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Long non-coding RNAs (lncRNAs) have been implicated in cancer progression and drug resistance development. Moreover, there is evidence that lncRNA HOX transcript antisense intergenic RNA (HOTAIR) is involved in colorectal cancer (CRC) progression. The present study aimed to examine the functional role of lncRNA HOTAIR in conferring radiotherapy resistance in CRC cells, as well as the underlying mechanism. The relative expression levels of HOTAIR were examined in 70 pairs of CRC tumor and para-cancerous tissues, as well as in radiosensitive and radioresistant samples. The correlations between HOTAIR expression levels and clinical features of patients with CRC were assessed using the Chi-square test. Functional assays such as cell proliferation, colony formation and apoptosis assays were conducted to determine the radiosensitivity in CRC cells with HOTAIR silencing after treatment with different doses of radiation. RNA pull-down assay and fluorescence in situ hybridization (FISH) were used to determine the interaction between HOTAIR and DNA damage response mediator ataxia-telangiectasia mutated- and Rad3-related (ATR). HOTAIR was significantly upregulated in CRC tumor tissues, especially in radioresistant tumor samples. The elevated expression of HOTAIR was correlated with more advanced histological grades, distance metastasis and the poor prognosis in patients with CRC. Silencing HOTAIR suppressed the proliferation and promoted apoptosis and radiosensitivity in CRC cells. HOTAIR knockdown also inhibited the tumorigenesis of CRC cells and enhanced the sensitivity to radiotherapy in a mouse xenograft model. Moreover, the data showed that HOTAIR could interact with ATR to regulate the DNA damage repair signaling pathway. Silencing HOTAIR impaired the ATR-ATR interacting protein (ATRIP) complex and signaling in cell cycle progression. Collectively, the present results indicate that lncRNA HOTAIR facilitates the DNA damage response pathway and promotes radioresistance in CRC cells by targeting ATR.
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Proteínas Mutadas de Ataxia Telangiectasia , Proliferação de Células , Neoplasias Colorretais , Dano ao DNA , Reparo do DNA , RNA Longo não Codificante , Tolerância a Radiação , RNA Longo não Codificante/genética , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Tolerância a Radiação/genética , Animais , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Camundongos , Proliferação de Células/genética , Apoptose/genética , Linhagem Celular Tumoral , Feminino , Masculino , Regulação Neoplásica da Expressão Gênica , Prognóstico , Pessoa de Meia-Idade , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos NusRESUMO
In this paper, a multi-strategy fusion enhanced Honey Badger algorithm (EHBA) is proposed to address the problem of easy convergence to local optima and difficulty in achieving fast convergence in the Honey Badger algorithm (HBA). The adoption of a dynamic opposite learning strategy broadens the search area of the population, enhances global search ability, and improves population diversity. In the honey harvesting stage of the honey badger (development), differential mutation strategies are combined, selectively introducing local quantum search strategies that enhance local search capabilities and improve population optimization accuracy, or introducing dynamic Laplacian crossover operators that can improve convergence speed, while reducing the odds of the HBA sinking into local optima. Through comparative experiments with other algorithms on the CEC2017, CEC2020, and CEC2022 test sets, and three engineering examples, EHBA has been verified to have good solving performance. From the comparative analysis of convergence graphs, box plots, and algorithm performance tests, it can be seen that compared with the other eight algorithms, EHBA has better results, significantly improving its optimization ability and convergence speed, and has good application prospects in the field of optimization problems.
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Functionalization of MoS2was achieved by treatment in a strongly reducing sodium naphthalene solution. Dodecyl was grafted onto MoS2nanosheets using alkyl sulphates as electrophiles to obtain dodecylated MoS2without affecting the MoS2crystalline structure. Superior electrocatalytic properties are obtained for dodecylated MoS2. The polarisation curve of this nanomaterial remained constant even after 1000 consecutive cycles. This route provides a new pathway for covalent functionalization of MoS2and might find a variety of applications, such as electrocatalysts.
