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1.
BMC Cardiovasc Disord ; 21(1): 210, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902450

RESUMO

BACKGROUND: Little is known regarding the effect of cardiopulmonary bypass (CPB) reoxygenation on cardiac function following tetralogy of Fallot repair. We hypothesized that hyperoxic reoxygenation would be more strongly associated with myocardial dysfunction in children with tetralogy of Fallot. METHODS: We investigated the association of perfusate oxygenation (PpO2) associated with myocardial dysfunction among children aged 6-72 months who underwent complete repair of tetralogy of Fallot in 2012-2018. Patients were divided into two groups: lower PpO2 group (≤ 250 mmHg) and higher PpO2 (> 250 mmHg) group based on the highest value of PpO2 during aortic occlusion. The odd ratio (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression models. RESULTS: This study included 163 patients perfused with lower PpO2 and 213 with higher PpO2, with median age at surgery 23.3 (interquartile range [IQR] 12.5-39.4) months, 164 female (43.6%), and median body mass index 15.59 (IQR 14.3-16.9) kg/m2. After adjustment for baseline, clinical and procedural variables, patients with higher PpO2 were associated with higher risk of myocardial dysfunction than those with lower PpO2 (OR 1.770; 95% CI 1.040-3.012, P = 0.035). Higher PpO2, lower SpO2, lower pulmonary annular Z-score, and longer CPB time were independent risk factors for myocardial dysfunction. CONCLUSIONS: Association exists between higher PpO2 and myocardial dysfunction risk in patients with tetralogy of Fallot, highlighting the modulation of reoxygenation during aortic occlusion to reduce cardiovascular damage following tetralogy of Fallot repair. TRIAL REGISTRATION: Clinical Trials. gov number NCT03568357. June 26, 2018.

2.
FASEB J ; 35(5): e21607, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33908664

RESUMO

Strand displacement DNA synthesis (SDDS) is an essential step in DNA replication. With magnetic tweezers, we investigated SDDS kinetics of wild-type gp90 and its exonuclease-deficient polymerase gp90 exo- at single-molecule level. A novel binding state of gp90 to the fork flap was confirmed prior to SDDS, suggesting an intermediate in the initiation of SDDS. The rate and processivity of SDDS by gp90 exo- or wt-gp90 are increased with force and dNTP concentration. The rate and processivity of exonuclease by wt-gp90 are decreased with force. High GC content decreases SDDS and exonuclease processivity but increases exonuclease rate for wt-gp90. The high force and dNTP concentration and low GC content facilitate the successive SDDS but retard the successive exonuclease for wt-gp90. Furthermore, increasing GC content accelerates the transition from SDDS or exonuclease to exonuclease. This work reveals the kinetics of SDDS in detail and offers a broader cognition on the regulation of various factors on SDDS at single-polymerase level.

3.
Animals (Basel) ; 11(3)2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33800015

RESUMO

Heat stress (HS) is one of the most important factors posing harm to the economic wellbeing of dairy industries, as it reduces milk yield as well as milk protein content. Recent studies suggest that HS participates in the induction of tissue oxidative stress (OS), as elevated levels of reactive oxygen species (ROS) and mitochondrial dysfunction were observed in dairy cows exposed to hot conditions. The OS induced by HS likely contributes to the reduction in milk protein content, since insulin resistance and apoptosis are promoted by OS and are negatively associated with the synthesis of milk proteins. The apoptosis in the mammary gland directly decreases the amount of mammary epithelial cells, while the insulin resistance affects the regulation of insulin on mTOR pathways. To alleviate OS damages, strategies including antioxidants supplementation have been adopted, but caution needs to be applied as an inappropriate supplement with antioxidants can be harmful. Furthermore, the complete mechanisms by which HS induces OS and OS influences milk protein synthesis are still unclear and further investigation is needed.

