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1.
Cancer Med ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33650320

RESUMO

Lung cancer is the leading cause of cancer-related mortality both in men and women and accounts for 18.4% of all cancer-related deaths. Although advanced therapy methods have been developed, the prognosis of lung cancer patients remains extremely poor. Over the past few decades, clinicians and researchers have found that chemical compounds extracted from natural products may be useful for treating lung cancer. Drug formulations derived from natural compounds, such as paclitaxel, doxorubicin, and camptothecin, have been successfully used as chemotherapeutics for lung cancer. In recent years, hundreds of new natural compounds that can be used to treat lung cancer have been found through basic and sub-clinical research. However, there has not been a corresponding increase in the number of drugs that have been used in a clinical setting. The probable reasons may include low solubility, limited absorption, unfavorable metabolism, and severe side effects. In this review, we present a summary of the natural compounds that have been proven to be effective for the treatment of lung cancer, as well as an understanding of the mechanisms underlying their pharmacological effects. We have also highlighted current controversies and have attempted to provide solutions for the clinical translation of these compounds.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33650804

RESUMO

OBJECTIVES: This study aimed to examine the association of less-certain indication of chronic total occlusion percutaneous coronary intervention (CTO-PCI) with subsequent clinical outcomes. BACKGROUND: The impact of patient symptoms, myocardial viability, and clinical and anatomic risk on long-term outcomes is underdetermined. METHODS: Consecutive patients undergoing CTO-PCI at a large-volume single center between 2010 and 2013 were included. Central adjudication was used to assess the appropriateness of three prespecified indications. The primary outcome was the 5-year composite endpoint of death or myocardial infarction (MI). RESULTS: Of 2,659 patients with 2,735 CTO lesions, the 348 (13.1%) asymptomatic patients, 164 (6.2%) patients without viable myocardium in the CTO territory, and 306 (11.5%) patients in whom the Synergy between PCI with Taxus and Cardiac Surgery Score II favored coronary artery bypass grafting (CABG) had higher 5-year death or MI compared with the rest patients in each category (12.0% vs. 8.6%, p = .04; 16.3% vs. 8.5%, p < .0001; 12.2% vs. 8.6%, p = .03), respectively. Multivariable regression analysis demonstrated that without symptom (hazard ratio: 1.51; 95% confidence interval: 1.06-2.15; p = .02), non-viable myocardium in CTO territory (hazard ratio: 1.77; 95% confidence interval: 1.16-2.72; p = .009), and deemed more favorable for CABG (hazard ratio:1.54; 95% confidence interval: 1.04-2.28; p = .03), but not the technical success (hazard ratio:0.85; 95% confidence interval: 0.62-1.18; p = .34), were independent predictors for the primary endpoint. CONCLUSIONS: In this large cohort of CTO-PCI, those who were asymptomatic, non-viable myocardium in the CTO territory, or deemed more favorable for CABG were associated with higher risk of long-term mortality or MI.

3.
JMIR Med Inform ; 9(2): e24572, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33534723

RESUMO

BACKGROUND: COVID-19 has overwhelmed health systems worldwide. It is important to identify severe cases as early as possible, such that resources can be mobilized and treatment can be escalated. OBJECTIVE: This study aims to develop a machine learning approach for automated severity assessment of COVID-19 based on clinical and imaging data. METHODS: Clinical data-including demographics, signs, symptoms, comorbidities, and blood test results-and chest computed tomography scans of 346 patients from 2 hospitals in the Hubei Province, China, were used to develop machine learning models for automated severity assessment in diagnosed COVID-19 cases. We compared the predictive power of the clinical and imaging data from multiple machine learning models and further explored the use of four oversampling methods to address the imbalanced classification issue. Features with the highest predictive power were identified using the Shapley Additive Explanations framework. RESULTS: Imaging features had the strongest impact on the model output, while a combination of clinical and imaging features yielded the best performance overall. The identified predictive features were consistent with those reported previously. Although oversampling yielded mixed results, it achieved the best model performance in our study. Logistic regression models differentiating between mild and severe cases achieved the best performance for clinical features (area under the curve [AUC] 0.848; sensitivity 0.455; specificity 0.906), imaging features (AUC 0.926; sensitivity 0.818; specificity 0.901), and a combination of clinical and imaging features (AUC 0.950; sensitivity 0.764; specificity 0.919). The synthetic minority oversampling method further improved the performance of the model using combined features (AUC 0.960; sensitivity 0.845; specificity 0.929). CONCLUSIONS: Clinical and imaging features can be used for automated severity assessment of COVID-19 and can potentially help triage patients with COVID-19 and prioritize care delivery to those at a higher risk of severe disease.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33578281

