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Objective: To analyze the clinical characteristics of patients with chronic obstructive pulmonary disease (COPD) and COPD overlapping obstructive sleep apnea hypopnea syndrome (overlap syndrome), and to study the relationship between overlap syndrome and cardiovascular diseases. Methods: A total of 126 stable COPD patients admitted to the Respiratory Department of Peking University Third Hospital from September 2016 to October 2018 were included in this study, including 112 males and 14 females, ranging in age from 48 to 89 years, with a median of 67 years. With apnea hypopnea index (AHI) 5 times/h for the cutoff value, we classified the patients into a simple COPD group (31 cases) and an overlap syndrome group (95 cases), and compared the patients' demographic characteristics, respiratory symptoms, lung function, the incidence of cardiovascular events and the cardiac function with echocardiography (E/e'), left atrium diameter (LAD) and left ventricular ejection fraction (LVEF), by using independent-samples T test and chi-square test. Results: There were no statistically significant differences in demographic characteristics, respiratory symptoms, pulmonary function, cardiac function between COPD patients and overlap syndrome patients, but significant differences in blood oxygen level at night and left ventricular mass index(LVMI) between these groups (P=0.014,P<0.001,P<0.001,P<0.001, P=0.047, respectively) were observed. By comparing the severe sleep apnea hypopnea syndrome (AHI≥30) with sleep apnea hypopnea syndrome patients(AHI<30), there were statistically significant differences in echocardiographic indicators, among which there were statistically significant differences in E/e'(P=0.013), LAD(P=0.006), LVMI (P=0.051) and LVEF (P=0.030).There were also significant differences in the history of coronary heart disease and congestive heart failure between the two groups (P=0.025, P<0.001). After dividing the patients with overlap syndrome by mild, moderate and severe severity, E/e' and LAD were significantly correlated with severity (P=0.045, P=0.011). In terms of blood oxygen level at night, there was a significant correlation between average blood oxygen saturation at night and E/e', LAD, and LVMI (r=-0.195, P=0.033; r=-0.197, P=0.030; r=-0.195, P=0.044); moreover, there was also a significant correlation between the ratio of blood oxygen≤90% and LAD (r=0.209, P=0.021). In the multiple linear regression model, E/e' increased by 0.070 on average for each unit increase in AHI, and 0.084 on average for each unit increase in oxygen desaturation index (ODI). Conclusions: Patients with COPD overlapping severe sleep apnea hypopnea syndrome showed worse left diastolic function and higher risk of congestive heart failure and coronary heart disease compared with the patients with COPD alone. In addition, the degree of impairment of left heart diastolic function was associated with the severity of COPD overlapping sleep apnea hypopnea syndrome. The higher the AHI and the ODI became, the more severe the left heart diastolic restriction and structures changed.
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Doença Pulmonar Obstrutiva Crônica , Apneia Obstrutiva do Sono , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicações , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/complicações , Volume Sistólico , Função Ventricular EsquerdaRESUMO
Fluorine is one of the most interesting elements in nuclear astrophysics, where the ^{19}F(p,α)^{16}O reaction is of crucial importance for Galactic ^{19}F abundances and CNO cycle loss in first generation Population III stars. As a day-one campaign at the Jinping Underground Nuclear Astrophysics experimental facility, we report direct measurements of the essential ^{19}F(p,αγ)^{16}O reaction channel. The γ-ray yields were measured over E_{c.m.}=72.4-344 keV, covering the Gamow window; our energy of 72.4 keV is unprecedentedly low, reported here for the first time. The experiment was performed under the extremely low cosmic-ray-induced background environment of the China JinPing Underground Laboratory, one of the deepest underground laboratories in the world. The present low-energy S factors deviate significantly from previous theoretical predictions, and the uncertainties are significantly reduced. The thermonuclear ^{19}F(p,αγ)^{16}O reaction rate has been determined directly at the relevant astrophysical energies.
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Objective: To analyze the distribution of blood eosinophils (EOS) in COPD patients in the community and outpatient clinics, and to study the clinical characteristics and influencing factors of COPD patients with high EOS counts. Methods: This study included 237 patients with stable COPD, of which the median age was 68 years and males accounted for 81.2%. There were 45 community patients from the China Pulmonary Health study conducted in 2012-2013 and another 192 outpatients who attended the Respiratory Department of Peking University Third Hospital from August 2013 to November 2014 or from September 2015 to May 2018. Taking 100 cells/µl as the cut-off value, it was divided into high EOS group (146 people, 61.6%) and low EOS group (91 people, 38.4%). We compared demographic characteristics, respiratory symptoms, acute exacerbation, lung function, inflammation, imaging and other indicators. Results: The median EOS count of community patients was 110.4 cells/µl, and that of outpatients was 110.0 cells/µl. There was no statistically significant difference in the distribution of blood EOS among community and outpatients. The median EOS count of the general population was 110.0 cells/µl, and the median percentage was 1.8%. EOS≥300 cells/µl accounted for 11.4%. In the high EOS group, the percentage of male gender was higher (85.6% vs 74.7%), the GOLD grade was more severe, and the percentage of neutrophils was lower (61.70% vs 64.70%) (P<0.05 for these three characteristics). After multivariate analysis, the high EOS group was closely related to older age (OR=1.035, 95%CI:1.004-1.067, P=0.029), heavier GOLD grade (P=0.015) and lower percentage of neutrophils (OR=0.956, 95%CI:0.923-0.991, P=0.015). Conclusion: The distribution of blood EOS of COPD patients between the community and the outpatient clinics is not significantly different. About 60% of COPD patients have blood EOS≥100 cells/µl, which is associated with advanced age, male, severe airflow limitation, and low neutrophils.
