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Alfvén wave instabilities in a reacting tokamak plasma are calculated both analytically and numerically. Two distinct classes of eigenmodes are considered, global Alfvén eigenmodes and kinetic Alfvén waves, each driven unstable by the free energy associated with the alpha particle density gradient. The growth rates of the global Alfvén eigenmodes are given for the first time. These are basically magnetohydrodynamic (MHD) modes, whose resonances with electrons and alpha particles are calculated using kinetic theory. The calculation of kinetic Alfvén wave growth rates is improved from earlier treatments. These modes depend on electron inertia and finite ion gyroradius for their existence and have no counterpart in MHD theory. In both sets of calculations toroidal coupling of the alpha particle response to sidebands in the poloidal mode number is fully taken into account. Global modes with small parallel phase velocity are identified as the most dangerous, both because of their substantial growth rates and the expected ineffectiveness of quasilinear stabilization. The kinetic waves, on the other hand, are likely to be stabilized easily by quasilinear flattening of the alpha particle profile. Calculations using both Maxwellian and slowing-down alpha distributions are performed, showing that, for the same alpha density and energy density, the slowing-down distribution yields somewhat larger growth rates. [ABSTRACT FROM AUTHOR]

This study aims to explore the mechanism of Dabugan Decoction in the treatment of generalized anxiety disorder(GAD) based on network pharmacology, molecular docking, and animal experiments. Network pharmacology and molecular docking technology were used to obtain the possible targets and related signaling pathways of Dabugan Decoction in the treatment of GAD. The GAD rat model was established, and the corresponding drugs were given by gavage after randomization. After 28 days of continuous intervention, the anxiety state of rats was detected, and the pathological changes of the hippocampus were detected in each group. ELISA and Western blot were used to detect the protein expression levels of related molecules. A total of 65 drug compounds in Dabugan Decoction were obtained, involving 403 targets of action, 7 398 disease targets of GAD, and 279 common targets of "drug-disease". The key nodes in the protein-protein interaction(PPI) network were Akt1, TNF, IL-6, TP53, IL-1β, etc. Function analysis of Gene Ontology(GO) and enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG) showed that the PI3K-Akt signaling pathway was the most important pathway. The results of molecular docking showed that the core components of the drug had good binding activity with the corresponding key targets. Animal experiments showed that Dabugan Decoction could effectively improve the anxiety behavior of rats and increase the open arm end movement distance and total distance of rats in the elevated cross labyrinth, the number and stay time of entering the open box, and the time(%) and the number of entering the center of the open field. At the same time, HE staining and Nicil staining showed that the number of hippocampal nerve cells in rats increased, and they were closely arranged. The damage to the cell body was improved, and there was an increase in Nissl substances in the cells. The expression of TNF-α, IL-6, and IL-1β in rat hippocampus decreased, and the expression of TP53, p-Akt1, and p-PI3K increased. The mechanism may be related to the activation of the PI3K-Akt signaling pathway and the inhibition of inflammatory response. Dabugan Decoction can play a good therapeutic and regulatory role in GAD, reflecting the overall effect of traditional Chinese medicine(TCM) compound and the characteristics of multiple targets and multiple pathways. At the same time, it is preliminarily discussed that the state of GAD may be improved by Dabugan Decoction via-activating PI3K-Akt signaling pathway and inhibiting inflammatory response and anti-apoptosis, thus providing experimental data support for the clinical application of Dabugan Decoction.

