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The pursuit of discovering new high-temperature superconductors that diverge from the copper-based model1-3 has profound implications for explaining mechanisms behind superconductivity and may also enable new applications4-8. Here our investigation shows that the application of pressure effectively suppresses the spin-charge order in trilayer nickelate La4Ni3O10-δ single crystals, leading to the emergence of superconductivity with a maximum critical temperature (Tc) of around 30 K at 69.0 GPa. The d.c. susceptibility measurements confirm a substantial diamagnetic response below Tc, indicating the presence of bulk superconductivity with a volume fraction exceeding 80%. In the normal state, we observe a strange metal behaviour, characterized by a linear temperature-dependent resistance extending up to 300 K. Furthermore, the layer-dependent superconductivity observed hints at a unique interlayer coupling mechanism specific to nickelates, setting them apart from cuprates in this regard. Our findings provide crucial insights into the fundamental mechanisms underpinning superconductivity, while also introducing a new material platform to explore the intricate interplay between the spin-charge order, flat band structures, interlayer coupling, strange metal behaviour and high-temperature superconductivity.
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INTRODUCTION: The prognostic value of the ratio of haemoglobin to red cell distribution width (HRR) in different types of heart failure (HF) is not well known. METHOD AND RESULTS: We analysed the long-term prognostic value of HRR in patients with HF using the Cox proportional risk model and Kaplan-Meier method. We reviewed consecutive 972 HF patients. The overall mortality rate was 45.68%. Mortality was 52.22% in the HFrEF group and 40.99% in the HFpEF + HFmrEF group. Cox regression showed that when HRR increased by 1 unit, the risk of all-cause death in all HF patients decreased by 22.8% (HR: 0.772, 95% CI: 0.724, 0.823, p < 0.001), in the HFpEF + HFmrEF group it decreased by 15.5% (HR: 0.845, 95% CI: 0.774, 0.923, p < 0.001), and in the HFrEF group it decreased by 36.1% (HR: 0.639, 95% CI: 0.576, 0.709, p < 0.0001). Subgroup analysis showed that there were interactions between the EF and HRR groups. The group in which HRR best predicted all-cause death from HF was group 1 (EF <40%, HRR <9.45), followed by group 2 (EF <40%, HRR ≥9.45), and group 3 (EF ≥40%, HRR <9.45). HRR had no predictive value in group 4 (EF ≥40%, HRR ≥9.45). CONCLUSION: HRR is an important predictor of all-cause mortality in patients with HF, especially HFrEF. There is an interaction between HRR group and LVEF group.
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Índices de Eritrócitos , Insuficiência Cardíaca , Hemoglobinas , Volume Sistólico , Humanos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/sangue , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Hemoglobinas/análise , Prognóstico , Modelos de Riscos Proporcionais , Valor Preditivo dos Testes , Estudos Retrospectivos , Estimativa de Kaplan-Meier , Causas de Morte , Idoso de 80 Anos ou maisRESUMO
OBJECTION: Inflammatory conditions and immune disorders may worsen the prognosis of chronic heart failure (CHF) patients. The aim of this study was to evaluate the prognostic value of a new indicator, C-NLR, composed of C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), for the risk of all-cause mortality in HF patients with different ejection fractions. METHODS: A total of 1221 CHF patients admitted to the First Affiliated Hospital of Kunming Medical University from January 2017 to October 2021 were enrolled in this study. All patients were divided into 2 groups according to the median C-NLR. Kaplan-Meier survival curves were used to compare the all-cause mortality among CHF patients with different ejection fractions. Cox proportional hazards analysis was used to evaluate the relationships between variables and mortality. The predictive value of the C-NLR was assessed by using receiver operating characteristic (ROC) analyses. RESULTS: We collected data from 1192 patients with CHF. Kaplan-Meier survival analysis revealed that patients with low LCR levels had better overall survival (OS). After multivariate adjustment Cox proportional hazards analysis, the level of C-NLR was still independently related to mortality. CONCLUSIONS: C-NLR was a competent independent predictor in HF with different ejection fractions, and routine measurement of C-NLR would help clinical doctors identify patients with a poor prognosis.
