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Drug-target interactions (DTIs) prediction is an important step in drug discovery. As traditional biological experiments or high-throughput screening are high cost and time-consuming, many deep learning models have been developed. Overfitting must be avoided when training deep learning models. We propose a simple framework, called OverfitDTI, for DTI prediction. In OverfitDTI, a deep neural network (DNN) model is overfit to sufficiently learn the features of the chemical space of drugs and the biological space of targets. The weights of trained DNN model form an implicit representation of the nonlinear relationship between drugs and targets. Performance of OverfitDTI on three public datasets showed that the overfit DNN models fit the nonlinear relationship with high accuracy. We identified fifteen compounds that interacted with TEK, a receptor tyrosine kinase contributing to vascular homeostasis, and the predicted AT9283 and dorsomorphin were experimentally demonstrated as inhibitors of TEK in human umbilical vein endothelial cells (HUVECs).
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BACKGROUND: This case report presents the case of a man with no known coagulopathy or preceding trauma, who spontaneously developed a spinal epidural hematoma (SEH). This is an uncommon condition which can have variable presentations including hemiparesis mimicking stroke, resulting in the potential for misdiagnosis and inappropriate treatment. CASE PRESENTATION: A 28-year-old Chinese male with no past medical history presented with sudden onset neck pain associated with bilateral upper limbs and right lower limb subjective numbness but intact motor function. He was discharged after adequate pain relief but re-attended the emergency department with right hemiparesis. A magnetic resonance imaging of his spine revealed an acute cervical spinal epidural hematoma at C5 and C6. While admitted, he had spontaneous improvement of his neurological function and was eventually managed conservatively. CONCLUSIONS: SEH, although uncommon, can be a mimic of stroke and it is important to avoid misdiagnosis as it is a time critical diagnosis, and administration of thrombolysis or antiplatelets can lead to unfavourable outcomes. Having a high clinical suspicion can help to guide us in the choice of imaging and interpretation of subtle signs to reach the correct diagnosis in a timely manner. Further research is required to better understand the factors that would favour a conservative approach as opposed to surgical treatment.
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Aim To investigate the effects of astragalus polysaccharides on the improvement of liver and kidney injury and the regulation of intestinal flora structure in cadmium exposed rats. Methods Rats exposed to cadmium were established by intraperitoneal injection of CdCl2. After continuous intragastric administration of astragalus polysaccharides for five weeks, urine, liver, kidney and feces were collected. The cadmium residues in urine, liver and kidney were detected by Graphite Furnace Atomic absorption spectrometry, the pathological changes of liver and kidney were observed by HE staining, and Illumina PE250 sequencing and bioinformatics software were used to analyze the structure of intestinal flora. Results After intraperitoneal injection of CdCl2, the accumulation of cadmium in urine, liver and kidney increased significantly, some liver and kidney cells showed pathological damage such as swelling, necrosis and inflammatory cell infiltration. Chao, ace and shannon indexes decreased significantly, while simpson index increased significantly. The number of OTU decreased. And the abundance of Ruminococcus, Bacteroides, Flavonifractor, Roseburia and Elusmicrobium decreased significantly, but Lactobacillus, that of Lachnospiracea_incertae_sedis, Parasutterella, Clostridium XlVb, Clostridium XI, Integinimonas and Fusobacterium increased significantly. Compared with the normal control group, the differences was statistically significant(P<0.05 or P<0.01). After intragastric administration of astragalus polysaccharides, cadmium accumulation in urine, liver and kidney decreased significantly, liver and kidney cell damage alleviated, and inflammatory cell infiltration reduced. Chao, ace and shannon index increased markedly, and simpson index decreased significantly. OTU number increased. And the bundance of Prevotella, Bacteroides, Parasutterella, Elismicrobium and Barnesiella raised significantly, that of Ruminococcus, Oscillibacter, Flavonifractor, Clostridium XlVa, Roseburia, Lactobacillus, Ruminococcus2, Lachnospiracea_incertae_sedis, Clostridium IV, Clostridium XlVb, Clostridium XI and integinimonas decreased significantly, which was statistically significant compared with the group exposed to cadmium alone(P<0.05 or P<0.01). Conclusions Astragalus polysaccharides may improve liver and kidney injury by reducing cadmium accumulation and regulating the structure of intestinal flora in cadmium exposed rats.
