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1.
Chemosphere ; 262: 128404, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33182127

RESUMO

BACKGROUND: Reduced growth velocity before birth increases the risk of adverse health outcomes in adult life. However, until recently, there has been a lack of studies demonstrating the impact of prenatal PM2.5 exposure on fetal growth velocity. METHODS: The current study was embedded in a previous cohort built between January 1, 2014, and April 30, 2015, in Shanghai First Maternity and Infant Hospital, China, in 6129 eligible singleton pregnancies. The PM2.5 concentration was estimated by an inverse distance weighted method according to the residential addresses of the participants. Repeated fetal biometry measurements, including head circumference (HC), abdominal circumference (AC), femur length (FL), and biparietal diameter (BPD), were measured through ultrasound between 14 and 41 gestational weeks. A principal component analysis through conditional expectation for sparse longitudinal data was used to estimate the corresponding velocities. RESULTS: A total of 22782 ultrasound measurements were conducted among 6129 participants with a median of 2 and a maximum of 9 measurements. With each 10 µg/m3 increase in cumulative PM2.5 exposure, the velocity of HC, AC FL and BPD decreased by 0.12 mm/week, 0.17 mm/week, 0.02 mm/week and 0.02 mm/week, respectively, on average. The results of the Generalized Functional Concurrent Model showed that the velocity decreased significantly with PM2.5 exposure between 22 and 32 gestational weeks, which might be the potential sensitive exposure window. CONCLUSIONS: There are negative associations between prenatal exposure to PM2.5 and fetal growth velocity, and the late second trimester and early third trimester might be the potential sensitive window.


Assuntos
Poluentes Atmosféricos/toxicidade , Exposição Materna , Material Particulado/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Adulto , China , Estudos de Coortes , Feminino , Desenvolvimento Fetal , Idade Gestacional , Humanos , Masculino , Material Particulado/análise , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Ultrassonografia Pré-Natal/métodos
2.
J Bone Miner Res ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33145809

RESUMO

Opportunistic screening for osteoporosis can be performed using low-dose computed tomography (LDCT) imaging obtained for other clinical indications. In this study we explored the CT-derived bone mineral density (BMD) and prevalence of osteoporosis from thoracic LDCT in a large population cohort of Chinese men and women. A total of 69,095 adults (40,733 men and 28,362 women) received a thoracic LDCT scan for the purpose of lung cancer screening between 2018 and 2019, and data were obtained for analysis from the China Biobank Project, a prospective nationwide multicenter population study. Lumbar spine (L1 -L2 ) trabecular volumetric bone mineral density (vBMD) was derived from these scans using quantitative computed tomography (QCT) software and the American College of Radiology QCT diagnostic criteria for osteoporosis were applied. Geographic regional differences in the prevalence of osteoporosis were assessed and the age-standardized, population prevalence of osteoporosis in Chinese men and women was estimated from the 2010 China census. The prevalence of osteoporosis by QCT for the Chinese population aged >50 years was 29.0% for women and 13.5% for men, equating to 49.0 million and 22.8 million, respectively. In women, this rate is comparable to estimates from dual-energy X-ray absorptiometry (DXA), but in men, the prevalence is double. Prevalence varied geographically across China, with higher rates in the southwest and lower rates in the northeast. Trabecular vBMD decreased with age in both men and women. Women had higher peak trabecular vBMD (185.4 mg/cm3 ) than men (176.6 mg/cm3 ) at age 30 to 34 years, but older women had lower trabecular vBMD (62.4 mg/cm3 ) than men (92.1 mg/cm3 ) at age 80 years. We show that LDCT-based opportunistic screening could identify large numbers of patients with low lumbar vBMD, and that future cohort studies are now required to evaluate the clinical utility of such screening in terms of fracture prevention and supporting national health economic analyses. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

3.
Artigo em Inglês | MEDLINE | ID: mdl-33145896

RESUMO

Inspired by the light-regulating capabilities of naturally occurring rhodopsin, we have constructed a visible light regulated Cl -  transport membrane channel based on a supramolecular host-guest interaction. A natural retinal chromophore, capable of a visible light response, is used as the guest and grafted into the artificial channel. Upon introduction of an ethyl urea derived pillar[6]arene (Urea-P6) host, threading or de-threading of the retinal and selective bonding of Cl -  can be utilized to regulate ion transport. Based on visible light-responsiveness of the host-guest interaction, Cl -  transport can be regulated by visible light between ON and OFF states. Visible light regulated Cl -  transport as a chemical model permits to understand the comparable biological ion selective transport behaviors. Furthermore, this result also supplies a smart visible light responsive Cl -  transporter, which may have applications in natural photoelectric conversion and photo-controlled delivery systems.