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Insuficiência Cardíaca , Neutrófilos , Humanos , Neutrófilos/metabolismo , Prognóstico , Estudos Retrospectivos , Linfócitos/metabolismo , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/metabolismoRESUMO
BACKGROUND: The prognostic nutritional index (PNI) and serum chloride level are related to adverse outcomes in patients with heart failure. However, little is known about the relationship between the PNI and serum chloride level in predicting the poor prognosis of patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: We reviewed 1221 consecutive patients with ADHF admitted to the First Affiliated Hospital of Kunming Medical University from January 2017 to October 2021. After excluding patients with in hospital death, missing follow-up data, missing chloride data, missing lymphocyte (LYM) count data, or missing serum albumin data, 805 patients were included. PNI was calculated using the formula: serum albumin (ALB) (g/L) + 5 × LYM count (10^9/L). Patients were divided into 4 groups according to the quartiles of the PNI, and the highest PNI quartile (PNI Q4: PNI ≥ 47.3) was set as the reference group. The patients in the lowest PNI quartile (PNI Q1: PNI < 40.8) had the lowest cumulative survival rate, and mortality risk decreased progressively through the quartiles (log-rank χ2 142.283, P < 0.0001). Patients with ADHF were divided into 8 groups by quartiles of PNI and median levels of serum chloride. After adjustment, the hazard ratio (HR) for all-cause mortality in ADHF patients in Group 1 was 8.7 times higher than that in the reference Group 8. Furthermore, the addition of serum chloride level and PNI quartile to the Cox model increased the area under the Receiver operating characteristic (ROC) curve by 0.05, and the area under the ROC curve of the new model was higher than that of the original model with traditional risk factors. CONCLUSIONS: Both the lowest PNI quartiles and low chloride level indicate a higher risk of all-cause death in patients with ADHF.
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Biomarcadores , Cloretos , Insuficiência Cardíaca , Avaliação Nutricional , Humanos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Masculino , Feminino , Prognóstico , Cloretos/sangue , Idoso , Estudos Retrospectivos , Doença Aguda , Biomarcadores/sangue , Valor Preditivo dos Testes , Medição de Risco/métodos , Pessoa de Meia-Idade , China/epidemiologia , Fatores de Risco , Curva ROC , Taxa de Sobrevida/tendências , Estado Nutricional , Idoso de 80 Anos ou mais , SeguimentosRESUMO
Fibroblast activation protein (FAP) is highly expressed in many tumor types and constitutes a promising target for tumor-specific delivery of therapeutic radionuclides. [177Lu]Lu-DOTAGA.(SA.FAPi)2 is a novel radiopharmaceutical based on a novel bidentate inhibitor of FAP that is excreted more slowly than its monomeric counterparts. Still, the efficacy of radiotherapy is mitigated by cascades of DNA damage repair signaling in tumor cells including those via Poly(ADP-ribose) polymerase (PARP). We hereby aimed to evaluate the efficacy of [177Lu]Lu-DOTAGA.(SA.FAPi)2 in combination with a PARP inhibitor, Olaparib, in the 4T1 murine triple negative breast cancer (TNBC) model. The therapeutic efficacy was visualized using 18F-FDG and [68Ga]Ga-FAPI-04 positron emission imaging/computer tomography (PET/CT). Our results demonstrated that Olaparib suppressed BALB/3T3 fibroblasts in vitro and sensitized the efficacy of [177Lu]Lu-DOTAGA.(SA.FAPi)2 in mice bearing 4T1 tumors via enhancement of DNA damage. Treatment-associated toxicity was tolerable with only mild leukopenia. Therefore, the combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and Olaparib is a feasible treatment against TNBC.
