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1.
Stroke ; : STROKEAHA119026872, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31597550

RESUMO

Background and Purpose- Stroke and Alzheimer disease are 2 major causes of neurological disability in aged people and shared overlapping predictors. In recent prospective studies, high Lp(a) [lipoprotein(a)] level is associated with high risk of stroke but low risk of Alzheimer disease. Whether this reflects a causal association remains to be established. The aim of this study is to examine the causal associations of Lp(a) concentrations on ischemic stroke, ischemic stroke subtypes, and Alzheimer disease. Methods- We used 9 single-nucleotide polymorphisms associated with Lp(a) concentrations as instrumental variables. Summary-level data on ischemic stroke and its subtypes were obtained from the Multiancestry Genome-Wide Association Study of Stroke consortium with European individuals ≤446 696 individuals. Summary-level data on Alzheimer disease were obtained from the International Genomics of Alzheimer Project With European individuals ≤54 162 individuals. Two-sample Mendelian randomization (MR) estimates were calculated with inverse-variance weighted, penalized inverse-variance weighted, simple median, weighted median, and MR Pleiotropy Residual Sum and Outlier approaches, and MR-Egger regression was used to explore pleiotropy. Results- Genetically predicted 1-SD log-transformed increase in Lp(a) concentrations was associated with a substantial increase in risk of large artery stroke (odds ratio, 1.20; 95% CI, 1.11-1.30; P<0.001) and a reduce in risk of small vessel stroke (odds ratio, 0.92; 95% CI, 0.88-0.97; P=0.001) and Alzheimer disease (odds ratio, 0.94; 95% CI, 0.91-0.97; P<0.001) using inverse-variance weighted method. No significant association was observed for total ischemic stroke or cardioembolic stroke. MR-Egger indicated no evidence of pleiotropic bias. Results were broadly consistent in sensitivity analyses using penalized inverse-variance weighted, simple median, weighted median, and MR Pleiotropy Residual Sum and Outlier approaches accounting for potential genetic pleiotropy or outliers. Conclusions- This study provides evidence to support that high Lp(a) concentrations was causally associated with an increased risk of large artery stroke but a decreased risk of small vessel stroke and Alzheimer disease. The mechanism underlying the double-edged sword effect of Lp(a) concentrations on neurological system requires further investigation.

2.
Sci China Life Sci ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31637576

RESUMO

In flowering plants, pollen tubes are attracted to the ovule by secreted peptides to release the sperm cells for double fertilization. This process is species-specific and acts as an important stage of reproductive isolation between species. Here we identified a cysteine-rich peptide TICKET2 in Arabidopsis thaliana and its orthologs in Arabidopsis lyrata and Capsella rebella that can attract the conspecific pollen tubes, but not the pollen tubes of relative species in Brassicaceae. Genetic knockout of the AtTICKET subclade compromised the pollen tube attraction efficiency. This study identified a new pollen tube attracting signal and shed light on the molecular basis of reproductive isolation.

3.
J Agric Food Chem ; 67(43): 11839-11847, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31589436

RESUMO

4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is an important target site for discovering new bleaching herbicides. To explore novel HPPD inhibitors with excellent herbicidal activity, a series of novel N-aroyl diketone/triketone derivatives were rationally designed by splicing active groups and bioisosterism. Bioassays revealed that most of these derivatives displayed preferable herbicidal activity against Echinochloa crus-galli (EC) at 0.045 mmol/m2 and Abutilon juncea (AJ) at 0.090 mmol/m2. In particular, compound I-f was more potent compared to the commercialized compound mesotrione. Molecular docking indicated that the corresponding active molecules of target compounds and mesotrione shared similar interplay with surrounding residues, which led to a perfect interaction with the active site of Arabidopsis thaliana HPPD.

