Time-course and dose-effect of omalizumab in treating chronic idiopathic urticaria/chronic spontaneous urticaria.

PURPOSE: Several studies have shown that subcutaneous injections of omalizumab can treat chronic idiopathic/spontaneous urticaria (CIU/CSU) patients by only assessing the efficacy on specific endpoints. This study aimed to quantitatively analyze different doses of omalizumab in CIU/CSU and compare it with ligelizumab. METHODS: Literature searches were performed in PubMed, Embase, and Web of Science databases. A model-based meta-analysis (MBMA) was utilized to develop a model incorporating time since the initiation of treatment and dose for omalizumab, with the change from baseline in Urticaria Activity Score (CFB-UAS7) as the primary efficacy endpoint. The time-course and dose-effect relationship throughout the omalizumab treatment period was analyzed, and the findings were compared with those of the investigational ligelizumab. RESULTS: The model equation for the CFB-UAS7 was established as E = -Emax × time/(ET50 + time) × (b0 + b1 × dose). The estimated values of the model parameters E max , ET 50 , b 0 , and b 1 were -1.16, 1.26 weeks, -9.90, and -0.0361 mg-1, respectively. At week 12 after the first dose, the model-predicted CFB-UAS7 for 150 mg and 300 mg of omalizumab were -16.0 (95% CI, -17.2 to -14.8) and -21.7 (95% CI, -22.9 to -20.5), respectively. In the PEARL-1 trial, the CFB-UAS7 for 72 mg and 120 mg of ligelizumab were -19.4 (95% CI, -20.7 to -18.1) and -19.3 (95% CI, -20.6 to -18.0), respectively. In the PEARL-2 trial, these values were -19.2 (95% CI, -20.5 to -17.9) and -20.3 (95% CI, -21.6 to -19.0), respectively. CONCLUSION: Omalizumab showed a significant dose-dependent effect in the treatment of CSU. Both 72 mg and 120 mg ligelizumab might have the potential to outperform 150 mg (but not 300 mg) omalizumab.

The association between brominated flame retardants exposure with bone mineral density in US adults: A cross-sectional study of the national health and nutrition examination survey (NHANES) 2005-2014.

BACKGROUND AND AIMS: Exposure to brominated flame retardants (BFRs) has been widely confirmed to impair the normal functioning of the human body system. However, there is a paucity of study on the effects of serum BFRs on bone mineral density (BMD). This study aims to investigate the relationship between exposure to BFRs and BMD in a nationally representative sample of U.S. adults. METHODS: 3079 participants aged between 20 and 80 years with complete data were included in the study. Serum levels of BFRs were measured using automated liquid-liquid extraction and subsequent sample clean-up. The BMD of all participants were assessed by DXA examinations. Generalize linear model, Restricted cubic spline (RCS), subgroup, weighted quantile sum (WQS) and bayesian kernel machine regression (BKMR) were used to estimate the association between serum BFRs and BMD. RESULTS: Multivariate linear regression analyses revealed that, after adjusting for covariates, PBB153 was significantly associated with TF-BMD (ß = 0.0177, 95%CI: 0.0103-0.0252), FN-BMD (ß = 0.009, 95%CI: 0.0036-0.0145), TS-BMD (ß = 0.0081, 95%CI: 0.0013-0.015) and L1-BMD (ß = 0.0144, 95%CI: 0.0075-0.0213). However, the associations lose their statistical significance after further adjustment for sex. BFRs exhibited S-shaped or line-plateau dose-response curves with BMD. In subgroup analyses, BFRs were significantly associated with BMD in participants who were younger than 55 years, female, overweight (BMI >25 kg/m2), and less alcohol consumption. In WQS and BKMR analyses, the effects of BFRs mixtures on BMD differed by sex, and PBDE153, PBDE209 and PBB153 had the highest weights in the WQS regression model. CONCLUSION: This study showed that serum BFRs negatively predicted BMD in men, but not in women or the general population. PBDE153, PBDE209, and PBB153 were significant BMD factors, especially in younger, overweight, and less alcohol consumption individuals.

