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1.
BMC Public Health ; 21(1): 2053, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753483

RESUMO

BACKGROUND: We investigated the association of alcohol consumption with cardiovascular and non-cardiovascular mortality in elderly Chinese men. METHODS: Our participants were recruited from residents living in a suburban town of Shanghai (≥60 years of age, n = 1702). Alcohol intake was classified as non-drinkers, past drinkers (stopped drinking for ≥12 months), and current light-to-moderate (1 to 299 g/week) and heavy drinkers (≥300 g/week). Alcoholic beverages were classified as beer/wine, rice aperitif and liquor/mix drinking. RESULTS: During 5.9 years (median) of follow-up, all-cause, cardiovascular and non-cardiovascular deaths occurred in 211, 98 and 113 participants, respectively. The corresponding incidence rates were 23.6/1000, 10.9/1000 and 12.6/1000 person-years, respectively. Both before and after adjustment for confounding factors, compared with non-drinkers (n = 843), past drinkers (n = 241), but not the current light-to-moderate (n = 241) or heavy drinkers (n = 377), had a higher risk of all-cause (adjusted hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.35-2.68, P = 0.0003) and non-cardiovascular mortality (HR 2.46, 95% CI 1.55-3.91, P = 0.0001). Similar trends were observed for cardiovascular mortality (HR 1.44, 95% CI 0.85-2.44, P = 0.18). In similar unadjusted and adjusted analyses, compared with the current beer/wine drinkers (n = 203), liquor/mix drinkers (n = 142), but not aperitif drinkers (n = 273), had a significantly higher risk of all-cause (HR 3.07, 95% CI 1.39-6.79, P = 0.006), and cardiovascular mortality (HR 10.49, 95% CI 2.00-55.22, P = 0.006). Similar trends were observed for non-cardiovascular mortality (HR 1.94, 95% CI 0.73-5.16, P = 0.18). CONCLUSIONS: Our study showed risks of mortality associated with past drinking and liquor drinking in the elderly Chinese men.

2.
Br J Clin Pharmacol ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34786743

RESUMO

AIM: To explore and describe the adverse reaction signals in the safety reporting for alpelisib. METHODS: We performed a disproportionality analysis of the World Health Organization's VigiBase® pharmacovigilance database from 1 January 2019 to 30 June 2021.Disproportionality analysis by information components (ICs) were used to evaluate the potential association between Adverse Events and Alpelisib. RESULTS: A total of 33327 reports were extracted, 5695 of them were chosen with alpelisib as the suspected drug. After combining the same ID,687 cases left. The 45-64years group had the largest number of cases (N=203, 29.55%). We got 129 preferred terms (PTs) with significant signals in the end. Hyperglycaemia (IC025=6.74), breast cancer metastatic (IC025=5.85), metastases to liver (IC025=4.70), were top 3 adverse events with the strongest signal. AEs with top 3 cases was hyperglycaemia (N=595), rash(N=535), diarrhoea(N=475). CONCLUSION: We established up a comprehensive list of adverse events (AEs) potentially associated with alpelisib. AEs with the most significant signals were hyperglycaemia, breast cancer metastatic, metastases to liver. Top 5 AEs with the most cases were hyperglycaemia, rash, diarrhoea, blood glucose increased, nausea.

3.
Brain Behav ; : e2428, 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34841724

RESUMO

OBJECTS: Abnormal blood pressure (BP) regulation is a feature of autonomic dysfunction in Parkinson's disease (PD) patients. The present study was to analyze the BP alterations by 24-h ambulatory BP monitoring in PD patients with different disease stages and subtypes. METHODS: 32 consecutive patients PD patients and 43 control patients in our hospital from 2017 to 2020 were included. The circadian BP rhythm was divided into three types according to the 24-h ambulatory BP monitoring. Dipping was defined as an average systolic BP (SBP) reduction during night-time of 10%-19%. Reverse dipping was defined as an average increase in night-time SBP values. The differences of the circadian BP rhythm and BP variability (BPV) were analyzed between PD group and the control group, the early PD group and the advanced PD group, as well as the tremor-dominant group and the nontremor-dominant group. RESULTS: There was statistical difference in circadian BP rhythm between PD group and control group (p < .05). There were statistical differences in circadian BP rhythm between the early PD group and the advanced PD group (p < .05). The mean values of night-time SBP and diastolic BP (DBP) in the advanced PD group were higher than those in the control group and the early PD group (p < .05). The DBP CV in the advanced PD group was higher than that in the control group and the early PD group (p < .05). There was no significant difference of circadian BP rhythm, mean BP, and BPV between the tremor-dominant and the nontremor-dominant PD group after matching the disease duration. CONCLUSIONS: Reverse dipping was more common in PD patients in this study, especially in the advanced PD patients. 24-h ambulatory BP monitoring is an important method to evaluate the BP alterations in PD patients. Clinicians should be alert to reverse dipping in PD patients and intervene to prevent serious clinical events.

