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A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive impairment. Davunetide, an active fragment of the activity-dependent neuroprotective protein (ADNP), has been implicated in social and cognitive protection. However, the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly understood. In this study, ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal mice. The neuropathological basis was also explored using Golgi staining, morphological analysis, western blotting, electrophysiological analysis, and behavioral analysis. Results indicated that ADNP was significantly down-regulated following developmental exposure to sevoflurane. In adulthood, anterior cingulate cortex (ACC) neurons exposed to sevoflurane exhibited a decrease in dendrite number, total dendrite length, and spine density. Furthermore, the expression levels of Homer, PSD95, synaptophysin, and vglut2 were significantly reduced in the sevoflurane group. Patch-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs). Notably, davunetide significantly ameliorated the synaptic defects, social behavior deficits, and cognitive impairments induced by sevoflurane. Mechanistic analysis revealed that loss of ADNP led to dysregulation of Ca 2+ activity via the Wnt/ß-catenin signaling, resulting in decreased expression of synaptic proteins. Suppression of Wnt signaling was restored in the davunetide-treated group. Thus, ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general anesthetics. This study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal mice and elucidates the regulatory pathways involved.
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Disfunción Cognitiva , Proteínas del Tejido Nervioso , Proteoma , Ribosomas , Sevoflurano , Conducta Social , Animales , Masculino , Ratones , Anestésicos por Inhalación/efectos adversos , Anestésicos por Inhalación/toxicidad , Anestésicos por Inhalación/farmacología , Animales Recién Nacidos , Conducta Animal/efectos de los fármacos , Disfunción Cognitiva/inducido químicamente , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Proteínas del Tejido Nervioso/metabolismo , Ribosomas/efectos de los fármacos , Ribosomas/metabolismoRESUMEN
Background: Silicosis shows an increasing trend with the development of new industries. However, the potential biomarkers for predicting the disease severity are lacking. A novel inflammatory marker, the systemic immune-inflammation Index (SII), has not been studied in silicosis. Methods: In this retrospective study, we used data from a big database platform of a tertiary general hospital in Beijing, which was established based on the electronic medical records of the hospital. The clinical data of adult patients diagnosed with silicosis at the Department of Occupational Medicine and Toxicology from 2013 to 2022 were collected. The data extracted from the database were in de-identified form. Only patients with a first diagnosis of silicosis and without conditions that might affect the parameters of routine blood tests were included in the analysis. Analyses were performed to assess the relationship between SII and the advanced stage of silicosis. Results: A total of 246 participants were included in the study. Most of the patients were exposed to silica particles during excavation and digging (n = 149, 60.6%). SII level was significantly higher in patients with advanced stages of silicosis. A multivariate logistic regression analysis revealed that a higher SII level was associated with the advanced stage of silicosis [odds ratio (OR) = 1.002; 95% confidence interval (CI): 1.000-1.003, p < 0.001] after adjusting for all covariates. The best cutoff value of SII was 444.1. The results of the subgroup analysis also showed a significant correlation between SII level over 444.1 and the advanced stage of silicosis in groups stratified by gender, history of smoking, and duration of silica exposure. Moreover, our results showed a significant but weak negative correlation between the level of SII and some lung function parameters in silicosis. Conclusion: Higher SII is associated with the advanced stage of silicosis and impaired lung function. More long-term, large-scale studies are needed to confirm these findings.
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INTRODUCTION: Traditional Chinese medicine (TCM) may have special advantages in facilitating smoking cessation, but consensus on effectiveness is lacking. We aim to comprehensively review, update, and refine current evidence on TCM effectiveness and safety. METHODS: Nine databases were searched from their inception up to 28 February 2023. Systematic reviews (SRs) and meta-analysis of TCM for smoking cessation were identified and retrieved. Additional databases and hand searches of RCTs from included SRs were performed for data pooling. Cochrane ROB tools and AMSTAR-2 were used to evaluate the methodological quality of RCTs and SRs, respectively. RCT data are presented as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI) using RevMan 5.4. RESULTS: Thirteen SRs involving 265 studies with 33081 participants were included. Among these 265 studies, 157 were duplicates (58.36%) and 52 were non-RCTs (19.62%). Combined with the remaining 56 RCTs identified through hand searches, 88 RCTs involving 12434 participants were finally included for data synthesis. All the SRs focused on acupoint stimulation, and the majority were of low or very low quality. The methodological quality of RCTs was either unclear or high risk. For continuous abstinence rate, TCM external interventions were better than placebo in 6 months to 1 year (RR=1.60; 95% CI: 1.14-2.25; I2=27%; n=5533 participants). Compared with placebo, TCM external application was effective in reducing nicotine withdrawal symptoms, and the effect was gradually stable and obvious in the fourth week (MD= -4.46; 95% CI: -5.43 - -3.49; n=165 participants). Twelve RCTs reported adverse events as outcome indicators for safety evaluation, and no serious adverse events occurred. CONCLUSIONS: Despite the methodological limitations of the original studies, our review suggests that TCM intervention shows potential effectiveness on the continuous abstinence rate. Extending the intervention time can enhance the effect of TCM on nicotine withdrawal symptoms. Referred to adverse events, more data for safety evaluation are required.