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Even though the existing studies have extensively investigated the impacts of information and communication technology and social capital on sustainable development, the literature overlooks the role of their interaction effect in the level of emissions. To fill this gap in the existing body of ICT-environment literature, this article analyzes the impact of ICT, social capital, terrorism, and income on sustainable development using panel data model for Asian and Middle East countries from 2005 to 2022. The findings show that ICT and education significantly reduce CO2 emissions, while income increases the CO2 emissions. Moreover, innovation, trade, and financial development reduce the CO2 emission from increased ICT. The findings suggest that ICT is an important factor in increasing income and social capital and improving investment in sustainable development. The region's economies have far more serious consequences for internet users than those of Asian countries. Nonetheless, according to the policy recommendations of this study, governments in Asia and the Middle East should invest more in technology and other systems to take advantage of technology and achieve sustainable development.
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Capital Social , Terrorismo , Dióxido de Carbono , Desenvolvimento Econômico , Comunicação , TecnologiaRESUMO
Wildfires affect forest succession and restoration by changing the community structure of soil microorganisms. Mycorrhizal formation is essential for plant growth and development. However, the driving mechanism of their natural succession after wildfire is still unclear. In this study, we examined the community structure of soil bacteria and fungi along a time series of natural recovery after wildfires in the Greater Khingan Range of China (2020 fires, 2017 fires, 2012 fires, 2004 fires, 1991 fires, and unburned). By exploring the effects of wildfire on plant traits, fruit nutrition, colonization of mycorrhizal fungi and its influencing mechanism. The results show that natural succession after wildfires significantly changed the community composition of bacteria and fungi, with ß diversity having a greater impact but less impact on the α diversity of microorganisms. Wildfires significantly changed plant traits and fruit nutrient content. The changes in colonization rate and customization intensity of mycorrhizal fungi were caused by increased MDA content and soluble sugar content and increased MADS-box gene and DREB1 gene expression in lingonberry (Vaccinium vitis-idaea L.). Our results showed that the soil bacterial and fungal communities in the boreal forest ecosystem changed significantly during wildfire recovery and changed the colonization rate of lingonberry mycorrhizal fungi. This study provides a theoretical basis for the restoration of forest ecosystems after wildfires.
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Incêndios , Micorrizas , Incêndios Florestais , Ecossistema , Solo/química , Florestas , China , Bactérias/genética , FungosRESUMO
Using a murine collagen-induced arthritis model, we characterized the heterogeneity of synovial CD8+ T cells based on the expression of chemokine receptors, cytokines, and nuclear transcription factors. Four subsets, i.e. CXCR3-CCR4- cells, CXCR3+CCR4- cells, CXCR3+CCR4+ cells, and CXCR3-CCR4+ cells, were present in synovial CD8+CD62L-CCR6+IL-23R+CCR10- T cells. CXCR3-CCR4- cells belonged to exhausted CD8+ T cells. CXCR3+CCR4- cells were Tc17.1 cells expressing both IL-17A and IFN-γ. CXCR3+CCR4+ cells were transitional Tc17.1 cells expressing IL-17A but lower IFN-γ, and CXCR3-CCR4+ cells were Tc17 cells expressing IL-17A but no IFN-γ. Transitional Tc17.1 cells can differentiate into Tc17.1 cells in vitro under the instruction of IL-12. Tc17.1 cells and transitional Tc17.1 cells strongly induced the expression of pro-inflammatory mediators in synovial fibroblasts, whereas Tc17 cells were less potent in doing so. IFN-γ was involved in the higher pathogenicity of Tc17.1 cells and transitional Tc17.1 cells on synovial fibroblasts. This study expands the understanding of Tc17 biology by unveiling the phenotypic and functional heterogeneity of synovial IL-17A-expressing CD8+ T cells. These heterogeneous IL-17A-expressing CD8+ T cells could be novel therapeutic targets in future arthritis treatment.
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Artrite Experimental , Linfócitos T CD8-Positivos , Interleucina-17 , Membrana Sinovial , Células Th17 , Animais , Camundongos , Artrite Experimental/imunologia , Artrite Experimental/patologia , Linfócitos T CD8-Positivos/imunologia , Interleucina-17/metabolismo , Membrana Sinovial/imunologia , Células Th17/imunologiaRESUMO
In recent years, many online communities have launched opinion-gathering activities to promote user participation in innovation and improve the quality of new products. The current methods for online innovation activities can be divided into two categories: cognitive guidance and affective guidance. However, the studies on online communities have mainly focused on user engagement motivations, and little attention has been paid to investigating the impact and underlying mechanism of innovation guidance on user participation at the linguistic level. This study first collected secondary data from NetEase.com and conducted an econometric model to explore the impact of cognitive guidance and affective guidance on users' participation in online innovation activities. Subsequently, we investigated the impact mechanism of different innovation guidance methods on user participation through two experiments, here by drawing on mental simulation theory. The experimental results showed that outcome simulation and process simulation imposed a dual mediating effect of innovation guidance on user participation. In addition, we also found that product types moderate the dual mediating effect of outcome simulation and process simulation. The findings can deepen and expand the research on user participation while providing practical implications for companies and platforms as they attempt to promote user participation in innovation activities.