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Eosinofilia , Doença Pulmonar Obstrutiva Crônica , Idoso , China/epidemiologia , Eosinófilos , Humanos , Contagem de Leucócitos , MasculinoRESUMO
Objective: To investigate the protective role of alprostadil on aortic dissection. Methods: 26 C57BL6 male mice were divided into control group (normal drinking water, n=13) and model group (1 g·kg-1·d-1 BAPN via drinking water, n=13). On day 14, mRNA expression of inflammatory-related genes as well as EP receptor families were detected by RT-PCR (n=6 each) and EP4 protein levels were determined by Western blot (n=7 each). Another 88 mice were divided into 3 groups: control group (n=22), model group (n=33) and treatment group (n=33). The mice in model group and treatment group were applied with BAPN (1 g·kg-1·d-1) via drinking water. The mice in treatment group received additional intraperitoneal injection with alprostadil (80 µg·kg-1·d-1) for 28 days. The mice in the control and model group received equal volume intraperitoneal injection with 0.9% saline respectively. The body weight and systolic blood pressure, the mortality and morbidity were monitored from the beginning until the designed end of the study. On day 28, the mice were sacrificed and aorta were fixed, embedded and sliced, followed by staining with HE and Victoria Blue. The distribution of EP4 was determined by immunohistochemistry in control (n=6) and model group (n=6). Furthermore, the concentration of PGE1 were tested among model (n=3) and treatment group (n=4). EP4 protein expression was determined in model group (n=7) and treatment group (n=6). Results: On day 14, mRNA expression level of MCP-1 ((2.74±1.55) vs. (1.00±0.49),<0.05) and MMP2((1.38±0.42) vs. (1.00±0.27), P<0.05) was significantly upregulated in model group compared with control group. Protein expression of EP4 receptor also increased in aorta in model group compared with control group (1.48±0.51 vs. 1.00±0.19, P<0.05). In the dissection area, the EP4 expression was also enriched compared with non-dissection area, particularly in endothelial cells and inflammatory cells on day 28. BAPN applied in drinking water (model and treatment groups) successfully induced the aortic dissection in mice, some mice died of the rupture. The elastic fibers were fractured, and the infiltrated immune cells were visible in dissected tissue. False lumen was formed. There was no dissection and death in the control group. Compared with control group, the morbidity and mortality rates were significantly increased in the model group (60.6%, 20/33, 30.3%, 10/33) and the treatment group (72.7%, 24/33, 24.2%, 8/33). The mortality and morbidity rates were similar between model and treatment groups. There is no difference in terms of SBP among three groups (P>0.05). Further study showed that after alprostadil injection, the blood concentration of PGE1 was increased in treatment group ((0.540±0.041 vs. 0.436±0.012)µmol/L, P<0.05). Besides, the EP4 receptor expression was downregulated in the treatment group compared to model group (0.60±0.30 vs. 1.00±0.20, P<0.05). Conclusion: EP4 expression is upregulated in BAPN induced aortic dissection mouse model. No protective effects are observed post alprostadil treatment in this model probably due to the reduced expression of EP4.
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Alprostadil , Dissecção Aórtica , Aminopropionitrilo , Animais , Modelos Animais de Doenças , Células Endoteliais , Masculino , CamundongosRESUMO
Cancer cells often evade apoptosis induced by anti-cancer drugs, which reduces the efficacy of the drugs. Autophagy/Beclin 1 regulator 1 (Ambra1) is a crucial proautophagic protein. It also plays an important role in the execution of apoptosis. However, the mechanism by which Ambra1 regulates apoptosis has not been fully clarified. Moreover, whether Ambra1 participates in the regulation of paclitaxel-induced apoptosis in breast cancer cells is not clear. Here, we show that Ambra1 inhibits paclitaxel-induced apoptosis in breast cancer cells. Moreover, Bim and mitochondria are key effectors of Ambra1 in this process. Thus, Ambra1 is a protein that makes breast cancer cells resistant to apoptosis by modulating the Bim/mitochondrial pathway. Therefore, Ambra1 may be a potential target for the treatment of breast cancer.