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Doxorubicin (DOX) is a chemotherapeutic drug for a variety of malignancies, while its application is restricted by the cardiovascular toxic effects characterized by oxidative stress. Ferroptosis is a novel iron-dependent regulated cell death driven by lipid peroxidation. Our study aimed to investigate the role of Elabela (ELA) in DOX-induced oxidative stress and ferroptosis. In cultured rat aortic adventitial fibroblasts (AFs), stimulation with DOX dramatically induced cytotoxicity with reduced cell viability and migration ability, and enhanced lactate dehydrogenase (LDH) activity. Importantly, ELA and ferrostatin-1 (Fer-1) mitigated DOX-mediated augmentation of reactive oxygen species (ROS) in rat aortic AFs, accompanied by upregulated levels of Nrf2, SLC7A11, GPX4, and GSH. In addition, ELA reversed DOX-induced dysregulation of apoptosis- and inflammation-related factors including Bax, Bcl2, interleukin (IL)-1ß, IL6, IL-10, and CXCL1. Intriguingly, knockdown of Krüppel-like factor 15 (KLF15) by siRNA abolished ELA-mediated alleviation of ROS production and inflammatory responses. More importanly, KLF15 siRNA impeded the beneficial roles of ELA in DOX-pretreated rat aortic AFs by suppressing the Nrf2/SLC7A11/GPX4 signaling. In conclusion, ELA prevents DOX-triggered promotion of cytotoxicity, and exerts anti-oxidative and anti-ferroptotic effects in rat aortic AFs via activation of the KLF15/GPX4 signaling, indicating a promising therapeutic value of ELA in antagonizing DOX-mediated cardiovascular abnormality and disorders.
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Ferroptosis , Animales , Ratas , Doxorrubicina/farmacología , Fibroblastos/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Hypertension is one of the leading causes of chronic kidney disease characterized with renal fibrosis. This study aimed to investigate roles and mechanisms of sirtuin 7 (SIRT7) in hypertensive renal injury. Mini-pumps were implanted to male C57BL/6 mice to deliver angiotensin (Ang) â ¡ (1.5 mg/kg/d) or saline for 2 weeks. Ang â ¡ infusion resulted in marked increases in systolic blood pressure levels, renal ferroptosis and interstitial fibrosis in hypertensive mice, concomitantly with downregulated SIRT7 and Krüppel-like factor 15 (KLF15) levels. Notably, administration of recombinant adeno-associated virus-SIRT7 or ferroptosis inhibitor ferrostatin-1 effectively mitigated Ang â ¡-triggered renal ferroptosis, epithelial-mesenchymal transition (EMT), interstitial fibrosis, renal functional and structural injury in hypertensive mice by blunting the KIM-1/NOX4 signaling and enforcing the KLF15/Nrf2 and xCT/GPX4 signaling, respectively. In primary cultured mouse renal tubular epithelial cells (TECs), Ang â ¡ pretreatment led to repressed SIRT7 expression and augmented ferroptosis as well as partial EMT, which were substantially antagonized by rhSIRT7 or ferrostatin-1 administration. Additionally, both Nrf2 inhibitor ML385 and KLF15 siRNA strikingly abolished the rhSIRT7-mediated beneficial roles in mouse renal TECs in response to Ang â ¡ with reduced expression of Nrf2, xCT and GPX4. More importantly, ML385 administration remarkably amplified Ang â ¡-mediated ROS generation, lipid peroxidation and ferroptosis in renal TECs, which were significantly reversed by ferrostatin-1. In conclusion, SIRT7 alleviates renal ferroptosis, lipid peroxidation, and partial EMT under hypertensive status by facilitating the KLF15/Nrf2 signaling, thereby mitigating renal fibrosis, injury and dysfunction. Targeting SIRT7 signaling serves as a promising strategy for hypertension and hypertensive renal injury.