4.
Anal Chem ; 91(19): 12587-12595, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31496223

RESUMO

Glioblastoma is a highly malignant brain tumor with poor prognosis and survival rate because of a lack of effective diagnostic methods. Hydrocyanines are a type of reactive oxygen species (ROS)-responsive fluorescent probes, allowing for distinguishing tumor cells from normal cells based on their different intracellular levels of ROS. However, their diagnostic applications for glioblastoma have been limited because of the inability to discriminate between tumor cells and other tissues with high ROS production, leading to high false-positive diagnosis. Therefore, tumor-responsive and -specific hydrocyanines with cooperative targeting ability have great potential for improving the diagnosis and treatment of glioblastoma. Integrin αvß3 plays a critical role in the progression and angiogenesis of glioblastoma and has become a promising target for diagnosing glioblastoma. Herein, we identify a specific peptide ligand for integrin αvß3, Arg-Trp-(d-Arg)-Asn-Arg (RWrNR), which shows high binding affinity to human glioblastoma U87MG cells. Importantly, hydro-Cy5-RWrNR conjugation allowed for distinguishing U87MG cells from normal cells in response to intracellular ROS. Particularly, hydro-Cy5-RWrNR could not only selectively accumulate in orthotopic U87MG tumor with minimal background fluorescence but also effectively discriminate between glioblastoma and inflammatory tissues for the first time, leading to detection of glioblastoma in vivo with high target-to-background ratios and minimal background fluorescence. Therefore, hydro-Cy5-RWrNR is the first integrin αvß3-specific hydrocyanine probe and has great potential in precise tumor diagnosis because of its cooperative targeting of integrin αvß3 and ROS.

5.
Chemosphere ; 239: 124678, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31494323

RESUMO

In the developing countries such as China, most well-developed areas have suffered severe haze pollution, which was associated with increased premature morbidity and mortality and attracted widespread public concerns. Since ground-based PM2.5 monitoring has limited temporal and spatial coverage, satellite aerosol remote sensing data has been increasingly applied to map large-scale PM2.5 characteristics through advanced spatial statistical models. Although most existing research has taken advantage of the polar orbiting satellite instruments, a major limitation of the polar orbiting platform is its limited sampling frequency (e.g., 1-2 times/day), which is insufficient for capturing the PM2.5 variability during short but intense heavy haze episodes. As the first attempt, we quantitatively investigated the feasibility of using the aerosol optical depth (AOD) data retrieved by the Geostationary Ocean Color Imager (GOCI) to estimate hourly PM2.5 concentrations during winter haze episodes in the Yangtze River Delta (YRD). We developed a three-stage spatial statistical model, using GOCI AOD and fine mode fraction, as well as corresponding monitoring PM2.5 concentrations, meteorological and land use data on a 6-km modeling grid with complete coverage in time and space. The 10-fold cross-validation R2 was 0.72 with a regression slope of 1.01 between observed and predicted hourly PM2.5 concentrations. After gap filling, the R2 value for the three-stage model was 0.68. We further analyzed two representative large regional episodes, i.e., a "multi-process diffusion episode" during December 21-26, 2015 and a "Chinese New Year episode" during February 7-8, 2016. We concluded that AOD retrieved by geostationary satellites could serve as a new valuable data source for analyzing the heavy air pollution episodes.