An alarm device for mechanical compression device displacement at femoral artery puncture sites.

OBJECTIVE: To develop an alarm device for the mechanical compression device displacement (MCD), and further evaluate its effectiveness in clinical use. MATERIAL AND METHODS: The alarm device is mainly composed of buzzer, indicator light, magnetic sheet. This is a prospective randomized and controlled study. Four hundred patients who met the inclusion/exclusion criteria were included and randomly assigned to two groups (MCD group vs alarm + MCD group). The primary outcome measures were the sensitivity and specificity of the alarm device to detect MCD displacement, time to hemostasis (TTH), time to ambulation (TTA), time to hospital discharge (TTHD), hospital costs (HC), complication rates, and patient satisfaction. RESULTS: The sensitivity and specificity of the alarm device in detecting MCD displacement were 94.44% and 88.46%, respectively. The study group achieved shorter TTH (p = .034), shorter TTA (p = .021), lower complication rates (p = .025), and better patients' satisfaction (p < .001) compared to the control group. However, no significant difference was observed in TTHD (p = .361) and HC (p = .583). CONCLUSION: The alarm device is highly sensitive in detecting MCD displacement, while achieving better clinical outcomes compared with artificial monitoring.

IL-25 or IL-17E Protects against High-Fat Diet-Induced Hepatic Steatosis in Mice Dependent upon IL-13 Activation of STAT6.

IL-25 or IL-17E is a member of IL-17 cytokine family and has immune-modulating activities. The role of IL-25 in maintaining lipid metabolic homeostasis remains unknown. We investigated the effects of exogenous IL-25 or deficiency of IL-25 on hepatic lipid accumulation. IL-25 expression was examined in paraffin-embedded tissue sections of liver from patients or in the livers from mice. Mouse model of steatosis was induced by feeding a high-fat diet (HFD). Extent of steatosis as well as expression of cytokines, key enzymes for lipid metabolic pathways, markers for Kupffer cells/macrophages, and lipid droplet (LD) proteins, were analyzed. Our results show that hepatic steatosis in mice was accompanied by increased LD proteins, but decreased IL-25 in the liver. Decreased hepatic IL-25 was also observed in patients with fatty liver. Administration of IL-25 to HFD-fed wild-type mice led to a significant improvement in hepatic steatosis. This effect was associated with increased expression of IL-13, development of alternatively activated Kupffer cells/macrophages, and decreased expression of LD proteins in the liver. In contrast, administration of IL-25 to HFD-fed mice deficient in STAT6 or IL-13 had no effects. In addition, stimulation of primary hepatocytes with IL-13, but not IL-25, resulted in downregulation of LD proteins. Finally, mice deficient in IL-25 had exacerbated hepatic lipid accumulation when fed the HFD. These data demonstrate that dysregulated IL-25 expression contributes to lipid accumulation, whereas exogenous IL-25 protects against hepatic steatosis through IL-13 activation of STAT6. IL-25 and IL-13 are potential therapeutic agents for hepatic steatosis and associated pathologies.

Interleukin-13 Receptor α1-Dependent Responses in the Intestine Are Critical to Parasite Clearance.

Nematode infection upregulates interleukin-4 (IL-4) and IL-13 and induces STAT6-dependent changes in gut function that promote worm clearance. IL-4 and IL-13 activate the type 2 IL-4 receptor (IL-4R), which contains the IL-13Rα1 and IL-4Rα chains. We used mice deficient in IL-13Rα1 (IL-13Rα1(-/-)) to examine the contribution of IL-13 acting at the type 2 IL-4R to immune and functional responses to primary (Hb1) and secondary (Hb2) infections with the gastrointestinal nematode parasite Heligmosomoides bakeri There were differences between strains in the IL-4 and IL-13 expression responses to Hb1 but not Hb2 infection. Following Hb2 infection, deficient mice had impaired worm expulsion and higher worm fecundity despite normal production of Th2-derived cytokines. The upregulation of IL-25 and IL-13Rα2 in Hb1- and Hb2-infected wild-type (WT) mice was absent in IL-13Rα1(-/-)mice. Goblet cell numbers and resistin-like molecule beta (RELM-ß) expression were attenuated significantly in IL-13Rα1(-/-)mice following Hb2 infections. IL-13Rα1 contributes to the development of alternatively activated macrophages, but the type 1 IL-4R is also important. Hb1 infection had no effects on smooth muscle function or epithelial permeability in either strain, while the enhanced mucosal permeability and changes in smooth muscle function and morphology observed in response to Hb2 infection in WT mice were absent in IL-13Rα1(-/-)mice. Notably, the contribution of claudin-2, which has been linked to IL-13, does not mediate the increased mucosal permeability following Hb2 infection. These results show that activation of IL-13Rα1 is critical for key aspects of the immune and functional responses to Hb2 infection that facilitate expulsion.