4.
Cancer Med ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34845857

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have elicited durable antitumor responses in multiple types of cancers. However, ICIs could also induce potential toxicities that involve all organs, including renal system. In this study, we aimed to conduct a comprehensive description of the ICIs-induced renal toxicities and the potential effects of chemotherapy. METHODS: We conducted a pharmacovigilance study based on US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database between 01 January 2014 and 30 June 2019. Disproportionality analysis was used to assess the association between ICIs and renal adverse events (AEs), including reporting odds ratio (ROR) and information component (IC). ROR025 and IC025 are, respectively, 95% confidence interval lower end of ROR and IC. If the value of ROR025 exceeding one or IC025 higher than zero, then a signal was considered statistically significant. RESULTS: A total of 30,602,758 reports were extracted from the database, with 4578 reports for ICIs-associated renal AEs. Renal AEs were more frequently reported in anti-PD-1/PD-L1 versus anti-CTLA-4 monotherapy group (ROR: 1.75, 95% CI: 1.52-2.01). Similarly, renal AEs were more commonly reported in ICIs polytherapy other than monotherapy group (ROR: 1.18, 95% CI: 1.10-1.27). Notably, ICIs plus chemotherapy strategies reported more renal toxicities compared to sole ICIs regimens (ROR: 1.30, 95% CI: 1.17-1.45), whereas exhibited lower fatality outcome rates. Importantly, acute kidney injury (1139, 24.88%) and renal failure (464, 10.14%) were the top two most commonly reported ICIs-associated renal AEs, and also observed with the top two highest level of fatality outcome rates. CONCLUSIONS: A spectrum of renal AEs was detected in ICIs regimens and could be reinforced by ICIs combination. Compared to sole ICIs regimens, ICIs plus chemotherapy strategy reported more renal toxicities but lower fatality outcome rates. With the increasing popularity of ICIs especially combination strategies, it is vital important for clinicians to guarantee balance between durable clinical effects and potential renal toxicities in latest immunotherapy strategies.

5.
Front Cardiovasc Med ; 8: 735466, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646873

RESUMO

Background: Carfilzomib, an effective proteasome inhibitor agent for the therapy of relapsed and refractory multiple myeloma, has been related to a significant number of cardiovascular events. However, patterns of cardiovascular complications associated with this agent remain poorly characterized in real-world settings. Objective: To gain further insight into the frequency, spectrum, clinical features, timing, and outcomes of carfilzomib-related cardiovascular toxicities. Methods: This disproportionality (case/non-case) study was conducted leveraging records from FAERS database from 2014 to 2019. Cardiovascular events were defined and broadly categorized eight entities using narrow version of the Standardized MedDRA Queries (SMQs). Reporting odds ratios (ROR) and information component (IC) were calculated to measure disproportionality. Additionally, statistical shrinkage was applied to reduce false-positive signals. Results: The final number of records involved was 28,479,963, with 3,370 records submitted for carfilzomib related cardiovascular events. Significant disproportionality association between carfilzomib administration and cardiovascular events was captured (IC025/ROR025 = 0.85/1.95) when exploring in the entire database. Upon further analysis, all eight broad categories of cardiovascular toxicities were disproportionately associated with carfilzomib with varying frequencies, time-to-onset, and severities. Cardiomyopathy-related complications (N = 1,301, 38.61%), embolic and thrombotic events (N = 821, 24.36%), and cardiac failure (N = 765, 22.70%) largely comprised the reported problems. Notably, the strongest signal was detected for cardiac failure (IC025/ROR025 = 1.33/2.59), followed by pulmonary hypertension (IC025/ROR025 = 1.19/2.34). Median onset time of cardiovascular events was 41days (Q1-Q3: 9-114 days), with the shortest median time being 16 days (Q1-Q3: 4-85 days) for ischemic heart disease, with the longest time being 68 days (Q1-Q3: 21-139 days) for embolic and thrombotic events. Torsade de pointes/QT prolongation was identified as a new complication (IC025/ROR025 = 0.33/1.29) and was particularly noteworthy for highest death proportion (44.11%). Conclusions: Treatment with carfilzomib can lead to severe and versatile cardiovascular events. Early and intensive monitoring is important, particularly in the first 3 months after carfilzomib initiation. Maximizing the benefit while reducing potential cardiovascular harms of carfilzomib should become a priority.