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Ferroptosis , Hipertensión , Enfermedades Renales , Sirtuinas , Animales , Masculino , Ratones , Angiotensina II/metabolismo , Ferroptosis/genética , Fibrosis , Hipertensión/metabolismo , Riñón/metabolismo , Enfermedades Renales/genética , Enfermedades Renales/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Sirtuinas/genética , Sirtuinas/metabolismoRESUMEN
Hypertensive renal injury is accompanied by tubular interstitial fibrosis leading to increased risk for renal failure. This study aimed to explore the influences of miR-122-5p in hypertension-mediated renal fibrosis and damage. 14-week-old male SHR and WKY rats were randomly assigned to treat with rAAV-miR-122-5p or rAAV-GFP for 8 weeks. There were marked increases in miR-122-5p and Kim-1 levels and decreases in FOXO3 and SIRT6 levels in hypertensive rats. Transfection with rAAV-miR-122-5p triggered exacerbation of renal fibrosis, apoptosis and inflammatory injury in SHR, associated with downregulated levels of FOXO3, SIRT6, ATG5 and BNIP3 as well as upregulated expression of Kim-1, NOX4, CTGF, and TGF-ß1. In cultured primary mouse renal tubular interstitial fibroblasts, exposure to angiotensin II resulted in obvious downregulation of FOXO3, SIRT6, ATG5, BNIP3 and nitric oxide levels as well as augmented cellular migration, oxidative stress, and inflammation, which were exacerbated by miR-122-5p mimic while rescued by miR-122-5p inhibitor and rhFOXO3, respectively. Notably, knockdown of FOXO3 strikingly blunted cellular protective effects of miR-122-5p inhibitor. In summary, miR-122-5p augments renal fibrosis, inflammatory and oxidant injury in hypertensive rats by suppressing the expression of FOXO3. Pharmacological inhibition of miR-122-5p has potential therapeutic significance for hypertensive renal injury and fibrosis-related kidney diseases.
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Proteína Forkhead Box O3/antagonistas & inhibidores , Hipertensión/metabolismo , Hipertensión/patología , Riñón/lesiones , Riñón/metabolismo , MicroARNs/genética , Animales , Apoptosis , Autofagia , Modelos Animales de Enfermedad , Regulación hacia Abajo , Fibroblastos/metabolismo , Fibroblastos/patología , Fibrosis , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/metabolismo , Técnicas de Silenciamiento del Gen , Hipertensión/complicaciones , Riñón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/antagonistas & inhibidores , MicroARNs/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Regulación hacia ArribaRESUMEN
Cardiovascular diseases (CVDs) are still the main cause of morbidity and mortality worldwide and include a group of disorders varying from vasculature, myocardium, arrhythmias and cardiac development. MicroRNAs (miRs) are endogenous non-coding RNAs with 18-23 nucleotides that regulate gene expression. The miR-34 family, including miR-34a/b/c, plays a vital role in the regulation of myocardial physiology and pathophysiological processes. Recently, miR-34a has been implicated in cardiovascular fibrosis, dysfunction and related cardiovascular disorders as an essential regulator. Interestingly, there is a pivotal link among miR-34a, cardiovascular fibrosis, and Smad4/TGF-ß1 signaling. Notably, both loss-of-function and gain-of-function approaches identified the critical roles of miR-34a in cardiovascular apoptosis, autophagy, inflammation, senescence and remodeling by modulating multifunctional signaling pathways. In this article, we focus on the current understanding of miR-34a in biogenesis, its biological effects and its implications for cardiac pathologies including myocardial infarction, heart failure, ischaemia reperfusion injury, cardiomyopathy, atherosclerosis, hypertension and atrial fibrillation. Thus, further understanding of the effects of miR-34a on cardiovascular diseases will aid the development of effective interventions. Targeting for miR-34a has emerged as a potential therapeutic target for cardiovascular dysfunction and related diseases.
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Purpose: Peripheral blood eosinophilic counts are susceptible to many factors and have variability over time. There are limited studies on association of blood eosinophilia with long-term mortality of chronic obstructive pulmonary disease (COPD) patients and these results remain controversial. Our aims were to explore the association of blood eosinophilia at index hospitalization and stability of blood eosinophilia stability over 5 years with all-cause mortality of patients hospitalized for acute exacerbation of COPD (AECOPD). Patients and Methods: Eight hundred twenty-nine patients hospitalized for AECOPD between 2013 and 2014 were included in this study and grouped into two groups according to blood eosinophil with 150 cells/µL used as the cutoff value to form eosinophilic and non-eosinophilic groups. Two hundred forty-one COPD inpatients with at least three blood eosinophils measured from different hospitalizations were used for analysis of longitudinally eosinophilic stability and divided into three groups according to the same cutoff value: predominantly (PE), intermittently (IE) and rarely (RE) eosinophilic groups. Cox regression analysis was used to determine the association of blood eosinophilia and all-cause mortality. Results: In patients hospitalized for AECOPD, 261 (31.5%) at baseline and 41 (17%) based on at least three measurements of blood eosinophils had increased blood eosinophils. For all-cause mortality, eosinophilic COPD patients at index hospitalization had a lower all-cause mortality compared with non-eosinophilic COPD patients (hazard ratio 0.77, 95% confidence interval 0.6-0.99, P=0.04). In patients readmitted for AECOPD by longitudinal eosinophil stability, with the RE group used as reference, the PE group was associated with a lower all-cause mortality of AECOPD patients (hazard ratio 0.43, 95% confidence interval 0.22-0.85, P=0.016), compared to the IE group (hazard ratio 0.72, 95% confidence interval 0.47-1.11, P=0.133). Conclusion: Patients with increased eosinophils (using eosinophil 150 cells/µL as a cutoff value), especially predominantly increased eosinophil levels based on multiple measurements, had a lower risk of all-cause mortality. Blood eosinophilia can be used as a biomarker in hospitalized COPD exacerbations for predicting the risk of all-cause mortality.