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Objective: To identify the internal nasal valve (INV) and to evaluate its key parameters in the established 3D models of nasal cavity space via Mimics from CT images, in order to provide evidence for quantitative diagnosis of nasal valve compromise. Methods: A total of 32 Han adults without nasal diseases who underwent maxillofacial CT test in Shanghai Ninth People's Hospital from January 2015 to December 2018 were retrospectively recruited, including 16 males and 16 females, with the age ranged from 20 to 80 years (50% age<50 years old). Maxillofacial CT images were used to create 3D model of nasal cavity space. The INV was identified and the following parameters were measured: the angle between the INV and the nasal bone (θINV-B), unilateral cross-sectional area of the INV (AINV-R, AINV-L), total cross-sectional area of the INV (AINV), unilateral height of the INV (HINV-R, HINV-L), unilateral nasal valve angle (αINV-R, αINV-L), and the sum of nasal valve angle (αINV). The AINV in our study was compared with the results of the previously adopted planes (PlaneC, perpendicular to the hard palate and PlaneB, plane perpendicular to the nasal bone). The parameters above were compared among genders, age and race groups. SPSS 26 and GraphPad Prism 9 software were used for statistical analysis and mapping of data. Results: The AINV in our study was (214.87±52.94) mm², which was significantly less than that of PlaneC (254.97±47.80) mm² and PlaneB (226.07±57.36) mm². The measured parameters were as follows: θINV-B was (82.07±7.06)°; AINV-R was (112.66±31.39) mm²; AINV-L was (102.21±27.14) mm²; AINV was (214.87±52.94) mm²; HINV-R was (24.87±4.62) mm; HINV-L was (24.35±4.86) mm; αINV-R was (20.48±2.99)°; αINV-L was (19.65±3.82)°; αINV was (40.13±6.24)°. The AINV-R was larger than AINV-L (t=2.33, P<0.05); The HINV, AINV-R, AINV-L and AINV of males were more than those of females (t value was 5.77, 3.21, 2.91 and 3.52, respectively, all P<0.01). The AINV of the young group (<50 years) was larger than that of the old group (t=2.83, P<0.01); The θINV-B was different between the Han people and the Caucasian (t=2.92,P<0.01). The αINV of the Han people was larger than that of Caucasians (Z=-6.92, P<0.01), but the HINV was smaller (Z=-3.89, P<0.01). Conclusion: The AINV carried out in 3D models of nasal cavity space is significantly smaller than that obtained by the previous methods of CT evaluation. INV static parameters differ among genders, age and race groups.
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Adulto , Femenino , Humanos , Masculino , Adulto Joven , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Cavidad Nasal/diagnóstico por imagen , Estudios Retrospectivos , China , Nariz , Hueso NasalRESUMEN
@#Migraine is acommon chronic neurovascular disorder, its pathophysiological mechanisms are not fully understood. There are various clinical phenotypes of migraine, among which visual migraine may present as visual aura. Retinal migraine and ophthalmoplegic migraine also belong to the category of visual migraine. Optical coherence tomography(OCT)and optical coherence tomography angiography(OCTA)can be used to detect the circulation of retinal nerve fiber layer, ganglion cell layer, optic papilla, retina and choroid qualitatively and quantitatively. Based on above two imaging findings, studies have addressed that during visual migraine pathogenesis, the transitory and recurrent constriction of the retinal and ciliary arteries, which may cause ischemic damage to the optic nerve, retina and choroid in patients with migraine, with the subsequent reduction in thickness of retinal nerve fiber layer, ganglion cell layer, and retinal microvasculature decrement. The fundus imaging examinations are helpful to improve our understanding on pathophysiological mechanisms of visual migraine, these imaging findings based on OCT and OCTA may serve as indicators to evaluate course and severity of visual migraine.