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Proteínas Adaptadoras de Transdução de Sinal , Apoptose , Neoplasias da Mama , Mitocôndrias , Paclitaxel , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/fisiopatologia , Linhagem Celular Tumoral , Humanos , Mitocôndrias/efeitos dos fármacos , Paclitaxel/farmacologiaRESUMO
Objective: To study the experience of preoperative evaluation, surgical planning and postoperative treatment of hilar cholangiocarcinoma (HCC) in our center. Method: The clinical data of 70 patients with HCC who underwent resection at the First Affiliated Hospital of Bengbu Medical College, from January 2011 to December 2017 were analyzed retrospectively. The treatment experience of HCC from the aspects of preoperative evaluation and treatment, surgical methods, postoperative recovery and prognosis were discussed. Results: The accurate evaluation of HCC by three-dimensional visualization technology was beneficial to the formulation of surgical plan preoperatively. Extended hemihepatectomy or combined resection of caudate lobe or portal vein was effective for type â ¢-â £ HCC. The R0 resection rate was 93% (53/57). Postoperative pathology showed that high/middle/low differentiated adenocarcinoma of 21/30/16, adenoma in 2 cases, inflammatory lesion in 1 case. The 1/3/5-year overall survival rates of patients with adenocarcinoma after chemotherapy were 87%(60/69)/47.0%(31/66)/30.2%(19/63) respectively. Conclusion: HCC patients who under radical surgery after preoperative evaluation and postoperative chemotherapy can obtain a good prognosis. Expanding hepatectomy can improve R0 resection rate and prognosis in patients with type â ¢-â £ HCC.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Ductos Biliares Intra-Hepáticos , Hepatectomia , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Objective: To investigate the effects of preoperative percutaneous transhepatic biliary drainage on surgical treatment of type â ¢ and â £ hilar cholangiocarcinoma. Methods: Clinical data of 72 patients with hilar cholangiocarcinoma of the Bismuth-Corlette type â ¢ and â £ treated at Department of General Surgery,First Affiliated Hospital of Bengbu Medical College from January 2010 to December 2017 were analyzed retrospectively.Patients were divided into two groups based on whether PTBD was performed:a drained group and an undrained group.In the drained group,there were 31 patients,20 males and 11 females,aged (59.9±9.7)years (range: 39-73 years).Among them,14 patients underwent hepatectomy with half or more than half of the liver removed (extended hepatectomy)and 17 patients underwent non-anatomical hepatectomy in the hilar region (limited hepatectomy).In the undrained group,there were 41 patients, 26 males and 15 females, aged (60.8±7.8)years(range: 45-75 years).Among them, 17 patients underwent hepatectomy with half or more than half of the liver removed (extended hepatectomy)and 24 patients underwent non-anatomical hepatectomy in the hilar region (limited hepatectomy).Percutaneous transhepatic biliary drainage(PTBD)was used in the drained group.Under the guidance of ultrasound,one or more hepatobiliary ducts could be sufficiently drained,which had good effect and was not restricted by the obstruction location of hilar cholangiocarcinoma.The analysis of the measurement data was performed using t test,and the analysis of the count data was performed using χ(2) test,and the survival curve was plotted using Kaplan-meier method. Results: In total, 72 jaundiced patients with hilar cholangiocarcinoma underwent surgical treatment: 31 had PTBD prior to operation while 41 did not had PTBD.There were significant differences in ALT((93.2±21.4)U/L vs.(207.4±65.1)U/L),AST((87.6±18.1)U/L vs.(188.9±56.6)U/L)and total bilirubin((68.8±12.6)µmol/L vs.(227.5±87.7)µmol/L)between the patients after treatment and those before treatment(t=10.958, P=0.000; t=10.845, P=0.000; t=10.386, P=0.000).Compared with those in the undrained group, the operation time was shorter, the amount of intraoperative bleeding and the incidence of complications were lower in the drained group(t=-2.840, P=0.006; t=-3.698, P=0.000; χ(2)=4.108, P=0.043).There were no perioperative death cases in drained group and 2 perioperative death cases in undrained group.There was no significant difference in R0 resection rate between the two groups(χ(2)=0.778,P=0.378).The 1-,3-,5-year survival rate of patients in the drained group and the undrained group was 72.7%,34.2%, 13.7% and 72.8%, 31.5%, 11.8%, respectively.The difference was not statistically significant(all P>0.05). Conclusions: The preoperative percutaneous transhepatic biliary drainage in patients with hilar cholangiocarcinoma of Bismuth-Corlette type â ¢ and â £ could effectively shorten operative time, reduce amount of intraoperative bleeding and incidence of postoperative complications,but have no significant effect on the R0 resection rate and survival rate.