Objective To explore the effect of microRNA-22-3p (miR-22-3p) regulating the expression of Kruppel-like factor 6 (KLF6) on the cardiomyocyte-like differentiation of bone marrow mesenchymal stem cell (BMSC). Methods Rat BMSC was isolated and cultured,and the third-generation BMSC was divided into a control group,a 5-azacytidine(5-AZA)group,a mimics-NC group,a miR-22-3p mimics group,a miR-22-3p mimics+pcDNA group,and a miR-22-3p mimics+pcDNA-KLF6 group.Real-time fluorescent quantitative PCR (qRT-PCR) was carried out to determine the expression of miR-22-3p and KLF6 in cells.Immunofluorescence staining was employed to detect the expression of Desmin,cardiac troponin T (cTnT),and connexin 43 (Cx43).Western blotting was employed to determine the protein levels of cTnT,Cx43,Desmin,and KLF6,and flow cytometry to detect the apoptosis of BMSC.The targeting relationship between miR-22-3p and KLF6 was analyzed by dual luciferase reporter gene assay. Results Compared with the control group,5-AZA up-regulated the expression of miR-22-3p ( q =7.971, P <0.001),Desmin ( q =7.876, P <0.001),cTnT ( q =10.272, P <0.001),and Cx43 ( q =6.256, P <0.001),increased the apoptosis rate of BMSC ( q =12.708, P <0.001),and down-regulated the mRNA ( q =20.850, P <0.001) and protein ( q =11.080, P <0.001) levels of KLF6.Compared with the 5-AZA group and the mimics-NC group,miR-22-3p mimics up-regulated the expression of miR-22-3p ( q =3.591, P <0.001; q =11.650, P <0.001),Desmin ( q =5.975, P <0.001; q =13.579, P <0.001),cTnT ( q =7.133, P <0.001; q =17.548, P <0.001),and Cx43 ( q =4.571, P =0.037; q =11.068, P <0.001),and down-regulated the mRNA ( q =7.384, P <0.001; q =28.234, P <0.001) and protein ( q =4.594, P =0.036; q =15.945, P <0.001) levels of KLF6.The apoptosis rate of miR-22-3p mimics group was lower than that of 5-AZA group ( q =8.216, P <0.001).Compared with the miR-22-3p mimics+pcDNA group,miR-22-3p mimics+pcDNA-KLF6 up-regulated the mRNA( q =23.891, P <0.001) and protein( q =13.378, P <0.001)levels of KLF6,down-regulated the expression of Desmin ( q =9.505, P <0.001),cTnT ( q =10.985, P <0.001),and Cx43 ( q =8.301, P <0.001),and increased the apoptosis rate ( q =4.713, P =0.029).The dual luciferase reporter gene experiment demonstrated that KLF6 was a potential target gene of miR-22-3p. Conclusion MiR-22-3p promotes cardiomyocyte-like differentiation of BMSC by inhibiting the expression of KLF6.

The environmental risks posed by heavy metals (HMs) in animal manure are increasing because of the use of trace metals as additives in feedstuffs. Manure samples were collected, and published literature was reviewed in this study to systematically analyze the HMs content in animal manure and compare the results to different sources of animal manures. Results show that the distribution of HMs content in animal manure was skewed. The ranges were between not detected (ND)-147 mg·kg -1 for Cd, ND-1919 mg·kg -1 for Pb, 0.003-2278 mg·kg -1 for Cr, ND-978 mg·kg -1 for As, ND-103 mg·kg -1 for Hg, ND-1747 mg·kg -1 for Cu, ND-11547 mg·kg -1 for Zn, and 1.22-1140 mg·kg -1 for Ni. The means (medians) of those elements were 2.31(0.72) mg·kg -1 , 13.5(8.96) mg·kg -1 , 36.3(12.0) mg·kg -1 , 14.0(3.52) mg·kg -1 , 0.97(0.07) mg·kg -1 , 282(115) mg·kg -1 , 656(366) mg·kg -1 , and 21.8 (13.1) mg·kg -1 for Cd, Pb, Cr, As, Hg, Cu, Zn, and Ni, respectively. Means were significantly higher (1-13 times) than the medians. According to maximum limits of Cd, Pb, Cr, As, and Hg for organic fertilizers NY 525-2012, about 12.3% (for Cd), 2.58% (for Pb), 2.76% (for Cr), 20.6% (for As), and 3.69% (for Hg) of the data were above the limits. According to the composting regulations of Germany, about 53.9% (for Cu), 45.7% (for Zn), and 0.59% (for Ni) exceeded the maximum limits. The heavy metal contents in animal manure of different regions differs significantly. As and Cd contents in animal manure in the Shandong Province tend to be higher with their average values at 1.7 times and 10.1 times of the mean contents for national scale, respectively; the heavy metal contents in eastern China tend to be higher. Cd and As contents in animal manure tend to be higher in Northeast and Eastern China, while Cu and Zn contents were higher in Eastern and South China. After comparing HMs content in different sources of manures, we found that Cd, As, Hg, Cu, Zn, and Ni mean contents in pig manure were 1.0-3.0 times, 1.8-6.8 times, 1.1-15.8 times, 4.9-17.5 times, 2.7-12.0 times, and 1.7-2.1 times that of cattle manure, sheep manure, and poultry manure. The Pb content in poultry manure was the highest, with the mean being 2.8, 2.5, and 2.2 times higher than pig manure, cattle manure, and sheep manure, respectively. When recycling animal manure into the crop field, the accumulation rates for Cd were under 0.02 mg·(kg·a) -1 in over 90% of the circumstances and the accumulation rates for Pb were all below 0.15 mg·(kg·a) -1 . When applying poultry manure, Cr in soil is easily accumulated with the maximum accumulation rate of 0.28 mg·(kg·a) -1 .