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Objective: To inhibit the stemness maintenance potential of endometrial cancer and increase the sensitivity of endometrial cancer side population cells to chemotherapy drugs by inducing extensive deSUMOylation modification of proteins. Methods: Flow cytometry was used to sort and culture CD133(+) CD44(+) KLE endometrial cancer cell clone spheres. Protein expression level of small ubiquitin-related modifier 1 (SUMO1) and two stemness maintenance genes of tumor side population cells, octamer binding transcription factor-4 (Oct4) and sex determining region Y-box2 (Sox2), were detected by western blotting method. Lentivirus-mediated Sentrin/SUMO-specific proteases 1 (SENP1) gene was stably transfected into KLE side population cells. Western blotting was used to detect the protein expressions of SENP1, SUMO1, Oct4 and Sox2. The clone formation rate was compared between KLE side population cells with or without SENP1 overexpression. Flow cytometry was applied to detect cell cycle changes. 3-(4, 5-Dimethylthiazole-2)-2, 5-diphenyl-tetrazolium bromide (MTT) experiment and flow cytometry apoptosis method were used to detect the chemosensitivity of the side population of endometrial cancer cells to cisplatin. Tumor-bearing mouse models of endometrial cancer were established to detect the effect of SENP1 overexpression on the chemotherapy sensitivity of cisplatin. Results: Compared with CD133(-)CD44(-) KLE cells, CD133(+) CD44(+) KLE side population cells could form clonal spheres and express higher levels of SUMO1, Oct4 and Sox2 proteins (P<0.05). Compared with KLE side population cells that were not transfected with SENP1 gene, the expression level of SENP1 protein in KLE side population cells overexpressing SUMO1、Oct4 and Sox2 were lower. The clonal sphere formation rate was reduced from (25.67±5.44)% to (7.46±1.42)%, and cell cycle shifted from G(0)/G(1) phase to G(2) phase. IC(50) of cisplatin decreased from (55.46±6.14) μg/ml to (11.55±3.12) μg/ml, and cell apoptosis rate increased from (9.76±2.09)% to (16.79±3.44)%. Overexpression of SENP1 could reduce the tumorigenesis rate of KLE side population cells in vivo and increase their chemotherapy sensitivity to cisplatin (P<0.05). Conclusion: Overexpression of SENP1 can induce protein deSUMOylation modification, inhibit the stemness maintenance potential of endometrial cancer side population cells, and enhance their chemotherapy sensitivity, which provides a new reference for gene therapy of endometrial cancer.
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Animales , Femenino , Humanos , Ratones , Apoptosis , Línea Celular Tumoral , Cisplatino/farmacología , Cisteína Endopeptidasas/metabolismo , Neoplasias Endometriales/genética , Células de Población Lateral/patología , SumoilaciónRESUMEN
Steroid receptor coactivator 1 (SRC-1) is one of the coactivators recruited by the nuclear receptors (NRs) when NRs are activated by steroid hormones, such as glucocorticoid. SRC-1 is abundant in hippocampus and hypothalamus and is also related to some major risk factors for depression, implicated by its reduced expression after stress and its effect on hypothalamus-pituitary-adrenal gland axis function. However, whether SRC-1 is involved in the formation of depression remains unclear. In this study, we firstly established chronic unpredictable stress (CUS) to induce depressive-like behaviors in mice and found that SRC-1 expression was reduced by CUS. A large number of studies have shown that neuroinflammation is associated with stress-induced depression and lipopolysaccharide (LPS) injection can lead to neuroinflammation and depressive-like behaviors in mice. Our result indicated that LPS treatment also decreased SRC-1 expression in mouse brain, implying the involvement of SRC-1 in the process of inflammation and depression. Next, we showed that the chronic unpredictable mild stress (CUMS) failed to elicit the depressive-like behaviors and dramatically promoted the expression of SRC-1 in brain of wild type mice. What's more, the SRC-1 knockout mice were more susceptible to CUMS to develop depressive-like behaviors and presented the changed expression of glucocorticoid receptor. However, SRC-1 deficiency did not affect the microglia activation induced by CUMS. Altogether, these results indicate a correlation between SRC-1 level and depressive-like behaviors, suggesting that SRC-1 might be involved in the development of depression induced by stress.