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Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Tumor de Klatskin , Adulto , Idoso , Drenagem , Feminino , Hepatectomia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Objective: To investigate the effects of tanshinone â ¡A on atherosclerosis plaque formation and adventitial mast cells activation in high-fat-diet induced Apo E(-/-) mice model. Methods: Sixteen 8-week-old Apo E(-/-)male mice and eight 8-week-old C57BL/6 male mice were randomly allocated into following group: the control group (C57BL/6 + carboxymethyl cellulose per gavage), the atherogenic group (Apo E(-/-)+carboxymethyl cellulose per gavage) and the tanshinoneâ ¡A intervention group (Apo E(-/-)+30 mg/kg tanshinone â ¡A per gavage). All three groups were fed with high-fat-diet for 26 weeks. Tanshinone â ¡A/carboxymethyl cellulose was applied by the method of gavage administration 6 weeks before execution. After 26 weeks, tumor necrosis factor-α (TNF-α) andinterleukin (IL)-6 levels in serum were assessed by ELISA. Carotid artery was removed, fixed with paraformaldehyde, embedded with paraffin and sectioned. Percentage of stenosis was evaluated on HE stained sections. Plaque progression was assessed by Movat staining. Toluidine blue staining was used to evaluate mast cells infiltration and activation. Immunochemistry staining was used to assess 5-HT, TNF-α and IL-6 expression. mRNA expression of mast cell marker Fcer1a in adventitial tissue was detected by real time-PCR. Results: After high-fat-diet for 26 weeks, the mice in the atherogenic group showed advanced atherosclerosis, tanshinoneâ ¡A intervention reduced the percentage of carotid artery stenosis caused by atherosclerotic plaque formation ((58.48±8.07)% vs. (80.31±4.08)%, P<0.05). Compared with the atherogenic group, tanshinone â ¡A intervention group had lower level of TNF-α ((12.39±1.62)pg/ml vs. (17.44±1.42)pg/ml) and IL-6 ((116.24±12.16)pg/ml vs. (166.05±19.09)pg/ml) in serum, lower TNF-α ((20 145±1 556) vs. (25 288±1 671)) and IL-6 ((25 688±1 604) vs. (35 286±4 198)) expression in adventitia (all P<0.05). Tanshinoneâ ¡A intervention also decreased the number of mast cells infiltration and activation, reduced 5-HT expression and mast cell marker Fcer1a mRNA relative expression in adventitia (all P<0.05). Conclusions: Tanshinone â ¡A could attenuate induced by high-fat-diet carotid artery atherosclerosis in Apo E(-/-) mice. The protective effect of tanshinoneâ ¡A is probably mediated through reducing the number and activation percentage of mast cells, decreasing the release of inflammatory cytokines and inflammation of carotid artery in adventitia.
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Túnica Adventícia , Aterosclerose , Animais , Apolipoproteínas E , Artérias Carótidas , Masculino , Mastócitos , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Objective: To investigate the association between hepatic controlled attenuation parameter (CAP) and metabolic syndrome (MetS) and the correlation of CAP and its changes with the incidence of MetS. Methods: A total of 2461 subjects who underwent physical examination from July 2013 to September 2015 were enrolled. Spearman correlation analysis was used to investigate the correlation of CAP with the number of MetS components and each MetS component, and the chi-square test was used to investigate the prevalence rates of MetS and each component under different CAP levels. Logistic regression analysis was used to analyze the odds ratio (95% confidence interval (CI)) of MetS under different CAP levels. A total of 230 subjects without baseline MetS were selected; in a prospective cohort study, these subjects were divided into groups according to the baseline CAP, change in CAP, and percent change in CAP, and the chi-square test was performed to compare the incidence of MetS. The Cox regression analysis was used to analyze the values of baseline CAP, change in CAP, and percent change in CAP in predicting MetS. Results: CAP was positively correlated with the number of MetS components (r = 0.309, P < 0.01) and significantly correlated with all components. There were significant differences in the prevalence rates of MetS and its components under different CAP levels (< 238 dB/m, 238-258 dB/m, 259-291 dB/m, and ≥292 dB/m) (P < 0.05). After the adjustment for sex and age, with < 238 dB/m as a reference, the odds ratios (95% CI) of MetS in patients with CAP levels of 238-258 dB/m, 259-291 dB/m, and ≥292 dB/m were 1.784 (1.369-2.325), 2.936 (2.292-3.760), and 4.363 (3.435-5.543), respectively (all P < 0.05). Follow-up data showed that 28 patients (12.2%) developed MetS. After the adjustment for related factors, the hazard ratios (95% CI) of MetS in patients with baseline CAP > 238 dB/m, change in CAP > 30 dB/m, and percent change in CAP > 25.0% were 3.337 (1.163-9.569), 7.732 (2.453-24.366), and 11.656 (3.329-40.813), respectively (all P < 0.05). Conclusion: CAP is closely associated with MetS and its components. CAP and its change can be used to predict the risk of MetS.