6.
J Neurointerv Surg ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475255

RESUMO

BACKGROUND: Futile recanalization-when patients have a successful recanalization but fail to achieve a satisfactory functional outcome- is a common phenomenon of endovascular treatment of acute ischemic stroke (AIS). The present study aimed to identify the predictors of futile recanalization in AIS patients who received endovascular treatment. METHODS: This is a post-hoc analysis of the DIRECT-MT trial. Demographics, clinical characteristics, acute stroke workflow interval times, biochemical parameters, and imaging characteristics were compared between futile and meaningful recanalization groups. Multivariate analysis was performed to identify the predictors of futile recanalization. RESULTS: Futile recanalization was observed in 277 patients. In multivariable logistic regression analysis, older age (p<0.001), higher baseline systolic blood pressure (SBP) (p=0.032), incomplete reperfusion defined by extended Thrombolysis In Cerebral Infarction (eTICI) grades (p=0.020), and larger final infarct volume (FIV) (p<0.001) were independent predictors of futile recanalization. CONCLUSIONS: Old age, high baseline SBP, incomplete reperfusion defined by eTICI, and large FIV were independent predictors of futile recanalization after endovascular therapy for AIS.

7.
Front Med (Lausanne) ; 8: 723904, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540870

RESUMO

The potential relationship among airway Candida spp. de-colonization, nebulized amphotericin B (NAB), and occurrence of ventilator-associated pneumonia (VAP) in patients who are critically ill has not been fully investigated, especially concerning effects on survival. In this observational, retrospective, cohort study in a 22-bed central intensive care unit, we included patients aged >18 years who required mechanical ventilation (MV) for >48 h, with at least two consecutive positive Candida spp. test results. Patients were categorized into NAB and no NAB (control) groups. Propensity matching at 1:1 was performed according to strict standards, and multiple Cox proportional hazard model and multivariate analyses were performed to evaluate the effects of NAB treatment. Throughout an 8-year study period, 526 patients had received MV and had positive respiratory tract Candida spp. cultures. Of these, we included 275 patients and excluded 251 patients. In total, we successfully matched 110 patients from the two groups (each group, n = 55; total population median age, 64 years; Acute Physiology and Chronic Health Evaluation II [APACHE II] score, 25.5; sequential organ failure assessment score, 9). The Candida spp. de-colonization rate was 69.1% in patients treated with NAB. VAP incidence did not differ significantly between the NAB (10.91%) and control (16.36%) groups (P = 0.405). Pseudomonas aeruginosa-related VAP rates differed significantly between the NAB (10.91%) and control (25.45%) groups (P = 0.048). Five (9.1%) patients in the NAB group died during hospitalization compared with 17 (30.9%) controls (P = 0.014). At 28 days, 9 (16.4%) and 16 (29.1%) deaths occurred in the NAB and control groups, respectively, (P = 0.088). The cumulative 90-day mortality rate differed significantly between the two groups (23.6 vs. 43.6%, P = 0.015). Multivariate logistic regression analyses indicated a decreased 90-day mortality in the NAB group (adjusted odds ratio 0.413; 95% confidence interval 0.210-0.812; P = 0.01). In subgroup analyses, the NAB-associated decreased risk of death at 90 days was consistent across subgroups of patients with a Candida score of 2, younger age (<64 years), a higher APACHE II score (≥25), fewer Candida sites (<2), or MV at admission. NAB treatment contributed to Candida spp. airway de-colonization, was associated with a reduced risk of P. aeruginosa-related VAP, and improved 90-day mortality in patients critically ill with Candida spp. tracheobronchial colonization who had received MV for >2 days. NAB may be an alternative treatment option for critically ill patients with VAP.