Critical Role for Interleukin-25 in Host Protective Th2 Memory Response against Heligmosomoides polygyrus bakeri.

Infection with parasitic nematodes, especially gastrointestinal geohelminths, affects hundreds of millions of people worldwide and thus poses a major risk to global health. The host mechanism of defense against enteric nematode infection remains to be fully understood, but it involves a polarized type 2 immunity leading to alterations in intestinal function that facilitate worm expulsion. We investigated the role of interleukin-25 (IL-25) in host protection against Heligmosomoides polygyrus bakeri infection in mice. Our results showed that Il25 and its receptor subunit, Il17rb, were upregulated during a primary infection and a secondary challenge infection with H. polygyrus bakeri Genetic deletion of IL-25 (IL-25-/-) led to an attenuated type 2 cytokine response and increased worm fecundity in mice with a primary H. polygyrus bakeri infection. In addition, the full spectrum of the host memory response against a secondary infection with H. polygyrus bakeri was severely impaired in IL-25-/- mice, including delayed type 2 cytokine responses, an attenuated functional response of the intestinal smooth muscle and epithelium, diminished intestinal smooth muscle hypertrophy/hyperplasia, and impaired worm expulsion. Furthermore, exogenous administration of IL-25 restored the host protective memory response against H. polygyrus bakeri infection in IL-25-/- mice. These data demonstrate that IL-25 is critical for host protective immunity against H. polygyrus bakeri infection, highlighting its potential application as a therapeutic agent against parasitic nematode infection worldwide.

Type 3 muscarinic receptors contribute to intestinal mucosal homeostasis and clearance of Nippostrongylus brasiliensis through induction of TH2 cytokines.

Despite increased appreciation for the role of nicotinic receptors in the modulation of and response to inflammation, the contribution of muscarinic receptors to mucosal homeostasis, clearance of enteric pathogens, and modulation of immune cell function remains relatively undefined. Uninfected and Nippostrongylus brasiliensis-infected wild-type and type 3 muscarinic receptor (M3R)-deficient (Chrm3(-/-)) mice were studied to determine the contribution of M3R to mucosal homeostasis as well as host defense against the TH2-eliciting enteric nematode N. brasiliensis Intestinal permeability and expression of TH1/TH17 cytokines were increased in uninfected Chrm3(-/-) small intestine. Notably, in Chrm3(-/-) mice infected with N. brasiliensis, small intestinal upregulation of TH2 cytokines was attenuated and nematode clearance was delayed. In Chrm3(-/-) mice, TH2-dependent changes in small intestinal function including smooth muscle hypercontractility, increased epithelial permeability, decreased epithelial secretion and absorption, and goblet cell expansion were absent despite N. brasiliensis infection. These findings identify an important role for M3R in host defense and clearance of N. brasiliensis, and support the expanding role of cholinergic muscarinic receptors in maintaining mucosal homeostasis.

Functional synergism of Human Defensin 5 and Human Defensin 6.