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Síndrome Metabólica/diagnóstico , Humanos , Incidência , Razão de Chances , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Fatores de RiscoRESUMO
Objective: To investigate the serum lipidomic profile in patients with nonalcoholic fatty liver disease (NAFLD), and to analyze the lipid metabolism characteristics of NAFLD. Methods: The subjects were divided into control group (23 patients) and pathologically confirmed NAFLD group (42 patients), and ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure serum lipidomic metabolites. The partial least squares-discriminant analysis (PLS-DA) model was established to analyze the differences in lipid metabolism with reference to the univariate analysis. The t-test and Mann-Whitney U test were used for data analysis. Results: A total of 239 lipids were identified and qualitative and quantitative analyses were performed. The PLS-DA model (R2 = 0.753, Q2 = 0.456) and the univariate analysis showed that 77 lipids were metabolized differentially between the NAFLD group and the control group (VIP > 1, P < 0.05), including free fatty acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylinositol (LPI), choline plasmalogen (PlsCho), ethanolamine plasmalogen (PlsEtn), ceramide (Cer), sphingomyelin, and triglyceride (TG). Compared with the control group, the NAFLD group had significant increases in monounsaturated fatty acids (increased by 39%, t = -3.954, P < 0.05) and TGs (increased by 36%, Z = -2.662, P < 0.05), mainly TGs with low numbers of carbon atoms and unsaturated bonds, while there were reductions in TGs with high numbers of carbon atoms and unsaturated bonds. In addition, compared with the control group, the NAFLD group had significant increases in the levels of LPI (increased by 223%, t = -3.858, P < 0.05) and Cer (increased by 21%, t = -2.481, P < 0.05) and significant reductions in PlsCho (reduced by 18%, t = 3.184, P < 0.05) and PlsEtn (reduced by 20%, t = 2.363, P < 0.05). Conclusion: There is a significant difference in lipid metabolism profile between NAFLD patients and healthy people, and a serum lipidomic analysis of NAFLD helps to further clarify the characteristics of lipid metabolism in patients with NAFLD.
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Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica/sangue , Estudos de Casos e Controles , Humanos , Lisofosfolipídeos/sangue , Fosfatidilcolinas/sangue , Plasmalogênios/sangue , Triglicerídeos/sangueRESUMO
Objective: To investigate the efficiency of FibroScan(FS)and FibroTouch(FT)in liver stiffness measurement(LSM)and fat quantification through a comparative analysis. Methods: The outpatients or hospitalized patients who underwent LSM and fat quantification using FS and FT were enrolled. The differences in success rate and detecting parameters between FS and FT were analyzed, as well as the correlation between FS and FT values. The t-test was used for comparison of normally distributed continuous data between groups, and a one-way analysis of variance or the Kruskal-Wallis test was used for comparison between multiple groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. Results: A total of 1621 patients were enrolled. The success rates of FT and FS were 100% and 94.96%, respectively, and the success rate of FS was influenced by sex, age, body mass index, and biochemical markers of liver function. FT has a significantly shorter duration of single detection and a significantly lower number of times of single detection than FS(duration of single detection: 190.21±38.78 s vs 220.89±68.36 s, P < 0.01; number of single detection times: 10.31±1.32 vs 11.81±3.76, P < 0.01), as well as a significantly lower ratio of interquartile range to median of fat quantification in the same patient(5.39%±4.81% vs 17.18%±14.07%, P < 0.01). The LSM and fat quantification of FS were significantly correlated with those of FT(r = 0.645 and 0.620, both Based on the duration and number of times of single detection, success rate, and stability of fat quantification, FT seems to have a better detection efficiency than FS. The detection values of FT and FS can be calculated with regression equations < 0.01). The equations of linear regression were LSM(FT)= 4.435+0.477×LSM(FS); CAP(FT)= 134.71+0.456×CAP(FS). Conclusion: Based on the duration and number of times of single detection, success rate, and stability of fat quantification, FT seems to have a better detection efficiency than FS. The detection values of FT and FS can be calculated with regression equations.
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Técnicas de Imagem por Elasticidade/métodos , Fígado Gorduroso/sangue , Fígado Gorduroso/diagnóstico por imagem , Fígado/diagnóstico por imagem , Adulto , Biomarcadores/sangue , Fígado Gorduroso/patologia , Feminino , Humanos , Fígado/patologia , Cirrose Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Fatores de TempoRESUMO
UNLABELLED: Acquired multidrug resistance (MDR) is the main mechanism of chemotherapeutic drugs resistance. Nevertheless, the mechanisms of MDR are complex and still not very clear. Recently, including our previous study, several studies have revealed that macroautophagy (here referred to as autophagy) induced by anti-cancer drugs in breast cancer cells may facilitate the development of resistance to epirubicin (EPI), paclitaxel (PTX), tamoxifen or herceptin. Whereas there are a few studies on the relationship between autophagy and MDR, especially the studies designed directly employing induced resistant breast cancer cells. Based on previous study, we explored the relationship between autophagy and MDR. The results showed that induced EPI-resistant MCF-7er and SK-BR-3er cells were simultaneously resistant to PTX and vinorelbine (NVB), which demonstrated that the cells obtained MDR phenotype. Furthermore, PTX and NVB could also induce autophagy in MCF-7er and SK-BR-3er cells, and the induced autophagy protected the cells from apoptosis, which facilitated the development of resistance to PTX and NVB. Thus, autophagy promoted the development of MDR in breast cancer cells through inhibition of apoptosis. In addition, we found that P-glycoprotein (Pgp) was overexpressed in MCF-7er and SK-Br-3er cells. And we preliminarily investigated the relationship between autophagy and P-glycoprotein (Pgp). The results showed that the expression of the protein did not obviously change despite the inhibition of autophagy. Therefore, the role of Pgp in the development of MDR might be independent of autophahy. Also this finding implies that autophagy might be a target to overcome MDR in breast cancer cells, and clinical use autophagy inhibitors might be one of the important strategies for overcoming MDR in breast cancer therapy. KEYWORDS: Autophagy, apoptosis, multidrug resistance, breast cancer, chemotherapy.