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Antineoplásicos , Neoplasias de Mama Triplo Negativas , Humanos , Camundongos , Animais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Poli(ADP-Ribose) Polimerases/metabolismo , Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/radioterapia , Neoplasias de Mama Triplo Negativas/genética , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Gálio/uso terapêuticoRESUMO
BACKGROUND: This study was undertaken to explore the predictive value of the advanced lung cancer inflammation index (ALI) combined with the geriatric nutritional risk index (GNRI) for all-cause mortality in patients with heart failure (HF). METHODS AND RESULTS: We enrolled 1123 patients with HF admitted to our cardiology department from January 2017 to October 2021. Patients were divided into four groups, according to the median ALI and GNRI. From the analysis of the relationship between the ALI and GNRI, we concluded that there was a mild positive linear correlation (r = 0.348, p < 0.001) and no interaction (p = 0.140) between the ALI and GNRI. KaplanâMeier analysis showed that the cumulative incidence of all-cause mortality in patients with HF was highest in Group 1 (log-rank χ2 126.244, p < 0.001). Multivariate Cox proportional hazards analysis revealed that ALI and GNRI were independent predictors of all-cause mortality in HF patients (ALI: HR 0.407, 95% CI 0.296-0.560, p < 0.001; GNRI: HR 0.967, 95% CI 0.954-0.980, p < 0.001). The area under the curve (AUC) for ALI combined with GNRI was 0.711 (p < 0.001), according to the time-dependent ROC curve. CONCLUSION: ALI and GNRI were independent predictors of all-cause mortality in HF patients. Patients with HF had the highest risk of all-cause mortality when the ALI was < 24.60 and the GNRI was < 94.41. ALI combined with the GNRI has good predictive value for the prognosis of HF patients.
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Insuficiência Cardíaca , Neoplasias Pulmonares , Humanos , Idoso , Avaliação Nutricional , Neoplasias Pulmonares/diagnóstico , Insuficiência Cardíaca/diagnóstico , Prognóstico , Inflamação/diagnóstico , Estado Nutricional , Fatores de Risco , Estudos RetrospectivosRESUMO
BACKGROUND: The goal of this study was to assess the effectiveness of machine learning models and create an interpretable machine learning model that adequately explained 3-year all-cause mortality in patients with chronic heart failure. METHODS: The data in this paper were selected from patients with chronic heart failure who were hospitalized at the First Affiliated Hospital of Kunming Medical University, from 2017 to 2019 with cardiac function class III-IV. The dataset was explored using six different machine learning models, including logistic regression, naive Bayes, random forest classifier, extreme gradient boost, K-nearest neighbor, and decision tree. Finally, interpretable methods based on machine learning, such as SHAP value, permutation importance, and partial dependence plots, were used to estimate the 3-year all-cause mortality risk and produce individual interpretations of the model's conclusions. RESULT: In this paper, random forest was identified as the optimal aools lgorithm for this dataset. We also incorporated relevant machine learning interpretable tand techniques to improve disease prognosis, including permutation importance, PDP plots and SHAP values for analysis. From this study, we can see that the number of hospitalizations, age, glomerular filtration rate, BNP, NYHA cardiac function classification, lymphocyte absolute value, serum albumin, hemoglobin, total cholesterol, pulmonary artery systolic pressure and so on were important for providing an optimal risk assessment and were important predictive factors of chronic heart failure. CONCLUSION: The machine learning-based cardiovascular risk models could be used to accurately assess and stratify the 3-year risk of all-cause mortality among CHF patients. Machine learning in combination with permutation importance, PDP plots, and the SHAP value could offer a clear explanation of individual risk prediction and give doctors an intuitive knowledge of the functions of important model components.
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Insuficiência Cardíaca , Humanos , Teorema de Bayes , Doença Crônica , Análise por Conglomerados , Aprendizado de MáquinaRESUMO
A hairpin DNA-enabled ratiometric electrochemical aptasensor is reported for sensitive and reliable detection of malathion (MAL). The approach employs hairpin DNA (ferrocene-labeled, Fc-hDNA) as a carrier to hybridize MAL aptamers (methylene blue-labeled, MB-Apt) to form double-stranded DNA structures on an electrode. The presence of MAL induces the removal of aptamers, and hDNA re-forms hairpin structures, causing a decrease in the oxidation current of MB (IMB) and an increase in the oxidation current of Fc (IFc). The ratiometric signal of IFc/IMB responds quantitatively to MAL concentrations. To compare analytical performances, a linear single-stranded DNA (ssDNA) is also used to construct the ssDNA-based aptasensor. We demonstrate that hairpin DNA possessing a rigid two-dimensional structure can improve the assembly efficiency of aptamers and the stability of redox probes. The approach combines the advantages of the ratiometric electrochemical method with hairpin DNA-based conformational switching probes, enabling hDNA-based aptasensor with enhanced sensitivity and reliability, offering a linear range of 0.001 to 1.0 ng mL-1. The platform was applied to detect MAL in lettuce, and the statistical analysis indicated that no significant differences were found between the developed platform and HPLC-MS.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Malation , Reprodutibilidade dos Testes , Aptâmeros de Nucleotídeos/química , DNA/química , DNA de Cadeia Simples , Técnicas Eletroquímicas/métodosRESUMO