The gut epithelium is critically involved in maintaining intestinal immune homeostasis. Acting as a physical barrier, it separates the intestinal microflora from cells of the immune system. In addition to its barrier function, the intestinal epithelium expresses defensins, natural, endogenous antimicrobial peptides. In humans, specialized epithelial cells, termed Paneth cells, located primarily in the small intestine express two defensins, Human Defensin-5 (HD-5) and Human Defensin-6 (HD-6). Previously, we have shown that HD-5 potently kills bacteria and induces secretion of interleukin-8 by intestinal epithelial cells. We show that HD-6 specifically and synergistically enhances the HD-5-induced IL-8 secretion, but does not alter its anti-bacterial activity. Further, we find that HD-5 decreases the trans-epithelial electrical resistance of intestinal epithelial cells and that HD-6 negates this effect of HD-5.

Enteric nematodes and the path to up-regulation of type 2 cytokines IL-4 and IL-13.

Protective immunity against enteric parasitic nematodes is dependent on IL-4, IL-13 activation of their exclusive transcription factor STAT6. The precise pathways by which enteric parasitic nematodes are recognized by the host is unclear, but elimination of this important interaction in developed nations is thought to contribute to the dysregulated immune responses that are a characteristic of autoimmune diseases. Nematode-derived products are involved in evading host defenses to promote their life cycle leading to modulation of host immune responses. Host protective immunity has adapted to enteric parasitic nematode infection by elaboration of mucins, increasing intraluminal fluid to control access to the surface epithelium, increasing cell turnover to maintain an effective barrier to their invasion, initiating immune responses through activation of resident immune cells, and recruitment of additional immune cells to release immune mediators that help orchestrate these responses. Both the immune and functional outcomes depend largely on IL-4/IL-13 signaling through STAT6, with a dominant role for IL-13 working through the type 2 IL-4 receptor (IL-4R). The recent observation that enteric nematode infection prevents the onset of a number of experimental models of IBD, diabetes, and several extraintestinal autoimmune diseases including multiple sclerosis has generated considerable interest in the identification of worm/egg products involved in the generation and maintenance of Th2 cytokines that may mediate the beneficial effects of nematode infection in autoimmune and inflammatory pathologies.

Dissociation of endotoxin tolerance and differentiation of alternatively activated macrophages.

Endotoxin tolerance is a complex phenomenon characterized primarily by decreased production of proinflammatory cytokines, chemokines, and other inflammatory mediators, whereas the expression of other genes are induced or unchanged. Endotoxin tolerance is induced by prior exposure of murine macrophages/human monocytes, experimental animals, or people to TLR ligands. Although recent studies reported a possible relationship between endotoxin tolerance and differentiation of alternatively activated macrophages (AA-MΦs or M2), we show in this study that LPS pretreatment of IL-4Rα(-/-) and STAT6(-/-) macrophages, which fail to develop into AA-MΦs, resulted in tolerance of proinflammatory cytokines, as well as molecules and chemokines previously associated with AA-MΦs (e.g., arginase-1, mannose receptor, CCL2, CCL17, and CCL22). In contrast to LPS, wild-type (WT) MΦs pretreated with IL-4, the prototype inducer of AA-MΦs, did not induce endotoxin tolerance with respect to proinflammatory cytokines, AA-MΦ-associated chemokines, negative regulators, NF-κB binding and subunit composition, and MAPKs; conversely, IL-13(-/-) macrophages were tolerized equivalently to WT MΦs by LPS pretreatment. Further, IL-4Rα deficiency did not affect the reversal of endotoxin tolerance exerted by the histone deacetylase inhibitor trichostatin A. Like WT mice, 100% of LPS-tolerized IL-4Rα-deficient mice survived LPS + d-galactosamine-induced lethal toxicity and exhibited decreased serum levels of proinflammatory cytokines and AA-MΦ-associated chemokines induced by LPS challenge compared with nontolerized mice. These data indicate that the signaling pathways leading to endotoxin tolerance and differentiation of AA-MΦs are dissociable.

SerpinB2 is critical to Th2 immunity against enteric nematode infection.