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Eosinofilia , Enfermedad Pulmonar Obstructiva Crónica , Progresión de la Enfermedad , Eosinofilia/diagnóstico , Eosinófilos , Humanos , Recuento de Leucocitos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/terapiaRESUMEN
BACKGROUND: Previous studies have shown that patients with diabetes mellitus (DM) respond poorly to clopidogrel treatment. AIM: To systematically evaluate the efficacy of clopidogrel for the treatment of acute coronary syndromes or ischemic stroke in patients with or without DM. METHODS: PubMed, the Cochrane Central Register of Controlled Trials, and EMBASE were searched from 1980 on 27 June 2019 to identify relevant randomized controlled trials that compared the effect of a combination of clopidogrel and aspirin with aspirin alone. A random-effects meta-analysis was used to estimate the hazard ratio (HR) and its 95% confidence interval (CI). Sensitivity analysis was performed using a fixed-effect model. The I 2 statistic was used to evaluate the heterogeneity of the study data. RESULTS: Six randomized controlled trials, comprising 43352 participants (13491 with and 29861 without DM) who had received antiplatelet therapy for ≥ 3 mo, were included in the meta-analysis. Compared with aspirin alone, a combination of clopidogrel and aspirin significantly reduced the risk of any cardiovascular event in patients without DM (HR = 0.78, 95%CI: 0.71-0.86, P < 0.001; I 2 = 23%, P = 0.26). Clopidogrel plus aspirin also significantly reduced cardiovascular risk in patients with DM, although the effect was smaller (HR = 0.89, 95%CI: 0.81-0.99, P = 0.030; I 2 = 0%, P = 0.74). Nevertheless, there was no significant difference in the efficacy of clopidogrel at reducing the risk of cardiovascular events in patients with DM vs those without (P for interaction = 0.062). CONCLUSION: Thus, the present study shows that the addition of clopidogrel to aspirin significantly lowers cardiovascular risk in patients with or without DM who have experienced ischemic cardiovascular disease. The beneficial effect of the addition of clopidogrel to aspirin for patients with DM was lower than that in patients without DM, although the modifying effect of DM did not reach significance.
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BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19) in China in December 2019, considerable attention has been focused on its elucidation. However, it is also important for clinicians and epidemiologists to differentiate COVID-19 from other respiratory infectious diseases such as influenza viruses. RESEARCH QUESTION: The aim of this study was to explore the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with ARDS. STUDY DESIGN AND METHODS: This analysis was a retrospective case-control study. Two independent cohorts of patients with ARDS infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Their clinical manifestations, imaging characteristics, treatments, and prognosis were analyzed and compared. RESULTS: The median age of patients with COVID-19 was higher than that of patients with H1N1, and there was a higher proportion of male subjects among the H1N1 cohort (P < .05). Patients with COVID-19 exhibited higher proportions of nonproductive coughs, fatigue, and GI symptoms than those of patients with H1N1 (P < .05). Patients with H1N1 had higher Sequential Organ Failure Assessment (SOFA) scores than patients with COVID-19 (P < .05). The Pao2/Fio2 of 198.5 mm Hg in the COVID-19 cohort was significantly higher than the Pao2/Fio2 of 107.0 mm Hg in the H1N1 cohort (P < .001). Ground-glass opacities was more common in patients with COVID-19 than in patients with H1N1 (P < .001). There was a greater variety of antiviral therapies administered to COVID-19 patients than to H1N1 patients. The in-hospital mortality of patients with COVID-19 was 28.8%, whereas that of patients with H1N1 was 34.7% (P = .483). SOFA score-adjusted mortality of H1N1 patients was significantly higher than that of COVID-19 patients, with a rate ratio of 2.009 (95% CI, 1.563-2.583; P < .001). INTERPRETATION: There were many differences in clinical presentations between patients with ARDS infected with either COVID-19 or H1N1. Compared with H1N1 patients, patients with COVID-19-induced ARDS had lower severity of illness scores at presentation and lower SOFA score-adjusted mortality.