Little is known regarding the prognostic value of serum chloride in patients with chronic heart failure (CHF) with different ejection fractions. We sought to determine the postdischarge outcomes associated with lower serum chloride between different CHF types.We reviewed the medical records of 1221 consecutive patients with CHF admitted to the First Affiliated Hospital of Kunming Medical University from January 2017 to October 2021. After excluding patients with in-hospital death, missing follow-up data, missing serum chloride level data, or chronic dialysis therapy, 791 patients were included. Of these patients, 343 had heart failure with reduced ejection fraction (HFrEF; i.e., left ventricular ejection fraction (LVEF) < 40%), and 448 had heart failure with preserved ejection fraction (HFpEF) or heart failure with median ejection fraction (HFmrEF; HFpEF plus HFmrEF; i.e., LVEF ≥40%). Over a median follow-up of 750 days, 344 patients (43.5%) had all-cause mortality. In the univariate analysis, serum sodium and chloride were strongly associated with mortality in both HF subgroups (P < 0.0001). A multivariable model including both serum sodium and chloride showed the highly significant association between serum chloride and survival (P < 0.0001), whereas the association between serum sodium and mortality was not reported (HFpEF plus HFmrEF, hazard ratio (HR) 0.975, 95% confidence interval [CI] 0.942-1.010, P = 0.158; HFrEF, HR 1.007, 95% CI 0.966-1.051, P = 0.734). Kaplan-Meier survival curve analysis revealed a significant difference in mortality risk with decreasing chloride levels in all patients with CHF. The optimal cutoff value of chloride in predicting all-cause mortality was 102.95 mmol/L with area under the curve value of 0.76 [HR 0.760, 95% CI 0.727-0.793, P < 0.0001], sensitivity of 60.2%, and specificity of 78.3%.Lower serum chloride is an independent predictor of death in CHF, regardless of heart failure subtype.
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OBJECTIVE: To ensure the supply of prevention materials in the tertiary public hospitals in prefecturelevel cities, and to make the process of allocating prevention materials more scientific and reasonable. METHODS: Open the green passage, simplify the procurement process, carry out emergency procurement of related materials, ensure timely delivery of prevention materials, distribute them at different levels, and strengthen the warehouse management of prevention materials. RESULTS: The scheme of emergancy supplies was constantly improved, and the supply of prevention materials was completed with good quality. CONCLUSIONS: Using scientific and efficient management methods, the supply of prevention materials in medical institutions has been guaranteed, which has experience and reference significance for the prevention and control of similar public health emergencies in the future.
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Emergências , Saúde Pública , Humanos , Centros de Atenção TerciáriaRESUMO
PURPOSE: The aim of this study was to retrospectively compare and analyze pregnancy outcomes of patients with uterine fibroids after high intensity focused ultrasound (HIFU) ablation and laparoscopic myomectomy (LM). MATERIALS AND METHODS: The study group consisted of 346 patients with uterine fibroids who wished to conceive, in which 152 patients received HIFU ablation treatment (HIFU group) and 194 patients received LM treatment (LM group). The parents' baseline characters were recorded and the pregnancy outcomes were evaluated in a median follow-up time of 42 months (range: 16 â¼ 81) after the treatment, and the differences of the two groups were compared. RESULTS: Patients with uterine fibroids in HIFU group had a significant shorter pregnancy interval than that in LM group (10 months VS. 13 months, p < .05). No significant differences were observed in pregnancy rate, miscarriage rate, live birth rate, natural pregnancy rate, cesarean section rate, and perinatal complications rate between the HIFU group and the LM group (p > .05). When stratified by age, infertility history, fibroid types, fibroid numbers, and fibroid sizes, there was no statistically significant difference in pregnancy rate between the HIFU group and the LM group (p > .05). CONCLUSIONS: Based on the results from this study, both HIFU and LM can be safely used to treat patients who wish to conceive. The pregnancy outcomes of post-HIFU are similar to that of post-LM.