SerpinB2, a member of the serine protease inhibitor family, is expressed by macrophages and is significantly upregulated by inflammation. Recent studies implicated a role for SerpinB2 in the control of Th1 and Th2 immune responses, but the mechanisms of these effects are unknown. In this study, we used mice deficient in SerpinB2 (SerpinB2(-/-)) to investigate its role in the host response to the enteric nematode, Heligmosomoides bakeri. Nematode infection induced a STAT6-dependent increase in intestinal SerpinB2 expression. The H. bakeri-induced upregulation of IL-4 and IL-13 expression was attenuated in SerpinB2(-/-) mice coincident with an impaired worm clearance. In addition, lack of SerpinB2 in mice resulted in a loss of the H. bakeri-induced smooth muscle hypercontractility and a significant delay in infection-induced increase in mucosal permeability. Th2 immunity is generally linked to a CCL2-mediated increase in the infiltration of macrophages that develop into the alternatively activated phenotype (M2). In H. bakeri-infected SerpinB2(-/-) mice, there was an impaired infiltration and alternative activation of macrophages accompanied by a decrease in the intestinal CCL2 expression. Studies in macrophages isolated from SerpinB2(-/-) mice showed a reduced CCL2 expression, but normal M2 development, in response to stimulation of Th2 cytokines. These data demonstrate that the immune regulation of SerpinB2 expression plays a critical role in the development of Th2-mediated protective immunity against nematode infection by a mechanism involving CCL2 production and macrophage infiltration.

Nurses' knowledge and attitudes on comfort nursing care for hospitalized patients.

To investigate the knowledge and attitudes of practicing nurses on comfort care for hospitalized patients, a survey was conducted in 311 registered nurses from a major teaching hospital. A total of 212 (68.1%) of the participants showed an adequate knowledge of comfort care. Participants who had 6 years or more working experience returned a higher mean scores on physiological and psychological aspects of comfort care (P < 0.05). The total scores were the highest among participants from intensive care unit and the lowest among participants from the oncology department. Although 282 (90.7%) participants were involved in comfort care, only 210 (67.5%) received formal hospital-based training in this practice. We conclude that there was a large difference in the knowledge between nurses from different departments on comfort care. Continuing education programmes are required to improve the knowledge and skills in comfort care.

Potential mechanism of Chai Gui Zexie Decoction for NSCLC treatment assessed using network pharmacology, bioinformatics, and molecular docking: An observational study.

To explore the potential mechanism of Chai Gui Zexie Decoction for non-small cell lung cancer (NSCLC) treatment using network pharmacology, bioinformatics, and molecular docking. The active ingredients of Chai Gui Zexie Decoction and the associated predicted targets were screened using the TCMSP database. NSCLC-related targets were obtained from GeneCards and OMIM. Potential action targets, which are intersecting drug-predicted targets and disease targets, were obtained from Venny 2.1. The protein-protein interaction network was constructed by importing potential action targets into the STRING database, and the core action targets and core ingredients were obtained via topological analysis. The core action targets were entered into the Metascape database, and Gene Ontology annotation analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed. Differentially expressed genes were screened using the Gene Expression Omnibus, and the key targets were obtained by validating the core action targets. The key targets were input into The Tumor IMmune Estimation Resource for immune cell infiltration analysis. Finally, the molecular docking of key targets and core ingredients was performed. We obtained 60 active ingredients, 251 drug prediction targets, and 2133 NSCLC-related targets. Meanwhile, 147 potential action targets were obtained, and 47 core action targets and 40 core ingredients were obtained via topological analysis. We detected 175 pathways related to NSCLC pharmaceutical therapy. In total, 1249 Gene Ontology items were evaluated. Additionally, 3102 differential genes were screened, and tumor protein P53, Jun proto-oncogene, interleukin-6, and mitogen-activated protein kinase 3 were identified as the key targets. The expression of these key targets in NSCLC was correlated with macrophage, CD4+ T, CD8+ T, dendritic cell, and neutrophil infiltration. The molecular docking results revealed that the core ingredients have a potent affinity for the key targets. Chai Gui Zexie Decoction might exert its therapeutic effect on NSCLC through multiple ingredients, targets, and signaling pathways.

Parasitic nematode-induced modulation of body weight and associated metabolic dysfunction in mouse models of obesity.

