Multitask deep learning for prediction of microvascular invasion and recurrence-free survival in hepatocellular carcinoma based on MRI images.

BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.

Downregulated long intergenic non-coding RNA 00,174 represses malignant biological behaviors of lung cancer cells by regulating microRNA-584-3p/ribosomal protein S24 axis.

The detailed regulatory mechanism of LINC00174 in lung cancer (LC) development remains largely unknown. This research was designed to probe into the impacts of LINC00174 in LC cells through modulating the microRNA (miR)-584-3p/ribosomal protein S24 (RPS24) axis. LINC00174, miR-584-3p, and RPS24 expression levels in LC cells and tissues were examined. The constructs altering LINC00174, miR-584-3p, or RPS24 expression were transfected into LC cells to examine the malignant phenotypes of LC cells. The relations among LINC00174, miR-584-3p, and RPS24 were validated. LINC00174 and RPS24 were high-expressed while miR-584-3p was low-expressed in LC. Downregulated LINC00174 or RPS24 or upregulated miR-584-3p inhibited the malignant biological behaviors of LC cells. The silenced miR-584-3p could reverse the repressive effects of reduced LINC00174 on the development of LC cells; while RPS24 overexpression inverted the repressive effects of miR-584-3p elevation on LC cells. Mechanically, LINC00174 bound to miR-584-3p that targeted RPS24. Repressed LINC00174 can relieve the malignant phenotypes of LC cells via modulating the miR-584-3p/RPS24 axis.

Comparative analysis on the immunoregulatory roles of ferritin M in hybrid fish (Carassius cuvieri ♀ × Carassius auratus red var ♂) and its parental species after bacterial infection.

Ferritin M is involved in the regulation of fish immunity. In this study, open reading frame (ORF) sequences of ferritin M from hybrid fish and its parental species were 534 bp. Tissue-specific analysis indicated that the highest level of ferritin M from red crucian carp was observed in kidney, while peaked expressions of ferritin M from white crucian carp and hybrid carp were observed in gill. Elevated levels of ferritin M from hybrid carp and its parental species were detected in immune-related tissues following Aeromonas hydrophila infection or in cultured fish cell lines after lipopolysaccharide (LPS) challenge. Ferritin M overexpression could attenuate NF-κB and TNFα promoter activity in their respective fish cells. Purified ferritin M fusion proteins elicited in vitro binding activity to A. hydrophila and Edwardsiella tarda, lowered bacterial dissemination to tissues and alleviated inflammatory response. Furthermore, treatment with ferritin M fusion proteins could mitigate bacteria-induced liver damage and rescue antioxidant activity. These results suggested that ferritin M in hybrid fish showed a similar immune defense against bacteria infection in comparison with those of its parental species.

Blood cell characterization and transcriptome analysis reveal distinct immune response and host resistance of different ploidy cyprinid fish following Aeromonas hydrophila infection.

Aeromonas hydrophila can pose a great threat to survival of freshwater fish. In this study, A. hydrophila infection could decrease blood cell numbers, promote blood cell damage as well as alter the levels of alkaline phosphatase (ALP), lysozyme (LZM), aspartate aminotransferase (AST), total antioxidant capacity (T-AOC), total superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in immune-related tissues of red crucian carp (RCC, 2 N = 100) and triploid cyprinid fish (3 N fish, 3 N = 150). In addition, the significant alternation of antioxidant status was observed in PBMCs isolated from RCC and 3 N following LPS stimulation. The core differential expression genes (DEGs) involved in apoptosis, immunity, inflammation and cellular signals were co-expressed differentially in RCC and 3 N following A. hydrophila challenge. NOD-like receptor (NLR) signals appeared to play a critical role in A. hydrophila-infected fish. DEGs of NLR signals in RCCah vs RCCctl were enriched in caspase-1-dependent Interleukin-1ß (IL-1ß) secretion, interferon (IFN) signals as well as cytokine activation, while DEGs of NLR signals in 3Nah vs 3Nctl were enriched in caspase-1-dependent IL-1ß secretion and antibacterial autophagy. These results highlighted the differential signal regulation of different ploidy cyprinid fish to cope with bacterial infection.