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The effect of different dietary protein levels and DL-methionine (Met) supplementation on hair growth and the resulting pelt quality in mink was studied. Four groups of male mink were fed with four isocaloric diets containing 32% (P32), 24% (P24), 16% (P16) or P24+Met (0.8%) crude protein of dry matter (DM) from September to December. Skin biopsies were taken at the pelting. Histological techniques and computer-assisted light microscopy were used to determine the ratio of activity (ROA) of under hairs and guard hairs respectively. The results showed that when the dietary protein level reduced from 32% to 16%, body length, number and diameter of under hairs and guard hairs of minks declined, and pelt length and pelt weight of minks decreased significantly (p < 0.05). These parameters were similar between P32 and P24 with Met supplementation (p > 0.05). The hair follicle density of the winter coat was not influenced by the dietary protein levels and Met supplementation (p > 0.05). Low-protein diets content led to a reduction of hair follicle developing to next phase. It was documented that 24% crude protein of DM with Met supplementation during growing-furring period was sufficient for minks to express their genetic capacity to develop hair follicles and achieve the prime fur characteristics. Overall this study demonstrated that hair growth and hair properties in pelts are very dependent on the dietary protein and Met supply in the growing-furring period of minks.
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Ração Animal/análise , Dieta/veterinária , Proteínas Alimentares/normas , Cabelo/fisiologia , Metionina/farmacologia , Vison/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Suplementos Nutricionais , Masculino , Metionina/administração & dosagemRESUMO
OBJECTIVE: We aimed to investigate the expression and specific molecular mechanism of circ-PRKCI in lung cancer (LCa). PATIENTS AND METHODS: The relationship between the expression level of circ-PRKCI and the prognosis of patients was analyzed. The impacts of circ-PRKCI on the invasiveness of LCa cells were examined by Cell Counting Kit-8 (CCK-8) experiments, clone formation experiments, and transwell invasion experiments. Subcellular localization of circ-PRKCI was determined through nuclear separation experiments. Downstream target genes that can bind to circ-PRKCI was predicted through bioinformatics analysis, and was then verified by Dual-Luciferase experiments, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) experiments, and Western blot experiments. RESULTS: Circ-PRKCI level was remarkably elevated in LCa tumor tissues and cell lines. At the same time, highly expressed circ-PRKCI was correlated with the poor prognosis of LCa patients. In vitro cell experiments revealed that inhibition of circ-PRKCI in LCa cell lines remarkably inhibited cell invasiveness and proliferation. In addition, circ-PRKCI can compete with MECP2 to bind microRNA-1324 and thus affect the progression of LCa. CONCLUSIONS: Our study shows for the first time that circ-PRKCI modulates the progression of LCa through microRNA-150-5p/MECP2 axis.
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Neoplasias Pulmonares/metabolismo , Proteína 2 de Ligação a Metil-CpG/genética , MicroRNAs/metabolismo , RNA Circular/metabolismo , Sítios de Ligação , Células Cultivadas , Humanos , Neoplasias Pulmonares/patologia , Proteína 2 de Ligação a Metil-CpG/metabolismo , MicroRNAs/genética , RNA Circular/genéticaRESUMO
OBJECTIVE: Concerns have been raised that patients with Coronavirus Disease 2019 (COVID-19) are still infectious with a re-positive nucleic acid test of the pharyngeal swab after hospital discharge. The aim of this study was to investigate the clinical relevance of induced sputum as an additional indicator for the current clinical discharge criteria of COVID-19 patients to prevent virus recurrence. PATIENTS AND METHODS: Twenty-one COVID-19 patients who met the national clinical discharge criteria were discharged from the hospital and tested daily for the presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) nucleic acid in their pharyngeal swabs and every other day for the presence of SARS-CoV-2 in their induced sputum. Once the patient's induced sputum was negative after two consecutive tests, testing was discontinued. RESULTS: Among 21 discharged patients from COVID-19, the first pharyngeal swab and induced sputum tests for viral nucleic acid were positive in 3 (14.3%) and 8 (38.1%) patients respectively. Induced sputum was significantly more positive than pharyngeal swab (p < 0.05). In our cohort, all pharyngeal swabs became negative at day 7, and all induced sputa turned negative at day 11 after discharge. Interestingly, patients with negative pharyngeal swabs experienced viral relapse, whereas patients with negative induced sputum did not revert to positivity. CONCLUSIONS: The detection rate of positive viral nucleic acid in induced sputum was high. Patients with negative induced sputum nucleic acid tests did not have a relapse of SARS-COV-2, indicating that viral nucleic acid testing of induced sputum should be used as an additional criterion for patients with national clinical discharge criteria COVID-19.