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Depresión/metabolismo , Coactivador 1 de Receptor Nuclear/deficiencia , Estrés Psicológico/metabolismo , Animales , Células Cultivadas , Depresión/etiología , Femenino , Suspensión Trasera , Hipocampo/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/metabolismo , Coactivador 1 de Receptor Nuclear/metabolismo , Embarazo , Estrés Psicológico/complicacionesRESUMEN
BACKGROUND: This study aimed to evaluate the efficacy and safety of using high-dose intravenous tranexamic acid (TXA) to reduce blood loss in idiopathic scoliosis surgery. METHODS: This study was a meta-analysis, which consisted of retrospective cohort studies (RCSs) and randomized control trials (RCTs) found by searching electronic databases, namely PubMed, Web of Science, The Cochrane Central Register of Controlled Trials (CENTRAL), and the Google Scholar Database, dating from 1960 to 2019. The points of interest included total blood loss, a need for transfusion and transfusion criteria, surgery time, and the evidence of intraoperative and postoperative complications, such as seizures or thromboembolic events. The weighted mean differences (WMD) and 95% confidence interval (CI) of blood loss in the TXA intervention group compared to the control or placebo group were extracted and combined using the random effects model. RESULTS: In this meta-analysis, there was a total of three RCSs and two RCTs, which involved 334 patients. The results showed that blood loss is significantly reduced, with a weighted mean difference in the TXA group (WMD = - 525.14, P = 0.0000, CI ranged from - 839.83, - 210.44, I2 = 82%). Heterogeneity was assessed using the random effects model. CONCLUSIONS: A high dose of intravenous TXA reduced blood loss during adolescent idiopathic scoliosis surgery and did not lead to any significant thromboembolic event. Therefore, a high dose appears to be effective and safe for adolescent idiopathic scoliosis surgery. However, more high-quality research based on larger randomized controlled trials is still needed.
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Pérdida de Sangre Quirúrgica/prevención & control , Escoliosis/cirugía , Fusión Vertebral , Ácido Tranexámico/administración & dosificación , Adolescente , Femenino , Humanos , Infusiones Intravenosas , Complicaciones Intraoperatorias/etiología , Masculino , Complicaciones Posoperatorias/etiología , Quimioterapia por Pulso , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Seguridad , Convulsiones/etiología , Fusión Vertebral/efectos adversos , Tromboembolia/etiología , Factores de Tiempo , Ácido Tranexámico/efectos adversosRESUMEN
Objective:To investigate the effects of Guiqi Dingnian prescription (GDP) on the expression of related molecules in Janus tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription (JAK2/STAT) signaling pathway of <italic>D</italic>-galactose (<italic>D</italic>-gal)-induced senescent mesangial cells. Method:The senescent mouse mesangial cells induced by 10 g·L<sup>-1</sup> <italic>D</italic>-gal were continuously treated with 40 mg·L<sup>-1 </sup>GDP for three days. The senescence of the treated cells was determined by senescence-associated (SA)-<italic>β</italic>-gal staining. The cell cycle was detected by flow cytometry. The cell viability was analyzed using the cell counting kit-8 (CCK-8). The mRNA expression levels of tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>), interleukin-6 (IL-6), nuclear transcription factor-<italic>κ</italic>B (NF-<italic>κ</italic>B), and IL-1<italic>α</italic> were detected by real-time polymerase chain reaction (Real-time PCR). The protein expression levels of STAT1, phosphorylated STAT1 (p-STAT1), STAT3, and p-STAT3 in the JAK2/STAT signaling pathway were determined by Western blot. Result:CCK-8 results showed that the optimal concentration of GDP was 40 mg·L<sup>-1</sup>. Compared with the blank group, the positive rate of SA-<italic>β</italic>-gal in the model group was significantly higher(<italic>P</italic><0.01), the percentage of cells in G<sub>0</sub>/G<sub>1</sub> phase was significantly increased(<italic>P</italic><0.05), the percentage of cells in G<sub>2</sub>/M and S phase was significantly decreased(<italic>P</italic><0.01). The mRNA expression levels of TNF-<italic>α</italic>,IL-6,NF-<italic>κ</italic>B and IL-1<italic>α </italic>were significantly increased(<italic>P</italic><0.01). Compared with the model group, the model + GDP group exhibited significantly decreased SA-<italic>β</italic>-gal-positive cells (<italic>P</italic><0.05), reduced cells in the G<sub>0</sub>/G<sub>1</sub> phase (<italic>P</italic><0.05), increased cells in the G<sub>2</sub>/M and S phases (<italic>P</italic><0.01), and down-regulated TNF-<italic>α</italic>, IL-6, NF-<italic>κ</italic>B, and IL-1<italic>α </italic>mRNA expression (<italic>P</italic><0.05) and STAT1, p-STAT1, STAT3, and p-STAT3 protein expression (<italic>P</italic><0.05). Conclusion:GDP delays the senescence of mouse mesangial cells possibly by down-regulating the expression of related molecules in the JAK2/STAT pathway.
