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1.
Cancer Res ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481499

RESUMO

Epstein-Barr virus (EBV) is a complex oncogenic symbiont. The molecular mechanisms governing EBV carcinogenesis remain elusive and the functional interactions between virus and host cells are incompletely defined. Here we present a comprehensive map of the host cell-pathogen interactome in EBV-associated cancers. We systematically analyzed RNA-sequencing from >1000 patients with 15 different cancer types, comparing virus and host factors of EBV+ to EBV- tissues. EBV preferentially integrated at highly accessible regions of the cancer genome with significant enrichment in super-enhancer architecture. Twelve EBV transcripts, including LMP1 and LMP2, correlated inversely with EBV reactivation signature. Over-expression of these genes significantly suppressed viral reactivation, consistent with a "virostatic" function. In cancer samples, hundreds of novel frequent missense and nonsense variations in virostatic genes were identified, and variant genes failed to regulate their viral and cellular targets in cancer. For example, one-third of EBV+ NK/T-cell lymphoma patients carried two novel nonsense variants (Q322X, G342X) of LMP1 and both variant proteins failed to restrict viral reactivation, confirming loss of virostatic function. Host cell transcriptional changes in response to EBV infection classified tumors into two molecular sub-types based on patterns of interferon signature genes and immune checkpoint markers, such as PD-L1 and IDO1. Overall, these findings uncover novel points of interaction between a common oncovirus and the human genome and identify novel regulatory nodes and druggable targets for individualized EBV and cancer-specific therapies.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31495725

RESUMO

BACKGROUND: Nonconcentric reduction of hip posterior dislocation caused by the acetabular labrum rim fracture is rare. There has been very little study on the feasibility of arthroscopically treatment and medium and mid-term evaluation to this pathology. The objectives of the current study were: (1) Is the arthroscopically assisted technique feasible to this manage this injury? (2) What is the effectiveness of arthroscopic treatment for nonconcentric reduction of hip posterior dislocation caused by acetabular labrum rim fracture. HYPOTHESIS: Arthroscopically assisted procedure is an alternative treatment modality for nonconcentric reduction of hip posterior dislocation caused by acetabular labrum rim fracture. PATIENTS AND METHODS: Thirteen of 257 posterior hip dislocations who were admitted to our hospital from February 2008 to March 2017 were included: 9 males and 4 females, with an average age of 23.7 (15-36) years. All of them underwent hip posterior dislocation and nonconcentric reduction related to acetabular labrum rim fracture. All of them had arthroscopic reduction and fixation of the rim fracture. Visual Analogic Score (VAS) score, modified Harris score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and the last follow-up radiographs were analyzed respectively. Postoperative complication and the need for secondary operation were recorded during the process. RESULTS: The incidence rate of this pathology was nearly 5%. Twelve out of 13 patients were followed up for an average of 42 (range, 26-68) months. At the final follow-up, VAS score was decreased from 5.2±0.9 (range, 4.0-6.1) preoperatively to 0.5±0.5 (range, 0.0-1.0) (p<0.0001), modified Harris score and WOMAC score were increased statistically significant from 32±8 (range, 28-40) and 30±5 (range, 25-35) to 94±5 (range, 89-99) and 95±4 (range, 91-99) respectively (p<0.0001). All patients have had completely concentric reduction and returned to activities of daily life. There was not any hip arthroscopic complication such as sciatic nerve injury and intra-abdominal fluid extravasation. Besides, there were no aseptic necrosis and revision case. CONCLUSION: Arthroscopically assisted procedure is an alternative treatment modality for nonconcentric reduction of hip posterior dislocation caused by the acetabular labrum rim fracture without surgical dislocation procedure. Good clinical results can be achieved without any complications related to the surgical procedure. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

3.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(9): 868-875, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31506144