RESUMO

ß-Elemonic acid is one of the main active ingredients isolated from Boswellia carterii Birdw. which has been reported to exhibit potential anti-inflammatory and anti-cancer activities. There is few information about pharmacokinetics and tissue distribution of ß-elemonic acid by now. In this study, an ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-MS/MS) method has been developed and validated to determine ß-elemonic acid in rat plasma and various tissues after intragastric administration. Oleanolic acid was chosen as an internal standard (IS) and the plasma/tissue samples were pretreated with one-step liquid-liquid extraction. Chromatographic separation was accomplished on Eclipse Plus C18 analytical column (2.1 × 50 mm, 1.8 µm) utilizing a gradient mobile phase system consisting of water (with 0.1% ammonia-solution) and acetonitrile. ß-Elemonic acid and IS were detected and quantified using negative electrospray ionization in multiple reaction monitoring (MRM) mode with transitions of m/z 453.3 â†’ 423.5 for ß-elemonic acid and m/z 455.3 â†’ 407.6 for IS. ß-Elemonic acid showed good linearity over the investigated concentration range (r > 0.9934) in rat plasma and tissue sample. The method was successfully applied for determination of ß-elemonic acid in bio-samples. A bimodal phenomenon appeared in the plasma concentration-time curve of the ß-elemonic acid. The highest tissue concentrations were found in the intestine including jejunum, ileum and colon.

5.
J Am Heart Assoc ; 10(5): e018236, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33586461

RESUMO

Background The FHOD3 (formin homology 2 domain-containing 3) gene has recently been identified as a causative gene of hypertrophic cardiomyopathy (HCM). However, the pathogenicity of FHOD3 variants remains to be evaluated. This study analyzed the spectrum of FHOD3 variants in a large HCM and control cohort, and explored its correlation with the disease. Methods and Results The genetic analysis of FHOD3 was performed using the whole exome sequencing data from 1000 patients with HCM and 761 controls without HCM. A total of 37 FHOD3 candidate variants were identified, including 25 missense variants and 2 truncating variants. In detail, there were 27 candidate variants detected in 33 (3.3%) patients with HCM, which was significantly higher than in the 12 controls (3.3% versus 1.6%; odds ratio, 2.13; P<0.05). On the basis of familial segregation, we identified one truncating variant (c.1286+2delT) as a causal variant in 4 patients. Furthermore, the FHOD3 candidate variant experienced significantly more risk of cardiovascular death and all-cause death (adjusted hazard ratio [HR], 3.71; 95%, 1.32-8.59; P=0.016; and adjusted HR, 3.02; 95% CI, 1.09-6.85; P=0.035, respectively). Conclusions Our study suggests that FHOD3 is a causal gene for HCM, and that the presence of FHOD3 candidate variants is an independent risk for cardiovascular death and all-cause death in HCM.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33605538

RESUMO

OBJECTIVES: This study aimed to assess the safety, blood pressure changes, and biochemical responses of superselective adrenal artery embolization (SAAE) in hypertensive patients with idiopathic hyperaldosteronism (IHA). BACKGROUND: SAAE is a minimally invasive procedure that has been used to successfully treat aldosterone-producing adenoma. However, its effect for patients with IHA is unevaluated. METHODS: A total of 41 hypertensive patients who were diagnosed with IHA and underwent SAAE at the Fuwai Hospital between December 2010 and June 2016 were prospectively enrolled. The blood pressure, antihypertensive medications, plasma aldosterone and potassium levels, and adverse events were assessed. The primary endpoint was the change in home blood pressure at 12 months, compared with baseline. RESULTS: SAAE was technically successful in 39 patients. Postoperatively, home and 24-hr mean blood pressures were reduced by 14/9 and 10/7 mmHg at 1 month, respectively, and by 13/7 and 11/7 mmHg at 12 months, respectively. The number of antihypertensive agents used reduced by 1.0 and 1.1 at 1 month and 12 months, respectively (all p < .001). Compared with baseline (524.0 pmol/L), the standing plasma aldosterone reduced to 293.4 pmol/L at 12 months (p < .001). Serum potassium increased from 3.0 to 4.1 mmol/L while the rate of potassium supplement and mineralocorticoid receptor antagonist use reduced from 87.1 and 89.7%, respectively, to 28.2 and 17.9%, respectively, at 12 months (all p < .001). There were no serious complications in the perioperative and 12-month follow-up periods. CONCLUSIONS: SAAE was effective and feasible for IHA treatment, without serious complications, therefore, maybe a potential treatment.