8.
Int J Med Mushrooms ; 23(8): 77-88, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34587427

RESUMO

Phellinus igniarius has been widely used as traditional herbal medicine in China, Korea, Japan, and other Asian countries for centuries. To gain a molecular understanding of this fungus, Illumina high-throughput technology was used to sequence and analyze the transcriptome of Ph. igniarius, and 11,847 unigenes were obtained. Additionally, based on similarity search with known proteins, unigenes were annotated with gene descriptions, gene ontology (GO), and clusters of orthologous groups (COG). Based on the GO annotation, a total of 6983 unigenes could be assigned to one or more terms, which were categorized into 39 functional groups under three main divisions (biological process, cellular component and molecular function). A total of 2315 Ph. igniarius unigenes were associated with 124 unique Kyoto Encyclopedia of Genes and Genomes pathways. A total of 832 simple sequence repeats were identified in these unigenes. In addition, nine candidate genes involved in laccases were discovered, 17 candidate genes involved in the biosynthesis of triterpenoid were identified and were worthy for further investigation. This is the first study to conduct transcriptome analyses on Ph. igniarius, which lays a basis for further functional genomics studies of Ph. igniarius.


Assuntos
Agaricales , Salix , Agaricales/genética , Perfilação da Expressão Gênica , Phellinus , Análise de Sequência de RNA , Transcriptoma
9.
Burns Trauma ; 9: tkab018, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34212064

RESUMO

Because China is becoming an aging society, the incidence of diabetes and diabetic foot have been increasing. Diabetic foot has become one of the main health-related killers due to its high disability and mortality rates. Negative pressure wound therapy (NPWT) is one of the most effective techniques for the treatment of diabetic foot wounds and great progress, both in terms of research and its clinical application, has been made in the last 20 years of its development. However, due to the complex pathogenesis and management of diabetic foot, irregular application of NPWT often leads to complications, such as infection, bleeding and necrosis, that seriously affect its treatment outcomes. In 2020, under the leadership of Burns, Trauma and Tissue Repair Committee of the Cross-Straits Medicine Exchange Association, the writing group for 'Consensus on the application of negative pressure wound therapy of diabetic foot wounds' was established with the participation of scholars from the specialized areas of burns, endocrinology, vascular surgery, orthopedics and wound repair. Drawing on evidence-based practice suggested by the latest clinical research, this consensus proposes the best clinical practice guidelines for the application and prognostic evaluation of NPWT for diabetic foot. The consensus aims to support the formation of standardized treatment schemes that clinicians can refer to when treating cases of diabetic foot.

10.
Neurourol Urodyn ; 40(7): 1740-1753, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34252243

RESUMO

AIMS: To investigate the clinical characteristics of health care-seeking men presenting with lower urinary tract symptoms (LUTS) in China and to reveal risk factors for symptom severity. METHODS: This multicenter, hospital-based, cross-sectional study recruited 1477 eligible male subjects, who were at least 45 years, seeking health care at 9 participating hospitals across the mainland China. The general medical information and subjective symptoms were recorded, followed by the measurement of prostate volume, urodynamic indices, and laboratory tests for kidney function, plus glucose/lipid metabolism. Univariate and multivariate linear regression were employed for the detection of risk factors for symptom severity. RESULTS: The proportion of mild, moderate, and severe LUTS was 14.6%, 32.6%, and 52.8%, respectively, with 62.2% reporting the triple combination of storage, voiding, and postmicturition symptoms. Median prostate volume was 44.6 ml, and 71.1% were experiencing comorbidities. Thirteen independent risk factors for LUTS severity were identified, namely, nocturnal voiding episodes and the presence of straining and weak steam; the triple combination of symptom subtypes; general and nocturia quality of life; Qmax and bladder outlet obstruction index; and numbers of comorbidities, hypertension, estimated glomerular filtration rate, and cholesterol and glycosylated hemoglobin. CONCLUSIONS: The majority of health care-seeking LUTS men present with moderate-to-severe and overlapping symptoms, with a high prevalence of both lower urinary tract dysfunction and systemic comorbidities. The evidence from both urological and nonurological independent risk factors demonstrate the multifactorial nature of LUTS, for which a multidisciplinary management is essential.


Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , China/epidemiologia , Estudos Transversais , Atenção à Saúde , Humanos , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/epidemiologia , Masculino , Hiperplasia Prostática/complicações , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/epidemiologia , Qualidade de Vida , Fatores de Risco
11.
J Clin Hypertens (Greenwich) ; 23(7): 1399-1404, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34092020

RESUMO

Dyslipidemia is an emerging disease in China, especially in the presence of hypertension and diabetes mellitus. We investigated the association of dyslipidemia with the use of antihypertensive and antidiabetic agents. The study participants (n = 2423) were hypertensive and diabetic patients enrolled in a China nationwide registry. Serum mean ± (SD, except for serum triglycerides, median [interquatile range]) concentrations were 1.38 (0.97-2.02) mmol/L, 4.85 ± 1.12 mmol/L, 1.30 ± 0.36 mmol/L, and 2.89 ± 0.92 mmol/L for triglycerides and total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol, respectively. The prevalence of dyslipidemia was 18.9%, 13.5%, 16.6%, and 37.7% for hypertriglyceridemia (serum triglycerides ≥2.3 mmol/L), hypercholesterolemia (total cholesterol ≥6.2 mmol/L or LDL cholesterol ≥4.1 mmol/L), low HDL cholesterol (HDL cholesterol <1.0 mmol/L), and any of the three lipid disorders, respectively. Treated (n = 1647), compared with untreated hypertensive patients (n = 303), had a significantly (P ≤ .0006) lower serum total, LDL, and HDL cholesterol, but similar serum triglycerides (P = .20). Treated (n = 1325), compared with untreated diabetic patients (n = 238), had a significantly (P ≤ .004) lower serum triglycerides, and total and LDL cholesterol, but similar serum HDL cholesterol (P = .81). After adjustment, the odds ratios (OR) were significant for hypercholesterolemia (OR 0.76, 95% confidence interval [CI] 0.58-0.997, P = .048) and low HDL cholesterol (OR 1.56, CI 1.19-2.03, P = .001) in treated versus untreated hypertension, and for low HDL cholesterol (OR 1.50, CI 1.18-1.89, P = .0008) in treated versus untreated diabetes. In conclusion, the prevalence of dyslipidemia differed between treated and untreated hypertension and diabetes.


Assuntos
Anti-Hipertensivos/uso terapêutico , Diabetes Mellitus , Dislipidemias , Hipertensão , Hipoglicemiantes/uso terapêutico , China/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Triglicerídeos/sangue
12.
Polymers (Basel) ; 13(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066516

RESUMO

The increasing use of functional aramids in a wide array of applications and the inert nature of aramids against conventional dye and print methods requires developing new dyeing methods. This study aims to use environmentally friendly method with a cationic dye as an alternative for dyeing para-aramid fabrics. Experiments used a multi-factorial design with functions of pretreatment, dye solvent (water and/or glycerol) and auxiliary chemical additives (swelling agent and surfactant) and a sequential experimentation methodology. The most effective dyeing procedures involved the following steps: (i) pretreatments of the fabrics with soybean oil and nonthermal plasma (NTP), (ii) using water at T = 100 °C as the dye solvent, and (iii) omitting other chemical additives. With a commercial cationic dye, these conditions achieved a color strength in K/S value of 2.28, compared to ~1 for untreated samples. FTIR analysis revealed that a functional network formed on the fibers and yarns of the fabrics by chemical reactions of excited plasma species with double bonds in the soybean oil molecules was responsible for significantly improving the color strength. These results extend the potential uses of a renewable material (soybean oil) and an environmentally friendly technology (NTP) to improve the dyeing of para-aramid textiles and reduce the use of harsh dye chemicals.

13.
Clin Microbiol Infect ; 27(10): 1488-1493, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34020032

RESUMO

OBJECTIVES: Intravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcome of such treatment remains unclear. This study evaluated the effectiveness of IVIG treatment in severe COVID-19 patients. METHODS: This retrospective multicentre study evaluated 28-day mortality in severe COVID-19 patients with or without IVIG treatment. Each patient treated with IVIG was matched with one untreated patient. Logistic regression and inverse probability weighting (IPW) were used to control confounding factors. RESULTS: The study included 850 patients (421 IVIG-treated patients and 429 non-IVIG-treated patients). After matching, 406 patients per group remained. No significant difference in 28-day mortality was observed after IPW analysis (average treatment effect (ATE) = 0.008, 95% CI -0.081 to 0.097, p 0.863). There were no significant differences between the IVIG group and non-IVIG group for acute respiratory distress syndrome, diffuse intravascular coagulation, myocardial injury, acute hepatic injury, shock, acute kidney injury, non-invasive mechanical ventilation, invasive mechanical ventilation, continuous renal replacement therapy and extracorporeal membrane oxygenation except for prone position ventilation (ATE = -0.022, 95% CI -0.041 to -0.002, p 0.028). DISCUSSION: IVIG treatment was not associated with significant changes in 28-day mortality in severe COVID-19 patients. The effectiveness of IVIG in treating patients with severe COVID-19 needs to be further investigated through future studies.