RESUMO

OBJECTIVE: To study the significance of plasma neutrophil extracellular trap (NET) and its markers in the diagnosis of community-acquired pneumonia (CAP) in children. METHODS: A total of 160 children with CAP were enrolled as the CAP group, and 50 healthy children were enrolled the control group. According to disease severity, the CAP group was further divided into a mild CAP subgroup with 137 children and a severe CAP subgroup with 23 children. According to the pathogen, the CAP group was further divided into a bacterial pneumonia subgroup with 78 children, a Mycoplasma pneumonia subgroup with 35 children, and a viral pneumonia subgroup with 47 children. The levels of plasma NET and its markers [antibacterial peptide (LL-37), extracellular free DNA (cfDNA), and deoxyribonuclease I (DNase I)] were measured. Receiver operating characteristic (ROC) curve was used to analyze the value of each index in diagnosing CAP and assessing its severity. RESULTS: Compared with the control group, the CAP group had significant increases in the levels of NET, LL-37, and cfDNA and a significant reduction in the activity of DNase I (P<0.05). Compared with the mild CAP subgroup, the severe CAP subgroup had significantly higher levels of NET, LL-37 and cfDNA and a significantly lower activity of DNase I (P<0.05). There were no significant differences in the levels of NET, LL-37, and cfDNA and the activity of DNase I among the bacterial pneumonia, Mycoplasma pneumonia, and viral pneumonia subgroups (P>0.05). In the CAP group, plasma NET levels were positively correlated with white blood cell count (WBC), percentage of neutrophils, and serum levels of C-reactive protein (CRP), procalcitonin and tumor necrosis factor-α (r=0.166, 0.168, 0.275, 0.181 and 0.173 respectively, P<0.05); LL-37 and cfDNA levels were positively correlated with WBC (r=0.186 and 0.338 respectively, P<0.05) and CRP levels (r=0.309 and 0.274 respectively, P<0.05); the activity of DNase I was negatively correlated with CRP levels (r=-0.482, P<0.05). The ROC curve analysis showed that NET, LL-37, cfDNA, and DNase I had an area under the ROC curve (AUC) of 0.844, 0.648, 0.727, and 0.913 respectively in the diagnosis of CAP, with optimal cut-off values of 182.89, 46.26 ng/mL, 233.13 ng/mL, and 0.39 U/mL respectively, sensitivities of 88.12%, 35.63%, 54.37%, and 91.25% respectively, and specificities of 74.00%, 92.00%, 86.00%, and 76.00% respectively. In the assessment of the severity of CAP, NET, LL-37, cfDNA, and DNase I had an AUC of 0.873, 0.924, 0.820, and 0.778 respectively, with optimal cut-off values of 257.7, 49.11 ng/mL, 252.54 ng/mL, and 0.29 U/mL respectively, sensitivities of 83.21%, 86.96%, 78.26%, and 95.65% respectively, and specificities of 78.26%, 83.94%, 76.64%, and 56.93% respectively. CONCLUSIONS: Plasma NET and its related markers have a certain value in diagnosing CAP and assessing its severity in children.

4.
Nanotoxicology ; : 1-20, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31502903

RESUMO

The pulmonary fibrosis could be caused by long-term inhalation of carbon black (CB) particles. Studies on the mechanisms of pulmonary fibrosis induced by CB are required to develop the stratagem of prevention and treatment on fibrosis. The RNA-binding protein DiGeorge syndrome critical region gene 8 (DGCR8)-dependent pri-miRNAs processing is regulated by N6-methyladenosine (m6A) modification, which targets the downstream signal pathway. However, its role in pulmonary fibrosis has not been known clearly. In the present study, rats inhaled CB at dose of 0, 5 or 30 mg/m3 for 28 days, 6 h/day, respectively. The rats inhaled CB at dose of 0 or 30 mg/m3 for 14 days, 28 days and 90 days, respectively. In vitro experiments, the normal human bronchial epithelial cell line (16HBE) was treated with CB (0, 50, 100 and 200 µg/mL) for 24 h. In vitro and vivo study, the levels of fibrosis indicators including α-SMA, vimentin, collagen-I and hydroxyproline in CB treatment groups statistically increased in dose- or time- dependent manners compared with the control. After CB treatment, PI3K-AKT-mTOR pathway was activated and regulated by miRNA-126. We found that both of m6A modifications of pri-miRNA-126 and its binding with DGCR8 were decreased after CB treatment, which resulted in the reduction of mature miRNA-126 accompanied by accumulation of unprocessed pri-miRNA-126. This work demonstrated that m6A modification of pri-miRNA-126 and its binding with DGCR8 decreases blocked miRNA-126 maturation, and then activated the PI3K/AKT/mTOR pathway, which drove the fibro genesis in the lung after CB exposure.