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Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus , Mortalidad Hospitalaria , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana , Pandemias , Neumonía Viral , Evaluación de Síntomas , Factores de Edad , Antivirales/uso terapéutico , COVID-19 , Estudios de Casos y Controles , China/epidemiología , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/fisiopatología , Diagnóstico Diferencial , Femenino , Humanos , Gripe Humana/diagnóstico , Gripe Humana/mortalidad , Gripe Humana/fisiopatología , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Neumonía Viral/diagnóstico , Neumonía Viral/mortalidad , Neumonía Viral/fisiopatología , Pronóstico , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factores Sexuales , Evaluación de Síntomas/métodos , Evaluación de Síntomas/estadística & datos numéricosRESUMEN
The aim of this study was to identify factors associated with the death of patients with COVID-19 pneumonia caused by the novel coronavirus SARS-CoV-2.All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between 25 December 2019 and 7 February 2020. Univariate and multivariate logistic regression analysis revealed that age ≥65 years (OR 3.765, 95% CI 1.14617.394; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 0.7558.044; p=0.007), CD3+CD8+ T-cells ≤75 cells·µL−1 (OR 3.982, 95% CI 1.13214.006; p<0.001) and cardiac troponin I ≥0.05â ng·mL−1 (OR 4.077, 95% CI 1.16614.253; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia." has been corrected to: "Univariate and multivariate logistic regression analysis revealed that age ≥65 years (OR 3.765, 95% CI 1.201−11.803; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 1.279−4.747; p=0.007), CD3+CD8+ T-cells ≤75 cells·µL−1 (OR 3.982, 95% CI 1.7619.004; p<0.001) and cardiac troponin I ≥0.05â ng·mL−1 (OR 4.077, 95% CI 1.7789.349; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia. In a sex-, age- and comorbid illness-matched case-control study, CD3+CD8+ T-cells ≤75â cells·µL-1 and cardiac troponin I ≥0.05â ng·mL-1 remained as predictors for high mortality from COVID-19 pneumonia.We identified four risk factors: age ≥65â years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells ≤75â cells·µL-1 and cardiac troponin I ≥0.05â ng·mL-1 The latter two factors, especially, were predictors for mortality of COVID-19 pneumonia patients.
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Infecciones por Coronavirus/mortalidad , Coronavirus , Neumonía Viral/mortalidad , Adulto , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Betacoronavirus , Linfocitos T CD8-positivos , COVID-19 , Enfermedades Cardiovasculares/epidemiología , Estudios de Casos y Controles , Trastornos Cerebrovasculares/epidemiología , China , Comorbilidad , Infecciones por Coronavirus/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/terapia , Estudios Prospectivos , SARS-CoV-2 , Troponina I/sangreRESUMEN
BACKGROUND: Not all adults with chronic insomnia respond to the recommended therapeutic options of cognitive behavioral therapy and approved hypnotic drugs. Transcranial alternating current stimulation (tACS) may offer a novel potential treatment modality for insomnia. OBJECTIVES: This study aimed to examine the efficacy and safety of tACS for treating adult patients with chronic insomnia. METHODS: Sixty-two participants with chronic primary insomnia received 20 daily 40-min, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas in the laboratory on weekdays for 4 consecutive weeks, followed by a 4-week follow-up period. The primary outcome was response rate measured by the Pittsburgh Sleep Quality Index (PSQI) at week 8. Secondary outcomes were remission rate, insomnia severity, sleep onset latency (SOL), total sleep time (TST), sleep efficiency, sleep quality, daily disturbances, and adverse events at the end of the 4-week intervention and at the 4-week follow-up. RESULTS: Of 62 randomized patients, 60 completed the trial. During the 4-week intervention, 1 subject per group withdrew due to loss of interest and time restriction, respectively. Based on PSQI, at 4-week follow-up, the active group had a higher response rate compared to the sham group (53.4% [16/30] vs. 16.7% [5/30], p = 0.009), but remission rates were not different between groups. At the end of the 4-week intervention, the active group had higher response and remission rates than the sham group (p < 0.001 and p = 0.026, respectively). During the trial, compared with the sham group, the active group showed a statistically significant decrease in PSQI total score, a shortened SOL, an increased TST, improved sleep efficiency, and improved sleep quality (p < 0.05 or p < 0.001). Post hoc analysis revealed that, in comparison with the sham group, the active group had improved symptoms, except for daily disturbances, at the end of the 4-week intervention, and significant improvements in all symptoms at the 4-week follow-up. No adverse events or serious adverse responses occurred during the study. CONCLUSION: The findings show that the tACS applied in the present study has potential as an effective and safe intervention for chronic insomnia within 8 weeks.