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As an anti-inflammatory strategy, MAPK-activated protein kinase-2 (MK2) inhibition can potentially avoid the clinical failures seen for direct p38 inhibitors, especially tachyphylaxis. CC-99677, a selective targeted covalent MK2 inhibitor, employs a rare chloropyrimidine that bonds to the sulfur of cysteine 140 in the ATP binding site via a nucleophilic aromatic substitutions (SNAr) mechanism. This irreversible mechanism translates biochemical potency to cells shown by potent inhibition of heat shock protein 27 (HSP27) phosphorylation in LPS-activated monocytic THP-1 cells. The cytokine inhibitory profile of CC-99677 differentiates it from known p38 inhibitors, potentially suppressing a p38 pathway inflammatory response while avoiding tachyphylaxis. Dosed orally, CC-99677 is efficacious in a rat model of ankylosing spondylitis. Single doses, 3 to 400 mg, in healthy human volunteers show linear pharmacokinetics and apparent sustained tumor necrosis factor-α inhibition, with a favorable safety profile. These results support further development of CC-99677 for autoimmune diseases like ankylosing spondylitis.
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Doenças Autoimunes , Espondilite Anquilosante , Trifosfato de Adenosina , Animais , Anti-Inflamatórios , Doenças Autoimunes/tratamento farmacológico , Cisteína , Proteínas de Choque Térmico HSP27/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Lipopolissacarídeos , Proteínas Serina-Treonina Quinases , Ratos , Enxofre , Fator de Necrose Tumoral alfa , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Forest fuels are the basis of fire occurrences, while ground dead fuels are an important part of forest fuels. Undestanding the pyrolysis characteristics and gas emissions of forest fuels is of great significance to explore the effects of forest fire on atmospheric environment and carbon balance, as well as to prevent and combat forest fire. In this study, the thermogravimetric analysis and gas emission analysis were conducted on leaf litter of six tree species (Pinus sylvestris var. mongolica, Picea koraiensis, Fraxinus mandshurica, Juglans mandshurica, Quercus mongolica, Betula platyphylla) in Heilongjiang Province to explore the pyrolysis process and combustibility of forest fuels, to analyze their pyrolysis characteristics, pyrolysis kinetics characteristics, gas emission characteristics. A four-dimensional evaluation of their combustibility was conducted based on pyrolysis parameters. The results showed that the pyrolysis temperature of holocellulose in the leaves of those six tree species ranged in 143.31-180.48 â at the beginning and 345.04-394.38 â at the end, lignin pyrolysis temperature ranged in 345.04-394.38 â at the beginning and 582.85-609.31 â at the end. The pyrolysis of the six kinds of arbor blades during the pyrolysis process affected fuel ash content, quality and temperature of the total pyrolysis. The activation energies of two main pyrolysis stages of leaves of six tree species were 18.88-27.08 kJ·mol-1 and 13.25-27.54 kJ·mol-1, respectively, and the pre-exponential factors were 3.13-26.28 min-1 and 1.30-22.55 min-1. The holocellulose activation energy and pre-exponential factor of the pyrolysis stage for P. koraiensis, F. mandshurica, Q. mongolica, and B. platyphylla were greater than that of the lignin pyrolysis stage, while the opposite was true for P. sylvestris var. mongolica and J. mandshurica. The release amounts of CO and CO2 at the pyrolysis stage of the holocellulose was 535.16-880.11 mg·m-3 and 7004.97-10302.05 mg·m-3, and that at the pyrolysis stage of lignin was 240.31-1104.67 mg·m-3 and 20425.60-33946.68 mg·m-3, respectively. The release of CO and CO2 at the pyrolysis stage of healdellulose was less, but mass loss was greater than that at the pyrolysis stage of lignin. In the four-dimensional combustibility ranking of the six tree species leaves, B. platyphylla was the best ignitable, P. koraiensis was the most combustible, and P. sylvestris var. mongolica was the most sustainable and consumable. The ignitability was significantly positively correlated with pyrolysis kinetics parameters of the holocellulose, while the sustainability was negatively correlated with that of lignin.