Transcriptome analysis and co-expression network reveal the mechanism linking mitochondrial function to immune regulation in red crucian carp (Carassius auratus red var) after Aeromonas hydrophila challenge.

Aeromonas hydrophila is a common pathogen of freshwater fish. In this study, A. hydrophila infection was shown to cause tissue damage, trigger physiological changes as well as alter the expression profiles of immune- and metabolic-related genes in immune tissues of red crucian carp (RCC). Transcriptome analysis revealed that acute A. hydrophila infection exerted a profound effect on mitochondrial oxidative phosphorylation linking metabolic regulation to immune response. In addition, we further identified cellular senescence, apoptosis, necrosis and mitogen-activated protein kinase signal pathways as crucial signal pathways in the kidney of RCC subjected to A. hydrophila infection. These findings may have important implications for understanding modulation of immunometabolic response to bacterial infection.

Application of a classifier combining bronchial transcriptomics and chest computed tomography features facilitates the diagnostic evaluation of lung cancer in smokers and nonsmokers.

Lung cancer screening by computed tomography (CT) reduces mortality but exhibited high false-positive rates. We established a diagnostic classifier combining chest CT features with bronchial transcriptomics. Patients with CT-detected suspected lung cancer were enrolled. The sample collected by bronchial brushing was used for RNA sequencing. The e1071 and pROC packages in R software was applied to build the model. Eventually, a total of 283 patients, including 183 with lung cancer and 100 with benign lesions, were included into final analysis. When incorporating transcriptomic data with radiological characteristics, the advanced model yielded 0.903 AUC with 81.1% NPV. Moreover, the classifier performed well regardless of lesion size, location, stage, histologic type or smoking status. Pathway analysis showed enhanced epithelial differentiation, tumor metastasis, and impaired immunity were predominant in smokers with cancer, whereas tumorigenesis played a central role in nonsmokers with cancer. Apoptosis and oxidative stress contributed critically in metastatic lung cancer; by contrast, immune dysfunction was pivotal in locally advanced lung cancer. Collectively, we devised a minimal-to-noninvasive, efficient diagnostic classifier for smokers and nonsmokers with lung cancer, which provides evidence for different mechanisms of cancer development and metastasis associated with smoking. A negative classifier result will help the physician make conservative diagnostic decisions.

Comparative analysis of erythrocyte hemolysis, plasma parameters and metabolic features in red crucian carp (Carassius auratus red var) and triploid hybrid fish following Aeromonas hydrophila challenge.

Aeromonas hydrophila can pose a great threat to survival of freshwater fish. In this study, A. hydrophila challenge could promote the erythrocyte hemolysis, increase free hemoglobin (FHB) level and generate malondialdehyde (MDA) production in plasma but decrease the levels of total antioxidant capacity (T-AOC), total superoxide dismutase (SOD), catalase (CAT), alkaline phosphatase (ALP) and lysozyme (LZM) of red crucian carp (RCC, 2 N = 100) and triploid hybrid fish (3 N fish, 3 N = 150) following A. hydrophila challenge. Elevated expression levels of heat shock protein 90 alpha (HSP90α), matrix metalloproteinase 9 (MMP-9), free fatty acid receptor 3 (FFAR3), paraoxonase 2 (PON2) and cytosolic phospholipase A2 (cPLA2) were observed in A. hydrophila-infected fish. In addition, A. hydrophila challenge could significantly increase expressions of cortisol, leucine, isoleucine, glutamate and polyunsaturated fatty acids (PUFAs) in RCC and 3 N, while glycolysis and tricarboxylic acid cycle appeared to be inactive. We identified differential fatty acid derivatives and their metabolic networks as crucial biomarkers from metabolic profiles of different ploidy cyprinid fish subjected to A. hydrophila infection. These results highlighted the comparative metabolic strategy of different ploidy cyprinid fish against bacterial infection.

A novel NK-lysin in hybrid crucian carp can exhibit cytotoxic activity in fish cells and confer protection against Aeromonas hydrophila infection in comparison with Carassius cuvieri and Carassius auratus red var.