7.
Nat Commun ; 12(1): 757, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536423

RESUMO

Chordoma is a rare bone tumor with an unknown etiology and high recurrence rate. Here we conduct whole genome sequencing of 80 skull-base chordomas and identify PBRM1, a SWI/SNF (SWItch/Sucrose Non-Fermentable) complex subunit gene, as a significantly mutated driver gene. Genomic alterations in PBRM1 (12.5%) and homozygous deletions of the CDKN2A/2B locus are the most prevalent events. The combination of PBRM1 alterations and the chromosome 22q deletion, which involves another SWI/SNF gene (SMARCB1), shows strong associations with poor chordoma-specific survival (Hazard ratio [HR] = 10.55, 95% confidence interval [CI] = 2.81-39.64, p = 0.001) and recurrence-free survival (HR = 4.30, 95% CI = 2.34-7.91, p = 2.77 × 10-6). Despite the low mutation rate, extensive somatic copy number alterations frequently occur, most of which are clonal and showed highly concordant profiles between paired primary and recurrence/metastasis samples, indicating their importance in chordoma initiation. In this work, our findings provide important biological and clinical insights into skull-base chordoma.


Assuntos
Cordoma/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença/genética , Proteína SMARCB1/genética , Neoplasias da Base do Crânio/genética , Fatores de Transcrição/genética , Sequenciamento Completo do Genoma/métodos , Adulto , Cordoma/patologia , Variações do Número de Cópias de DNA , Feminino , Genômica/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Neoplasias da Base do Crânio/patologia , Adulto Jovem
8.
Drug Chem Toxicol ; : 1-7, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557643

RESUMO

Psoralen is the main coumarin component of Fructus psoraleae. Previously, we have found that psoralen induced hepatocytes apoptosis via PERK and ATF6 related ER stress pathways in vitro. In this study, we investigated the toxicity and ER stress induced by psoralen in female C57 mice. Mice were fed with 80 mg/kg of psoralen intra-gastrically for either 3, 7, or 21 days. Liver and kidney were weighed and their coefficients were calculated. The serum was isolated to examine the biochemical parameters including alanine aminotransferase (ALT) activity, aspartate aminotransferase (AST) activity, alkaline phosphatase (ALP) activity, blood urea nitrogen (BUN), total bile acid (TBA), total bilirubin (TBIL), and creatinine (CRE). The transcription and expression of ER stress-related markers were determined by Wes-automated Protein Simple system, Western blot and RT-PCR. Psoralen administration for 3 days significantly increased liver coefficients but decreased kidney coefficients of mice. Histopathological examination showed minimal inflammatory cell foci and vacuolar degeneration in the liver. Besides, serum levels of ALT, TBA, BUN, and CRE were markedly altered by psoralen. Moreover, psoralen significantly increased expression and transcription levels of ER stress related markers, including Grp78, PERK, eIF2α, ATF4, IRE1α, ATF6, and XBP1. These results illustrated that psoralen induced liver injuries through ER stress signaling in female mice.