5.
Nat Commun ; 10(1): 4067, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492885

RESUMO

ARID1A inactivation causes mitotic defects. Paradoxically, cancers with high ARID1A mutation rates typically lack copy number alterations (CNAs). Here, we show that ARID1A inactivation causes defects in telomere cohesion, which selectively eliminates gross chromosome aberrations during mitosis. ARID1A promotes the expression of cohesin subunit STAG1 that is specifically required for telomere cohesion. ARID1A inactivation causes telomere damage that can be rescued by STAG1 expression. Colony formation capability of single cells in G2/M, but not G1 phase, is significantly reduced by ARID1A inactivation. This correlates with an increase in apoptosis and a reduction in tumor growth. Compared with ARID1A wild-type tumors, ARID1A-mutated tumors display significantly less CNAs across multiple cancer types. Together, these results show that ARID1A inactivation is selective against gross chromosome aberrations through causing defects in telomere cohesion, which reconciles the long-standing paradox between the role of ARID1A in maintaining mitotic integrity and the lack of genomic instability in ARID1A-mutated cancers.

6.
MBio ; 10(5)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481383

RESUMO

Eukaryotic cells share a basic scheme of internal organization featuring membrane-based organelles. The use of fluorescent proteins (FPs) greatly facilitated live-cell imaging of organelle dynamics and protein trafficking. One major limitation of this approach is that the fusion of an FP to a target protein can and often does compromise the function of the target protein and alter its subcellular localization. The optimization process to obtain a desirable fusion construct can be time-consuming or even unsuccessful. In this work, we set out to provide a validated set of FP-based markers for major organelles in the budding yeast (Saccharomyces cerevisiae). Out of over 160 plasmids constructed, we present a final set of 42 plasmids, the recommendations for which are backed up by meticulous evaluations. The tool set includes three colors (green, red, and blue) and covers the endoplasmic reticulum (ER), nucleus, Golgi apparatus, endosomes, vacuoles, mitochondria, peroxisomes, and lipid droplets. The fidelity of the markers was established by systematic cross-comparison and quantification. Functional assays were performed to examine the impact of marker expression on the secretory pathway, endocytic pathway, and metabolic activities of mitochondria and peroxisomes. Concomitantly, our work constitutes a reassessment of organelle identities in this model organism. Our data support the recognition that "late Golgi" and "early endosomes," two seemingly distinct terms, denote the same compartment in yeast. Conversely, all other organelles can be visually separated from each other at the resolution of conventional light microscopy, and quantification results justify their classification as distinct entities.IMPORTANCE Cells contain elaborate internal structures. For eukaryotic cells, like those in our bodies, the internal space is compartmentalized into membrane-bound organelles, each tasked with specialized functions. Oftentimes, one needs to visualize organelles to understand a complex cellular process. Here, we provide a validated set of fluorescent protein-based markers for major organelles in budding yeast. Yeast is a commonly used model when investigating basic mechanisms shared among eukaryotes. Fluorescent proteins are produced by cells themselves, avoiding the need for expensive chemical dyes. Through extensive cross-comparison, we make sure that each of our markers labels and only labels the intended organelle. We also carefully examined if the presence of our markers has any negative impact on the functionality of the cells and found none. Our work also helps answer a related question: are the structures we see really what we think they are?