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Pinus , Árvores , China , Florestas , PiróliseRESUMO
We report the first case of a woman with Behcet's disease (BD) with multiple hand ulcers secondary to coninfection by Eikenella corrodens and Staphylococcus aureus resulting in necrotizing fasciitis. She had a long history of BD including long courses of prednisone and immunosuppressants. The patient was hospitalized for multiple superficial ulcers, swelling, and infection of the hands. After admission, pus culture examination revealed rare coinfection by E. corrodens and S. aureus. We administered moxifloxacin and vancomycin to control infection and methylprednisolone to control BD. We performed incision, drainage, and debridement of the ulcer surface on the hands to reduce the pus on the wound surface. E. corrodens infections occur in immunosuppressed patients and contribute to coinfections, particularly in patients with BD in whom destruction of the skin immune barrier increases risk to secondary infections. For severe and complicated hand infections, efforts should be made to identify pathogenic microorganisms so appropriate antibiotics and other interventions can be given to control the infection.
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Síndrome de Behçet , Coinfecção , Infecções por Bactérias Gram-Negativas , Síndrome de Behçet/complicações , Síndrome de Behçet/tratamento farmacológico , Eikenella corrodens , Feminino , Humanos , Staphylococcus aureusRESUMO
Retinoic acid receptor-related orphan nuclear receptor (ROR) γt is a member of the RORC nuclear hormone receptor family of transcription factors. RORγt functions as a critical regulator of thymopoiesis and immune responses. RORγt is expressed in multiple immune cell populations including Th17 cells, where its primary function is regulation of immune responses to bacteria and fungi through IL-17A production. However, excessive IL-17A production has been linked to numerous autoimmune diseases. Moreover, Th17 cells have been shown to elicit both pro- and anti-tumor effects. Thus, modulation of the RORγt/IL-17A axis may represent an attractive therapeutic target for the treatment of autoimmune disorders and some cancers. Herein we report the design, synthesis and characterization of three selective allosteric RORγt inhibitors in preclinical models of inflammation and tumor growth. We demonstrate that these compounds can inhibit Th17 differentiation and maintenance in vitro and Th17-dependent inflammation and associated gene expression in vivo, in a dose-dependent manner. Finally, RORγt inhibitors were assessed for efficacy against tumor formation. While, RORγt inhibitors were shown to inhibit tumor formation in pancreatic ductal adenocarcinoma (PDAC) organoids in vitro and modulate RORγt target genes in vivo, this activity was not sufficient to delay tumor volume in a KP/C human tumor mouse model of pancreatic cancer.
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Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/antagonistas & inibidores , Células Th17/efeitos dos fármacos , Animais , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Inflamação/metabolismo , Interleucina-17/metabolismo , Camundongos , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Células Th17/metabolismoRESUMO
Owing to economics are usually linked with energy production, economic policy may have an instantaneous adjustment according to the current monetary, financial, cultural circumstances. This research thus investigates the dynamic co-movement as well as cointegration relationships between economic policy uncertainty (EPU) and disparate energy productions, i.e., Chinese coal, natural gas, crude oil, electricity as well as renewable energy, during the period from January 1995 to October 2019 in China. We compare the two EPU indices and make empirical and robust analysis to get more evidence for the time-varying co-movement between energy production and EPU. The empirical results show that there are stationary properties and cointegration relationships between energy production and EPU. By utilizing wavelet co-movement analysis in the time-frequency domain, our results show a significant positive co-movement among disparate energy productions and EPU at high frequencies, i.e., in the short term, but weaker co-movement at low frequencies, i.e., in the long term. Hence, the phase-difference series are mostly around the zero line, implying the variables behave to the dynamics of the co-movement with positive causality. Policy recommendations are offered in accordance with our finding.