Assuntos
COVID-19/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Idoso , COVID-19/diagnóstico , COVID-19/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Imunização Passiva/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Resultado do Tratamento
14.
Front Oncol ; 11: 656060, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34026629

RESUMO

Objective: To develop and prospective validate an ultrasound (US) prediction model to differentiate between benign and malignant subpleural pulmonary lesions (SPLs). Methods: This study was conducted retrospectively from July 2017 to December 2018 (development cohort [DC], n = 592) and prospectively from January to April 2019 (validation cohort [VC], n = 220). A total of 18 parameters of B-mode US and contrast-enhanced US (CEUS) were acquired. Based on the DC, a model was developed using binary logistic regression. Then its discrimination and calibration were verified internally in the DC and externally in the VC, and its diagnostic performance was compared with those of the existing US diagnostic criteria in the two cohorts. The reference criteria were from the comprehensive diagnosis of clinical-radiological-pathological made by two senior respiratory physicians. Results: The model was eventually constructed with 6 parameters: the angle between lesion border and thoracic wall, basic intensity, lung-lesion arrival time difference, ratio of arrival time difference, vascular sign, and non-enhancing region type. In both internal and external validation, the model provided excellent discrimination of benign and malignant SPLs (C-statistic: 0.974 and 0.980 respectively), which is higher than that of "lesion-lung AT difference ≥ 2.5 s" (C-statistic: 0.842 and 0.777 respectively, P <0.001) and "AT ≥ 10 s" (C-statistic: 0.688 and 0.641 respectively, P <0.001) and the calibration curves of the model showed good agreement between actual and predictive malignancy probabilities. As for the diagnosis performance, the sensitivity and specificity of the model [sensitivity: 94.82% (DC) and 92.86% (VC); specificity: 92.42% (DC) and 92.59% (VC)] were higher than those of "lesion-lung AT difference ≥ 2.5 s" [sensitivity: 88.11% (DC) and 80.36% (VC); specificity: 80.30% (DC) and 75.00% (VC)] and "AT ≥ 10 s" [sensitivity: 64.94% (DC) and 61.61% (VC); specificity: 72.73% (DC) and 66.67% (VC)]. Conclusion: The prediction model integrating multiple parameters of B-mode US and CEUS can accurately predict the malignancy probability, so as to effectively differentiate between benign and malignant SPLs, and has better diagnostic performance than the existing US diagnostic criteria. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR1800019828.

15.
Int J Biol Macromol ; 183: 295-304, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33894258

RESUMO

In order to take full advantage of the gastrointestinal digestive function, the effects of S-type ultrasound-assisted sodium bisulfite (UASB) pretreatment on the preparation of cholesterol-lowering peptide precursors derived from soybean protein were investigated and the structural characterizations of pretreated proteins were explored. UASB pretreatment with the operational mode of mono-frequency ultrasound at 28 kHz, ultrasonic power density of 200 W/L and ultrasonic time of 50 min exhibited the highest cholesterol-lowering activity (56.90%) of soybean protein hydrolysates (SPH) after simulated gastrointestinal digestion, which increased by 87.17% compared to the control. Under these conditions, the peptide content of SPH after simulated gastrointestinal digestion was not significantly different (p > 0.05) compared to the control. Further FTIR analysis showed that UASB pretreatment increased ß-turn and ß-sheet content and decreased α-helix and random coil content. The changes in the surface hydrophobicity and microstructures of soybean protein indicated that UASB pretreatment loosened soybean protein structure and exposed more hydrophobic groups. SDS-PAGE indicated that the restriction sites changed after UASB pretreatment. In conclusion, UASB pretreatment is an efficient method for the preparation of cholesterol-lowering peptide precursors.