4.
Clin Imaging ; 79: 56-63, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33887507

RESUMO

PURPOSE: There are currently few specific artificial intelligence (AI) studies for Breast Imaging Reporting and Data System (BI-RADS) category 4A lesions. This study aimed to establish an AI diagnostic model of breast lesions using two-dimensional grayscale ultrasound imaging and to compare its performance with that of radiologists. METHODS: The ultrasound images of 1311 lesions were evaluated by radiologists according to the BI-RADS categories, using pathology results as reference. Two classification standards (standards 1 and 2) for benign and malignant lesions were defined and used to calculate the diagnostic performance of radiologists, altogether and individually. The breast lesion images were also used to develop an AI diagnostic model. RESULTS: The diagnostic performance of AI and that of the radiologists were compared using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). All parameters of diagnostic performance, except for sensitivity and NPV, improved with standard 2. For the 202 lesions in the test set, the diagnostic performance of the AI model had 77.0% accuracy, 82.0% sensitivity, 71.7% specificity, 79.3% PPV, 75.1% NPV, and an AUC of 0.846. When the AI model was used to analyze category 4A lesions, the PPV was 9.3%, which was better than that of the radiologists, although not significantly. CONCLUSIONS: Deep learning technology shows a good performance in classifying benign and malignant breast lesions. It may be potentially used in practice to improve diagnostic accuracy and reduce unnecessary biopsies of breast lesions.

5.
Medicine (Baltimore) ; 100(17): e25764, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907173

RESUMO

ABSTRACT: Inflammation plays an important role in the pathophysiology of subarachnoid hemorrhage (SAH). Recent studies have indicated that the albumin to fibrinogen ratio (AFR) is a useful biomarker of inflammation.This research aimed to determine the ability of AFR to predict the prognosis of patients with SAH.A total of 440 patients with SAH who had been diagnosed within 72 hours of symptom onset were retrospectively reviewed. Clinical findings and laboratory data were retrieved from the hospital database. Functional outcome was measured according to the modified Rankin scale at 30 days. Logistic regression analysis was used to evaluate the correlation between AFR and the prognosis of patients with SAH. Receiver operating characteristic (ROC) analysis was performed to determine the prognostic ability of AFR at admission to predict the 30-day outcomes.The average age of all 440 patients with SAH was 56.75 ±â€Š11.19 years and 31.4% (138) were male. Of these patients, 161 exhibited unfavorable outcomes at 30 days. According to the multivariate logistic regression analysis, the AFR was positively correlated with the outcome of patients with SAH (odds ratio 0.939, 95% confidence interval 0.885-0.996, P = .038). The ROC analysis revealed an area under the curve of 0.713 for AFR's ability to predict the 30-day outcomes.AFR is independently associated with the outcome of SAH patients. As a parameter that can be easily assessed at admission, AFR could be used to help the decision-making of clinical treatment.


Assuntos
Fibrinogênio/análise , Albumina Sérica/análise , Hemorragia Subaracnóidea , Biomarcadores/análise , China/epidemiologia , Tomada de Decisão Clínica , Testes Diagnósticos de Rotina/métodos , Diagnóstico Precoce , Feminino , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Valor Preditivo dos Testes , Prognóstico , Recuperação de Função Fisiológica , Estudos Retrospectivos , Hemorragia Subaracnóidea/sangue , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/epidemiologia
6.
Environ Sci Technol ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33871985

RESUMO

Precious metal catalysts with superior low-temperature activity and excellent thermal stability are highly needed in environmental catalysis field. In this work, a novel two-step incipient wetness impregnation (T-IWI) method was developed for the fabrication of a unique and highly stable CeO2/Al2O3 support (CA-T). Pd anchored on CA-T exhibited a much higher low-temperature catalytic activity and superior thermal stability in carbon monoxide (CO) and hydrocarbon (HC) oxidations, compared to Pd anchored on conventional CeO2/Al2O3 (CA), which was prepared by a one-step IWI method. After aging treatment at 800 °C, the CO oxidation rate on Pd/CA-T (1.69 mmol/(gPd s)) at 120 °C was 4.1 and 84.5 times of those on Pd/CA (0.41 mmol/(gPd s)) and Pd/Al2O3 (0.02 mmol/(gPd s)), respectively. It was revealed that the CA-T support with well-controlled small CeO2 particles (ca. 12 nm) possessed abundant defects for Pd anchoring, which created rich Pd-CeO2 interfaces with strengthened interaction between Pd and CeO2 where oxygen could be efficiently activated. This resulted in the significantly improved oxidation activity and thermal stability of Pd/CA-T catalysts. The T-IWI method developed herein can be applied as a universal approach to prepare highly stable metal oxide-alumina-based supports, which have broad application in environmental catalyst design, especially for automobile exhaust aftertreatment.