9.
Glob Chang Biol ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33560594

RESUMO

Nitrogen immobilization usually leads to nitrogen retention in soil and, thus, influences soil nitrogen supply for plant growth. Understanding soil nitrogen immobilization is important for predicting soil nitrogen cycling under anthropogenic activities and climate changes. However, the global patterns and drivers of soil nitrogen immobilization remain unclear. We synthesized 1350 observations of gross soil nitrogen immobilization rate (NIR) from 97 articles to identify patterns and drivers of NIR. The global mean NIR was 8.77 ± 1.01 mg N kg-1 soil day-1 . It was 5.55 ± 0.41 mg N kg-1 day-1 in croplands, 15.74 ± 3.02 mg N kg-1 soil day-1 in wetlands and 15.26 ± 2.98 mg N kg-1 soil day-1 in forests. The NIR increased with mean annual temperature, precipitation, soil moisture, soil organic carbon, total nitrogen, dissolved organic nitrogen, ammonium, nitrate, phosphorus, and microbial biomass carbon. But it decreased with soil pH. The results of structural equation models showed that soil microbial biomass carbon was a pivot to drive NIR, because temperature, total soil nitrogen, soil pH mostly indirectly influenced NIR via changing soil microbial biomass. Moreover, microbial biomass carbon accounted for most of the variations in NIR among all direct relationships. Furthermore, the efficiency of transforming the immobilized nitrogen to microbial biomass nitrogen was lower in croplands than natural ecosystems (i.e., forest, grassland, and wetland). These findings suggested that soil nitrogen retention may decrease under the land use change from forests or wetlands to croplands, but NIR was expected to increase due to increased microbial biomass under global warming. The identified patterns and drivers of soil nitrogen immobilization in this study is crucial to project the changes in soil nitrogen retention.

10.
JACC Cardiovasc Interv ; 14(3): 278-288, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33541539

RESUMO

OBJECTIVES: The aim of this study was to determine the association of procedural outcomes with long-term mortality and myocardial infarction (MI) after chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND: The association between acute procedural results and subsequent outcomes has received limited study. METHODS: Between January 2010 and December 2013, a total of 2,659 CTO PCI patients were consecutively enrolled. Procedural results were categorized into 3 groups: 1) optimal recanalization, with reperfusion of the occluded vessel and side branches (if any) with TIMI (Thrombolysis In Myocardial Infarction) flow grade 3; 2) suboptimal recanalization, meeting any of the following criteria: persistence of significant side branch occlusion, final TIMI flow grade 1 or 2, or residual percentage diameter stenosis >30%; and 3) procedural failure (i.e., failure to cross a lesion with a balloon angioplasty catheter). The primary outcome was the 5-year composite endpoint of cardiac death and MI. RESULTS: Overall, optimal recanalization was achieved in 1,562 patients (58.7%), suboptimal recanalization was achieved in 399 patients (15.0%), and recanalization failed in 698 patients (26.3%). The 5-year incidence of the primary outcome was significantly higher in the suboptimal recanalization group compared with the optimal recanalization and the failure groups (10.1% vs. 6.5% vs. 6.3%; p = 0.046), which was driven mainly by higher risk for MI. In subgroup analysis, significant side branch occlusion was associated with numerically higher risk for 5-year MI (hazard ratio: 1.55; 95% confidence interval: 0.99 to 2.43; p = 0.054). CONCLUSIONS: In this large cohort of CTO PCI patients, suboptimal recanalization was associated with significantly higher long-term incidence of cardiac death and MI compared with optimal recanalization or procedural failure.

11.
J Am Chem Soc ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33599474

RESUMO

Nanoparticles (NPs) decorated with a high density of DNA strands, also known as spherical nucleic acids (SNAs), are widely used in DNA-programmable assembly, sensing, imaging, and therapeutics. A regular SNA synthesis is very time-consuming, which requires great caution to avoid NP aggregation. Herein we report an extremely simple, efficient, and scalable process to realize instant (in seconds) synthesis of SNAs with record-high DNA density. Our method relies on a rapid water removal from a DNA/NP mixture in contact with a butanol phase. This process generates a dehydrated "solid solution" that greatly accelerates DNA anchorage on NPs via Au-S bonding. Compared to a state-of-the-art DNA conjugation strategy in the literature, up to 3-time increase of DNA density is achieved by the instant dehydration in butanol (INDEBT). The ultradense DNA grafting is accomplished in a few seconds, which is highly hybridizable to form core-satellite assemblies. Our work turns SNA synthesis into an easy job, and enables future explorations of physical, chemical, and biological effects of SNAs with ultrahigh DNA density.