Obesity is associated with a chronic low-grade inflammation characterized by increased levels of proinflammatory cytokines that are implicated in disrupted metabolic homeostasis. Parasitic nematode infection induces a polarized Th2 cytokine response and has been explored to treat autoimmune diseases. We investigated the effects of nematode infection against obesity and the associated metabolic dysfunction. Infection of RIP2-Opa1KO mice or C57BL/6 mice fed a high-fat diet (HFD) with Nippostrongylus brasiliensis decreased weight gain and was associated with improved glucose metabolism. Infection of obese mice fed the HFD reduced body weight and adipose tissue mass, ameliorated hepatic steatosis associated with a decreased expression of key lipogenic enzymes/mediators, and improved glucose metabolism, accompanied by changes in the profile of metabolic hormones. The infection resulted in a phenotypic change in adipose tissue macrophages that was characterized by upregulation of alternative activation markers. Interleukin-13 (IL-13) activation of the STAT6 signaling pathway was required for the infection-induced attenuation of steatosis but not for improved glucose metabolism, whereas weight loss was attributed to both IL-13/STAT6-dependent and -independent mechanisms. Parasitic nematode infection has both preventive and therapeutic effects against the development of obesity and associated features of metabolic dysfunction in mice.

IL-33-induced alterations in murine intestinal function and cytokine responses are MyD88, STAT6, and IL-13 dependent.

IL-33 is a recently identified cytokine member of the IL-1 family. The biological activities of IL-33 are associated with promotion of Th2 and inhibition of Th1/Th17 immune responses. Exogenous IL-33 induces a typical "type 2" immune response in the gastrointestinal tract, yet the underlying mechanisms remain to be fully elucidated. In addition, the role of IL-33 in the regulation of gastrointestinal function is not known. The present study investigated IL-33-dependent intestinal immunity and function in mice. Exogenous IL-33 induced a polarized type 2 cytokine response in the intestine that was entirely MyD88 dependent but STAT6 and IL-13 independent. Mice injected with recombinant IL-33 exhibited intestinal smooth muscle hypercontractility, decreased epithelial responses to acetylcholine and glucose, and increased mucosal permeability. IL-33 effects on intestinal epithelial function were STAT6 dependent, and both IL-4 and IL-13 appeared to play a role. The effects on smooth muscle function, however, were attributable to both STAT6-dependent and -independent mechanisms. In addition, IL-13 induction of insulin-like growth factor-1 was implicated in IL-33-induced smooth muscle hypertrophy. Finally, alternative activation of macrophages induced by IL-33 revealed a novel pathway that is IL-4, IL-13, and STAT6 independent. Thus manipulating IL-33 or related signaling pathways represents a potential therapeutic strategy for treating inflammatory diseases associated with dysregulated intestinal function.

Membrane-anchored serine protease matriptase regulates epithelial barrier formation and permeability in the intestine.

The intestinal epithelium serves as a major protective barrier between the mammalian host and the external environment. Here we show that the transmembrane serine protease matriptase plays a pivotol role in the formation and integrity of the intestinal epithelial barrier. St14 hypomorphic mice, which have a 100-fold reduction in intestinal matriptase mRNA levels, display a 35% reduction in intestinal transepithelial electrical resistance (TEER). Matriptase is expressed during intestinal epithelial differentiation and colocalizes with E-cadherin to apical junctional complexes (AJC) in differentiated polarized Caco-2 monolayers. Inhibition of matriptase activity using a specific peptide inhibitor or by knockdown of matriptase by siRNA disrupts the development of TEER in barrier-forming Caco-2 monolayers and increases paracellular permeability to macromolecular FITC-dextran. Loss of matriptase was associated with enhanced expression and incorporation of the permeability-associated, "leaky" tight junction protein claudin-2 at intercellular junctions. Knockdown of claudin-2 enhanced the development of TEER in matriptase-silenced Caco-2 monolayers, suggesting that the reduced barrier integrity was caused, at least in part, by an inability to regulate claudin-2 expression and incorporation into junctions. We find that matriptase enhances the rate of claudin-2 protein turnover, and that this is mediated indirectly through an atypical PKCzeta-dependent signaling pathway. These results support a key role for matriptase in regulating intestinal epithelial barrier competence, and suggest an intriguing link between pericellular serine protease activity and tight junction assembly in polarized epithelia.