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Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Sueño , Estimulación Transcraneal de Corriente Directa/métodos , Adulto , Enfermedad Crónica , Método Doble Ciego , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Polisomnografía , Inducción de Remisión , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND:: Preoperative anatomical scoring system is conducive to comparison between treatment options and evaluation of postoperative outcomes in patients with small renal tumors. This study aimed to evaluate the clinical application efficacy of the R.E.N.A.L. nephrometry score (RNS) in predicting perioperative outcomes in patients with renal tumor who underwent laparoscopic partial nephrectomy (LPN). METHODS:: The clinical data of 139 patients with renal tumors who underwent LPN between 2009 and 2015 were collected and analyzed. Patients were divided into three groups according to their RNS (low, moderate, and high). Clinical characteristics including perioperative variables, complications, and RNS were compared to evaluate the differences between the three groups. Multivariable logistic regression analysis was used to analyze the risk factors of postoperative complications. RESULTS:: According to the RNS, there were 74, 50, and 15 patients in the low, moderate, and high RNS groups, respectively. There were significant differences in estimated blood loss (EBL; χ2 = 7.285, P = 0.026), warm ischemia time (WIT; χ2 = 13.718, P = 0.001), operation time (OT; χ2 = 6.882, P = 0.032), perioperative creatinine clearance change (PCCC; χ2 = 6.206, P = 0.045), and number of patients with complications (NPC; P = 0.002) among the three groups. The values for EBL, WIT, OT, PCCC, and NPC for patients in the high RNS group were higher than those for patients in the low RNS group. After adjustment for OT, WIT, and EBL, RNS was statistically significantly associated with the risk of postoperative complications in a multivariable logistic regression model (odds ratio = 1.541, 95% confidence interval: 1.059-2.242, P = 0.024). CONCLUSIONS:: The RNS is a valuable tool for evaluating the complexity of renal tumor anatomy. It can aid surgeons in preoperative decision-making concerning management therapy. Future multicenter, large sample size studies are warranted for evaluating its predicting performance of perioperative outcomes.
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Neoplasias Renales/cirugía , Nefrectomía/métodos , Adulto , Anciano , Índice de Masa Corporal , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Riñón/patología , Riñón/cirugía , Laparoscopía , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios RetrospectivosRESUMEN
OBJECTIVE: To develop a life quality scale suitable for idiopathic pulmonary fibrosis (IPF) patients, objectively reflecting its changes. METHODS: Authors first put forward a theoretical structure model of a scale according to patient-reported outcome (PRO) scale formulation principle by combining basic theories of Chinese medicine (CM). Then authors developed an initial scale on the basis of various life quality scales for respiratory disease patients by using structural decision making. Totally 34 patients with confirmed diagnosis of IPF were tested by questionnaire. Items were screened using expert importance scoring method, factor analysis, correlation coefficient method, Cronbach's alpha coefficient method. IPF patient reported outcomes (IPF PRO, IP) were finally defined. RESULTS: A new IP scale was developed covering three areas and 38 items. Pearson correlation coefficient for correlation analysis of clinical symptom scores in ST-George Respiratory Questionnaire and IP scale was 0.828 (P < 0.01). Pearson correlation coefficient for correlation analysis of activity ability scores was 0.929 (P < 0.01). Pearson correlation coefficient for correlation analysis of total scores was 0.862 (P < 0.01). By reliability of IP scale itself (reliability) analysis, Cronbach's alpha coefficient was 0.713. By using factor analysis method for data analysis, KMO statistics was 0.902. CONCLUSION: IP scale fully reflected the connotation of IPF patients' quality of life, so it could be used as CM clinical therapeutic effect evaluation tool.
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Fibrosis Pulmonar Idiopática/diagnóstico , Medicina Tradicional China , Calidad de Vida , Encuestas y Cuestionarios , Humanos , Reproducibilidad de los Resultados , Proyectos de InvestigaciónRESUMEN
OBJECTIVE: To assess the incidence and outcome of in-hospital cardiac arrests (IHCAs) in Beijing, China. METHODS: The incidence and outcome of IHCAs over a 12-month period were evaluated in this prospective study. Between January 1 and December 31, 2014, 12 Beijing hospitals prospectively participated in this study for calculation of the incidence of IHCA. Data were collected according to the Utstein style for all cases of attempted resuscitation for IHCA that occurred in the participating hospitals. Surviving patients were followed for 1 month. RESULTS: The total number of admissions across the 12 hospitals during this 1-year period was 582,242; the IHCA incidence was 17.5 per 1000 admissions. Of the 10,198 IHCAs recorded, cardiopulmonary resuscitation (CPR) was initiated in 26.6%. Among CPR recipients, 1292 (47.6%) had a presumed cardiac aetiology and 1255 occurred in the Emergency Department. With regards to initial rhythm, 1340 had asystole and 423 had shockable rhythms. Of those receiving CPR, 1451 (53.5%) patients received it in less than 1min. Restoration of spontaneous circulation was achieved in 962 (35.5%) patients; 247 (9.1%) patients were discharged alive and 174 (6.4%) patients had good neurological outcomes. At 1 month after discharge, 236 patients remained alive. On multivariate regression analysis, factors associated with survival included female sex, age <60 years, and ventricular fibrillation/ventricular tachycardia as the initial rhythm. CONCLUSION: The incidence of IHCA in Beijing hospitals is high and the survival is poor compared to other industrialized countries.