12.
J Colloid Interface Sci ; 588: 164-174, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33388582

RESUMO

Recently, the increasing demands of the portable devices and flexible electronics have caused lots of electromagnetic wave pollution. MXene, a novel two-dimensional material, was considered as a promising two-dimensional material for preparing flexible electromagnetic interference (EMI) shielding films. Herein, we firstly synthesized a series of flexible and self-healable EMI shielding waterborne polyurethane (ADWPU) films by mechanically blending with Ti3C2Tx (ADWPU-T). Interestingly, the self-assembling between ADWPU and Ti3C2Tx constructed a tunable analogical structure providing reflection-absorption-multiple reflection shielding mechanism. Furthermore, the ADWPU-T emulsions were prepared from castor oil which is a low-cost and eco-friendly biomass polyol. The chain extender 2-aminophenyl disulfide endow a reversible dynamic polymer network which leading to shape memory performance (45°C heat treatment) and self-healing ability (60°C, 5 min healed). Above all, these multifunctional flexible films also exhibited outstanding EMI shielding performance (51.37 dB) and performed less decrement after 200 times bending and 80°C aging test for five days. Therefore, this work would provide a novel promising method for preparing responsive electromagnetic interference shielding products and smart electronic devices.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33420791

RESUMO

OBJECTIVES: Metabolic abnormalities have been associated with long-term cardiac mortality in patients with hypertrophic cardiomyopathy (HCM). Obstructive sleep apnea (OSA) is a risk factor for metabolic abnormalities in general populations, but association between OSA and metabolic abnormalities in HCM is still undefined. This study aimed to investigate the relationship between OSA and metabolic dysfunction in a large series of patients with HCM. METHODS: A total of 587 patients with HCM who underwent sleep evaluations at Fuwai Hospital were included. Data from clinical characteristics, polysomnography studies and metabolic measurements were collected. RESULTS: OSA was present in 344 patients (58.6%). Patients with OSA were older, more often male and had more clinical comorbidities. Body mass index, blood pressure, fasting glucose and triglycerides all increased (all P<0.001) and high-density lipoprotein cholesterol decreased (P=0.046) with the severity of OSA. In multivariate analysis, moderate to severe OSA and Log (AHI[apnea-hypopnea index]+1) were independently associated with obesity (OR, 2.42; 95%CI [1.48-3.95] and OR, 1.60; 95%CI [1.31-1.95]), elevated blood pressure (OR, 1.99; 95%CI [1.42-3.26] and OR, 1.31; 95%CI [1.08-1.60]) and elevated triglycerides (OR, 1.71; 95%CI [1.05-2.78] and OR, 1.24; 95%CI [1.02-1.51] but not elevated fasting glucose (OR, 0.88; 95%CI [0.50-1.52] and OR, 1.02; 95%CI [0.82-1.28]) and reduced high-density lipoprotein cholesterol (OR, 1.30; 95%CI [0.83-2.04] and OR, 1.06; 95%CI [0.89-1.27]). CONCLUSIONS: Severity of OSA is independently associated with some profiles of metabolic abnormalities. Clinical trials are required to determine whether OSA treatment improves metabolic abnormalities and long-term outcomes in patients with HCM.

15.
Cardiovasc Diabetol ; 20(1): 16, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430864

RESUMO

BACKGROUND: Patients with diabetes and triple-vessel disease (TVD) are associated with a high risk of events. The choice of treatment strategies remains a subject of discussion. In the real-world, we aim to compare the outcomes of medical therapy (MT), coronary artery bypass grafting (CABG), and percutaneous coronary intervention (PCI) treatment strategies in patients with diabetes and TVD. METHODS: A total of 3117 consecutive patients with diabetes and TVD were enrolled. The primary endpoint was all-cause death and the secondary endpoint was major adverse cardiac and cerebrovascular events (MACCE, composite of all-cause death, myocardial infarction, or stroke). RESULTS: During the mean follow-up of 6.3 ± 2.6 years, 573 (18.4%) deaths and 1094 (35.1%) MACCE occurred. Multivariate analysis showed that PCI (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.32-0.51) and CABG (HR 0.33, 95% CI 0.26-0.44) were associated with a lower risk of death compared with MT, with no difference between the PCI and CABG groups. When MACCE was the endpoint, PCI (HR 0.71, 95% CI 0.60-0.84) and CABG (HR 0.48, 95% CI 0.39-0.57) had a lower risk than MT. CABG was associated with a significantly lower risk of MACCE compared with PCI (HR 0.67, 95% CI 0.55-0.81), which was mainly attributed a lower risk in myocardial infarction, but a higher risk of stroke. CONCLUSIONS: In this big real-world data and intermediate-term follow-up study, for patients with diabetes and TVD, PCI and CABG were associated with a lower risk of death and MACCE more than MT. The results suggest the importance of appropriate revascularization for diabetic patients with TVD. However, CABG was not associated with a lower risk of death, but with a lower risk of MACCE, compared with PCI. In the future, we perhaps should strengthen comprehensive treatment in addition to PCI or CABG.