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Teste de Ácido Nucleico para COVID-19 , COVID-19/diagnóstico , Faringe/virologia , RNA Viral/análise , Escarro/virologia , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Faringe/química , Recidiva , Escarro/química , Eliminação de Partículas Virais , Adulto JovemRESUMO
We have constructed a physical map of the human genome by using a panel of 90 whole-genome radiation hybrids (the TNG panel) in conjunction with 40,322 sequence-tagged sites (STSs) derived from random genomic sequences as well as expressed sequences. Of 36,678 STSs on the TNG radiation hybrid map, only 3604 (9.8%) were absent from the unassembled draft sequence of the human genome. Of 20,030 STSs ordered on the TNG map as well as the assembled human genome draft sequence and the Celera assembled human genome sequence, 36% of the STSs had a discrepant order between the working draft sequence and the Celera sequence. The TNG map order was identical to one of the two sequence orders in 60% of these discrepant cases.
Assuntos
Genoma Humano , Mapeamento de Híbridos Radioativos , Análise de Sequência de DNA , Algoritmos , Cromossomos Artificiais Bacterianos , Biologia Computacional , Mapeamento de Sequências Contíguas , Bases de Dados Factuais , Projeto Genoma Humano , Humanos , Hibridização in Situ Fluorescente , Mapeamento Físico do Cromossomo , Reação em Cadeia da Polimerase , Sitios de Sequências Rotuladas , SoftwareRESUMO
OBJECTIVE: To study the regulatory effect of long non-coding ribonucleic acid (lncRNA) HOX transcript antisense RNA (HOTAIR) on acute kidney injury (AKI) in sepsis rats and its regulatory mechanism. MATERIALS AND METHODS: The sepsis-induced AKI model was established in Sprague-Dawley (SD) male rats through cecal ligation puncture. A total of 30 SD rats were randomly divided into the control group, model group and lncRNA HOTAIR mimic group, with 10 rats in each group. Relative levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in kidney tissues were detected via enzyme-linked immunosorbent assay (ELISA). Apoptosis of kidney tissues was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Moreover, the target gene of miR-34a was searched using the miRNA online database. The messenger RNA (mRNA) expression levels of miR-34a and B-cell lymphoma-2 (Bcl-2) were detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). RESULTS: Compared with those in the control group, the rats in the model group showed injured pathological morphology of kidney, elevated contents of TNF-α and IL-1ß, and apoptosis in kidney tissues. The target gene of miR-34a was Bcl-2, according to the miRNA online database. MiR-34a level in kidney tissues was upregulated, while the mRNA level of Bcl-2 significantly decreased in the model group. Compared with those in the model group, the pathological morphology of kidney tissues was improved, the content of TNF-α and IL-1ß markedly declined, and the apoptotic rate of kidney tissues also reduced in lncRNA HOTAIR mimic group. The miR-34a level in kidney tissues decreased, while the Bcl-2 mRNA level remarkably increased in lncRNA HOTAIR mimic group. CONCLUSIONS: LncRNA HOTAIR overexpression can alleviate AKI in sepsis rats by inhibiting the apoptosis of kidney tissues by downregulating the miR-34a/Bcl-2 signaling pathway.