NK-lysin, an effector of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), not only exhibits cytotoxic effect in fish cells, but also participates in the immune defense against pathogenic infection. In this study, ORF sequences of RCC-NK-lysin, WCC-NK-lysin and WR-NK-lysin were 369 bp. Tissue-specific analysis revealed that the highest expressions of RCC-NK-lysin and WCC-NK-lysin were observed in gill, while the peaked level of WR-NK-lysin mRNA was observed in spleen. A. hydrophila infection sharply increased RCC-NK-lysin, WCC-NK-lysin and WR-NK-lysin mRNA expression in liver, trunk kidney and spleen. In addition, elevated levels of NK-lysin mRNA were observed in cultured fin cell lines of red crucian carp (RCC), white crucian carp (WCC) and their hybrid offspring (WR) after Lipopolysaccharide (LPS) challenge. RCC-NK-lysin, WCC-NK-lysin and WR-NK-lysin exerted regulatory roles in inducing ROS generation, modulating mitochondrial membrane potential, decreasing fish cell viability and antagonizing survival signalings, respectively. RCC/WCC/WR-NK-lysin-overexpressing fish could up-regulate expressions of inflammatory cytokines and decrease bacterial loads in spleen. These results indicated that NK-lysin in hybrid fish contained close sequence similarity to those of its parents, possessing the capacities of cytotoxicity and immune defense against bacterial infection.

[Effect of different melatonin treatment regimens on white matter damage in neonatal rats with hypoxic-ischemic brain damage].

OBJECTIVE: To study the effect of different melatonin treatment regimens on long-term behavior and white matter damage in neonatal rats with hypoxic-ischemic brain damage (HIBD), and to seek an optimal melatonin treatment regimen. METHODS: Healthy Sprague-Dawley rats, aged 7 days, were randomly divided into four groups: sham-operation, HIBD, single-dose immediate treatment (SDIT), and 7-day continuous treatment (7DCT), with 8 rats in each group. A neonatal rat model of HIBD was prepared according to the classical Rice-Vannucci method. On day 21 after HIBD, the Morris water maze test was used to evaluate spatial learning and memory abilities. On day 70 after HIBD, immunofluorescence assay was used to measure the expression of neuronal nuclear antigen (NeuN) in the cerebral cortex and the hippocampal CA1 region of neonatal rats, and double-label immunofluorescence was used to measure the expression of myelin basic protein (MBP) and neurofilament 200 (NF200) in the corpus striatum and the corpus callosum. RESULTS: The results of the Morris water maze test showed that the SDIT and 7DCT groups had a significantly shorter mean escape latency than the HIBD group, and the 7DCT group had a significantly shorter mean escape latency than the SDIT group (P < 0.05). The results of immunofluorescence assay for NeuN showed that the SDIT and 7DCT groups had a significantly higher number of NeuN+ cells in the cerebral cortex and the hippocampal CA1 region than the HIBD group, and the 7DCT group had a significantly higher number than the SDIT group (P < 0.05). MBP/NF200 double-label immunofluorescence showed that compared with the HIBD group, the SDIT group and the 7DCT group had significantly higher fluorescence intensities of MBP and NF200 in the corpus striatum, and the 7DCT group had significantly higher fluorescence intensities than the SDIT group (P < 0.05); the 7DCT group had significantly higher fluorescence intensities of MBP and NF200 in the corpus callosum than the SDIT and HIBD groups (P < 0.05). CONCLUSIONS: Both SDIT and 7DCT can improve long-term behavior and reduce white matter damage in neonatal rats with HIBD, and 7DCT is more effective than SDIT.

Induction of ferroptosis-like cell death of eosinophils exerts synergistic effects with glucocorticoids in allergic airway inflammation.