6.
Biomaterials ; 223: 119471, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31525693

RESUMO

Prostate cancer is one of the most commonly diagnosed cancers in men, leading to a high mortality rate due to a lack of effective anticancer treatment. Current anticancer chemotherapeutics are often administrated at suboptimal doses because of nonspecific toxicities to normal tissues, resulting in the eventual failure of therapy as well as the development of drug resistance and metastatic disease. Therefore, ligand-targeted therapeutics have the great potential of improving the selective anticancer toxicity. Integrins ß3 (αvß3 and αIIbß3) are an important cell adhesion molecular family, overexpressed on both cell membrane and perinuclear region of prostate cancer cells, and play a key role in the progression and metastasis of prostate cancer, making them an attractive target for anticancer therapy. However, their clinical impacts have been limited due to lack of specific ligands. Here, for the first time, we have identified a peptide Arginine-Tryptophan-(D-Arginine)-Asparagine-Arginine as an integrins ß3 specific ligand, named B3int, which shows superior selectivity to integrins ß3 over other integrin subunits. B3int has high affinity to integrins ß3 with a Kd value of 0.2 nM, which is 7-fold higher than c-RGDyK (1.4 nM), a well-established integrin αvß3 ligand. In addition, B3int shows high specificity for integrins ß3, and can selectively target integrin ß3 overexpressed cancer cells in vitro and in vivo. Most importantly, B3int-modified liposomes (B3int-LS-DOX) can selectively deliver DOX not only into prostate cancer cells, but into nucleus via targeting integrins ß3, thereby significantly improving anticancer effects in 2D prostate cancer cells and 3D tumor spheroids. Particularly, B3int-LS-DOX effectively inhibits tumor growth with an effective dose of as low as 1.5 mg/kg, which is 3.3-fold less than c-RGDyK-LS-DOX (5 mg/kg), indicating that integrins ß3 specific therapy is a promising anticancer strategy which can greatly improve the anticancer therapeutic index. In summary, we have identified B3int as the first integrins ß3 specific ligand with high affinity and specificity, and holds a great potential of improving the diagnosis and treatment for integrins ß3-overexpressed cancers.

7.
BMC Vet Res ; 15(1): 319, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488137

RESUMO

BACKGROUND: Small non-coding RNAs (sRNAs) regulate bacterial gene expression at the post-transcriptional level. STnc640 is a type of sRNA that was identified in Salmonella Typhimurium. RESULTS: In this study, STnc640 in Salmonella Enteritidis was confirmed to be an Hfq-dependent sRNA. TargetRNA software analysis showed that fimbrial genes fimA and bcfA were likely to be the target genes of STnc640. To investigate the target mRNAs and function of STnc640 in pathogenicity, we constructed the deletion mutant strain 50336△stnc640 and the complemented strain 50336△stnc640/pstnc640 in Salmonella Enteritidis 50336. The RT-qPCR results showed that the mRNA level of fimA was decreased, while bcfA was unchanged in 50336△stnc640 compared with that in the wild type (WT) strain. The adhesion ability of 50336△stnc640 to Caco-2 cells was increased compared to the 50336 WT strain. The virulence of 50336△stnc640 was enhanced in a one-day-old chicken model of S. Enteritidis disease as determined by quantifying the 50% lethal dose (LD50) of the bacterial strains. CONCLUSIONS: The results demonstrate that STnc640 contributes to the virulence of Salmonella Enteritidis.

8.
JAMA Neurol ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31424481

RESUMO

Importance: Dual antiplatelet therapy with clopidogrel and aspirin is effective for secondary prevention after minor ischemic stroke or transient ischemic attack (TIA). Uncertainties remained about the optimal duration of dual antiplatelet therapy for minor stroke or TIA. Objective: To obtain precise estimates of efficacy and risk of dual antiplatelet therapy after minor ischemic stroke or TIA. Design, Setting, and Participants: This analysis pooled individual patient-level data from 2 large-scale randomized clinical trials that evaluated clopidogrel-aspirin as a treatment to prevent stroke after a minor stroke or high-risk TIA. The Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) trial enrolled patients at 114 sites in China from October 1, 2009, to July 30, 2012. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial enrolled patients at 269 international sites from May 28, 2010, to December 19, 2017. Both were followed up for 90 days. Data analysis occurred from November 2018 to May 2019. Interventions: In the 2 trials, patients with minor stroke or high-risk TIA were randomized to clopidogrel-aspirin or aspirin alone within 12 hours (POINT) or 24 hours (CHANCE) of symptom onset. Main Outcomes and Measures: The primary efficacy outcome was a major ischemic event (ischemic stroke, myocardial infarction, or death from ischemic vascular causes). The primary safety outcome was major hemorrhage. Results: The study enrolled 5170 patients (CHANCE) and 4881 patients (POINT). Analysis included individual data from 10 051 patients (5016 in the clopidogrel-aspirin treatment group and 5035 in the control group) with a median age of 63.2 (interquartile range, 55.0-72.9) years; 6106 patients (60.8%) were male. Clopidogrel-aspirin treatment reduced the risk of major ischemic events at 90 days compared with aspirin alone (328 of 5016 [6.5%] vs 458 of 5035 [9.1%]; hazard ratio [HR], 0.70 [95% CI, 0.61-0.81]; P < .001), mainly within the first 21 days (263 of 5016 [5.2%] vs 391 of 5035 [7.8%]; HR, 0.66 [95% CI, 0.56-0.77]; P < .001), but not from day 22 to day 90. No evidence of heterogeneity of treatment outcome across trials or prespecified subgroups was observed. Major hemorrhages were more frequent in the clopidogrel-aspirin group, but the difference was nonsignificant. Conclusions and Relevance: In this analysis of the POINT and CHANCE trials, the benefit of dual antiplatelet therapy appeared to be confined to the first 21 days after minor ischemic stroke or high-risk TIA.