7.
Cell Rep ; 28(5): 1307-1322.e8, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31365872

RESUMO

CD40 has major roles in B cell development, activation, and germinal center responses. CD40 hypoactivity causes immunodeficiency whereas its overexpression causes autoimmunity and lymphomagenesis. To systematically identify B cell autonomous CD40 regulators, we use CRISPR/Cas9 genome-scale screens in Daudi B cells stimulated by multimeric CD40 ligand. These highlight known CD40 pathway components and reveal multiple additional mechanisms regulating CD40. The nuclear ubiquitin ligase FBXO11 supports CD40 expression by targeting repressors CTBP1 and BCL6. FBXO11 knockout decreases primary B cell CD40 abundance and impairs class-switch recombination, suggesting that frequent lymphoma monoallelic FBXO11 mutations may balance BCL6 increase with CD40 loss. At the mRNA level, CELF1 controls exon splicing critical for CD40 activity, while the N6-adenosine methyltransferase WTAP negatively regulates CD40 mRNA abundance. At the protein level, ESCRT negatively regulates activated CD40 levels while the negative feedback phosphatase DUSP10 limits downstream MAPK responses. These results serve as a resource for future studies and highlight potential therapeutic targets.

8.
Opt Lett ; 44(17): 4203-4206, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31465363

RESUMO

The capability to overcome Kirchhoff's law of thermal radiation provides new opportunities in energy harvesting and thermal radiation control. Previously, design towards demonstrating such capability requires a magnetic field of 3 T, which is difficult to achieve in practice. In this work, we propose a nanophotonic design that can achieve such capability with a far more modest magnetic field of 0.3 Tesla, a level that can be achieved with permanent magnets. Our design uses guided resonance in low-loss dielectric gratings sitting on a magneto-optical material, which provides significant enhancement on the sensitivity to the external magnetic field.

9.
J Sci Food Agric ; 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31368537

RESUMO

BACKGROUND: Myostatin (MSTN) negatively regulates skeletal muscle development; however, its functions in internal organs have not been thoroughly investigated. Here, we compared the morphological, molecular, and biological characteristics of the heart, liver, spleen, lungs, kidneys, and tongue of homozygous MSTN mutant (MSTN-/- ), heterozygous MSTN mutant (MSTN+/- ), and wild-type (WT) piglets. RESULTS: The heart and liver were lighter in MSTN-/- piglets than in MSTN+/- piglets, while the tongue was heavier in MSTN-/- piglets than in WT piglets (P < 0.05). Furthermore, the tongue was longer in MSTN-/- piglets than in WT piglets, and myofibers of the tongue were significantly larger in the former piglets than in the latter ones (P < 0.01). mRNA expression of MSTN in all organs was significantly lower in MSTN-/- and MSTN+/- piglets than in WT piglets (P < 0.05). Meanwhile, mRNA expression of follistatin, which is closely related to MSTN, in the heart and liver was significantly higher in MSTN-/- piglets than in MSTN+/- and WT piglets (P < 0.05). In addition, protein expression of MSTN in the heart, kidneys, and tongue was significantly lower in MSTN-/- piglets than in WT piglets (P < 0.01). CONCLUSION: These results suggest that MSTN is widely expressed and has marked effects in multiple internal organs. Myostatin has crucial functions in regulating internal organ size, especially the tongue. © 2019 Society of Chemical Industry.