Prognostic values of serum tenascin-C in patients with ischaemic heart disease and heart failure.

OBJECTIVE: The aim of this study was to evaluate the prognostic values of serum tenascin-C in patients with heart failure and ischaemic heart disease. METHODS: Serum tenascin-C levels were assessed in 83 patients with heart failure and in 30 healthy subjects. The correlations between serum tenascin-C levels and left ventricular ejection fraction, serum B-type natriuretic peptide and procollagen III were analysed. Patients were followed up for 12 months, and the relations between the serum levels of tenascin-C and cardiac events (re-hospitalisation for worsening heart failure and mortality) were analysed. RESULTS: Serum tenascin-C levels in patients with heart failure were higher than in healthy volunteers (72.24 ± 11.02 vs. 22.78 ± 2.51 µg/L, p<0.01). Serum tenascin-C levels in patients of NYHA class IV were higher than in patients with NYHA class II (88.56 ± 3.73 vs. 64.88 ± 3.15 µg/L, p<0.01). The levels of tenascin-C were negatively correlated with the left ventricular ejection fraction (r=-0.636, p<0.01), but were positively correlated with serum B-type natriuretic peptide (r=0.553, p<0.01) or procollagen III levels (r=0.665, p<0.01). An increased level of tenascin-C was an independent predictor for combined re-hospitalisation and mortality (OR 1.22, 95% CI: 0.86-2.14). CONCLUSION: Serum tenascin-C levels were elevated in patients with heart failure. The levels of tenascin-C were associated with the severity of left ventricular dysfunction and 12-month major adverse cardiac events.

Spatio-temporal variations and drought of spring maize in Northeast China between 2002 and 2020.

A lot of spring maize is grown in Northeast China (Liaoning, Jilin, and Heilongjiang), an area that is highly susceptible to drought. Here, remote sensing indexes from 2002 to 2020 were studied using the 8-day surface reflectance and land surface temperature of Moderate-resolution Imaging Spectroradiometer data. Spring maize distribution was extracted using a decision tree classification, and the results were compared to the known distribution based on field investigation data and published statistics. The results showed that mixed pixels of spring maize and soybeans had limited influence on the study of spatio-temporal variations of spring maize, and the error was acceptable. The overall accuracy of verifying the spring maize distribution from 2018 to 2020 was above 85%. The stable, fluctuating, and low-frequency planting areas of spring maize accounted for 11.86%, 17.41%, and 34.86% of the study area, respectively. In 2015, the government directed a reduction of the planting area of spring maize in the "Liandaowan" region of Northeast China. The planting area of spring maize was characterized by a continuous increase before this change (2002-2014), exhibited changes and reductions in response to the change (2015-2017), and exhibited optimization and recovery after this change (2018-2020). Compared with the fluctuating and low-frequency planting areas, moderate and severe droughts were higher in stable planting areas. From 2002 to 2020, the most severe droughts occurred in the expanded planting areas. This rapid and large-scale monitoring of spatio-temporal variations and drought of spring maize provides a foundation for improving grain yield. This method could be easily applied to the study of other regions and combined with high-resolution and hyperspectral satellite data to improve monitoring accuracy.

[Systematic Evaluation of Low-carbon Operation of Typical A2O Processes in Municipal Sewage Plant].