7.
Respir Res ; 22(1): 128, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910560

RESUMO

BACKGROUND: Positive associations between ambient PM2.5 and cardiorespiratory disease have been well demonstrated during the past decade. However, few studies have examined the adverse effects of PM2.5 based on an entire population of a megalopolis. In addition, most studies in China have used averaged data, which results in variations between monitoring and personal exposure values, creating an inherent and unavoidable type of measurement error. METHODS: This study was conducted in Wuhan, a megacity in central China with about 10.9 million people. Daily hospital admission records, from October 2016 to December 2018, were obtained from the Wuhan Information center of Health and Family Planning, which administrates all hospitals in Wuhan. Daily air pollution concentrations and weather variables in Wuhan during the study period were collected. We developed a land use regression model (LUR) to assess individual PM2.5 exposure. Time-stratified case-crossover design and conditional logistic regression models were adopted to estimate cardiorespiratory hospitalization risks associated with short-term exposure to PM2.5. We also conducted stratification analyses by age, sex, and season. RESULTS: A total of 2,806,115 hospital admissions records were collected during the study period, from which we identified 332,090 cardiovascular disease admissions and 159,365 respiratory disease admissions. Short-term exposure to PM2.5 was associated with an increased risk of a cardiorespiratory hospital admission. A 10 µg/m3 increase in PM2.5 (lag0-2 days) was associated with an increase in hospital admissions of 1.23% (95% CI 1.01-1.45%) and 1.95% (95% CI 1.63-2.27%) for cardiovascular and respiratory diseases, respectively. The elderly were at higher PM-induced risk. The associations appeared to be more evident in the cold season than in the warm season. CONCLUSIONS: This study contributes evidence of short-term effects of PM2.5 on cardiorespiratory hospital admissions, which may be helpful for air pollution control and disease prevention in Wuhan.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33921784

RESUMO

Shortening of the gestational duration has been found associated with ambient air pollution exposure. However, the critical exposure windows of ambient air pollution for gestational duration remain inconsistent, and the association between ambient air pollution and early term births (ETB, 37 to 38 weeks) has rarely been studied relative to preterm births (PTB, 28-37 weeks). A time-series study was conducted in Shiyan, a medium-sized city in China. Birth information was collected from the Shiyan Maternity and Child Health Hospital, and 13,111 pregnant women who gave birth between 2015 and 2017 were included. Data of the concentrations of air pollutants, including PM10, PM2.5, NO2, and SO2 and meteorological data, were collected in the corresponding gestational period. The Cox regression analysis was performed to estimate the relationship between ambient air pollution exposure and the risk of preterm birth after controlling the confounders, including maternal age, education, Gravidity, parity, fetal gender, and delivery mode. Very preterm birth (VPTB, 28-32 weeks) as a subtype of PTB was also incorporated in this study. The risk of VPTB and ETB was positively associated with maternal ambient air pollution exposure, and the correlation of gaseous pollutants was stronger than particulate matter. With respect to exposure windows, the critical trimester of air pollutants for different adverse pregnancy outcomes was different. The exposure windows of PM10, PM2.5, and SO2 for ETB were found in the third trimester, with HRs (hazard ratios) of 1.06 (95%CI: 1.04, 1.09), 1.07 (95%CI: 1.04, 1.11), and 1.28 (95%CI: 1.20, 1.35), respectively. However, for NO2, the second and third trimesters exhibited similar results, the HRs reaching 1.10 (95%CI: 1.03, 6.17) and 1.09 (95%CI: 1.03,1.15), respectively. This study extends and strengthen the evidence for a significant correlation between the ambient air pollution exposure during pregnancy and the risk of not only PTB but, also, ETB. Moreover, our findings suggest that the exposure windows during pregnancy vary with different air pollutants and pregnancy outcomes.

9.
Brief Bioinform ; 2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33778867

RESUMO

Multi-omics allows the systematic understanding of the information flow across different omics layers, while single omics can mainly reflect one aspect of the biological system. The advancement of bulk and single-cell sequencing technologies and related computational methods for multi-omics largely facilitated the development of system biology and precision medicine. Single-cell approaches have the advantage of dissecting cellular dynamics and heterogeneity, whereas traditional bulk technologies are limited to individual/population-level investigation. In this review, we first summarize the technologies for producing bulk and single-cell multi-omics data. Then, we survey the computational approaches for integrative analysis of bulk and single-cell multimodal data, respectively. Moreover, the databases and data storage for multi-omics, as well as the tools for visualizing multimodal data are summarized. We also outline the integration between bulk and single-cell data, and discuss the applications of multi-omics in precision medicine. Finally, we present the challenges and perspectives for multi-omics development.