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Reanimación Cardiopulmonar/métodos , Servicios Médicos de Urgencia/estadística & datos numéricos , Paro Cardíaco/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Femenino , Estudios de Seguimiento , Paro Cardíaco/terapia , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia/tendencias , Adulto JovenRESUMEN
It has been suggested that propofol can modulate microglial activity and hence may have potential roles against neuroinflammation following brain ischemic insult. However, whether and how propofol can inhibit post-cardiac arrest brain injury via inhibition of microglia activation remains unclear. A rat model of asphyxia cardiac arrest (CA) was created followed by cardiopulmonary resuscitation. CA induced marked microglial activation in the hippocampal CA1 region, revealed by increased OX42 and P2 class of purinoceptor 7 (P2X7R) expression, as well as p38 MAPK phosphorylation. Morris water maze showed that learning and memory deficits following CA could be inhibited or alleviated by pre-treatment with the microglial inhibitor minocycline or propofol. Microglial activation was significantly suppressed likely via the P2X7R/p-p38 pathway by propofol. Moreover, hippocampal neuronal injuries after CA were remarkably attenuated by propofol. In vitro experiment showed that propofol pre-treatment inhibited ATP-induced microglial activation and release of tumor necrosis factor-α and interleukin-1ß. In addition, propofol protected neurons from injury when co-culturing with ATP-treated microglia. Our data suggest that propofol pre-treatment inhibits CA-induced microglial activation and neuronal injury in the hippocampus and ultimately improves cognitive function. We proposed a possible mechanism of propofol-mediated brain protection after cardiac arrest (CA). CA induces P2X7R upregulation and p38 phosphorylation in microglia, which induces release of TNF-α and IL-1ß and consequent neuronal injury. Propofol could inhibit microglial activation and alleviate neuronal damage. Our results suggest propofol-induced anti-inflammatory treatment as a plausible strategy for therapeutic intervention in post-CA brain injury.
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Isquemia Encefálica/prevención & control , Región CA1 Hipocampal/patología , Paro Cardíaco/complicaciones , Microglía/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Propofol/uso terapéutico , Adenosina Trifosfato/fisiología , Animales , Asfixia/complicaciones , Isquemia Encefálica/etiología , Región CA1 Hipocampal/efectos de los fármacos , Antígeno CD11b/biosíntesis , Antígeno CD11b/genética , Reanimación Cardiopulmonar , Células Cultivadas , Interleucina-1beta/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Aprendizaje por Laberinto , Ratones , Microglía/fisiología , Minociclina/farmacología , Minociclina/uso terapéutico , Modelos Animales , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Fármacos Neuroprotectores/farmacología , Fosforilación , Propofol/farmacología , Procesamiento Proteico-Postraduccional , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Receptores Purinérgicos P2X7/biosíntesis , Receptores Purinérgicos P2X7/genética , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
AIM: The purpose of this study was to assess the outcome of out-of-hospital cardiac arrests (OHCAs) in Beijing, China. METHODS: In this prospective study, data were collected according to the Utstein style on all cases of OHCA that occurred between January and December 2012 in urban areas covered by Beijing Emergency Medical Services (EMS). The cases were followed-up for 1 year. RESULTS: Out of the 9897 OHCAs recorded, cardiopulmonary resuscitation (CPR) was initiated in 2421 patients (24.4%). Among the CPR-receivers (n=2421), 1804 patients (74.5%) had collapsed at home, while 375 patients (15.5%) at a public place. The average time interval from call to EMS arrival at the collapse location was 16 min (range, 4-43 min). Of the 1693 OHCA cases with cardiac aetiology, 1246 cases (73.6%) were witnessed, and basic CPR was performed by bystanders before arrival of the EMS personnel in 193 patients (11.4%). Of the OHCAs with cardiac aetiology, 1054 patients (62.3%) had asystole, 131 patients (7.7%) had shockable rhythms, restoration of spontaneous circulation was achieved in 85 patients (5.0%), 71 patients (4.2%) were admitted to the hospital alive, and of the 22 patients (1.3%) who were discharged alive, 17 patients (1%) had good neurological outcomes. At 1 year post-OHCA, 17 patients were alive. CONCLUSION: In the urban areas of Beijing with EMS services, survival rate after OHCA was unsatisfactory. Improvements are required in every link of the 'chain of survival'.