INTRODUCTION: Eosinophils are critical in allergic disorders, and promoting eosinophil death effectively attenuates allergic airway inflammation. Ferroptosis is a recently described novel form of cell death; however, little is known about ferroptosis in eosinophils and related diseases. This study aimed to investigate the effects of ferroptosis-inducing agents (FINs) on eosinophil death and allergic airway inflammation, and to explore their potential synergistic effect with glucocorticoids (GCs). METHODS: Eosinophils isolated from the peripheral blood of humans or mice were incubated with FINs, and eosinophil ferroptosis was assessed. The in vivo effects of FINs alone or in combination with dexamethasone (DXMS) were examined in a mouse model of allergic airway inflammation. Bronchoalveolar lavage fluid and lung tissue were collected to examine airway inflammation. RESULTS: Treatment with FINs time and dose dependency induced cell death in human and mouse eosinophils. Interestingly, FINs induced non-canonical ferroptosis in eosinophils, which generated morphological characteristics unique to ferroptosis and was iron dependent but was independent of lipid peroxidation. The antioxidants glutathione and N-acetylcysteine significantly attenuated FIN-induced cell death. Treatment with FINs triggered eosinophil death in vivo and eventually relieved eosinophilic airway inflammation in mice. Furthermore, FINs exerted a synergistic effect with DXMS to induce eosinophil death in vitro and to alleviate allergic airway inflammation in vivo. CONCLUSIONS: FINs induced ferroptosis-like cell death of eosinophils, suggesting their use as a promising therapeutic strategy for eosinophilic airway inflammation, especially due to the advantage of their synergy with GCs in the treatment of allergic disorders.

Homeostatic and early-recruited CD101- eosinophils suppress endotoxin-induced acute lung injury.

INTRODUCTION: Acute lung injury (ALI) is a fatal but undertreated condition with severe neutrophilic inflammation, although little is known about the functions of eosinophils in the pathogenesis of ALI. Our objectives were to investigate the roles and molecular mechanisms of eosinophils in ALI. METHODS: Pulmonary eosinophils were identified by flow cytometry. Mice with abundant or deficient eosinophils were used. Cellularity of eosinophils and neutrophils in bronchoalveolar lavage fluid, inflammatory assessment, and survival rate were determined. Human samples were also used for validating experimental results. RESULTS: Blood eosinophils were increased in surviving patients with acute respiratory distress syndrome (ARDS) independent of corticosteroid usage. There existed homeostatic eosinophils in lung parenchyma in mice and these homeostatic eosinophils, originating from the bone marrow, were predominantly CD101-. More CD101- eosinophils could be recruited earlier than lipopolysaccharide (LPS)-initiated neutrophilic inflammation. Loss of eosinophils augmented LPS-induced pulmonary injury. Homeostatic CD101- eosinophils ameliorated, while allergic CD101+ eosinophils exacerbated, the neutrophilic inflammation induced by LPS. Likewise, CD101 expression in eosinophils from ARDS patients did not differ from healthy subjects. Mechanistically, CD101- eosinophils exhibited higher levels of Alox15 and Protectin D1. Administration of Protectin D1 isomer attenuated the neutrophilic inflammation. CONCLUSIONS: Collectively, our findings identify an uncovered function of native CD101- eosinophils in suppressing neutrophilic lung inflammation and suggest a potential therapeutic target for ALI.

UPLC-QTOF/MS-based metabolomics reveals the mechanism of chronic unpredictable mild stress-induced hypertension in rats.

Hypertension is a common chronic disease, and it is the strongest risk factor for cardiovascular disease. Recently, the number of patients with hypertension-related complications has increased significantly, adding a heavy burden to the public health system. It is known that chronic stress plays an important role in the pathogenesis of cardiovascular diseases such as hypertension and stroke. However, the impact of hypertension on the dysfunctions induced by chronic stress remains poorly understood. In this study, using LC-MS-based metabolomics, we established a chronic stress model to demonstrate the mechanisms of stress-induced hypertension. We found that 30 metabolites in chronically stressed rats were changed; of these metabolites, seven had been upregulated, and 23 had been downregulated, including amino acids, phospholipids, carnitines and fatty acids, many of which are involved in amino acid metabolism, cell membrane injury, ATP supply and inflammation. These metabolites are engaged in dysregulated pathways and will provide a targeted approach to study the mechanism of stress-induced hypertension.

[Effects of different melatonin treatment regimens on the proliferation of endogenous neural stem cells in neonatal rats with hypoxic-ischemic brain damage].