4.
Endocrine ; 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33222122

RESUMO

PURPOSE: The benefits of growth hormone (GH) therapy in Prader-Willi syndrome (PWS) children are well established, but there is still considerable controversy regarding whether GH treatment can improve cognitive, motor, and behavioral development in PWS children. The objectives of this meta-analysis were to quantitatively evaluate the effects of GH on cognitive, motor function, and behavioral development in PWS children. METHODS: Randomized controlled trials (RCTs) examining the effects of GH on cognitive, motor, and behavioral development in PWS children were identified by searching the MEDLINE, EMBASE, and Cochrane Library databases. Intervention effects were represented by Hedges'g and pooled to calculate effect sizes using a random-effects model. RESULTS: Ten relevant studies comprising data from 302 participants were finally included. We observed no significant difference in cognitive performance between the GH treatment group and the control group (p = 0.197). GH treatment was shown to remarkably improve motor development in PWS children compared with the control treatment (p < 0.001), with moderate positive treatment effects (Hedges'g [95% CI] = 0.71 [0.38, 1.03]). There were no significant differences between the GH group and the control group based on objective assessments of behavioral development (p = 0.53). CONCLUSIONS: The meta-analysis suggested that GH treatment had a significantly positive effect on motor development, with moderate treatment effects in PWS children; however, there was no evidence of effects on cognitive or behavioral development.

5.
J Chin Med Assoc ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33230060

RESUMO

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrythmia and increasing numbers of patients receiving AF ablation nowadays. So, in cardiology division, residents need to familiar with the AF ablation procedure-related knowledge for primary care. This study evaluated the baseline residents and patients self-efficacy to AF ablation procedure-related knowledge, developed the specific virtual reality (VR) informative aids, evaluated the effects of VR training and resident-led VR aids-based patient education on their self-efficacy, in the aspects of familiarity, confidence and anxiety, and satisfaction. METHODS: From 2019, April to 2020, April, this 1-year prospective pre- and post-study was undergone in cardiology division. Between 2019, April to 2019, December, the experienced physicians were invited to develop virtual reality (VR) informative aids for AF ablation procedure-related knowledge. Between January 2020 to April 2020, newly developed VR informative aids was implemented in educational program of training rotated residents for giving patient education. RESULTS: A total of 20 residents and 32 patients were enrolled. The baseline self-reported self-efficacy and knowledge score were relatively low among rotated residents and their patients. In addition to high level of satisfaction, self-efficacy and knowledge score of residents and their patients were increased after VR aids-based training and resident-led patient education. Higher degree of improvement in self-efficacy was noted among patients with depression/anxiety history than those without history. The follow-up assessments among residents showed that the positive effects of VR aids was sustained until 2 weeks later. CONCLUSION: Overall, residents and patients reported that the VR aids increase the effectiveness of patient education, achieve the purpose of a paperless environment, and motivate them to recommend it to others. Implementation of resident-to-patient education have a positive impact on trainees and patients understanding about AF ablation procedures-related knowledge.

6.
Psychol Res ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33170355

RESUMO

In visual statistical learning (VSL), one can extract and exhibit memory for the statistical regularities of target locations in an incidental manner. The current study examined the development of VSL using the probability cueing paradigm with salient perceptual cues. We also investigated the elicited attention gradient phenomenon in VSL. In a visual search task, the target first appeared more often in one quadrant (i.e., rich) than the other quadrants (i.e., sparse). Then, the participants rotated the screen by 90° and the targets appeared in the four quadrants with equal probabilities. Each quadrant had a unique background color and was, hence, associated with salient perceptual cues. 1st-4th graders and adults participated. All participants showed probability cueing effects to a similar extent. We observed an attention gradient phenomenon, as all participants responded slower to the sparse quadrant that was distant from, rather than the ones that were adjacent to the rich quadrant. In the testing phase, all age groups showed persistent attentional biases based on both egocentric and allocentric perspectives. These findings showed that probability cueing effects may develop early, that perceptual cues can bias attention guidance during VSL for both children and adults, and that VSL can elicit a spaced-based attention gradient phenomenon for children and adults.