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Ablação por Ultrassom Focalizado de Alta Intensidade , Laparoscopia , Leiomioma , Miomectomia Uterina , Neoplasias Uterinas , Cesárea , Feminino , Humanos , Leiomioma/cirurgia , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Uterinas/cirurgiaRESUMO
STUDY OBJECTIVE: To identify factors that affect reproductive outcomes after hysteroscopic adhesiolysis in patients with severe intrauterine adhesions (IUAs, scored between 9 and 12 according to the American Fertility Society classification) and amenorrhea. DESIGN: A retrospective cohort study. SETTING: A university-affiliated hospital. PATIENTS: One hundred fifty-one patients with severe IUAs and amenorrhea. INTERVENTION: Patients were diagnosed via hysteroscopy and underwent at least 1 hysteroscopic adhesiolysis between May 2012 and January 2016. MEASUREMENTS AND MAIN RESULTS: Of 151 patients, 12 were lost to follow-up, and 139 were included in the study with a follow-up period ranging from 2 to 6 years. Of the 139 evaluable patients, 107 (77%) recovered with a normal uterine cavity (free of IUAs), 28 (20.1%) had improved uterine cavity (fewer IUAs), and 4 (2.9%) showed no improvement. Moreover, 79 patients (56.8%) recovered with normal menstruation, 54 (38.9%) showed increased frequency of menstruation, and 6 (4.3%) had persistent amenorrhea. Seventy-seven (55.4%) became pregnant, of whom 13 had a spontaneous miscarriage, 11 birthed prematurely (at 31-36 gestational weeks), 44 experienced term delivery, and 9 were still pregnant at the end of the study. Age >32 years (pâ¯=â¯.002, odds ratio [OR]â¯=â¯3.442), >2 surgeries (pâ¯=â¯.027, ORâ¯=â¯2.969), cervical canal adhesions (pâ¯=â¯.047, ORâ¯=â¯2.112), and disease course >6 months (pâ¯=â¯.037, ORâ¯=â¯2.335) were risk factors for infertility in patients with severe IUAs and amenorrhea. CONCLUSION: Younger age, earlier treatment within the disease course, fewer cervical canal adhesions, and fewer surgical procedures improve the reproductive outcome in patients with severe IUAs and amenorrhea.
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Amenorreia/cirurgia , Histeroscopia/métodos , Infertilidade Feminina/etiologia , Aderências Teciduais/cirurgia , Doenças Uterinas/cirurgia , Adulto , Amenorreia/epidemiologia , Amenorreia/etiologia , Estudos de Coortes , Dissecação/métodos , Feminino , Humanos , Histeroscopia/efeitos adversos , Histeroscopia/reabilitação , Histeroscopia/estatística & dados numéricos , Infertilidade Feminina/epidemiologia , Menstruação/fisiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/cirurgia , Estudos Retrospectivos , Fatores de Risco , Aderências Teciduais/complicações , Aderências Teciduais/epidemiologia , Resultado do Tratamento , Doenças Uterinas/complicações , Doenças Uterinas/epidemiologia , Adulto JovemRESUMO
STUDY OBJECTIVE: To investigate risk factors for infertility and recurrent cesarean scar pregnancy (CSP) after previous CSP. DESIGN: A retrospective cohort study (Canadian Task Force classification II-1). SETTING: University hospital. PATIENTS: Between January 2007 and April 2016, a total of 650 patients were included, all diagnosed with CSP and treated by high-intensity focused ultrasound (HIFU) and uterine artery embolization (UAE), followed by suction curettage under hysteroscopic guidance. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Follow-up of the reproductive outcomes ended in June 2017. A total of 135 of the 650 patients with CSP were involved in the study, among whom 32 became infertile, 78 had an intrauterine pregnancy, and 25 had recurrent CSP after previous CSP. Age (≥35 years; odds ratio [OR], 4.252; pâ¯=â¯.002), ß-human chorionic gonadotropin (≤5000 mIU/mL; OR, 3.778; pâ¯=â¯.011), and longer duration of amenorrhea (>56 days; OR, 2.507; pâ¯=â¯.05) were risk factors for infertility. Treatment with UAE (OR, 5.796; pâ¯=â¯.003), more abortions (≥4; OR, 2.851; pâ¯=â¯.022), and being asymptomatic (OR, 4.175; pâ¯=â¯.039) were risk factors for recurrent CSP. There was no statistically significant difference in the subsequent outcomes of pregnant women in the HIFU and UAE groups (p >.05). CONCLUSION: More attention should be given to subsequent reproductive outcomes after CSP, not only for intrauterine pregnancy, but also for infertility and recurrent CSP. Early diagnosis and treatment of CSP could reduce the risk of infertility and recurrent CSP. HIFU seemed to be superior to UAE in reducing the risk of recurrent CSP. Patients with CSP should adhere to strict contraception if they do not desire more children.