Liquid biopsy is an emerging and promising detection tool for cancer, with the benefit of being non-invasive and convenient. It analyzes tumor-derived information in the blood or other body fluids including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA) and exosomes. Nowadays, with the expansion of liquid biopsy research contents and the development of capture and detection technologies, liquid biopsy is increasingly utilized in clinical applications, promoting the development of tumor precision medicine. Here, we mainly focus on reviewing the objects and technologies about liquid biopsy, as well as its applications, development and challenges in clinical practices.

Long noncoding RNAs (lncRNAs) are a class of non-protein coding transcripts exceeding 200 nucleotides in length. Accumulating evidence achieved by several sophisticated techniques such as chromatin conformation capture and RNA-seq has led to new questions concerning correlations between lncRNAs and chromatin structures. Many studies have revealed that lncRNAs exert great influences on gene expression through regulating chromatin 3D structures. In addition, lncRNAs play a crucial role in tumorigenesis and therefore hold great promises in disease diagnosis and prognosis. Here, we mainly focus on introducing how lncRNAs regulate gene expression by modulating nuclear architecture and discussing clinical values of lncRNAs in oncotherapy.

Melanoma is a malignant cutaneous cancer of high metastasis and lethal rates. Epithelial-mesenchymal transition (EMT) plays an important role in the embryonic developmental process that is often activated during tumorigenesis and metastasis. In this study, we integrated of mRNA and miRNA transcriptome sequencing data of melanocyte and melanoma cell lines to identify genes involved in the process of tumor EMT in the first place, and uncovered 11 miRNAs including miR-130a-3p, miR-130b-3p, miR-125a-5p, miR-30a-3p, miR-195-5p, miR-345-5p, miR-509-3-5p, miR-374a-5p, miR-509-5p, miR-148a-3p and miR-330-3p, negatively related with EMT genes using the Mirsystem software. Bioinformatics analysis with target genes of these miRNAs revealed two networks closely related with cellular development and cell-to-cell interactions, as well as multiple signaling pathways participating in EMT. Validation of the 11 miRNAs with molecular biology experiments demonstrated that four miRNAs regulated oncogenes in melanomas, including miR-195-5p, miR-130a-3p, miR-509-5p, and miR-509-3-5p. Our study integrates two kinds of omics data to screen for EMT-related miRNAs, providing a new research idea in the precision genomics of cancer research.

Reference to relative literatures in recent years, model building and calculation on volatile organic compound (VOC) emission inventory of plants were summarized in different spatial scales, the total annual VOC emission amounts from Vegetation in China are in the range from 12.4 Tg x a(-1) to 28.4 Tg x a(-1). For garden plants in Beijing, the annual VOC emissions are approximately 38 500 tons C in 2000. Furthermore, in order to determine reduction strategies for Beijing urban atmospheric major pollutants, the contribution of garden plant VOC emissions to the ozone and secondary organic aerosol (SOA) formation was presented, compared to garden plant in the same period, the largest contribution to ozone formation comes from aromatic hydrocarbons and olefin which are exhausted from anthropogenic activity, besides, the aromatic hydrocarbons exhausted from anthropogenic activity is also a main contribution source for the potential formation of SOA. In the meantime, it is suggested to focus on emission control of VOCs which are emitted from urban anthropogenic sources.

Objective: To explore the disease course and outcomes of severe or critical pregnant women with 2009 pandemic H1N1 (pH1N1) infection in China., Methods: A retrospective observational study was conducted for 394 severe or critical pregnant women with pH1N1 influenza admitted into hospital in 27 Chinese provinces from September 1, 2009 to December 31, 2009. Their clinical features in different trimesters were analyzed. The viral infection of pH1N1 was verified by real-time reverse transcription (rRT)-PCR. Severe and critical cases were defined according to the 2009 H1N1 clinical guidelines., Results: Among them, 374 (94.9%) were infected in the second or third trimester. Fever and cough were the most common symptoms in all trimesters. However, hemoptysis, dyspnea and associated pneumonia were likely to occur in the second or third trimester. The ratio of required mechanical ventilation in the second or third trimester (44.7%, 167/374) was significantly higher than that in the first trimester (3/20). Among 77 mortality cases, 72.7% (56/77) died in the third trimester. Pregnancy was terminated after the onset of pH1N1 symptoms in 52.5%(207/394) pregnant women. And 57.0%(118/207) of them had delivery < 37 weeks and 29.0%(60/207) fetuses deceased., Conclusion: A clinician should be on a high alert for pH1N1 infection in pregnant women, particularly in the second or third trimester.