OBJECTIVE: To study the effects of different melatonin treatment regimens on the proliferation of neural stem cells (NSCs) and long-term histopathology in neonatal rats with hypoxic-ischemic brain damage (HIBD), and to identify better melatonin treatment regimens. METHODS: A total of 96 Sprague-Dawley rats aged 7 days were randomly divided into normal control, HIBD, single-dose immediate melatonin treatment (SDIT), and 7-day continuous melatonin treatment (7DCT) groups, with 24 rats in each group. The rat model of HIBD was prepared by isolation and electrocoagulation of the right common carotid artery as well as hypoxic treatment in a hypoxic chamber (oxygen concentration 8.00% ±â€…0.01%) for 2 hours. On day 7 after modeling, proliferating cell nuclear antigen/Nestin double-labeling immunofluorescence was used to measure the proliferation of endogenous NSCs in the subventricular zone (SVZ) and the hippocampal dentate gyrus (DG) region in 8 rats in each group, and Western blot was used to measure the protein expression of Nestin in brain. On day 28 after modeling, hematoxylin-eosin (HE) staining and Nissl staining were used to observe the changes in the histopathology and the number of pyramidal cells in the hippocampal CA1 region in 8 rats in each group. RESULTS: Immunofluorescent staining showed that compared with the HIBD group, the SDIT and 7DCT groups had a significant increase in the number of PCNA+Nestin+DAPI+ cells, and the 7DCT group had a significantly higher number than the SDIT group (P<0.01). Western blot showed that the SDIT and 7DCT groups had significantly higher protein expression of Nestin than the HIBD group, and the 7DCT group had significantly higher expression than the SDIT group (P<0.05). HE staining showed that the SDIT and 7DCT groups had alleviated cell injury, and Nissl staining showed that compared with the HIBD group, the SDIT and 7DCT groups had a significant increase in the number of pyramidal cells, and the 7DCT group had a significantly higher number than the SDIT group (P<0.01). CONCLUSIONS: Both single-dose immediate melatonin treatment and 7-day continuous melatonin treatment can promote the proliferation of endogenous NSCs and alleviate long-term histological injury in the brain of neonatal rats with HIBD. A 7-day continuous melatonin treatment has a better effect than single-dose immediate melatonin treatment.

lncRA ANCR Inhibits Non-Small Cell Lung Cancer Cell Migration and Invasion by Inactivating TGF-ß Pathway.

BACKGROUND lncRNA ANCR is proved to be a tumor suppressor gene only in colorectal cancer and breast cancer. Our study aimed to explore the possible involvement of ACNR in non-small cell lung cancer (NSCLC). MATERIAL AND METHODS In this study, we first detected the expression of ACNR in lung biopsies and plasma of both NSCLC patients and healthy controls. The diagnostic value of ANCR for NSCLC was analyzed by ROC curve analysis. Follow-up data of NSCLC patients was analyzed and the prognostic value of ANCR was analyzed by survival curve analysis. ANCR expression vector was transfected into cells of human NSCLC cell lines, and the effects on cell migration and invasion were explored by Transwell migration and invasion assays, respectively. TGF-ß1 expression after ANCR overexpression was detected by Western blot analysis. RESULTS ANCR was significantly downregulated in NSCLC patients compared with healthy controls in lung biopsies and plasma. Downregulated expression of ANCR distinguishes NSCLC patients from healthy controls and low NSCLC expression level indicates shorter postoperative survival time of NSCLC patients. ANCR overexpression inhibited NSCLC cell migration and invasion and downregulated TGF-ß1 expression, while TGF-ß1 treatment showed no significant effects on ANCR expression but promoted NSCLC cell migration and invasion. In addition, TGF-ß1 treatment also attenuated the inhibitory effects of ANCR overexpression on NSCLC cell migration and invasion. CONCLUSIONS ANCR can inhibit NSCLC cell migration and invasion by downregulating TGF-ß1 expression.

[Correlations of thyroid hormone with deceleration capacity of heart rate and heart rate variability in children with hyperthyroidism].