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Desenvolvimento Econômico , Energia Renovável , Dióxido de Carbono/análise , China , Gás Natural , IncertezaRESUMO
An increase in liver gluconeogenesis is an important pathological phenomenon in type 2 diabetes mellitus (T2DM) and oxymatrine is an effective natural drug used for T2DM treatment. The present study aimed to explore the effect of oxymatrine on gluconeogenesis and elucidate the underlying mechanism. Male Sprague-Dawley rats were treated with a high-fat diet and streptozotocin for 4 weeks to induce T2DM, and HepG2 cells were treated with 55 mM glucose to simulate T2DM in vitro. T2DM rats were treated with oxymatrine (10 or 20 mg/kg weight) or metformin for 4 weeks, and HepG2 cells were treated with oxymatrine (0.1 or 1 µM), metformin (0.1 µM), or oxymatrine combined with MK-2206 (AKT inhibitor) for 24 h. Fasting blood glucose and insulin sensitivity of rats were measured to evaluate insulin resistance. Glucose production and uptake ability were measured to evaluate gluconeogenesis in HepG2 cells, and the expression of related genes was detected to explore the molecular mechanism. Additionally, the body weight, liver weight and liver index were measured and hematoxylin and eosin staining was performed to evaluate the effects of the disease. The fasting glucose levels of T2DM rats was 16.5 mmol/l, whereas in the control rats, it was 6.1 mmol/l. Decreased insulin sensitivity (K-value, 0.2), body weight loss (weight, 300 g), liver weight gain, liver index increase (value, 48) and morphological changes were observed in T2DM rats, accompanied by reduced AKT phosphorylation, and upregulated expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). High-glucose treatment significantly increased glucose production and decreased glucose uptake in HepG2 cells, concomitant with a decrease in AKT phosphorylation and increase of PEPCK and G6Pase expression. In vivo, oxymatrine dose-dependently increased the sensitivity of T2DM rats to insulin, increased AKT phosphorylation and decreased PEPCK and G6Pase expression in the liver, and reversed the liver morphological changes. In vitro, oxymatrine dose-dependently increased AKT phosphorylation and glucose uptake of HepG2 cells subjected to high-glucose treatment, which was accompanied by inhibition of the expression of the gluconeogenesis-related genes, PEPCK and G6Pase. MK-2206 significantly inhibited the protective effects of oxymatrine in high-glucose-treated cells. These data indicated that oxymatrine can effectively prevent insulin resistance and gluconeogenesis, and its mechanism may be at least partly associated with the regulation of PEPCK and G6Pase expression and AKT phosphorylation in the liver.
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We summarized research progress of forest fire occurrence prediction model in China based on the literature review, from the prospects of forest fire drivers, models of forest fire occurrence probability, models of forest fire occurrence frequency and model validation methods. The main conclusions are: 1) Meteorology, terrain, vegetation, fuel and human activities were the main driving factors of forest fire occurrence and model prediction accuracy. 2) In the models of forest fire occurrence probability, the geographically weighted logistic regression model considered the spatial correlation between model variables, the Gompit regression model could fit the asymmetric structure fire data. The random forest algorithm had a high prediction accuracy without the requirement of multicollinearity test and excessive fitting, which made it as one of the optimal methods of forest fire occurrence probability prediction. 3) Among all the forest fire occurrence frequency models, the negative binomial regression model was suitable for fitting the over discrete data, the zero-inflated model and hurdle model could deal with fire data that contained a large number of zeros. 4) ROC test, AIC test, likelihood ratio test, and Wald test were the most common methods for evaluating the accuracy of fire occurrence probability and frequency models. The study of forest fire occurrence prediction model should be the main focus of the forest fire management. Model selection should base on fire data structure of different forests. More influencing factors should be taken into account to improve the prediction accuracy of model. In addition, it was necessary to further explore the application of other mathematical methods in forest fire prediction, to improve the accuracy of the models.
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Incêndios Florestais , China , Humanos , Modelos Logísticos , Meteorologia , Modelos EstatísticosRESUMO
Given the global spread of coronavirus disease (COVID-19), strict discharge standard is of great significance for the prevention and control of the epidemic, thus, the purpose of this study is to formulate more strict and scientific discharge standards. A total of 845 patients with mild and general COVID-19 who were considered to be discharged from hospital were included in this study. The median time from the onset of COVID-19 to the occurrence of two consecutive negative nucleic acid tests of these patients was 21 days. 223 of the 845 patients were tested again after two consecutive negative nucleic acid tests and 17.49% of the patients were positive. Moreover, 82.51% (184 of 223) of these patients experienced negative results from three consecutive nucleic acid tests, the median time from the onset of COVID-19 to the occurrence of three consecutive negative nucleic acid tests was 23 days (range: 3-56 days), and 38 of which were further tested after three consecutive negative nucleic acid tests, while about 5.26% (2 of 38) patients showed positive nucleic acid test results. Thus, we suggested that the patient should be negative for at least 3 consecutive nucleic acid tests before discharge, and the test time should be no earlier than the 23rd day since the onset of the disease.