Objective: To investigate the etiology and clinical characteristics of hospital-acquired pneumonia (HAP) in China and to provide evidence for appropriate therapy., Methods: We performed a prospective multicenter study in 13 Chinese urban tertiary hospitals. All HAP cases diagnosed at respiratory general ward and respiratory intensive care unit (RICU) from August 2008 to December 2010 were studied. Epidemiological data, etiology and clinical characteristics of enrolled patients were collected. Sputum or tracheal aspirate and blood cultures, Legionella antibodies and Streptococcus pneumoniae urinary antigen tests were performed. Bacteria to antimicrobial susceptibility test was performed., Results: A total of 610 cases of HAP were diagnosed during the study, with an overall incidence of 1.4% among 42 877 hospitalized patients, while the incidence was 0.9% (362/41 261) in respiratory general ward and 15.4% (248/1616) in RICU. 93.9% (573 cases) of patients had at least one underlying disease, and 91.0% (555 cases) had exposure to at least one antimicrobial agent within 90 days prior to HAP diagnosis. Pathogens were identified in 487 patients, with Acinetobacter baumannii [30.0% (183/610)], Pseudomonas aeruginosa [22.0% (134/610)], Staphylococcus aureus [13.4% (82/610)] and Klebsiella pneumonia [9.7% (59/610)] being the most common pathogens. Eighteen patients (3.0%) had infection with fastidious bacteria. A. baumannii and S. aureus were the more frequent pathogens in the ventilator-associated pneumonia (VAP) cases [50.5% (97/192) and 21.4% (41/192)] as compared to non-VAP cases [20.6% (86/418) and 9.8% (41/418), P < 0.01]. A. baumannii and S. aureus were also frequent pathogens in cases with a score of more than 20 by the acute physiology and chronic health evaluation II (APACHEII) scoring [45.7% (69/151) and 20.5% (31/151)], as compared to cases with a score of less than 20 of APACHE II [24.8% (114/459) and 11.1% (51/459), P < 0.01]. A. baumannii showed high resistance rates to carbapenems [more than 70% (109/142)], and the susceptibility to cefoperazone/sulbactam, polymyxin B and tigecycline were 40.8% (58/142), 99.3% (141/142) and 95.8% (136/142) respectively. Resistance rates of P. aeruginosa to meropenem and imipenem were 48.8% (40/82) and 70.7% (58/82) respectively. Methicillin-resistant S. aureus (MRSA) accounted for 87.8% (43/49) in all strains of S. aureus. Mortality rate of VAP cases was 34.5% (61/177), significantly more than that of HAP patients [22.3% (135/605), P < 0.05]. The average hospital stay of patients with HAP was (23.8 ± 20.5) days, significantly more than that of the average for inpatients [(13.2 ± 13.6) days, P < 0.01] during the study period. Mean costs of HAP were (108 950 ± 116 608) yuan, significantly higher than the average hospital costs of respiratory inpatients (17 999 ± 33 364) yuan., Conclusions: Among Chinese patients hospitalized in urban tertiary medical centers, HAP incidence and mortality rate were high, which increased the patients' hospital stay and the medical costs. Common pathogens were A. baumannii, P. aeruginosa, S. aureus and K. pneumonia. The common bacteria of HAP in China showed high resistance rates to antibiotics.