10.
Pediatr Res ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531680

RESUMO

BACKGROUND: The aim of the study was to examine correlates of sleep and assess its associations with weight status and related behaviors. METHODS: Data were collected in 2015-2017 for 3298 children aged 6-17 years and their parents in 5 Chinese mega-cities. One thousand six hundred and ninety-one children with measured weight, height, and waist circumference in ≥2 surveys were included for longitudinal data analyses. Sleep and behaviors were self-reported. RESULTS: Cross-sectional data analyses found that older (ß = -0.29, 95% CI: -0.32, -0.27) and secondary school children (ß = -1.22, 95% CI: -1.31, -1.13) reported shorter sleep than their counterparts. Children with ≥college-educated (vs

11.
Obes Rev ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33533189

RESUMO

This study for the first time quantified concurrent and bidirectional relationships between weight stigma and weight status in children, with age and gender as moderators. A literature search was conducted in PubMed, Web of Science, and PsycINFO for studies examined associations between weight stigma and weight status among children aged 6-18 years. Twenty-five studies (20 cross-sectional studies and five longitudinal studies) from six countries with 101,036 participants were included in review, and 18 were included in meta-analysis. Weight and height were self-reported in nine studies, otherwise objectively measured. With data from 17 cross-sectional studies and baseline portions of four longitudinal studies, meta-analysis showed weight stigma and overweight/obesity were associated (pooled OR = 3.12, 95% CI: 2.71, 3.60), they were also associated across age and gender. Body mass index (BMI) was associated with greater weight stigma (pooled r = 0.38, 95% CI: 0.32, 0.43). Age modified such association. Weight stigma predicted increased BMI from three longitudinal studies (pooled ß = 1.12, 95% CI: 0.78, 1.45); another two longitudinal studies reported BMI predicted greater weight stigma. Data were inadequate for age- or gender-stratified analyses. Findings supported positive concurrent and bidirectional relationships between weight stigma and weight status. Timely obesity and weight stigma interventions to protect children well-being are needed.

12.
Small ; 17(12): e2007486, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33590671

RESUMO

Layered metal oxides including MoO3 and WO3 have been widely explored for biological applications owing to their excellent biocompatibility, low toxicity, and easy preparation. However, they normally exhibit weak or negligible near-infrared (NIR) absorption and thus are inefficient for photo-induced biomedical applications. Herein, the structural engineering of layered MoO3 and WO3 nanostructures is first reported to activate their NIR-II absorption for efficient photothermal cancer therapy in the NIR-II window. White-colored micrometre-long MoO3 nanobelts are transformed into blue-colored short, thin, defective, interlayer gap-expanded MoO3-x nanobelts with a strong NIR-II absorption via the simple lithium treatment. The blue MoO3-x nanobelts exhibit a large extinction coefficient of 18.2 L g-1 cm-1 and high photothermal conversion efficiency of 46.9% at 1064 nm. After surface modification, the MoO3-x nanobelts can be used as a robust nanoagent for photoacoustic imaging-guided photothermal therapy to achieve efficient cancer cell ablation and tumor eradication under irradiation by a 1064 nm laser. Importantly, the biodegradable MoO3-x nanobelts can be rapidly degraded and excreted from body. The study highlights that the structural engineering of layered metal oxides is a powerful strategy to tune their properties and thus boost their performances in given applications.

13.
Chem Commun (Camb) ; 57(23): 2867-2870, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33629086

RESUMO

P3-Na0.65Mn0.5Al0.5O2 (NMAO) has been synthesized and studied as a cathode for sodium batteries, and shows anionic redox reaction (ARR) and exhibits a first charging capacity of ∼110 mA h g-1. The electrochemical mechanism of NMAO was comprehensively investigated by X-ray absorption spectroscopy (XAS), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and density functional theory (DFT) calculations. The reversible oxygen redox behaviour is triggered by Al3+ through oxygen quasi non-bonding states generated by the relatively ionic interaction of Al and O. Furthermore, the presence of Al3+ can suppress oxygen loss in ARR. This work provides new insights into the design and mechanism of anionic redox active cathode materials.