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The aim of this paper was to explore the mechanism of Shenxiong Glucose Injection antagonizing apoptosis of H9 c2 cells induced by H_2O_2. H9 c2 cells were pretreated with 1. 7%,3. 4% and 6. 8% Shenxiong Glucose Injection,and then H_2O_2 was introduced to induce apoptosis in vitro. Cell viability was detected by MTS assay,morphological changes of apoptosis were observed by AO/EB fluorescence staining,apoptosis rate was detected by Annexin/PI method,cell expression profile was detected by gene chip technology,the mRNA of PIK3 CA,Bcl-2,Bax,caspase-3 and GAPDH were detected by qRT-PCR,the protein expression levels of PIK3 CA,AKT,P-AKT,Bcl-2,Bax and caspase-3 were detected by Western blot,and the contents of LDH and MDA were detected by kit. The results showed that Shenxiong Glucose Injection of different concentrations significantly increased the viability of H9 c2 cells treated with H_2O_2( P<0. 01),and reversed H_2O_2-induced apoptosis( P< 0. 01). The microarray experiments showed that 138 genes were altered in H9 c2 cells after treatment with Shenxiong Glucose Injection. The differential expression fold of PIK3 CA associated with PI3 K/AKT pathway was 3. 59. The results of qRT-PCR and Western blot showed that Shenxiong Glucose Injection could down-regulate the mRNA and protein expression levels of caspase-3( P<0. 01),up-regulate the mRNA and protein expression level of PIK3 CA and Bcl-2( P<0. 01),and up-regulate the phosphorylation levels of AKT( P<0. 01) in H_2O_2-treated H9 c2 cells. The protective effect of Shenxiong Glucose Injection on H_2O_2 cells injury was significantly inhibited by LY294002,a PI3 K/AKT pathway inhibitor. The results suggested that Shenxiong Glucose Injection may inhibit H_2O_2-induced H9 c2 cells apoptosis by regulating PI3 K/AKT signaling pathway.
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Animales , Ratas , Apoptosis , Línea Celular , Cromonas , Medicamentos Herbarios Chinos , Farmacología , Glucosa , Morfolinas , Fosfatidilinositol 3-Quinasas , Metabolismo , Proteínas Proto-Oncogénicas c-akt , Metabolismo , Transducción de SeñalRESUMEN
Signal transducer and activator of transcription 3 (STAT3) was found in an abnormal constitutively active status in certain cancer tissues, and under these circumstances the interruption of STAT3 signaling pathway was proposed with the potential anti-cancer efficacy. In this study, our previous reported STAT3 inhibitor Bt354 can inhibit tumor growth in DU145 xenograft mice without affecting body weight. In groups treated with Bt354, the inhibition rate of tumor weight was 58.8%, 62.7% and 73.5% in 10, 20, 40 mg·kg-1 group, respectively. Particularly, the number of Ki 67 positive cells in the tumor sections was significantly decreased in Bt354 groups. Furthermore, Bt354 inhibited the nuclear translocation of STAT3 and consequently induced cell growth inhibition, apoptosis in DU145 cells. These findings suggest that Bt354 may be a potent anticancer agent for STAT3 activated prostate cancer cells. Procedures for animal study were performed with approval of the Animal Care and Use Committee of the Chinese Academy of Medical Sciences and Peking Union Medical College.