16.
Environ Int ; 147: 105975, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33385923

RESUMO

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10-26). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10-3). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.

17.
Chin Med J (Engl) ; 134(3): 292-301, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33470655

RESUMO

BACKGROUND: Generic drugs are bioequivalent to their brand-name counterparts; however, concerns still exist regarding the effectiveness and safety of generic drugs because of small sample sizes and short follow-up time in most studies. The purpose of this study was to evaluate the long-term antihypertensive efficacy, cost-effectiveness and cardiovascular outcomes of generic drugs compared with brand-name drugs. METHODS: In a multicenter, community-based study including 7955 hypertensive patients who were prospectively followed up for an average of 2.5 years, we used the propensity-score-matching method to match the patients using brand-name drugs to those using generic drugs in a ratio of 1:2, 2176 patients using brand-name drugs and 4352 patients using generic drugs. RESULTS: There were no significant differences between generic drugs and brand-name drugs in blood pressure (BP)-lowering efficacy, BP control rate, and cardiovascular outcomes including coronary heart disease and stroke. The adjusted mean (95% confidence interval [CI]) of systolic BP (SBP)-lowering was -7.9 mmHg (95% CI, -9.9 to -5.9) in the brand-name drug group and -7.1 mmHg (95% CI, -9.1 to -5.1) in the generic drug group after adjusting for age, sex, body mass index, number of antihypertensive drugs and traditionally cardiovascular risk factors. Among patients aged <60 years, brand-name drugs had a higher BP control rate (47% vs. 41%; P = 0.02) and a greater effect in lowering SBP compared with generic drugs, with the between-group difference of 1.5 mmHg (95% CI, 0.2-2.8; P = 0.03). BP control rate was higher in male patients using brand-name drugs compared with those using generic drugs (46% vs. 40%; P = 0.01). Generic drugs treatment yielded an average annual incremental cost-effectiveness ratio of $315.4 per patient per mmHg decrease in SBP compared with brand-name drugs treatment. CONCLUSIONS: Our data suggested that generic drugs are suitable and cost-effective in improving hypertension management and facilitating public health benefits, especially in low- and middle-income areas.

18.
J Mater Sci Mater Med ; 32(1): 17, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33506368

RESUMO

Osteoporosis is the most common disease involving bone degeneration. As the age of the population increases, the prevalence of the disease is expected to rise. However, current treatment methods do not provide a desirable solution for the restoration of the function of degenerated bones in patients with osteoporosis. This led to emergence of controlled delivery systems to increase drug bioavailability and efficacy specifically at the bone regeneration. In this study, an epimedin A (EA) complex drug system was prepared by solution blending method. In vitro cell-based experiments showed that the EA complex drug could significantly promote the differentiation and proliferation of osteoblasts and increase the alkaline phosphatase activity, calcium nodule formation, and the expression of osteogenesis-related genes and proteins. In vivo experiments further demonstrated that this novel drugs remarkably enhanced bone regeneration. These results suggest that EA may be used for the treatment of osteoporosis.

