005; F = 5.523, P = 0.007; and F = 5.402, P = 0.008, respectively). Third, the N2 area significantly increased with age by presentation of target stimuli (F = 5.26, P = 0.01). The N2 area increased most significantly from 21 to 28 days (Group 3). Finally, the N2 latency significantly decreased with age (Fz lead: F = 4.66, P = 0.023; Cz lead: F = 7.18, P = 0.005). The N2 latency decreased most significantly from 11 to 20 days of age (Group 2). CONCLUSION: Rapid cognitive development occurs during the neonatal period. In the first several days after birth, the EEG δ power and N2 area manifested the characteristic performance of identifying task information. QEEG and aERP measurement can be used as objective indices with which to evaluate auditory perception development in neonates.