OBJECTIVE: To investigate deceleration capacity of heart rate (DC), acceleration capacity of heart rate (AC), and heart rate variability (HRV) in children with hyperthyroidism and the correlations of serum thyroid hormone levels with DC, AC, and HRV. METHODS: A total of 47 children with hyperthyroidism were enrolled as hyperthyroidism group and 50 healthy children were enrolled as control group. The subjects in the two groups underwent 24-hour ambulatory electrocardiography. The two groups were compared in terms of DC, AC, heart rate (HR), HRV parameters [standard deviation of normal-to-normal RR intervals (SDNN), standard deviation of average normal-to-normal RR intervals (SDANN), root mean square of successive differences between adjacent RR intervals (RMSSD), low-frequency power (LF), and high-frequency power (HF)]. The correlations of thyroid hormone indices [free triiodothyronine (FT3) and free thyroxin (FT4)] with DC, AC, and HRV were analyzed. RESULTS: Compared with the control group, the hyperthyroidism group had significantly lower DC, SDNN, SDANN, RMSSD, LF, and HF and significantly higher AC and HR (P<0.05). In the children with hyperthyroidism, serum FT3 and FT4 levels showed significant negative correlation with DC, SDNN, SDANN, RMSSD, LF, and HF and significant positive correlation with AC and HR (P<0.05). CONCLUSIONS: Children with hyperthyroidism have cardiac autonomic nerve dysfunction manifested as reduced vagal tone. Vagal tone decreases with the increasing serum thyroid hormone levels, suggesting an increased risk of cardiovascular disease.

[Effect of vitamin D deficiency on cardiac autonomic nerve function in obese pre-school children].

OBJECTIVE: To study the effect of vitamin D (VitD) deficiency on cardiac autonomic nerve function in obese pre-school children. METHODS: A total of 242 pre-school children with simple obesity were enrolled, and according to the serum 25-(OH) VitD level, they were divided into VitD deficiency group (76 children), VitD insufficiency group (83 children), and VitD sufficiency group (83 children). The three groups were compared in terms of deceleration capacity (DC) of heart rate, acceleration capacity (AC) of heart rate, and heart rate variability (HRV). The correlations of VitD level with DC, AC, and HRV were analyzed for the VitD insufficiency and VitD deficiency groups. RESULTS: The VitD deficiency group had the lowest DC, root mean square of successive differences between adjacent RR intervals (RMSSD), and low-frequency power (LF) and the highest AC (P<0.05). The VitD insufficiency group had significantly lower DC, RMSSD, and LF and significantly higher AC compared with the VitD sufficiency group (P<0.05). The VitD deficiency group had significantly lower standard deviation of normal-to-normal RR intervals (SDNN) and high-frequency power (HF) than the VitD sufficiency group (P<0.05). In the VitD deficiency group, VitD level was positively correlated with DC, SDNN, standard deviation of average normal-to-normal RR intervals, RMSSD , LF, and HF and was negatively correlated with AC (P<0.05). In the VitD insufficiency group, VitD level was negatively correlated with AC (P<0.05). CONCLUSIONS: Obese pre-school children with VitD insufficiency or deficiency have cardiac autonomic dysfunction, and cardiac vagal tone decreases with the reduction in VitD level.

Proteomic analysis of sputum reveals novel biomarkers for various presentations of asthma.

BACKGROUND: It is now recognized that asthma can present in different forms. Typically, asthma present with symptoms of wheeze, breathlessness and cough. Atypical forms of asthma such as cough variant asthma (CVA) or chest tightness variant asthma (CTVA) do not wheeze. We hypothesize that these different forms of asthma may have distinctive cellular and molecular features. METHODS: 30 patients with typical or classical asthma (CA), 27 patients with CVA, 30 patients with CTVA, and 30 healthy control adults were enrolled in this prospective study. We measured serum IgE, lung function, sputum eosinophils, nitric oxide in exhaled breath (FeNO). We performed proteomic analysis of induced-sputum supernatants by mass spectrometry. RESULTS: There were no significant differences in atopy and FEV1 among patients with CA, CVA, and CTVA. Serum IgE, sputum eosinophil percentages, FeNO, anxiety and depression scores were significantly increased in the three presentations of asthmatic patients as compared with healthy controls but there was no difference between the asthmatic groups. Comprehensive mass spectrometric analysis revealed more than a thousand proteins in the sputum from patients with CA, CVA, and CTVA, among which 23 secreted proteins were higher in patients than that in controls. CONCLUSIONS: Patients with CA, CVA, or CTVA share common clinical characteristics of eosinophilic airway inflammation. And more importantly, their sputum samples were composed with common factors with minor distinctions. These findings support the concept that these three different presentations of asthma have similar pathogenetic mechanism in terms of an enhanced Th2 associated with eosinophilia. In addition, this study identified a pool of novel biomarkers for diagnosis of asthma and to label its subtypes. Trial registration http://www.chictr.org.cn (ChiCTR-OOC-15006221).