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The research aims to study the effects of different stimulants on the activation of human lymphocytes. Human peripheral blood mononuclear cells were prepared by density centrifugation. The blood's sample was provided by National Institutes for Food and Drug Control and approved by its Ethics Committee. The expressions of CD69 in CD3+CD4+ and CD3+CD8+ human T cells were detected by flow cytometry after administrated with CD3/CD28 antibody, phytohaemagglutinin (PHA), Staphylococcus auresus enterooxin B (SEB), interleukin (IL27) and PMA plus ionomycin for 24 h. The proliferation of lymphocyte was detected by CellTiter-Glo kit. The secreted IFNγ in supernatant of medium was examined by ELISA kit. The proliferation of lymphocytes had no change after exposed of CD3/CD28 antibody, SEB, IL27 and PMA plus ionomycin for 24 h. However, the CD69 expressions in CD3+CD4+ and CD3+CD8+ T cells and IFNγ productions were significantly increased by CD3/CD28 antibody, SEB, IL27 and PMA plus ionomycin at 24 h, indicating that CD3+CD4+ and CD3+CD8+ T cells were activated under above-mentioned stimulated condition. CD3/CD28 antibody, SEB, IL27 and PMA plus ionomycin were valid stimulants for T cell activation.
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In this study, we used the tumor immunotherapy protein indoleamine 2,3-dioxygenase 1 (IDO1) as the target, and proposed an enzyme-cell-based tertiary IDO1 inhibitor high throughput screening platform. Firstly, the recombinant human IDO1 protein was expressed by genetic engineering and efficient IDO enzymatic screening system was established. Secondly, A172 cells stimulated with interferon-γ (IFNγ) or constructed plasmid which could highly express human IDO1 protein in HEK293 cells with transient transfection were used to construct the specific IDO1 cell based screening system. Finally, the effect of the compound on kynurenine and tryptophan in mouse plasma was determined by LC/MS/MS method on C57 mice, which could further verify the inhibitory effect of the selected compounds on IDO1 in vivo. The established and optimized enzyme-cell based screening model in this study can efficiently and effectively obtain IDO1 inhibitors in vitro, which lays a good foundation for the rapid development of clinical drugs. Procedures for animal study were performed with approval of the Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College.
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We explore and verify the optimized condition for HEK-Blue IL-17 screening model, and screen the compounds that inhibits IL-17-medited signaling pathway. HEK-Blue IL-17 cells (5×104 cells per well) were seeded into the 96 plates followed by different concentrations of IL-17A or IL-17F alone, or in combination with tested compounds for 16 h. Then, the supernatant medium was incubated with QUANTI-Blue for 1 or 3 h to detect the OD value at λ655nm. The secreted alkaline phosphatase (SEAP) production was an index of IL-17-mediated signaling activation in HEK-Blue IL-17 cells. We found that both IL-17A and IL-17F can significantly activate the IL-17 signaling pathway in HEK-Blue IL-17 cells. The available dosage of IL-17A and IL-17F were 10 and 100 ng·mL-1, respectively. The reaction time of SEAP and QUANTI-Blue was 1 h. In this model, arctigenin and epigallocatechin gallate (EGCG) could inhibit the IL-17A and IL-17F-mediated signaling pathway. This established and optimized screening model of HEK-Blue IL-17 cells was suitable for screening inhibitors of IL-17-mediated signaling pathway.