Assuntos
Anticolesterolemiantes/química , Peptídeos/química , Hidrolisados de Proteína/química , Proteínas de Soja/química , Sulfitos/química , Ondas Ultrassônicas , Animais , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier
16.
Cell Death Dis ; 12(5): 419, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33911074

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoid malignancy and a highly heterogeneous disease. In this study, we performed whole-genome and transcriptome sequencing, and a genome-wide CRISPR-Cas9-knockout screen to study an activated B-cell-like DLBCL cell line (RC-K8). We identified a distinct pattern of genetic essentialities in RC-K8, including a dependency on CREBBP and MDM2. The dependency on CREBBP is associated with a balanced translocation involving EP300, which results in a truncated form of the protein that lacks the critical histone acetyltransferase (HAT) domain. The synthetic lethal interaction between CREBBP and EP300 genes, two frequently mutated epigenetic modulators in B-cell lymphoma, was further validated in the previously published CRISPR-Cas9 screens and inhibitor assays. Our study suggests that integration of the unbiased functional screen results with genomic and transcriptomic data can identify both common and unique druggable vulnerabilities in DLBCL and histone acetyltransferases inhibition could be a therapeutic option for CREBBP or EP300 mutated cases.


Assuntos
Proteína de Ligação a CREB/genética , Proteína de Ligação a CREB/metabolismo , Proteína p300 Associada a E1A/genética , Proteína p300 Associada a E1A/metabolismo , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Linhagem Celular Tumoral , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Técnicas de Silenciamento de Genes , Humanos , Linfoma Difuso de Grandes Células B/patologia
17.
Int J Med Mushrooms ; 23(4): 59-69, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33822508

RESUMO

This study used a He-Ne laser with pulsed light irradiation to produce mutant strains of Phellinus igniarius strain JQ9 with enhanced characteristics for fermentation (17.685 ± 3.092 g/L) compared with the parent strain (12.062 ± 1.119 g/L). The combined treatment conditions were as follows: He-Ne laser irradiation for 30 min using a spot diameter of 10 mm, pulsed light treatment power set at 100 J, a treatment distance of 14.5 cm, and a flash frequency of 0.5 s. The production of bioactive polysaccharides and small biocompounds such as polyphenols, flavonoids, and triterpenes increased together with mycelium production. The results showed that polyphenol content was significantly correlated with L*, a*, and b* values (R = -0.594, P < 0.01; R = 0.571, P < 0.01; and R = 0.500, P < 0.05; respectively). Antagonistic and random amplified polymorphic DNA analyses indicated that the genetic material of the screened mutants was altered. The mutant screening using a He-Ne laser with pulsed light irradiation could be an effective method for the development of Phellinus strains and could thus improve mycelium production.


Assuntos
Lasers de Gás , Phellinus/crescimento & desenvolvimento , Phellinus/efeitos da radiação , Colorimetria , Meios de Cultura , Fermentação , Flavonoides/isolamento & purificação , Mutagênese , Micélio/química , Micélio/crescimento & desenvolvimento , Micélio/efeitos da radiação , Phellinus/química , Phellinus/genética , Pigmentação , Polifenóis/isolamento & purificação , Polissacarídeos/isolamento & purificação , Polissacarídeos/metabolismo , Protoplastos , Triterpenos/isolamento & purificação
18.
Front Pharmacol ; 12: 616505, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33643048