Assuntos
Injúria Renal Aguda/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Longo não Codificante/metabolismo , Sepse/complicações , Injúria Renal Aguda/patologia , Animais , Apoptose/genética , Modelos Animais de Doenças , Humanos , Rim/patologia , Masculino , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Transdução de Sinais/genética , Regulação para CimaRESUMO
This study was conducted to determine the effects of residual superdoses of phytase on growth performance, tibia mineralization, and relative organ weight in ducks fed phosphorus-deficient diets. In Exp. 1, 4 kinds of commercial phytase were used to determine retention rate of phyatse with the phytase C being the highest via both high water-bath temperature (90%) and pelleting (50%), followed by phytase A, B, and D. In Exp. 2, a total of 560 male ducks were blocked based on body weight, and then allocated randomly to 7 treatments (5 replicates with 16 birds per replicate). Treatments included a maize-soybean meal-based diet with recommended calcium and 4.0 g non-phytate phosphorus (nPP)/kg starter diet or 3.8 g nPP/kg grower diet (positive control; PC), an nPP-deficient diet with 1.3 g nPP/kg starter diet or 1.1 g nPP/kg grower diet (negative control; NC), NC diets with increasing levels of residual phytase C (500, 1,000, 2,000, 3,000, and 4,000 units/kg feed) after pelleting. Birds fed NC diets had lower (P < 0.05) average daily gain (ADG) and average daily feed intake (ADFI) throughout the experiment compared with those fed PC diet. Supplementing NC diet with increasing residual superdoses of phytase improved (P < 0.05) ADG and ADFI quadratically in the entire experiment, while reduced feed-to-gain ratio (P < 0.05) quadratically during day 0 to 14. On day 14 and 35, birds fed NC diet had lower (P < 0.05) tibia length, weight, ash, calcium, phosphorus, and manganese contents than those fed PC diet. Increasing residual superdoses of phytase in NC diet increased (P < 0.05) tibia weight and ash, calcium, phosphorus contents quadratically on day 14 and 35. NC treatment increased (P < 0.05) the duodenum, jejunum, ileum, and cecum index compared with other treatments on day 14 and 35. Taken together, feeding increasing residual superdoses of phytase could counteract or exceed the negative effects of NC diet on growth performance, tibia mineralization, and relative organ weight in ducks.
Assuntos
6-Fitase/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Patos/fisiologia , Fósforo na Dieta/análise , Tíbia/efeitos dos fármacos , 6-Fitase/administração & dosagem , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Patos/crescimento & desenvolvimento , Masculino , Tamanho do Órgão/efeitos dos fármacos , Distribuição Aleatória , Tíbia/fisiologiaRESUMO
Landfill leachates are composed of a complex mixture of organic matter, including a wide range of potentially fluorescent organic compounds. The fluorescence excitation-emission matrix (FEEM) of leachates during treatment processes is investigated. Particular attention is paid to the fluorescence evolution of leachates during treatment processes. Two typical types of landfill, landfill A (a direct municipal solid waste (MSW) landfill) and landfill B (disposal of bottom ashes from MSW incinerators), in a city in Southern China were selected. The results show that two characteristic and intense excitation-emission peaks located at Ex/Em = 310-330 nm/395-410 nm (peak alpha) and Ex/Em = 250-260 nm/450-460 nm (peak alpha') are observed. As the aromatic chemicals, capable of emitting fluorescence, are more recalcitrant to biodegradation than aliphatic chemicals, enhancement of the dissolved organic carbon normalized fluorescence intensities is demonstrated during treatment processes of leachate A and leachate B. This is confirmed by the variation of ultraviolet absorptivity of leachates at 254 nm. Peak alpha' and peak alpha are attributed to a mixture of xenobiotic organic compounds with low molecular weight and relatively stable aromatic fulvic-like matters with high molecular weight, respectively. Humic substances are more resistant to biodegradation than xenobiotic organic compounds, so a significant reduction in the Ialpha'/Ialpha values (fluorescence intensity ratios of peak alpha' and peak a) of leachate A was observed during treatment processes. However, no evident variation for the Ialpha/Ialpha values of leachate B was found during treatment processes owing to the low concentrations of xenobiotic organic compounds in leachate B after incineration.
Assuntos
Fluorescência , Compostos Orgânicos/análise , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Compostos Orgânicos/química , Poluentes Químicos da Água/químicaRESUMO
OBJECTIVE: The study aims to investigate whether Long non-coding RNA (LncRNA)-UCA1 can regulate the progression of Parkinson's disease (PD) by mediating a-synuclein (SNCA) expression. MATERIALS AND METHODS: PD mouse model was first constructed by intraperitoneal injection of MPTP. SH-SY5Y cells were treated with MPP+ for inducing in vitro PD model. Expression levels of lncRNA-UCA1 and SNCA in brain tissues extracted from PD mice and MPP+-induced SH-SY5Y cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression of SNCA was accessed by Western blot. After transfection of pcDNA-NC+DMSO, pcDNA-UCA1+DMSO, pcDNA-NC+α-amantin or pcDNA-UCA1+α-amanitin in SH-SY5Y cells, SNCA expression was detected. Cell viability and SNCA expression were determined after UCA1 overexpression or knockdown in SH-SY5Y cells. Neuronal apoptosis in MPP+-induced SH-SY5Y cells was detected by flow cytometry after the UCA1 knockdown. RESULTS: UCA1 and SNCA were highly expressed in brain tissues extracted from PD mice and MPP+-induced SH-SY5Y cells. UCA1 overexpression remarkably upregulated mRNA and protein expressions of SNCA in SH-SY5Y cells. Higher viability was seen after the UCA1 knockdown in MPP+-induced SH-SY5Y cells. UCA1 knockdown remarkably inhibited caspase-3 activity and decreased MPP+-induced neuronal apoptosis in SH-SY5Y cells. CONCLUSIONS: LncRNA-UCA1 promotes the occurrence and progression of PD by upregulating SNCA expression.