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Cesárea/efeitos adversos , Cicatriz/cirurgia , Ablação por Ultrassom Focalizado de Alta Intensidade , Gravidez Ectópica/cirurgia , Embolização da Artéria Uterina/efeitos adversos , Curetagem a Vácuo/efeitos adversos , Aborto Induzido/efeitos adversos , Aborto Espontâneo/etiologia , Adulto , Gonadotropina Coriônica Humana Subunidade beta , Cicatriz/etiologia , Feminino , Seguimentos , Humanos , Infertilidade/prevenção & controle , Gravidez , Resultado da Gravidez , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Artéria Uterina/cirurgia , Adulto JovemRESUMO
Objective: To explore the molecular mechanisms of fat metabolism and deposition in pigs, an experiment was conducted to identify hepatic mRNAs and miRNAs expression and determine the potential interaction of them in two phenotypically extreme pig breeds. Methods: mRNA and miRNA profiling of liver from 70-day Jinhua (JH) and Landrace (LD) pigs were performed using RNA sequencing. Blood samples were taken to detect results of serum biochemistry. Bioinformatics analysis were applied to construct differentially expressed miRNA-mRNA network. Results: Serum total triiodothyronine (TT3) and total thyroxine (TT4) were significantly lower in Jinhua pigs, but the content of serum total cholesterol (TCH) and low-density lipoprotein cholesterol (LDLC) were strikingly higher. A total of 467 differentially expressed genes (DEGs) and 35 differentially expressed miRNAs (DE miRNAs) were identified between JH and LD groups. Gene ontology analysis suggested that DEGs were involved in oxidation-reduction, lipid biosynthetic and lipid metabolism process. Interaction network of DEGs and DE miRNAs were constructed, according to target prediction results. Conclusion: We generated transcriptome and miRNAome profiles of liver from Jinhua and Landrace pig breeds which represent distinguishing phenotypes of growth and metabolism. The potential miRNA-mRNA interaction networks may provide a comprehensive understanding in the mechanism of lipid metabolism. These results serve as a basis for further investigation on biological functions of miRNAs in the porcine liver.
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BACKGROUND: Our published data have indicated that the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) provides beneficial effects by attenuating neuronal damage induced by interleukin-1ß (IL-1ß), and up-regulation of the expression of brain-derived neurotrophic factor (BDNF) represents a crucial part in the neuroprotective effect of EPA. However, the mechanisms of how EPA regulates BDNF expression remains incompletely understood. The present study investigated the role of Akt/CREB signaling in the effect of EPA on BDNF expression and its neuroprotective effect. RESULTS: The present results showed that IL-1ß reduced hippocampal neuronal viability and that EPA showed a concentration-dependent neuroprotective effect, but the neuroprotective effects of EPA were abolished by inhibition of Akt using KRX-0401, an inhibitor of Akt. Treatment of hippocampal neurons with EPA also ameliorated the decrease in Akt and CREB phosphorylation induced by IL-1ß and BDNF down-regulation mediated by IL-1ß. However, inhibition of Akt reversed the effect of EPA on levels of p-Akt, p-CREB, and BDNF. CONCLUSIONS: Our data indicate that EPA elicited neuroprotection toward IL-1ß-induced cell damage and BDNF decrease and that its effects potentially occurred via the Akt/CREB signaling pathway.