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Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Alta do Paciente , Pneumonia Viral/diagnóstico , RNA Viral/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Teste para COVID-19 , Criança , China/epidemiologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Adulto JovemRESUMO
Hexagonal boron nitride is well known for its unique structure and excellent physical properties, particularly in hexagonal boron nitride nanosheets (BNNSs) with high potential in multiple technological applications. However, its severe layer-by-layer aggregation and incompatibility with processing liquids or condensed phase materials pose a great challenge. Covalent functionalization of BNNSs has been a common approach to address these critical issues, yet it is extremely difficult to carry out due to the chemical inertness of BNNSs. In this study, we report a novel and general route to covalently functionalize BNNSs via a simple reduction reaction. This involves initial negative charging through effective reductive activation which enables subsequent reactions with various organic alkyl halides. Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA) results confirm that linear alkyl chains with varying lengths are successfully grafted onto BNNSs, which leads to matched compatibility with organic media and the exfoliation level of few-layer thickness. The increase of the alkyl chain length considerably promotes their solubility in organic solvents with iodoalkanes as the most efficient grafting agents. Incorporation of alkylated BNNSs into a polymer matrix at low filler loadings leads to significant enhancements in mechanical properties over neat polymers, suggesting their exceptional reinforcement for polymer nanocomposites. This facile and scalable reductive chemistry route is applicable to versatile chemical modifications of BNNSs with diverse functional groups and grafting agents by reactions with suitable electrophiles.
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This paper investigates the long-run cointegration relationship between shale gas production and natural gas prices during the period from January 2007 to December 2016 for 16 states in the U.S., by utilizing the Generalized Least Squares (GLS) based univariate unit root test, the PANICCA panel unit root test, the cointegration tests of Gregory and Hansen (1996), Westerlund and Edgerton (2008) as well as Banerjee and Carrión-i-Silvestre (2015) tests with structural breaks. The empirical finding shows that the mean-reverting property exists in both variables, and most structural breaks emerge around 2007-2009 and 2011-2014, during the period when shale gas production sharply increased, the global financial crisis erupted, and external energy shocks emerged. We also find a strong cointegrated relationship, denoting a long-run equilibrium property appears among the variables. Overall, we demonstrate an interaction nexus between price and production variables and put forward some vital implications for authorities and gas market participants.
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BACKGROUND: We investigated the efficacy of esomeprazole for the treatment of gastroesophageal reflux disease (GERD) in a meta-analysis of clinical trials results. METHODS: Medline, Embase, PubMed and Web of Science databases were systematically searched for suitable studies, and double-blind, randomized controlled trials (RCTs) were involved. A meta-analysis of RCTs was performed to analyze the efficacy of esomeprazole on clinical outcomes that associated with the severity of GERD. RESULTS: A total of 8 clinical trials were selected in our meta-analysis (N=4495, patients with GERD). Esomeprazole treatment yielded a significant improvement in clinical signs and symptoms of GERD compared to placebo group. Funnel plot and Egger test showed there was no significant bias in the publication. Cochrane collaboration tool and Jadad scale were used to indicate that all 8 RCTs were of high quality. The results of Galbraith radial plot showed that no study was the major source of heterogeneity. Esomeprazole treatment significantly decreased the relapse rates more than that of placebo group (RR = 0.729; 95% CI: 0.670 to 0.794; P<0.001). It seems to be lower rates of heartburn (RR = 0.747; 95%CI: 0.665-0.839; P <0.001) and epigastric pain (RR = 0.795; 95%CI: 0.679-0.932; P =0.005) in esomeprazole-treated group compared with the placebo group. Moreover, serious adverse events was less likely to happen after esomeprazole therapy (RR = 1.406, 95% CI: 1.030-1.918; P =0.032). CONCLUSION: Compared with the control group, esomeprazole is a promising therapeutic agent that improves the management of patients with GERD.