7.
Inflammation ; 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33130921

RESUMO

Dendritic cells (DCs) are the most powerful antigen-presenting cells known to date and play an important role in initiating and amplifying both innate and adaptive immune responses. Extracellular acidosis is an important hallmark of a variety of inflammatory processes and solid tumors. However, few studies have focused on the effect of extracellular acidosis on DCs and their functions. Cellular mechanical properties reflect the relationship between cell structure and function, including cytoskeleton (especially F-actin organization), membrane negative charges, membrane fluidity, and osmotic fragility. The study investigated the effects of extracellular acidosis on the DCs functions from the perspective of cellular migration and mechanical properties. The results showed that migration ability, F-actin contents, and membrane negative charges of DCs were reduced by extracellular acidosis no matter whether LPS stimulated its maturation or not. And these functions could not return to normal after removing acidic microenvironment, which revealed that the function impairment induced by extracellular acidosis might be irreversible. In addition, the proliferation capacity of stimulated allogeneic T cells was impaired by extracellular acidosis. Our results suggest extracellular acidosis may play an immunosuppressive role in DCs-mediated immune process.

9.
Arch Osteoporos ; 15(1): 155, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025208

RESUMO

We compared the effect of anthropometric factors on osteoporosis diagnosis by quantitative computed tomography (QCT) and dual energy X-ray absorptiometry (DXA) and found QCT spine volumetric bone mineral density (vBMD) was not associated with body weight, body mass index (BMI) or DXA anteroposterior spine thickness. In contrast, DXA spine and hip areal bone mineral density (aBMD) were strongly associated with all three factors. Adjustment of DXA aBMD measurements improved consistency with QCT vBMD. PURPOSE: Although the diagnosis of osteoporosis using DXA T scores preferentially targets patients with BMI, there is evidence that obesity is not protective against fractures. The aim of this study was to compare the effect of anthropometric factors on osteoporosis diagnosis by QCT and DXA and investigate whether adjustment of DXA aBMD can achieve a more even distribution of diagnoses between slimmer and heavier individuals consistent with QCT. METHODS: The participants were 964 men and 682 women referred for low-dose chest CT and DXA examinations as part of their employers' health check-up programs. QCT vBMD was measured in the L1-L2 vertebrae and DXA aBMD in the spine and hip. The prevalence of osteoporosis in each tertile of BMI in participants aged > 50 years was evaluated based on their QCT and DXA findings, and then re-evaluated after adjustment to the mean BMI in each sex. Similar investigations were performed for body weight and DXA anteroposterior (AP) spine thickness. The effect of the adjustment of DXA aBMD for anthropometric factors on the correlation with QCT vBMD was also examined. RESULTS: For spine QCT, correlations of age adjusted vBMD residuals against BMI were not statistically significant in men (P = 0.44) or women (P = 0.32). In contrast, slopes for aBMD residuals were all highly statistically significant (P < 0.001). There were similar findings for weight and AP spine thickness. Adjustment of DXA aBMD for anthropometric factors resulted in a more equal spread of diagnoses of osteoporosis and greater consistency with QCT. CONCLUSION: Our study highlights differences between DXA and QCT in their correlation with anthropometric factors and its effect on the diagnosis of osteoporosis. Adjustment of DXA T scores for anthropometric factors gave greater consistency with QCT vBMD. Further studies are required into whether adjusting DXA aBMD for anthropometric factors has a beneficial impact on the discriminative or predictive power for vertebral fracture.


Assuntos
Osteoporose , Absorciometria de Fóton , Antropometria , Densidade Óssea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Tomografia Computadorizada por Raios X
10.
Aging (Albany NY) ; 12(20): 20085-20094, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33065552

RESUMO

In this study, we tested the effect of ticagrelor versus clopidogrel on platelet reactivity in patients with minor stroke or transient ischemic attack (TIA). A pre-specified subgroup analysis of a randomized controlled trial was conducted. Platelet reactivity was assessed by thrombelastography (TEG) platelet mapping. Patients were divided into carriers and non-carriers according to the carrier status of CYP2C19 loss-of-function (LOF) alleles. The primary outcome was the proportion of patients with high on-treatment platelet reactivity (HOPR) (defined as maximum amplitude induced by adenosine diphosphate > 47mm) at 90±7 days. Clinical outcomes within 90±7 days were followed up. Among 339 patients, 170 were randomized to ticagrelor/aspirin and 169 to clopidogrel/aspirin. Compared with clopidogrel/aspirin, the proportion of HOPR at 90±7 days in ticagrelor/aspirin was significantly lower (12.2% versus 30.0%, P < 0.001). Ticagrelor/aspirin had a lower proportion of HOPR among carriers (11.0% versus 35.6%, P < 0.001), but not among non-carriers (13.5% versus 22.4%, P = 0.17). Ticagrelor was superior to clopidogrel in inhibiting platelet reactivity measured by TEG platelet mapping among patients with acute minor stroke or TIA, particularly in carriers of the CYP2C19 LOF alleles. Large randomised controlled trials are needed to confirm our findings.