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Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Ácido Eicosapentaenoico/farmacologia , Hipocampo/efeitos dos fármacos , Interleucina-1beta/metabolismo , Fármacos Neuroprotetores/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Hipocampo/metabolismo , Interleucina-1beta/toxicidade , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: An experiment was conducted to identify and characterize the circular RNA expression and metabolic characteristics in the liver of Jinhua pigs and Landrace pigs. METHODS: Three Jinhua pigs and three Landrace pigs respectively at 70-day were slaughtered to collect the liver tissue samples. Immediately after slaughter, blood samples were taken to detect serum biochemical indicators. Total RNA extracted from liver tissue samples were used to prepare the library and then sequence on HiSeq 2500. Bioinformatic methods were employed to analyze sequence data to identify the circRNAs and predict the potential roles of differentially expressed circRNAs between the two breeds. RESULTS: Significant differences in physiological and biochemical traits were observed between growing Jinhua and Landrace pigs. We identified 84,864 circRNA candidates in two breeds and 366 circRNAs were detected as significantly differentially expressed. Their host genes are involved in lipid biosynthetic and metabolic processes according to the gene ontology analysis and associated with metabolic pathways. CONCLUSION: Our research represents the first description of circRNA profiles in the porcine liver from two divergent phenotype pigs. The predicted miRNA-circRNA interaction provides important basis for miRNA-circRNA relationships in the porcine liver. These data expand the repertories of porcine circRNA and are conducive to understanding the possible molecular mechanisms involved in miRNA and circRNA. Our study provides basic data for further research of the biological functions of circRNAs in the porcine liver.
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BACKGROUND: Hypertension is an important public health issue in China, but there are few studies examining hypertension in ethnic groups in Yunnan, China. This study, Yunnan Minority Eye Study (YMES), was initially designed to determine the prevalence and impact of eye diseases, including hypertension and diabetes mellitus. As a part of YMES, the prevalence, awareness, treatment, and control of hypertension and the associated risk factors among the Yi ethnic population in rural China are reported. METHODS: A population-based survey was conducted in 2012 with adult participants over 50 from rural communities in Shilin Yi Autonomous County, Yunnan Province, located in southwest China. A random cluster sampling method was used to select a representative sample. The participants' blood pressure, height, weight, and waist circumference were measured. Hypertension was defined as mean systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, and/or current use of antihypertensive medications. RESULTS: A total of 2208 adults were assessed. The prevalence of hypertension was 38.5%, and the age- and gender-adjusted prevalence was 37.0%. The proportion of patients who were aware of their hypertension among those diagnosed with hypertension was 24.8%. Of those aware of having hypertension, 23.6% took antihypertensive drugs. Among all hypertensive patients, only 7.2% had controlled their hypertension (<140/90 mmHg). Risk factors for hypertension were older age, smoking, alcohol consumption, family history of high blood pressure, overweight, and obesity. Protective factors included being slim and higher education. CONCLUSIONS: Hypertension was highly prevalent among this population of the Yi ethnic group in China. The ratio of awareness, treatment, and control of hypertension were considerately low. Hypertension education and screening programs in rural China are recommended to improve the health status of this population.
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Anti-Hipertensivos/uso terapêutico , Etnicidade/estatística & dados numéricos , Hipertensão/tratamento farmacológico , Hipertensão/etnologia , População Rural , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Conscientização , Pressão Sanguínea , Pesos e Medidas Corporais , China/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso/epidemiologia , Prevalência , Fatores de Risco , Fumar/epidemiologiaRESUMO
Objective: Explainable machine learning (XAI) was introduced in this study to improve the interpretability, explainability and transparency of the modelling results. The survex package in R was used to interpret and compare two survival models - the Cox proportional hazards regression (coxph) model and the random survival forest (rfsrc) model - and to estimate overall survival (OS) and its determinants in heart failure (HF) patients using these models. Methods: We selected 1159 HF patients hospitalised at the First Affiliated Hospital of Kunming Medical University. First, the performance of the two models was investigated using the C-index, the integrated C/D AUC, and the integrated Brier score. Second, a global explanation of the whole cohort was carried out using the time-dependent variable importance and the partial dependence survival profile. Finally, the SurvSHAP(t) and SurvLIME plots and the ceteris paribus survival profile were used to obtain a local explanation for each patient. Results: By comparing the C-index, the C/D AUC, and the Brier score, this study showed that the model performance of rfsrc was better than coxph. The global explanation of the whole cohort suggests that the C-reactive protein, lg BNP (brain natriuretic peptide), estimated glomerular filtration rate, albumin, age and blood chloride were significant unfavourable predictors of OS in HF patients in both the cxoph and the rfsrc models. By including individual patients in the model, we can provide a local explanation for each patient, which guides the clinician in individualising the patient's treatment. Conclusion: By comparison, we conclude that the model performance of rfsrc is better than that of coxph. These two predictive models, which address not only the whole population but also selected patients, can help clinicians personalise the treatment of each HF patient according to his or her specific situation.