9.
J Clin Hypertens (Greenwich) ; 21(10): 1534-1541, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31468708

RESUMO

Using data from the Blood Pressure and Clinical Outcome in TIA or Ischemic Stroke (BOSS) study, we aim to test the applicability and feasibility of stroke secondary prevention recommendations from the 2017 American College of Cardiology/American Heart Association guideline. Patients were categorized based on their blood pressure (BP) status at 3 months. The nonhypertension group was defined as those without a diagnosis of hypertension. The other patients were further divided into three subgroups according to office BP measured at 3-month visit (BP <130/80, 130-139/80-89, and ≥140/90 mm Hg). The primary outcome was any stroke within one year. The associations between BP status and 1-year prognosis (recurrent stroke, recurrent stroke/TIA, and poor functional outcome [modified Rankin scale score 3-6]) were estimated. Among 2341 IS/TIA patients, additional 1056 patients were classified as uncontrolled hypertension at the 90-day visit according to the new guidelines. Adjusted hazard/odds ratios (95% confidence intervals [CI]) for recurrent stroke in BP <130/80, 130-139/80-89, and ≥140/90 compared with nonhypertension group were 2.42 (95% CI: 0.87-6.76), and 4.30 (95% CI: 1.73-10.70), respectively. The prevalence of hypertension and uncontrolled BP among BOSS study population was substantially higher based on the new guidelines. BP of 130-139/80-89 did not show the worsened clinical outcomes compared with people without hypertension. Our study adds to the growing uncertainty about secondary prevention BP goal for IS/TIA patients.

10.
Chem Commun (Camb) ; 55(61): 8975-8978, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31290492
11.
J Dairy Sci ; 102(9): 8264-8272, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31255277

RESUMO

Staphylococcus aureus is an important pathogen causing chronic and subclinical mastitis of cows. Autophagy is an important regulatory mechanism that participates in the elimination of invading pathogenic organisms. Here, we hypothesize that autophagy is involved in the process of Staph. aureus survival in bovine mammary epithelial cells (BMEC). In this study, we detected the expression of autophagy-related proteins during infection and assessed the effect of autophagosome formation and degradation on the proliferation of intracellular Staph. aureus. Infection with Staph. aureus increased the protein expression of microtubule-associated protein 1 light chain 3-II (MAP1LC3, also called LC3-II) and sequestosome-1 (SQSTM1, also called p62) in BMEC. After infection, the formation of the autophagosomes increased but the autophagosomes and lysosomes could not fuse normally to form autolysosomes. When the formation of the autophagosomes was enhanced or the degradation of the autolysosomes was inhibited, the number of Staph. aureus in the BMEC increased. However, the intracellular proliferation of Staph. aureus was slowed when formation of autophagosomes was inhibited. Therefore, autophagy was induced in BMEC challenged by Staph. aureus but the autophagic flux was obstructed. Inhibiting the formation of autophagosomes in BMEC facilitated the clearance of intracellular Staph. aureus, which may offer a new strategy for the treatment of mastitis in cows.