RESUMO

This study was to scientifically and systematically explore the association between cardiotoxicity and immune checkpoint inhibitors (ICIs) and also to characterize the spectrum of ICI-related cardiac complications. From the first quarter of 2014 to the fourth quarter of 2019, data from the FDA Adverse Event Reporting System database were selected to conduct the disproportionality analysis. Reporting odds ratios and information components were used to evaluate the signal after statistical shrinkage transformation. In total, 7,443,137 cases and 36,326,611 drug-adverse event pairs were collected, among which 9,271 cases were identified to be related to ICI-induced cardiotoxicities. The number of male patients was much higher than that of females (5,579 vs. 3,031) and males presented a slightly higher reporting frequency than females in general, which was statistically significant (ROR = 1.04, 95%CI: 0.99-1.09, p < 0.001). Simultaneously, the proportion of serious or life-threatening outcomes in males was significantly higher than in females (ROR = 1.05, 95%CI: 0.96-1.15, p < 0.001). Importantly, ICIs were associated with over-reporting frequencies of cardiotoxicities in general (ROR025 = 1.06, IC025 = 0.08). PD-1 and PD-L1 were found to be related to cardiac adverse events, corresponding to ROR025 = 1.06, IC025 = 0.08, and ROR025 = 1.06, IC025 = 0.08, respectively, while anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) was significantly associated with some specific adverse events rather than common adverse events. The spectrum of cardiotoxicities induced by ICIs mostly differed among individual agents, but also demonstrated some common features. Dyspnea (N = 2,527, 21.25%), myocarditis (N = 614, 5.16%), atrial fibrillation (N = 576, 4.84%), cardiac failure (N = 476, 4.00%), and pericardial effusion (N = 423, 3.56%) were the top five cardiac adverse events reported in the database. Among them, myocarditis was the only one caused by all ICIs with strong signal value and high risk, warranting further attention. Overall, this investigation mainly showed the profile of cardiotoxicities caused by ICIs, which varied between different ICI therapies, but also shared some similarities in specific symptoms such as myocarditis. Therefore, it is vital and urgent to recognize and manage ICI-related cardiotoxicities, known to frequently occur in clinical practice, at the earliest point.

19.
BMC Neurol ; 21(1): 62, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568099

RESUMO

BACKGROUND: Persistent inflammation is an important driver of disease progression and affects prognosis. Some indicators of inflammation predict short-term outcomes. The relationship between prognosis, especially mortality, and persistent inflammation in massive stroke has not been studied, and this has been the subject of our research. METHODS: From April 1, 2017 to February 1, 2020, consecutive patients were prospectively enrolled. Clinical data, laboratory data, imaging data and follow-up infections morbidity were compared between 2 groups according to modified Rankin scale (mRS) scores (mRS < 3 and ≥ 3) at 1 month. The binomial logistic analysis was used to determine independent factors of 1-month prognosis. Short-term functional outcome, mortality and infection rates in massive stroke with and without persistent inflammation were compared. RESULTS: One hundred thirty-nine patients with massive stroke were included from 800 patients. We found that admission blood glucose levels (p = 0.005), proportions of cerebral hemispheric (p = 0.001), posterior circulatory (p = 0.035), and lacunar (p = 0.022) ischemia were higher in poor outcome patients; neutrophil-to-lymphocyte ratio (odd ratio = 1.87, 95%CI 1.14-3.07, p = 0.013) and blood glucose concentrations (odd ratio = 1.34, 95%CI 1.01-1.79, p = 0.043) can independently predict the short-term prognosis in massive stroke patients. We also found that the incidence of pulmonary infection (p = 0.009), one-month mortality (p = 0.003) and adverse outcomes (p = 0.0005) were higher in patients with persistent inflammation. CONCLUSIONS: This study suggested that persistent inflammation is associated with poor prognosis, 1-month mortality and the occurrence of in-hospital pulmonary infection and that higher baseline inflammation level predicts short-term poor outcomes in massive stroke.


Assuntos
Inflamação/imunologia , Recuperação de Função Fisiológica/imunologia , Acidente Vascular Cerebral/imunologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Inflamação/etiologia , Inflamação/mortalidade , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/mortalidade
20.
Medicine (Baltimore) ; 100(6): e24602, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578564

RESUMO

ABSTRACT: The purpose of this study was to identify and compare the diagnostic performance of gadolinium-ethoxybenzyl-diethyltriethylenetriacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) in hepatocellular carcinoma (HCC).Two researchers searched PubMed, EMBASE, and Cochrane Library databases from the inception of each database to 10 February 2020, to find comparative studies of Gd-EOB-DTPA-MRI and CEUS in detection of HCC.The study included eight studies (374 patients). MRI is superior to CEUS in diagnostic sensitivity of HCC, P = .03. The diagnostic sensitivity of MRI in lesions with a diameter of less than 30 mm was significantly higher than that of CEUS, P = .04. MRI and CEUS had no significant difference in diagnostic specificity of HCC, P = .95. Summary Receiver Operating Characteristics (SROC) of MRI showed a larger than that of CEUS, but with P > .05.Gd-EOB-DTPA-MRI showed higher sensitivity than CEUS for hepatocellular carcinoma lesions, especially for lesions of less than 30 mm across.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Gadolínio DTPA , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Ultrassonografia , Humanos , Estudos Observacionais como Assunto
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