10.
Neuroscience ; 417: 70-80, 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31430527

RESUMO

Neuroinflammation in the hippocampus plays essential roles in postoperative cognitive dysfunction (POCD). Histone deacetylases (HDACs) have recently been identified as key regulators of neuroinflammation. MS-275, an inhibitor of HDAC, has been reported to have neuroprotective effects. Therefore, the present study aimed to test the hypothesis that pretreatment with MS-275 prevents POCD by inhibiting neuroinflammation in rats. In this study, anesthesia/surgery impaired cognition, demonstrated by an increase escape latency and reduction in the number of platform crossings in Morris water maze (MWM) trials, through activating microglia neuroinflammation and decreasing PSD-95 expression. However, pretreatment with MS-275 attenuated postoperative cognitive impairment severity. Furthermore, pretreatment with MS-275 decreased activated microglia levels and increased PSD95 protein expression in the hippocampus. Pretreatment with MS-275 reduced NF-κB-p65 protein expression and nuclear accumulation as well as the neuroinflammatory response (production of proinflammatory cytokines including TNF-α and IL-1ß) in the hippocampus. Additionally, MS-275 reduced HDAC2 expression and HDAC activity in the hippocampus, which were enhanced in vehicle-treated rats. These results suggest that MS-275 alleviates postoperative cognitive dysfunction by reducing neuroinflammation in the hippocampus of rats via HDAC inhibition.

11.
Dalton Trans ; 48(35): 13472-13482, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31454007

RESUMO

Four chair-like hexanuclear Fe-Ln complexes containing mixed organic ligands, namely, [Fe4Ln2{(py)2CO2}4(pdm)2(NO3)2(H2O)2Cl4]·xCH3CN·yH2O (Ln = GdIII (1, x = 1, y = 0), DyIII (2, x = 1, y = 1), HoIII (3, x = 0, y = 2), and ErIII (4, x = 1, y = 3); (py)2CO2H2 = the gem-diol form of di-2-pyridyl ketone and pdmH2 = 2,6-pyridinedimethanol) have been obtained by employing di-2-pyridyl ketone and 2,6-pyridinedimethanol reacting with FeCl3 and Ln(NO3)3 in MeCN. The structures of 1-4 are similar to each other except for the number of lattice solvent molecules. Four FeIII and two LnIII in these complexes comprise a chair-like core with the "body" constructed by four FeIII ions and the "end" constructed by two LnIII ions. Among the four compounds, 2 shows field-induced single molecule magnet behavior as revealed by ac magnetic susceptibility studies, with the effective energy barrier and the pre-exponential factor of 22.07 K and 8.44 × 10-7 s, respectively. Ab initio calculations indicated that, among 2_Dy, 3_Ho and 4_Er fragments, the energy gap between the lowest two spin-orbit states for 2_Dy is the largest, while the tunneling gap for 2 is the smallest. These might be the reasons for complex 2 exhibiting SMM behavior. Additionally, the orientations of the magnetic anisotropy of DyIII in 2 were obtained by electrostatic calculations and ab initio calculations, both indicating that the directions of the main magnetic axis of Dy1 ions are almost aligned along Dy1-O5 (O5 from the pdm2- ligand).

12.
Oral Oncol ; 96: 21-26, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31422209

RESUMO

OBJECTIVES: The aim of this study was to estimate the direct 2-year mean incremental medical care costs for incident oropharyngeal cancer (OPC) from the perspective of the Texas Medicaid program. METHODS: OPC patients treated from 2008 to 2012 were selected in the Texas Medicaid database. Using a two-step 1:1 propensity score matching method, we selected controls to determine the differential cost associated with OPC. Monthly and yearly direct costs were estimated for 2 years after the cancer diagnosis. For patients without 2-year complete follow-up, a generalized linear model with gamma distribution and log link function was applied to predict costs for the censored months. RESULTS: A total of 352 patients with OPC and the same number of controls were included in the study. Among OPC patients, 204 (58%) were covered by Medicaid and Medicare, and 148 patients (42%) were insured under Medicaid only. The adjusted first- and second-year mean differential costs were $45,102 and $11,684 for Medicaid-only enrollees and $5734 and $2162 for Medicaid-Medicare dual-eligible enrollees, respectively. Being male, Hispanic, Medicaid-only eligible, living in the Harlingen region, and having more comorbidities were positively associated with monthly cost. Lubbock residents experienced lower costs. CONCLUSIONS: The direct incremental medical costs associated with OPCs among patients insured by Texas Medicaid were substantial in the first 2 years after cancer diagnosis and should be considered in assessing the economic consequences of increasing the investment in HPV vaccination in Texas.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31444521