RESUMO
Cardiac Vascular disease particularly myocardial infarction (MI) is a threat to health worldwide. microRNAs (miRNAs) have been shown to regulate myocardial fibrosis. Therefore, it is potential to investigate the mechanism of miRNA and fibrosis following myocardial infarction. Hypoxia human cardiac microvascular endothelial cells (HCMECs) were selected for the vitro experimental model. The miR-146a-5p expression was tested via RT-qPCR. The level of endothelial-to-mesenchymal transition (EndMT) and fibrosis markers were detected by Western blotting and immunofluorescence. Then, the inflammation, cell viability and apoptosis were investigated. The target was predicted by an online database and verified by a dual-luciferase activity assay. An MI mouse model was created to validate that miR-146a-5p regulates cardiac fibrosis in vivo. MI mouse was transfected with miR-146a-5p lentivirus. Subsequently, its effect on cardiac fibrosis of infarcted hearts was assessed by In situ hybridization (ISH), Immunohistochemistry (IHC), Triphenylterazolium chloride (TTC) staining and Masson staining. Herein, we confirmed that miR-146a-5p was down-regulated in hypoxia HCMECs. Overexpression of miR-146a-5p inhibited hypoxia-induced cardiac fibrosis following myocardial infarction by inhibiting EndMT in HCMECs. Thioredoxin-interacting protein (TXNIP) was a target that was negatively regulated by miR-146a-5p. Up-regulation of miR-146a-5p inhibited cardiac fibrosis via regulating EndMT by targeting TXNIP, and it also regulated EndMT to inhibit cardiac fibrosis in vivo.
Assuntos
Cardiomiopatias , MicroRNAs , Infarto do Miocárdio , Animais , Humanos , Camundongos , Apoptose , Cardiomiopatias/metabolismo , Células Endoteliais , Transição Endotélio-Mesênquima , Fibrose , Hipóxia/complicações , Hipóxia/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/metabolismoRESUMO
The ratio of fibrinogen to albumin (FAR) is considered a new inflammatory biomarker and a predictor of cardiovascular disease risk. However, its prognostic value for patients with chronic heart failure (CHF) with different ejection fractions (EFs) remains unclear. A total of 916 hospitalized patients with CHF from January 2017 to October 2021 in the First Affiliated Hospital of Kunming Medical University were included in the study. Death occurred in 417 (45.5%) patients out of 916 patients during a median follow-up time of 750 days. Among these patients, 381 patients suffered from HFrEF (LVEF <40%) and 535 patients suffered from HFpEF or HFmrEF (HFpEF plus HFmrEF, LVEF ≥ 40%). Patients were categorized into high-level FAR (FAR-H) and low-level FAR (FAR-L) groups based on the optimal cut-off value of FAR (9.06) obtained from receiver operating characteristic (ROC) curve analysis. Upon analysing the Kaplan - Meier plots, the incidence of death was significantly higher in all patients with FAR-H and patients in both HF subgroups (p < 0.001). The multivariate Cox proportional hazard analyses indicated that the FAR was an independent predictor of all-cause mortality, regardless of heart failure subtype. (HR 1.115, 95% CI 1.089-1.142, p < 0.001; HFpEF plus HFmrEF, HR 1.109, 95% CI 1.074-1.146, p < 0.0001; HFrEF, HR 1.138, 95% CI 1.094-1.183, p < 0.0001) The optimal cut-off value of FAR in predicting all-cause mortality was 9.06 with an area under the curve value of 0.720 (95% CI: 0.687-0.753, p < 0.001), a sensitivity of 68.8% and a specificity of 65.6%. After adjusting for the traditional indicators (LVEF, Lg BNP, etc.), the new model with the FAR had better prediction ability in patients with CHF. Elevated FAR is an independent predictor of death in CHF and is not related to the HF subtype.