12.
J Clin Hypertens (Greenwich) ; 21(8): 1108-1114, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31256446

RESUMO

High blood pressure (BP) is frequent in acute ischemic stroke (IS). However, the impact of BP change patterns during acute phase on clinical outcomes is not conclusive. This study aims to investigate the association between the acute-phase BP trajectories and clinical outcomes in IS patients with high admission BP. The cohort consisted of 316 IS patients with admission systolic BP (SBP) ≥160 mm Hg. SBP trajectories during the first 7 days after onset were characterized using a random effects model. The patients were classified into three groups based on the SBP trajectory curve parameters: sustained high SBP (T1), moderate decrease (T2), and rapid decrease in SBP (T3). Poor outcomes were defined as modified Rankin scale score ≥3 in 3 months after onset. The relationship between SBP trajectory groups and the outcome was examined in multivariable logistic regression models. The decreasing trend was greater in the favorable than in the poor outcome group (P = 0.028 for difference in linear slopes). The incidence of poor outcomes was 25.9%, 13.5%, and 9.8% in T1 (n = 54), T2 (n = 170), and T3 (n = 92) groups, respectively. Compared with T1 group, the decrease in SBP in T2 and T3 groups was significantly associated with lower risk of the poor outcome (odds ratio = 0.25, 95% confidence interval = 0.10-0.67, P = 0.006). These findings suggest that a decrease in BP in the acute phase is predictive of favorable outcomes in IS patients. BP trajectories have a greater power to detect the association than individual BP values at one time-point.

13.
Mol Pharm ; 16(9): 3977-3984, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31306580

RESUMO

Integrin αvß3 is a cell adhesion molecule involved in the progression and invasion of glioblastoma, making it an attractive target for the diagnosis of glioblastoma. Although some integrin αvß3 specific ligands, such as RGD and its mimetic peptides (Cilengitide), have been devoted in detecting glioblastoma, their clinical practices have been limited due to low specificity and affinity. Herein, we have identified a linear peptide RWrNK, containing an unnatural d-arginine (r), as the integrin αvß3-specific ligand. RWrNK shows high binding affinity to integrin αvß3 with a Kd value of 1.6 nM, which is 2-fold higher than Cilengitide (3.2 nM), a well-established integrin αvß3 ligand. In addition, RWrNK can not only rapidly transport in human glioblastoma U87MG cells but effectively label U87MG tumor spheroids, compared to Cilengitide, indicating that it possesses an ability to sensitively detect glioblastoma. Importantly, RWrNK can pass through blood-brain tumor barrier (BBTB) and selectively accumulate in orthotopic U87MG tumor within 2 h, allowing for imaging glioblastoma in vivo with high sensitivity and specificity. Overall, RWrNK has the great potential in theranostic applications for glioblastoma, in consideration of its high specificity and affinity for integrin αvß3.

14.
Neurol Res ; 41(10): 893-899, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31328681

RESUMO

Objectives: Although statin therapy is associated with lower recurrence in patients with acute ischaemic stroke, data-evaluating associations between inpatient statin use and stroke recurrence in diabetic patients after acute stroke onset are limited. Methods: This study was based on population data from the Chinese National Stroke Registry. Patients with acute ischaemic stroke and no history of statin therapy were selected. Individuals treated regularly with any type or dosage of statins during acute hospitalization were defined as having inpatient statin therapy. The subjects were divided into two groups according to statin use status during acute hospitalization. Multivariate logistic regression analysis was used to analyse the associations between statin use and stroke recurrence in patients with or without diabetes. Results: A total of 11,429 patients, 2341 (20.48%) with diabetes, were selected for analysis. Statin therapy during hospitalization was documented in 4982 (43.59%). Logistic analysis showed no significant associations between inpatient statin use and stroke recurrence in diabetic subjects at 3 months (OR = 0.90, 95% CI = 0.69-1.16, P = 0.40) or 1 year (OR = 0.92, 95% CI = 0.74-1.16, P = 0.48), but statin use was significantly associated with lower recurrence in non-diabetic patients at both 3 months (OR = 0.80, 95% CI = 0.69-0.92, P = 0.002) and 1 year (OR = 0.82, 95% CI = 0.72-0.93, P = 0.002) after discharge. Conclusion: Inpatient statin use was associated with lower stroke recurrence in non-diabetic patients after acute ischaemic stroke, but no definite association between inpatient statin use and stroke recurrence in patients with diabetes mellitus was found.