19.
Biomed Pharmacother ; 134: 111165, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33370633

RESUMO

High platelet reactivity and gastric mucosal injury after aspirin (ASA) treatment are associated with poor compliance and an increased risk of cardiovascular events. Panax notoginseng saponins (PNS) have been widely used for the treatment of coronary heart disease (CHD) in addition to antiplatelet drugs in China; however, the joint effect and possible mechanism of PNS in addition to ASA on platelet activation and gastric injury remain unclear. This study was designed to investigate the combinational effects of PNS with ASA, and to explore the underlying mechanism via arachidonic acid (AA) metabolism pathway using lipidomic analysis. In a randomized, assessor-blinded trial, 42 patients with stable coronary heart disease (SCHD) and chronic gastritis were randomly assigned to receive ASA (n = 21) or PNS + ASA (n = 21) for 2 months. Compared with ASA alone, PNS + ASA further inhibited CD62p expression, GPIIb-IIIa activation and platelet aggregation and led to increased platelet inhibition rate. PNS + ASA suppressed the activity of platelet cyclooxygenase (COX)-1, and decreased the production of TXB2, PGD2, PGE2, 11-HETE, the downstream oxylipids of AA/COX-1 pathway in platelets, compared with ASA alone. The severity of dyspepsia assessment (SODA) results showed that patients in PNS + ASA group exhibited relieved dyspeptic symptoms as compared with those in ASA group, which might be associated with enhanced secretion of gastrin and motilin. In vivo study of myocardial infarction rats demonstrated that PNS attenuated ASA-induced gastric mucosal injury, which was related to markedly boosted gastric level of 6,15-diketo-13,14-dihydro-prostaglandin (PG)F1α, 13,14-dihydro-15-keto-PGE2 and PGE2 from AA/PG pathway in response to PNS + ASA compared with ASA alone. In summary, our study demonstrated that the combination of PNS and ASA potentiated the antiplatelet effect of ASA via AA/COX-1/TXB2 pathway in platelets, and mitigated ASA-related gastric injury via AA/PG pathway in gastric mucosa.


Assuntos
Ácido Araquidônico/metabolismo , Aspirina/uso terapêutico , Plaquetas/efeitos dos fármacos , Doença das Coronárias/tratamento farmacológico , Mucosa Gástrica/efeitos dos fármacos , Gastrite/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Panax notoginseng , Extratos Vegetais/uso terapêutico , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/uso terapêutico , Saponinas/uso terapêutico , Adulto , Idoso , Animais , Aspirina/efeitos adversos , Pequim , Plaquetas/metabolismo , Doença Crônica , Doença das Coronárias/diagnóstico , Doença das Coronárias/metabolismo , Citoproteção , Sinergismo Farmacológico , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Gastrite/diagnóstico , Gastrite/metabolismo , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/isolamento & purificação , Humanos , Lipidômica , Masculino , Pessoa de Meia-Idade , Panax notoginseng/química , Extratos Vegetais/efeitos adversos , Extratos Vegetais/isolamento & purificação , Inibidores da Agregação de Plaquetas/efeitos adversos , Ratos Wistar , Saponinas/efeitos adversos , Saponinas/isolamento & purificação , Fatores de Tempo , Resultado do Tratamento
20.
J Hazard Mater ; 404(Pt A): 124106, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33053472

RESUMO

Recently, black phosphorous (BP) nanosheets as an emerging nanomaterial have presented significant fire safety improvement in polymer nanocomposites. However, as elemental phosphorus, fire safety improvement effect of BP nanosheets on polymer composites builds on the conversion of gaseous pyrolysis products into smoke particles, which inevitably promotes the formation and release of smoke particles. From the perspective of overall fire safety improvement, it is vital to simultaneously suppress the heat release and smoke production of polymer/BP composites. Herein, melamine-mediated graphene/black phosphorous nanohybrids (GNS/MA/BP) were fabricated through electrostatic-driving self-assembly process and introduced into polyether thermoplastic polyurethane (TPU). During combustion, the barrier function provided by thermally stable layered structure of graphene (GNS) enables more pyrolysis products of BP nanosheets to be kept within condensed phase and react with polymer matrix. Compared to pure TPU, the incorporated hierarchical nanostructure (GNS/MA/BP-2) decreases PHRR, THR, and total CO2 release of TPU composite by 54.7%, 23.5%, and 32.5%, respectively. Beside, in contrast to TPU-BP composite, the release rate of toxic smoke and CO gas of TPU-GNS/MA/BP-2 composite are reduced by 46.7% and 49.4%. With barrier function of graphene, the heat and smoke release behavior of polymer/BP nanocomposites is effectively suppressed.

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