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Objective To evaluate the systolic and diastolic function of the left ventricular regional myocardium in patients with anterior descending lesion by real-time three-dimensional speckle tracking imaging (RT3D-STI) and investigate the value of RT 3D-STI in the diagnosis of anterior descending stenosis.Methods According to coronary angiography,112 patients were divided into four groups:normal group (20 coronary artery branches without stenosis),mild stenosis group ( 30 coronary artery branches with stenosis<50% ),moderate stenosis group(26 coronary artery branches with stenosis 50% -75% ) and sever stenosis group (36 coronary artery branches with stenosis > 75% ). Transthoracic acquisition of conventional 2D and full-volume real-time three-dimensional image,the routine parameters and the globle longitudinal strain (GLS),globle radial strain (GRS),globle circumferential strain (GCS) and globle area strain (GAS) at the end of the anterior descending blood supply area and corresponding strain of 1/3 of pre-diastolic period were obtained to calcute L-SI-DI,R-SI-DI,C-SI-DI,and A-SI-DI. The diagnostic value of each parameter to the stenosis degree of the anterior descending branch was analyzed. Results Compared among the anterior descending group without stenosis group,mild stenosis group,moderate stenosis group and severe stenosis group,there were no significant differences in conventional ultrasonic parameters such as LVEDV,LVESV,LVEF,E,A,E/A and E/e (all P >0.05).There was no significant difference in GLS, GRS,GCS and GAS between mild stenosis group and no stenosis group(all P >0.05),but the difference in L-SI-DI,R-SI-DI,C-SI-DI and A-SI-DI were statistically significant (all P <0.05).The ROC curve showed that the sensitivity and specificity of the middle anterior segment L-SI-DI were the highest,with 90.0% and 81.5%.Conclusions RT3D-STI can quantitative evaluate myocardial function changes in patients with anterior descending lesion,the anterior septal L-SI-DI can reflect the stenosis degree of the anterior descending branch to a certain extent,it has important guiding significance for clinical diagnosis of the stenosis degree of the anterior descending branch.
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Interleukin-6 (IL-6)/janus kinase (JAK)/signal transducers and activators of transcription 3 (STAT3) is a pivotal signaling pathway in the regulation of cell proliferation, survival, differentiation and T cell activation. Aberration of this pathway is involved in multiple autoimmunity diseases and cancers, therefore the pathway is considered as a hot target for drug development. In our study, we validated a cell-based model of IL-6/JAK/STAT3 and used it in screening of its inhibitors. HEK-Blue IL-6 cells of Invivogen Inc. were used to stably express IL-6 receptor and STAT3-induced secreted embryonic alkaline phosphatase (SEAP) report gene. After stimulation by IL-6, SEAP was secreted from cells and reacted with QUANTI-Blue. The product can be detected at 655 nm. The inhibitory effect of compounds on STAT3 signaling showed as IC50 was calculated by OD value. The results shown that IL-6 specifically activated the cells, which could be applied to screen the inhibitors for IL-6/JAK/STAT3 signaling pathway. The optimized screening conditions were described as below:50 000 cells/well, 1 ng·mL-1 IL-6 incubation for 20 h and reaction with QUANTI-Blue for 1 h. Based on this condition, we screened 14 natural products based on this cell model and arctigenin, cryptotanshinone and curcumin showed potential inhibitory activities on STAT3 signaling pathway with IC50 of 1.28, 2.96 and 6.61 μmol·L-1. Our study suggests that HEK-Blue IL-6 cells were suitable for screening inhibitors for the IL-6/JAK/STAT3 signaling pathway.
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Poly(ADP-ribose) polymerase (PARP)-1 and PARP2 function as ADP-ribosylases involved in DNA repair. PARP1/2 is highly expressed in cancers and emerged as an attractive target for antitumor drug. In this study, we investigated the antitumor activity of a novel PARP1/2 inhibitor YHP-743 in vitro and in vivo. The results showed that YHP-743 had potent enzymatic inhibitory activity against PARP1 and PARP2 to down-regulate the PAR level. YHP-743 not only inhibited breast cancer cells with genes deficiency of homologous recombination repair, but also potentiated chemotherapy agent's cytotoxicity, such as temozolomide, topotecan, cisplatin and doxorubicin. YHP-743 elicited good antitumor activity in combination with temo-zolomide in vivo.