15.
BMC Womens Health ; 19(1): 95, 2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31299947

RESUMO

BACKGROUND: The combination of intrapelvic and extrapelvic endometriosis is a very rare condition in gynecology. Patients with endometriosis involving the sciatic nerve are easily misdiagnosed because they usually present with atypical symptoms of endometriosis. Here, we present a rare case of an endometrioma passing through the left greater sciatic foramen. Removal of the endometriotic lesion was performed with a concomitant laparoscopic and transgluteal approach through the cooperation of gynecologists and orthopedic (neuro)surgeons. CASE PRESENTATION: A 20-year-old woman presented with complaints of severe dysmenorrhea lasting for more than 6 years and dysfunction of her left lower limb lasting for approximately 4 months. Both CT and MRI demonstrated a suspected intrapelvic and extrapelvic endometriotic cyst (7.3 cm × 8.1 cm × 6.5 cm) passing through the left greater sciatic foramen. Laparoscopic exploration showed a cyst full of dark fluid occupying the left obturator fossa and extending outside the pelvis. A novel combination of transgluteal laparoscopy was performed for complete resection of the cyst and decompression of the sciatic nerve. Postoperative pathology confirmed the diagnosis of endometriosis. Long-term follow-up observation showed persistent pain relief and lower limb function recovery in the patient. DISCUSSION AND CONCLUSIONS: When a woman complains of unexplained unilateral sciatica, especially a woman suffering from dysmenorrhea, endometriosis of the sciatica nerve should be considered as a potential etiology. Complete excision of the endometriotic lesion and adequate neurolysis (or decompression) of the sciatic nerve through the multidisciplinary cooperation of experienced gynecologists with proper training in laparoscopic pelvic (neuro)surgery and orthopedic (neuro)surgeons is effective.

16.
Environ Pollut ; 253: 130-140, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31306820

RESUMO

Skin cancer is the most common type of cancer in the United States, the majority of which is caused by overexposure to ultraviolet (UV) irradiance, which is one component of sunlight. National Environmental Public Health Tracking Program at CDC has collaborated with partners to develop and disseminate county-level daily UV irradiance (2005-2015) and total solar irradiance (1991-2012) data for the contiguous United States. UV irradiance dataset was derived from the Ozone Monitoring Instrument (OMI), and solar irradiance was extracted from National Solar Radiation Data Base (NSRDB) and SolarAnywhere data. Firstly, we produced daily population-weighted UV and solar irradiance datasets at the county level. Then the spatial distributions and long-term trends of UV irradiance, solar irradiance and the ratio of UV irradiance to solar irradiance were analyzed. The national average values across all years are 4300 Wh/m2, 2700 J/m2 and 130 mW/m2 for global horizontal irradiance (GHI), erythemally weighted daily dose of UV irradiance (EDD) and erythemally weighted UV irradiance at local solar noon time (EDR), respectively. Solar, UV irradiances and the ratio of UV to solar irradiance all increased toward the South and in some areas with high altitude, suggesting that using solar irradiance as indicator of UV irradiance in studies covering large geographic regions may bias the true pattern of UV exposure. National annual average daily solar and UV irradiances increased significantly over the years by about 0.3% and 0.5% per year, respectively. Both datasets are available to the public through CDC's Tracking network. The UV irradiance dataset is currently the only publicly-available, spatially-resolved, and long-term UV irradiance dataset covering the contiguous United States. These datasets help us understand the spatial distributions and temporal trends of solar and UV irradiances, and allow for improved characterization of UV and sunlight exposure in future studies.