RESUMO

Because of the emergence of antibiotic resistance, we must investigate new antibiotical agents. The present study was designed to find new compounds with antibacterial activity from metabolites of Bacillus pumilus. We found that the concentrated fermentation broth of Bacillus pumilus has antibacterial property. By high-performance liquid chromatography (HPLC), three compounds with antibacterial activity were first isolated from the ethyl acetate layer of fermentation broth of Bacillus pumilus. And then their structures were identified by nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis. According to the data, the compound 1, compound 2, and compound 3 were determined to be 3,4-dipentylhexane-2,5-diol, 1,1'-(4,5-dibutylcyclohexane-1,2-diyl)bis(ethan-1-ol), and 1,1'-(4,5-dibutyl-3,6-dimethylcyclohexane-1,2-diyl)bis(ethan-1-one). And all of them exhibited potent inhibitory effects against a panel of pathogenic bacteria including Staphylococcus aureus ATCC6538, Micrococcus luteus CMCC28001, Variant Salmonella gallinarum CVCC79207, Pasteurella multocida CVCC474, Swine Salmonella, Salmonella enterica ATCC13076, Swine Escherichia coli K88, Chicken Escherichia coli O78. Given its antibacterial activity, 3,4-dipentylhexane-2,5-diol, 1,1'-(4,5-dibutylcyclohexane-1,2-diyl)bis(ethan-1-ol), 1,1'-(4,5-dibutyl-3,6-dimethylcyclohexane-1,2-diyl)bis(ethan-1-one) are assumed to be promising agents for further development as antibacterial agents.

14.
Phys Rev Lett ; 122(25): 253201, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31347860

RESUMO

Stimulated Raman adiabatic passage (stirap) allows efficiently transferring the populations between two discrete quantum states and has been used to prepare molecules in their rovibrational ground state. In realistic molecules, a well-resolved intermediate state is usually selected to implement the resonant stirap. Because of the complex molecular level structures, the detuned stirap always coexists with the resonant stirap and may cause unexpected interference phenomenon. However, it is generally accepted that the detuned stirap can be neglected if compared with the resonant stirap. Here we report on the first observation of interference between the resonant and detuned stirap in the adiabatic creation of ^{23}Na^{40}K ground-state molecules. The interference is identified by observing that the number of Feshbach molecules after a round-trip stirap oscillates as a function of the hold time, with a visibility of about 90%. This occurs even if the intermediate excited states are well resolved, and the single-photon detuning of the detuned stirap is about 1 order of magnitude larger than the linewidth of the excited state and the Rabi frequencies of the stirap lasers. Moreover, the observed interference indicates that if more than one hyperfine level of the ground state is populated, the stirap prepares a coherent superposition state among them, but not an incoherent mixed state. Further, the purity of the hyperfine levels of the created ground state can be quantitatively determined by the visibility of the oscillation.

15.
Nanotechnology ; 30(42): 425202, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31307022

RESUMO

TiO2 nanowire memristors were fabricated by dielectrophoresis. The responding current of the memristor continuously increases and decreases with the consecutive positive and negative sweep voltage, which is similar to the nonlinear transmission characteristics of biological synapses. Spike-rate-dependent plasticity and learning behaviors of TiO2 memristor were studied by applying programmed pulses. The pulses with higher amplitude, bigger width and smaller interval cause a larger excitatory postsynaptic current. The number of relearning pulses is decreased with the learning experience, and a deepening memory will be consolidated by the repeated learning process. A mechanism based on the oxygen vacancy migration is proposed for the learning behavior. Excess oxygen vacancies are generated during the learning process and the conducting pathways are formed by the vacancy drift under the applied voltage. After removing the voltage at the forgetting process, back diffusion and electron trapping of the oxygen vacancies dominate the relaxation time, and the metastable atoms are formed with the involvement of the oxygen atoms. However, weak chemical bonding among the metastable atoms leads to the migration of the regenerated oxygen vacancies again, contributing to the enhanced current in the relearning process.