14.
Ann Hum Biol ; 48(1): 15-22, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33563083

RESUMO

BACKGROUND: The relation between neighbourhood built environment and obesity has been described as both nuanced and complex. AIM: The objective of this study was to examine the relationship between the built environment, physical activity, and obesity in a rapidly urbanised area of China. SUBJECTS AND METHODS: This is a cross-sectional study. Descriptive statistics were used to describe the socio-demographic variables, physical activity levels and BMI status. Multivariable logistic regression models were used to examine the association between neighbourhood environment, the likelihood of engaging in different types of physical activity, and BMI. RESULTS: A total of 842 respondents completed the questionnaires and were included (84.1% response rate). Among them, 56.4% reported meeting high physical activity levels, while 40.7% were overweight or obese. Multivariable regression analysis showed that better road conditions (ß = 0.122, t = 2.999, p = 0.003) and access to physical activity facilities (ß = 0.121, t = 3.193, p = 0.001) were significantly associated with higher levels of physical activity. Physical activity levels were inversely associated with the likelihood of being overweight (OR = 0.565, 95%CI: 0.3 4 9-0.917) or obese (OR = 0.614, 95%CI: 0.3 9 0-0.966). CONCLUSION: The built environment has an important impact on physical activity. However, the direct impact of leisure physical activity on BMI is not significant. This research provides a summary of recent evidence in Pingshan District on built environments that are most favourable for physical activity and obesity.

15.
J Integr Med ; 19(2): 111-119, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33589406

RESUMO

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m2, and 24-hour proteinuria level of 0.5-3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg. MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER: NCT02063100 on ClinicalTrials.gov.

16.
Biochemistry ; 60(7): 494-499, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33570402

RESUMO

The candidate anticancer drug curaxins can insert into DNA base pairs and efficiently inhibit the growth of various cancers. However, how curaxins alter the genomic DNA structure and affect the DNA binding property of key proteins remains to be clarified. Here, we first showed that curaxin CBL0137 strongly stabilizes the interaction between the double strands of DNA and reduces DNA bending and twist rigidity simultaneously, by single-molecule magnetic tweezers. More importantly, we found that CBL0137 greatly impairs the binding of CTCF but facilitates trapping FACT on DNA. We revealed that CBL0137 clamps the DNA double helix that may induce a huge barrier for DNA unzipping during replication and transcription and causes the distinct binding response of CTCF and FACT on DNA. Our work provides a novel mechanical insight into CBL0137's anticancer mechanisms at the nucleic acid level.

17.
J Dairy Res ; 88(1): 29-32, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33594969

RESUMO

This research communication addressed the hypothesis that late lactation cows offered an oat-grain-based supplement or a high level of α-TOC supplementation at pasture would have improved milk composition and processability. Over a grazing period of 49 d, 48 Holstein Friesian dairy cows were randomly assigned to one of four dietary treatments. The dietary treatments were: control, pasture only (CTRL), pasture + 2.65 kg DM barley-based concentrate + 350 IU α-TOC/kg (BARLO), pasture + 2.65 kg DM oat-based concentrate + 350 IU α-TOC/kg (OATLO) and pasture + 2.65 kg DM oat-based concentrate + 1050 IU α-TOC/kg (OATHI). Within this randomised complete block design experiment cows were blocked on days in milk (DIM) and balanced for parity, milk yield and composition. Rennet coagulation time (RCT) was reduced in milk from cows offered OATHI compared to CTRL cows and OATLO. Concentration of conjugated linoleic acid (CLA) was increased by OATHI compared to OATLO and in OATLO compared to CTRL. Supplementation with OATHI reduced individual saturated fatty acids (SFAs) in milk compared to OATLO. In conclusion, supplementing grazing dairy cows with an oat-based supplement improved total milk CLA concentration compared to pasture only. Offering a high level of α-TOC (2931 IU/d) to dairy cows reduced RCT, individual SFA and increased total CLA concentration of milk compared to a lower α-TOC level (738 IU α-TOC/d).

18.
Hum Exp Toxicol ; : 960327120988880, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33501840

RESUMO

Arsenic is a naturally occurring environmental toxicant, chronic exposure to arsenic can cause multiorgan damage, except for typical skin lesions, liver damage is the main problem for health concern in population with arsenic poisoning. Abnormal apoptosis is closely related to liver-related diseases, and p53 is one of the important hallmark proteins in apoptosis progression. This study was to investigate whether arsenic poisoning-induced hepatocyte apoptosis and the underlying role of p53 signaling pathway. A rat model of arsenic poisoning was established by feeding corn powder for 90 days, which was baked with high arsenic coal, then were treated with Ginkgo biloba extract (GBE) for 45 days by gavage. The results showed that arsenic induced liver damage, increased hepatocyte apoptosis and elevated the expression level of Chk1 and the ratios of p-p53/p53 and Bax/Bcl-2 in liver tissues, which were significantly attenuated by GBE. Additionally, to further demonstrate the potential apoptosis-associated mechanism, L-02 cells were pre-incubated with p53 inhibitor pifithrin-α (PFTα), ataxia telangiectasia-mutated (ATM)/ataxia telangiectasia-mutated and Rad3-related (ATR) inhibitor (CGK733) or GBE, then treated with sodium arsenite (NaAsO2) for 24 h. The results showed that GBE, PFTα or CGK733 significantly reduced arsenic-induced Chk1 expression and the ratios of p-p53/p53 and Bax/Bcl-2. In conclusion, Chk1-p53 pathway was involved in arsenic poisoning-induced hepatotoxicity, and inhibiting of Chk1-p53 pathway ameliorated hepatocyte apoptosis caused by coal-burning arsenic poisoning. The study provides a pivotal clue for understanding of the mechanism of arsenic poisoning-induced liver damage, and possible intervention strategies.