The functions of the Hippo signaling pathway in immune cells.

The Hippo signaling pathway, first identified in Drosophila, has emerged as a critical regulator for controlling the size of organs. Activation of the Hippo signaling pathway negatively regulates the Yorkie ortholog YAP in multiple organs, important in the regulation of cell proliferation, differentiation, and apoptosis during development. The Serine/Threonine protein kinases MST1 and MST2, mammalian homologs of the Drosophila Hippo kinase, play central roles in the Hippo signaling pathway in mammals. Recent studies reveal that non-canonical Hippo signaling pathways are also involved in the regulation of various other biological processes, particularly the important roles of MST1 and MST2 kinases in immune cell activation, adhesion, migration, growth, and apoptosis. In this review, we summarize the recent advances in understanding the roles of MST1 and MST2 kinases in the regulation of the functions of T lymphocytes and innate immune cells.

[Cardiac autonomic nerve function in obese school-age children].

OBJECTIVE: To analyze the deceleration capacity (DC) of heart rate, acceleration capacity (AC) of heart rate, and heat rate variability (HRV) in obese school-age children, and to observe the correlations of BMI with DC, AC, and HRV in these children. METHODS: A total of 108 obese school-age children were selected, including 75 cases of ortholiposis and 33 cases of dyslipidemia. A total of 103 healthy school-age children were selected as control group. All the subjects underwent 24-hour ambulatory electrocardiography. The comparisons of DC, AC, and HRV were made between the obese and control groups, as well as between children with ortholiposis and dyslipidemia in the obese group. The correlations of BMI with DC, AC, and HRV were analyzed in the obese group. RESULTS: The obese group showed lower DC, standard deviation of normal-to-normal R-R intervals (SDNN), standard deviation of the average normal-to-normal intervals (SDANN), root mean square of successive differences (RMSSD), low-frequency power (LF), and high-frequency power (HF) than the control group. The AC of the obese group was significantly higher than that of the control group (P<0.05). In the obese group, children with dyslipidemia had significantly lower DC, SDNN, SDANN, RMSSD, LF, and HF, but significantly higher AC and BMI, as compared with those with ortholiposis (P<0.01). In the obese group, BMI was negatively correlated with DC, SDNN, SDANN, RMSSD, and HF (P<0.05), but positively correlated with AC (P<0.05). CONCLUSIONS: Obese school-age children have impaired autonomic nerve function, presenting with reduced vagal tone, which is particularly prominent in those with dyslipidemia. The more obese the children, the lower the vagal tone, which may increase the risks of cardiovascular diseases.

[An analysis of cardiac autonomic nerve function in girls with idiopathic central precocious puberty].

OBJECTIVE: To investigate the cardiac autonomic nerve function in girls with idiopathic central precocious puberty (ICPP). METHODS: A total of 66 girls with ICPP were enrolled, among whom 36 were obese and 30 were not obese. A total of 68 age-matched healthy girls (normal controls) and 51 girls with simple obesity were enrolled as controls. All the subjects underwent 24-hour ambulatory electrocardiography, and deceleration capacity of heart rate (DC), acceleration capacity of heart rate (AC), and heart rate variability (HRV), and body mass index (BMI) were compared between groups. RESULTS: Compared with the normal control group, the ICPP group had significantly lower DC, standard deviation of normal-to-normal R-R intervals (SDNN), standard deviation of the average normal-to-normal intervals (SDANN), root mean square of successive differences (RMSSD), and high-frequency power (HF) and significantly higher AC and BMI. The ICPP group had significantly lower RMSSD and BMI than the simple obesity group (P<0.05). Compared with the ICPP girls without obesity, those with obesity had significantly lower DC, RMSSD, and HF and significantly higher AC and BMI (P<0.05). CONCLUSIONS: Cardiac autonomic dysfunction is seen in girls with ICPP, especially those with obesity, mainly presenting with reduced vagal tone.