16.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2353-2358, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359663

RESUMO

In this paper, Xixian Tongshuan Preparation was used as the research object, and all the chemical components of the 13 traditional Chinese medicines were collected. The target finding technique was used to obtain the key targets of the neuroprotective effect of Xixian Tongshuan Preparation, including 5 glutamate receptors, TGFR-1 and VEGFR-2. Molecular docking technology was used to screen out the potential active components of the above targets and to analyze their mechanism of action. It was found that single component, such as neo-complanatoside and neo-carthamin, in Xixian Tongshuan Preparation could simultaneously act on different targets. The chemical constituents in Ligusticum chuanxiong, Angelica sinensis, Carthamus tinctorius, and Panax pseudo-ginseng could simultaneously act on different neuroprotective-related targets, which reflected the application of multi-components to multi-targets. Point and multiple sites played a key role in protecting neurons against cerebral ischemic injury. This study explains the multi-target mechanism of anti-cerebral ischemic injury in neuroprotection at the molecular level, and provides a certain direction for the clinical application and experimental research of Xixian Tongshuan Preparation.

17.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2379-2389, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359667

RESUMO

To evaluate the efficiency and safety between Wenxin Granule and antiarrhythmic drugs in the treatment of atrial fibrillation(AF). A total of 8 major electronic databases(CNKI, WanFang, VIP, CBM, Cochrane Library, Web of Science, PubMed, EMbase) were retrieved since the establishment of the database to January 10, 2019. Two reviewers extracted data, and assessed the methodological quality of the included studies. The Meta-analysis was made by RevMan 5.3 software. Finally, 42 studies involving 4 657 patients were included. The results of Meta-analysis showed that compared with antiarrhythmic drug, the combined administration with Wenxin Granule and antiarrhythmic drug had a better clinical efficiency(OR=3.37, 95%CI[2.69,4.22],I~2=0%,P<0.000 01)and efficacy on cardioversion(OR=2.32,95%CI[1.67,3.22],I~2=0%,P<0.000 01), with reduction in P_d(MD=-5.48,95%CI [-7.32,-3.64],I~2=0%,P<0.000 01)and P_(max)(MD=-9.91,95%CI[-12.86,-6.95],I~2=0%,P<0.000 01). The comparison between the combined application with Wenxin Granule and the single application of amiodarone showed a clinical efficiency(OR=2.89,95%CI[1.96,4.26],I~2=44%,P<0.000 01),and efficacy on sinus rhythm maintenance(OR=2.58,95%CI[1.82,3.66],I~2=3%,P<0.000 01). The comparison between the combined application with Wenxin Granule and the single application of amiodarone showed a clinical efficiency(OR=0.88,95%CI[0.53,1.46],I~2=0%,P=0.63). The combined treatment with Wenxin Granule has a better clinical efficiency in AF better than amiodarone, with no evidence for more benefits from the single administration with Wenxin Granules.