Under the "Carbon Peak, Carbon Neutral" goal, the systematic evaluation of the carbon emission equivalent (CO2eq) and its compositions of the typical A2O process has important guiding significance for the low-carbon operation of most municipal sewage plants in China. Based on the operational data on the first municipal sewage plant of Jiaozuo in 2020 and the methods presented in "2019 Refinement to the 2006 IPCC Guidelines for National Greenhouse Gas Inventories, " a systematic evaluation of the CO2eq of the typical A2O process was established, including direct emissions that were built on the Arrhenius model introducing the water temperature factor and indirect emissions from the three aspects of electricity consumption, agent addition, and sludge transportation. The results showed that the daily emission intensities of CH4 and N2O were (115±56) kg·d-1 and (30±18) kg·d-1, respectively. Additionally, indirect carbon emissions from electricity consumption and agent addition accounted for 48.4% and 51.3% in the biochemical treatment section, respectively. In 2020, CO2eq amounts of total research plant and per unit sewage were 2.17×104 t and (0.63±0.07) kg·m-3, respectively. The magnitude of the proportion of different carbon emission compositions was as follows:sewage electricity (36.5%)>sewage agent (26.6%)>N2O direct (15.4%)>sludge agent (9.6%)>sludge electricity (6.7%)>CH4 direct (4.9%)>sludge transportation (0.3%). System import/export fluxes of carbon and nitrogen elements were calculated, followed by the carbon to nitrogen mass ratio in the sewage plant. Direct carbon emission characteristics of CH4 and N2O and their influencing factors were discussed, respectively. Based on the balance theory of carbon and nitrogen elements in the system, it is proposed that the selective introduction of industrial wastewater may become an important reference measure for the low-carbon operation of municipal sewage plants in the future.

[Factors Affecting Nitrate Concentrations and Nitrogen and Oxygen Isotope Values of Effluents from Waste Water Treatment Plant].

Urban domestic sewage is one of the important nitrate (NO-3) sources for surface water; however, their NO-3 concentrations and nitrogen and oxygen isotope values (δ15N-NO-3 and δ18O-NO-3) remain unclear, and the factors affecting NO-3 concentrations and δ15N-NO-3 and δ18O-NO-3 values of effluents in the waste water treatment plant (WWTP) are still unknown. Water samples in the Jiaozuo WWTP were collected to illustrate this question. Influents, clarified water in the secondary sedimentation tank (SST), and effluents of the WWTP were sampled every 8 h. The ammonia (NH+4) concentrations, NO-3 concentrations, and δ15N-NO-3 and δ18O-NO-3 values were analyzed to elucidate the nitrogen transfers through different treatment sections and illustrate the factors affecting the effluent NO-3 concentrations and isotope ratios. The results indicated that ① the mean NH+4 concentration was (22.86±2.16) mg·L-1 in the influent and decreased to (3.78±1.98) mg·L-1 in the SST and continuously reduced to (2.70±1.98) mg·L-1 in the effluent of the WWTP. The median NO-3 concentration was 0.62 mg·L-1 in the influent, and the average NO-3 concentration increased to (33.48±3.10) mg·L-1 in the SST and gradually increased to (37.20±4.34) mg·L-1 in the effluent of the WWTP. ② The mean values of δ15N-NO-3 and δ18O-NO-3 were (17.1±10.7)‰ and (19.2±2.2)‰ in the influent of the WWTP, the median values of δ15N-NO-3 and δ18O-NO-3 were 11.9‰ and 6.4‰ in the SST, and the average values were (12.6±1.9)‰ and (5.7±0.8)‰ in the effluent of the WWTP. ③ The NH+4 concentrations of influent had significant differences compared to those in the SST and the effluent (P<0.05). The reduction of NH+4 concentrations in the SST was due to the above nitrification during the aerobic treatment process, which transferred NH+4 to NO-3. The NH+4 concentrations in the SST had no significant differences with that in the effluent of the WWTP (P>0.05). ④ The NO-3 concentrations in the influent had significant differences with those in the SST and the effluent (P<0.05), and minor NO-3 concentrations but relatively high δ15N-NO-3 and δ18O-NO-3 values in the influent were probably due to denitrification during the pipe sewage transportation. The obviously increased NO-3 concentrations (P<0.05) but decreased δ18O-NO-3 values (P<0.05) in the SST and the effluent resulted from water oxygen incorporation during the nitrification. The above results confirmed the impacts of aerobic and anaerobic treatment processes on NO-3 concentrations and isotope ratios of effluent from the WWTP and provided scientific basis for the identification of sewage contributions to surface water nitrate via average δ15N-NO-3 and δ18O-NO-3 values.