Assuntos
Energia Solar , Raios Ultravioleta , Exposição Ambiental , Humanos , Ozônio/análise , Neoplasias Cutâneas , Análise Espaço-Temporal , Luz Solar , Estados Unidos
17.
Taiwan J Obstet Gynecol ; 58(4): 447-453, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307731

RESUMO

Polycystic ovary syndrome (PCOS) is widely accepted as the most common endocrine abnormality in women of childbearing age and may be accompanied by dyslipidemia, hyperandrogenism, hyperinsulinemia, oxidative stress and infertility. Dyslipidemia is now known to play an important role in the development of PCOS. Lipid abnormalities, including elevated low-density lipoprotein and triglyceride levels and reduced high-density lipoprotein levels, are often found in women with PCOS and play an important role in PCOS; therefore, we summarize the effect of lipid abnormalities on hyperandrogenism, insulin resistance, oxidative stress and infertility in PCOS and review the effects of common lipid-lowering drugs on patients with PCOS. The purpose of this article is to elucidate the mechanisms of lipid metabolism abnormalities in the development of PCOS.

18.
Ann Neurol ; 86(3): 419-426, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31237713

RESUMO

OBJECTIVE: Dual antiplatelet therapy (DAT) with clopidogrel plus aspirin has been suggested by American Heart Association/American Stroke Association guidelines for minor stroke (MS) and transient ischemic attack (TIA) patients. The purpose of this study was to find the potential subgroups that benefit from DAT. We aimed to compare the efficacy of clopidogrel-aspirin therapy with that of aspirin therapy in MS/TIA patients stratified by CYP2C19 genotype and risk profiles. METHODS: CYP2C19 loss-of-function allele (LoFA) carriers were defined as patients with LoFA of either *2 or *3. Low- and high-risk profile was defined as Essen Stroke Risk Score (ESRS) <3 and ≥3, respectively. Stroke recurrence at 1 year was considered primary outcome. RESULTS: Of a total 2,933 MS/TIA patients, there were 1,726 (58.8%) LoFA carriers and 1,068 (36.4%) patients at high risk (ESRS ≥3). No significant difference for stroke recurrence between the clopidogrel-aspirin group and aspirin alone group was found in LoFA carriers (11.2% vs 13.3%, hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.64~1.09). In stratified analyses by CYP2C19 genotype and ESRS, HRs (95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 1.00 (0.70~1.42), 0.63 (0.41~0.97), 0.62 (0.40~0.96), and 0.52 (0.31~0.88) among subgroups of LoFA carriers at low risk, LoFA carriers at high risk, LoFA noncarriers at low risk, and LoFA noncarriers at high risk, respectively, with p = 0.021 for interaction. INTERPRETATION: Overall, LoFA carriers do not benefit from DAT, but there is significant benefit for LoFA carriers who are at high risk. The benefit of clopidogrel in Chinese MS/TIA patients depends on CYP2C19 genotype and risk profile. ANN NEUROL 2019;86:419-426.