18.
Zhongguo Zhong Yao Za Zhi ; 44(12): 2572-2579, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359726

RESUMO

Inflammatory response is caused by exogenous and endogenous stimuli,resulting in a non-specific resistance reaction.After acute ischemic cerebral infarction,inflammatory factors gather and adhere in the ischemic area of leukocyte infiltration,and the released inflammatory factors causes the injury cascade,aggravate the brain tissue damage and the symptoms of neurological deficits,and hinder the repair of brain neurons and the recovery of nerve function. In this paper,the key targets in the arachidonic acid metabolic pathway were studied. The Hiphop pharmacophore model of s PLA2-ⅡA and COX-2 inhibitors was built. According tothe two previously constructed 5-LOX and LTA4 H target inhibitors,the pharmacophore model was used to initially screen out the composition database of all of 13 traditional Chinese medicines in Xixian Tongshuan Preparation. The molecular matching study was carried out by selecting the matching value greater than 0. 6,and the component with the CDOCKER score greater than 80% of the original ligand score was used as the potential active inhibitor of the target. Considering the pharmacophore matching value,the molecular docking score and the interaction between the components and the target,one Chuanxiong component and one safflower component were selected as potential inhibitors of s PLA2-ⅡA; two Chuanxiong components,two Panax notoginseng,one safflower component,one angelica component,one valerian component were taken as a potential inhibitor of COX-2; two Gentiana components,one safflower component,one valerian component,one P. notoginseng component and one Angelica component were taken as potential inhibitors of 5-LOX; and two Gentiana components,two Chuanxiong components,and two safflower components were taken as potential inhibitors of LTA4 H. This study screened out the potential inhibitors of the four targets in a high-efficiency and low-cost manner,and explained that Xixian Tongshuan Preparation showed an effect in the treatment of inflammatory responses caused by ischemic stroke by acting both LOX pathway and COX pathway in the metabolic pathway.

19.
World J Pediatr ; 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31347021

RESUMO

BACKGROUND: Herpangina is a common infectious disease in childhood caused by an enterovirus. This consensus is aiming to standardize and improve herpangina prevention and clinical diagnosis. METHODS: The Subspecialty Group of Infectious Diseases, the Society of Pediatric, Chinese Medical Association and Nation Medical Quality Control Center for Infectious Diseases gathered 20 experts to develop the consensus, who are specialized in diagnosis and treatment of herpangina. RESULTS: The main pathogenic serotypes of herpangina include Coxsackievirus-A, Enterovirus-A and Echovirus. Its diagnosis can be rendered on the basis of history of epidemiology, typical symptoms, characteristic pharyngeal damage and virological tests. The treatment is mainly symptomatic, and incorporates topical oral spray with antiviral drugs. The course of herpangina generally lasts 4-6 days with a good prognosis. CONCLUSION: The consensus could provide advices and references for the diagnosis, treatment and management of herpangina in children.

20.
Zhongguo Zhong Yao Za Zhi ; 44(9): 1882-1888, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31342717

RESUMO

The thrombus is a deposit that is formed on the surface of the endovascular or at the site of repair,and known as the main complication of cardiovascular disease and the cause of death. At the same time,thrombus is mainly treated by the following three ways: anticoagulation,anti-platelet aggregation and thrombolysis. In this study,the chemical constituents of seven traditional Chinese medicines in the Xixian Tongshuan Preparation were collected to construct a component database. Subsequently,the pharmacophore were used to screen out the component database,and molecular docking was used to screen out the results of pharmacophore for explaining the material basis and mechanism that Xixian Tongshuan Preparation exerts anti-thrombotic activity by inhibiting platelet aggregation. First of all,P2 Y12,GPⅡb/Ⅲa and PAR1 were selected as study vectors,the optimal models of inhibitors were obtained respectively through verification and evaluation of the pharmacophore models. Afterwards,the component database was screened out by the optimal pharmacophore models of PAR1,P2 Y12 and GP Ⅱ b/Ⅲ a,and the molecular docking method was used to further refine the screening results. The screening results indicated that the anti-platelet aggregation effect of Xixian Tongshuan Preparation was correlated with the inhibition of P2 Y12,PAR1 and GPⅡb/Ⅲa expressions with saffower yellower,hirudin and candidin and notoginseng triterpenes,folinic acid,respectively. The material basis and mechanism of anti-platelet aggregation of Xixian Tongshuan Preparation provided a theoretical basis for the clinical use of the preparation and the lead compounds for the development of anti-platelet aggregation drugs.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Inibidores da Agregação de Plaquetas/farmacologia , Agregação Plaquetária , Trombose , Bases de Dados de Produtos Farmacêuticos , Humanos , Simulação de Acoplamento Molecular
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