19.
Neurosurg Rev ; 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33389342

RESUMO

The use of prophylactic anticonvulsants among patients with subarachnoid hemorrhage (SAH) is controversial. We sought to assess the effectiveness of different durations of prophylactic antiepileptic drug (AED) use among SAH patients. We searched the MEDLINE, Embase, Cochrane, and ClinicalTrials.gov databases until March 1, 2020. Randomized controlled trials or observational studies comparing different durations or different drugs were selected. The primary outcome was poor clinical outcomes. The secondary outcome was in-hospital seizure. Bayesian network meta-analysis was also performed to indirectly compare the effectiveness of different prophylaxes. A total of 5 papers were included. Three studies with a total of 959 patients were included in the analysis of the primary outcome; the results showed that long-term exposure to prophylactic AEDs (more than 3 days) led to poor clinical outcomes (OR 1.55; 95% CI 1.01-2.39; p = 0.045). Four studies with 1024 patients were included in the analysis of the secondary outcome; the results showed no association between the duration of prophylactic AED use and the occurrence of in-hospital seizures (OR 0.62; 95% CI 0.18-2.15; p = 0.447). In the network meta-analysis, no significant difference was found among the four different prophylaxes. Our findings suggested that, when compared with the short-term use, the long-term use of prophylactic AEDs in SAH patients has a similar effect on in-hospital seizure prevention but is associated with poor clinical outcomes. However, these findings were based on a small number of available studies with obvious heterogeneity in study design and different prescription regimens. Further well-designed studies are warranted to elucidate these questions.

20.
Acta Neurochir (Wien) ; 163(4): 1167-1179, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33427988

RESUMO

BACKGROUND: Many blood blister aneurysms (BBAs) have been documented with a rapid progression history in repeated angiography. The underlying mechanism and clinical significance remained elusive. This current study aims to clarify the clinical and histopathological differences between short-term progressive BBA and non-progressive BBAs. METHODS AND MATERIALS: Eighty-one patients with BBAs were consecutively included for this single-center retrospective analysis. Clinical and radiological data on these patients were retrieved from 2017 to 2019. BBAs were defined as either progressive or non-progressive based on observed growth based on repeated imaging. Histopathological examinations of a saccular aneurysm, a progressive BBA, and a non-progressive BBA were conducted using representative aneurysm samples. RESULTS: Among all enrolled patients, 26 of the them were identified with progressive BBAs, while the other 55 with non-progressive BBAs. Progressive BBAs were diagnosed significantly earlier in angiography (3.36 ± 0.61 vs. 6.53 ± 1.31 days, p < 0.05) and showed a higher presence rate of daughter sacs (61.5 vs. 38.2%, p < 0.05). Three different progression patterns were identified. BBAs that developed daughter sac enlargement are diagnosed significantly later than BBAs exhibiting other progression patterns. Patients with progressive and non-progressive BBAs exhibited similar overall clinical outcomes and incidence for complications. For patients with non-progressive BBAs, microsurgery appears to be inferior to endovascular treatment, while for patients with progressive BBAs, the short-term outcomes between microsurgery and endovascular treatment were identical. Histopathological analysis revealed that both subtypes shared a similar pseudoaneurysms structure, but non-progressive BBAs had more histologically destructed aneurysm wall with less remnant fibrillar collagen in adventitia. CONCLUSIONS: Progressive and non-progressive BBAs may not be distinct pathological lesions but represent different stages during the BBA development. Early intervention, regardless of treatment methods, is recommended for salvageable patients with progressive BBAs, but microsurgery should be performed with caution for non-progressive BBAs due to increased surgical risk.

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