Objective: To evaluate the value of plasma 1, 3-β-D-glucan (G), serum mannan, galactomannan (GM) and cryptococcus capsular antigen assays for diagnosis of invasive fungal infections (IFI) in non-neutropenic adult patients., Methods: This was a prospective case control study. Plasma and serum samples from 25 patients with IFI (candidiasis, aspergillosis, cryptococcosis, zygomycosis, pneumocystis carinii pneumonia), 27 patients with bacterial infections, and 25 healthy adults were collected from February 2007 to February 2009 in Beijing Hospital. The serum antigenic assays were performed and their sensitivity and specificity were analyzed. Optimal cut-off level of G test and mannan was established with receiver operating characteristic curve (ROC)., Results: The concentration of G test in plasma of patients with IFI [89.4 (25.8, 336.9) ng/L] was significantly higher than that of patients with bacterial infection [8.1 (5.0, 34.9) ng/L, U = 120.5, P < 0.001] and healthy adults [3.8 (3.8, 26.0) ng/L, U = 76.5, P < 0.001]. The area under curve (AUC) was 0.858, and the optimal cut-off value was 71.7 ng/L. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 65.0% (13/20), 92.3% (48/52), 76.5% (13/17) and 87.2% (48/55) respectively. The concentration of mannan in serum from patients with candidiasis [1.13 (0.44, 1.22) µg/L] was significantly higher than that from patients with non-candidiasis IFI [0.21 (0.14, 0.27) µg/L, U = 19, P < 0.05], bacterial infection [0.26 (0.22, 0.32) µg/L, U = 36.5, P < 0.001] and healthy adults [0.25 (0.22, 0.30) µg/L, U = 29.5, P < 0.001]. The AUC was 0.894, and the optimal cut-off value was 0.41 µg/L. The sensitivity, specificity, PPV and NPV were 83.3% (10/12), 90.4% (47/52), 66.7% (10/15) and 96.0% (47/49) respectively. The sensitivity, specificity, PPV and NPV of GM antigen to diagnose aspergillosis were 25.0% (1/4), 96.1% (50/52), 33.3% (1/3) and 92.6% (50/54) respectively. The sensitivity, specificity, PPV and NPV of cryptococcus capsular antigen to diagnose cryptococcosis were all 100%., Conclusions: 1,3-β-D-glucan, mannan and cryptococcus capsular antigen were useful for diagnosis of IFI in non-neutropenic adult patients. GM antigen did not show a good sensitivity for diagnosis of aspergillosis in non-neutropenic adult patients.

ISL1 is a LIM homeodomain protein that plays an important role in insulin gene transcriptional activation and islet cell formation. BETA2 is a transcription factor in the basic helix-loop-helix (bHLH) family, which activates expression of tissue-specific genes in several developmental systems. In this study, we investigated the functional and physical interactions of ISL1 and BETA2 in promoting insulin gene transcription in non-beta cells. Using the luciferase assay, we demonstrated that ISL1 and BETA2 could activate insulin gene transcription synergistically. Co-immunoprecipitation also supported that ISL1 and BETA2 appear in one complex and this physical interaction mediates the synergy between these two proteins.

Objective: To study the efficacy of montelukast, a cysteinyl leukotriene receptor antagonist, in the treatment and prevention of exercise-induced bronchoconstriction (EIB) in mild asthmatic patients and patients with exercise-induced asthma (EIA)., Methods: Thirty mild asthmatic patients with positive standardized exercise challenge test were enrolled. The subjects received montelukast 10 mg once daily in the evening. Standard exercise challenge was performed before, three days and twenty-eight days after the administration of the drug. The end points included: (1) Area under the percent fall in forced expiratory volume in one second (FEV1) versus time curve (AUC0 to approximately 60 min); (2) Time of recovery to within 5% of the pre-exercise baseline FEV1 value; and (3) Maximal percent fall in FEV1 from pre-exercise baseline., Results: Montelukast caused significant reduction in AUC0 to approximately 60 min, which was (39 +/- 21)%.min before treatment as compared to (13 +/- 14)%.min and (12 +/- 14)%.min three days and twenty-eight days respectively after the treatment with montelukast. Time of recovery to within 5% of the pre-exercise baseline FEV1 value were (51 +/- 36) min, (26 +/- 28) min and (25 +/- 33) min respectively. The mean maximal percentage decrease in FEV1 after exercise was 44.4% before treatment, 26.8% and 18.2% following montelukast. FEV1 and peak expiratory flow rate (PEFR) were maintained to nearly normal during all the study. Inhale corticosteroid did not prevent EIB/EIA., Conclusion: Montelukast attenuates and protects against EIB/EIA.

Objective: To explore the reason of delayed diagnosis or misdiagnosis of pulmonary tuberculosis., Method: The clinical data of 458 patients pulmonary tuberculosis patients undergoing treatment between January 1999 and December 2003 in our hospital were retrospectively analysed., Results and Conclusion: The reasons for delayed diagnosis or misdiagnosis are as follows: A careless attitude towards health condition by patients themselves; neglected bacteriological evidence or ignorance of tuberculosis by physicians.