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Objective:To study the effect of different doses of oxycodone on the serum thromboxane A2 (TXA2),plasma endothelin (ET) levels and immune function of patients underwent laparoscopic cholecystectomy.Methods:90 patients of elective laparoscopic cholecystectomy who were treated from August 2013 to August 2016 in our hospital were selected and divided into 3 groups by random number table,with 30 cases in each group.At the beginning of operation,they were given intravenous oxycodone,group A was given 0.1 mg/kg oxycodone,group B was given 0.2 mg/kg oxycodone,group C was given 0.3 mg/kg oxycodone.The changes of hemodynamics,serum TXA2 and ET levels were compared between the three groups at T0 (after admission),T1 (after anesthesia induction),T2 (after intubation),T3 (gallbladder separation),T4 (end of surgery) and the changes of immune function was compared at T0,T5 (postoperative 2h),T6(postoperative 1d),T7 (postoperative 3d);and the extubation time,recovery time,hypotensor,additional analgesics situationin and adverse reactions were recorded.Results:The diastolic pressure (DBP),systolic blood pressure (SBP),heart rate (HR) in three groups at T2,T3 point was significantly higher than T0 point(P<0.05),the DBP,SBP and HR in the B,C groups were significantly lower than the A group at T2 and T3 point(P<0.05);the TXA2 in three groups at T2,T3,T4 point was significantly higher than T0 point(P<0.05),and A group>B group>C group,there was significant difference between the two groups (P<0.05);the ET in three groups at T2,T3 point was significantly higher than T0 point(P<0.05),the ET in the B,C group was significantly higher than the A group at T2,T3 point(P< 0.05);the CD3+,CD4+,CD8+ and CD4+/CD8+ of the three groups at T5 point were significantly lower than that ofT0 point (P<0.05),the CD3+,CD4+,CD8+ and CD4+/CD8+ in A group were significantly lower than that of B,C group at T5 point (P<0.05);the extubation time in C group was significantly longer than that of A,B group(P<0.05);the total incidence of adverse reactions in C group was significantly higher than that the A,B group (P<0.05).Conclusion:In the laparoscopic cholecystectomy,application of 0.2 mg/kg oxycodone had little effect on hemodynamics,serum TXA2,ET levels and immune function with higher safety.
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Objective To investigate the distribution of avian influenza A viruses in external environment in Urumqi City in order to provide reference for the prevention and control of human infection with avian influenza virus in Urumqi City.Methods Environmental specimens were collected from 2013 to 2015 to detect avian influenza A virus nucleic acid with real-time fluorescent PCR.The positive specimens were further analyzed to identify the subtypes of avian influenza A viruses.Results A total of 1 043 environmental specimens were collected and tested.Among them,123 specimens were positive for avian influenza A virus nucleic acid with an overall positive rate of 11.79%.H9 was the predominant subtype,accounting for 7.77% of all specimens.Quarterly detection rates of avian influenza A virus in the three years peaked in different quarters of the year.Of all surveillance sites,live poultry markets in urban and rural areas had the highest positive rate (14.23%).Specimens collected from poultry drinking water (18.44%) and other specimens (19.44%) were highly positive for avian influenza A virus.Conclusion Avian influenza A viruses,especially the subtypes of H5,H7 and H9,exist in live poultry markets in Urumqi City.It is necessary to conduct surveillance and health education among people exposed to poultry in live poultry markets.
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Objective To observe the effects of acupuncture treatment on the levels of HPA axis related hormones and acupoint compatibility in insomnia rats; To discuss the mechanism of action for acupuncture treatment. Methods Chlorophenylalanine suspension was under intraperitoneal injection to establish insomnia model rats. Sixty SD rats were randomly divided into blank group, model group, Baihui+Shenmen group, Baihui+Sanyinjiao group, Baihui+non-acupoint group, with 12 rats in each group. Each treatment group received acupuncture in relevant acupoints, 30 min each time, for 7 d. ELISA was used to measure the levels of CRH, ACTH and CORT. Results Compared with the model group, the levels of CRH, ACTH and CORT of the acupuncture groups decreased to some extent. In the three acupuncture groups, the efficacy of Baihui+Shenmen group was better than that of Baihui+Sanyinjiao group and Baihui+non-non-acupoint group. Conclusion Acupuncture treatment may calm and soothe the nerves to release the insomnia through regulating HPA axis related hormones. Acupuncture acupoints at different meridians may be one of the factors that cause the difference of acupoints compatibility effect.