19.
BMJ ; 365: l2211, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171523

RESUMO

OBJECTIVE: To test the hypothesis that ticagrelor plus aspirin is safe and superior to clopidogrel plus aspirin for reducing high platelet reactivity at 90 days and stroke recurrence in patients with minor stroke or transient ischaemic attack, particularly in carriers of the CYP2C19 loss-of-function allele and patients with large artery atherosclerosis. DESIGN: Open label, blinded endpoint, randomised controlled phase II trial. SETTING: Prospective studies conducted at 26 centres in China, August 2015 to March 2017. PARTICIPANTS: 675 patients with acute minor stroke or transient ischaemic attack. INTERVENTION: Ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300 mg loading dose, 75 mg daily thereafter) on a background of aspirin (100 mg daily for the first 21 days) within 24 hours of symptom onset. MAIN OUTCOME MEASURES: Primary outcome was the proportion of patients with high platelet reactivity at 90 days. High platelet reactivity was defined as P2Y12 reaction units of more than 208. Secondary outcomes included high platelet reactivity at 90 days (7 days either way) in patients carrying genetic variants that would affect clopidogrel metabolism, and any stroke (ischaemic or haemorrhagic) recurrence at 90 days (7 days either way), six months, and one year. RESULTS: At 90 days, high platelet reactivity occurred in 35 (12.5%) of 280 patients in the ticagrelor/aspirin group and 86 (29.7%) of 290 patients in the clopidogrel/aspirin group (risk ratio 0.40; 95% confidence interval 0.28 to 0.56; P<0.001), and in 10.8% versus 35.4% (0.31; 0.18 to 0.49; P<0.001) of patients carrying CYP2C19 loss-of-function alleles. Stroke occurred in 21 (6.3%) of 336 patients in the ticagrelor/aspirin group and 30 (8.8%) of 339 patients in the clopidogrel/aspirin group (hazard ratio 0.70; 95% confidence interval 0.40 to 1.22; P=0.20). Patients with large artery atherosclerosis in the ticagrelor/aspirin group had a lower stroke recurrence at 90 days than those in the clopidogrel/aspirin group (6.0% v 13.1%; hazard ratio 0.45, 95% confidence interval 0.20 to 0.98; P=0.04). No difference was seen in the rates of major or minor haemorrhagic events between the ticagrelor/aspirin and clopidogrel/aspirin groups (4.8% v 3.5%; P=0.42). CONCLUSION: Patients with minor stroke or transient ischaemic attack who are treated with ticagrelor plus aspirin have a lower proportion of high platelet reactivity than those who are treated with clopidogrel plus aspirin, particularly for those who are carriers of the CYP2C19 loss-of-function allele. The results of this study should be evaluated further in large scale, phase III trials and in different populations. TRIAL REGISTRATION: Clinicaltrials.gov NCT02506140.


Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Ataque Isquêmico Transitório/tratamento farmacológico , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Ticagrelor/uso terapêutico , Adulto , Idoso , Plaquetas/efeitos dos fármacos , China , Quimioterapia Combinada , Feminino , Humanos , Ataque Isquêmico Transitório/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/fisiologia , Estudos Prospectivos , Acidente Vascular Cerebral/fisiopatologia , Resultado do Tratamento
20.
Environ Sci Pollut Res Int ; 26(20): 20560-20572, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104243

RESUMO

Papillary thyroid cancer (PTC) has inflicted huge threats to the health of mankind. Metal pollution could be a potential risk factor of PTC occurrence, but existing relevant epidemiological researches are limited. The current case-control study was designed to evaluate the relationships between exposure to multiple metals and the risk of PTC. A total of 262 histologically confirmed PTC cases were recruited. Age- and gender-matched controls were enrolled at the same time. Urine samples were used as biomarkers to reflect the levels of environmental exposure to 13 metals. Conditional logistic regression models were adopted to assess the potential association. Single-metal and multi-metal models were separately conducted to evaluate the impacts of single and co-exposure to 13 metals. The increased concentration of urinary Cd, Cu, Fe, and Pb quartiles was found significant correlated with PTC risk. We also found the decreased trends of urinary Se, Zn, and Mn quartiles with the ORs for PTC. These dose-response associations between Pb and PTC were observed in the single-metal model and remained significant in the multi-metal model (OR25-50th=1.39, OR50-75th=3.32, OR>75th=7.62, p for trend <0.001). Our study suggested that PTC was positively associated with urinary levels of Cd, Cu, Fe, Pb, and inversely associated with Se, Zn, and Mn. Targeted public health policies should be made to improve the environment and the recognition of potential risk factors. These findings need additional studies to confirm in other population.


Assuntos
Exposição Ambiental , Poluentes Ambientais/toxicidade , Metais Pesados/toxicidade , Câncer Papilífero da Tireoide/induzido quimicamente , Neoplasias da Glândula Tireoide/induzido quimicamente , Estudos de Casos e Controles , China/epidemiologia , Poluentes Ambientais/urina , Feminino , Humanos , Masculino , Metais Pesados/urina , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Câncer Papilífero da Tireoide/epidemiologia , Câncer Papilífero da Tireoide/urina , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/urina
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