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Causas de Muerte , Servicios Médicos de Urgencia/organización & administración , Paro Cardíaco Extrahospitalario/mortalidad , Paro Cardíaco Extrahospitalario/terapia , Evaluación de Resultado en la Atención de Salud , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , China , Estudios de Cohortes , Intervalos de Confianza , Bases de Datos Factuales , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Estudios Prospectivos , Medición de Riesgo , Factores Sexuales , Tasa de Supervivencia , Tiempo de Tratamiento , Servicios Urbanos de Salud , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: According to US Food and Drugs Administration (FDA), 2 hour recombinant tissue plasminogen activator (rt-PA) 100mg infusion is recommended for eligible patients with acute pulmonary embolism (PE). However,there exists evidence implying that a lower dosage of rt-PA can be equally effective but potentially safer compared with rt-PA 100mg regimen. The aim of this systematic review and meta-analysis is to assess the efficacy and safety of low dose rt-PA in the treatment of acute PE. MATERIAL AND METHOD: We searched Pubmed, EMBASE, the Cochrane library and CBM Literature Database for randomized controlled trials (RCT) focusing on low dose rt-PA for acute PE. Outcomes were described in terms of changes of image tests and echocardiography, major bleeding events, all-cause death, and recurrence of PE. RESULTS: Five studies (440 patients) were included, three of which compared low dose rt-PA (0.6 mg/kg, maximum 50mg or 50mg infusion 2h) with standard dose (100mg infusion 2h). There were more major bleeding events in standard dose rt-PA group than in low dose group (OR 0.33, 95%CI 0.12-0.91;P=0.94,I(2)=0%), while there were no statistical differences in recurrent PE or all cause mortality between these two groups. Two studies compared low dose (0.6 mg/kg, maximum 50mg/2 min bolus or 10mg bolus, ≤40 mg/2 h) with heparin. There was no significant difference in major bleeding events (OR 0.73, 95% CI 0.14-3.98;P=0.72), recurrent PE or all cause mortality. No dose-related heterogeneity was found for all the included studies. CONCLUSIONS: The results of this meta-analysis were hypothesis-generating. Based on the limited data, our systematic review suggested that low dose rt-PA had similar efficacy but was safer than standard dose of rt-PA. In addition, compared with heparin, low dose rt-PA didn't increase the risk of major bleeding for eligible PE patients.
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Embolia Pulmonar/tratamiento farmacológico , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/administración & dosificación , Relación Dosis-Respuesta a Droga , Humanos , Proteínas Recombinantes/administración & dosificaciónRESUMEN
OBJECTIVE: To explore the proportion and prevention status of venous thromboembolism (VTE) among hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Beijing. METHODS: Based on a multi-center retrospective study, a total of 636 hospitalized AECOPD patients from 17 class 2/3 hospitals in Beijing were examined from September 1, 2011 to March 31, 2012. They fulfilled one of the following criteria: respiratory failure type II, on invasive or non-invasive mechanical ventilation, hospitalization for pulmonary infection, bedridden duration ≥ 3 days and congestive heart failure. All investigators received standardized training and used a standardized questionnaire to collect data on VTE risk factors, the diagnosis of VTE and the utilization of VTE prophylaxis. According to Caprini score, they were categorized into 3 groups of lower risk (Caprini score ≤ 3), moderate risk (Caprini score 4-6) and high risk ( ≥ 7) to compare the intergroup differences in the VTE proportion and the utilization of VTE prophylaxis. RESULTS: A total of 636 patients were assessed. There were 416 males and 220 females with a mean (SD) age of 74.9 ± 9.3 years. Among them, 133 patients received lower extremity venous ultrasonic examination and 92 were diagnosed with deep venous thrombosis (DVT) including 2 patients with pulmonary thromboembolism (PTE). Thus the overall incidence of VTE was 14.5% (92/636) and increased with age (Ptrend = 0.044). The proportion of VTE in asymptomatic patients was higher in those symptomatic ones (21.1% vs 8.0%, P = 0.000). And it was the highest in high risk group, followed by lower risk and moderate risk groups at 17.9% (14/78), 16.0% (26/163) and 13.2% (52/395) respectively, There was no statistical significance (P = 0.450 for group difference, Ptrend = 0.946). Among 544 patients without VTE, only 19.1% (104/544) employed the pharmacologic and/or mechanical methods for preventing VTE. The prevention proportion gradually increased with rising Caprini score, i.e. 17.5%, 18.4% and 26.6% for lower, moderate and higher risk group respectively. There was no statistical significance (P = 0.266 for group difference, Ptrend = 0.201). CONCLUSIONS: The proportion of VTE is relatively higher. However, the preventive methods are significantly underutilized among hospitalized AECOPD patients in Beijing.