12.
Sci Total Environ ; 746: 142032, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33027874

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are one of the most widespread persistent organic pollutants (POPs) in marine environment. Benzo[a]pyrene (B[a]P), the most toxic carcinogen of PAHs, is widely studied as a representative that interferes with lipid metabolism. However, the underlying molecular mechanisms of lipid metabolism by B[a]P interference towards bivalve, one of the marine-pollution bio-indicators have not been elucidated yet, especially during gonadal development which is closely associated with lipids. In this study, female scallops Chlamys farreri were cultured with natural and 4 µg/L B[a]P exposed seawater, respectively, and a multi-stage (proliferative, growth, mature, and spawn stage) ovarian transcriptome profiling was performed to decipher the reproductive stage-dependence disturbing mechanisms on lipid metabolism caused by B[a]P in bivalves. The results revealed the potential molecular mechanism of B[a]P-induced triglycerides (TGs) accumulation, which probably resulted from the collaboration of promoting synthesis and inhibiting metabolization of TGs, notably, this mechanism also occurred at spawn stage. Correspondingly, B[a]P and TGs contents measured in ovary offered direct biochemical evidences for the interference effects and stage-dependent accumulation patterns of B[a]P. Moreover, the gene expressions of fatty acids synthesis related enzymes were down-regulated cooperatively, illustrating the molecular compensatory mechanism that reduced susceptibility from oxidative damage. And these results further emphasized the important role of prostaglandins (PGs) in immune response mediated by arachidonic acid metabolism. In addition, this study explored the underlying molecular mechanism affected by B[a]P on sterol metabolism, which possibly posed a threat to normal reproductive functions in bivalves. Taken together, our findings filled the gap of the stage-dependent interference molecular mechanisms on lipid metabolism behind bivalves, and provided a new perspective for investigating the adaptive mechanisms of bivalves under POPs stress.


Assuntos
Benzo(a)pireno , Pectinidae , Animais , Benzo(a)pireno/toxicidade , Feminino , Perfilação da Expressão Gênica , Metabolismo dos Lipídeos , Pectinidae/genética , Reprodução
13.
Neuroendocrinology ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33049741

RESUMO

INTRODUCTION: To describe a Chinese case of X-linked acrogigantism (X-LAG) and summarize the characteristics and treatment of all reported cases. METHODS: Clinical materials and biological samples from a 5-year and 2-month-old female due to "growth acceleration for 4 years" were collected. Array comparative genomic hybrid (aCGH) and further verification were performed. All X-LAG cases from the PubMed and Web of Science databases were collected and summarized using available data. RESULTS: The patient presented accelerating growth since 1 year of age, and her height reached 134.6 cm (+5.24 standard deviation score, SDS) when she was 5 years and 2 months old. She also had coarsening facial features, snoring, and acral enlargement. Growth hormone (GH) was not suppressed by the glucose-GH inhibition test, and insulin-like growth factor 1 (IGF-1) and prolactin levels were elevated. Pituitary magnetic resonance imaging (MRI) revealed a pituitary enlargement with a maximum diameter of 22.3 mm. Octreotide imaging indicated the presence of a pituitary adenoma. The tumor shrank slightly after three courses of somatostatin analog but without clinical or biochemical remissions, of which the GH nadir value was 9.4 ng/ml, and IGF-1 was elevated to 749 ng/ml. Therefore, she underwent transsphenoidal surgery. Immunohistochemistry showed GH-positive and PRL-positive cells in the pituitary adenoma. Xq26.3 microduplication of the patient's germline DNA was identified by aCGH. Of all 35 reported cases, females accounted for 71.43%. There were 93.10% and 53.83% patients with hyperprolactinemia and hyperinsulinemia, respectively. Pathology showed that 75.00% of cases were adenomas. Ninety percent of cases had germline variants. The clinical and biochemical remission rates were 78.26% and 82.61%, respectively. However, the rate of complication occurrence during therapy reached 80%. CONCLUSION: It is important to recognize the possibility of X-LAG when a child under 2 years old presents overgrowth. Early diagnosis and treatment are of great importance for better treatment efficacy and clinical outcome.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33000123

RESUMO

CONTEXT: Cushing Disease (CD) is a life-threatening disorder. Therapeutic goals include symptom relief, biochemical control and tumor growth inhibition. Current medical therapies for CD by and large exert no action on tumor growth. OBJECTIVE: To identify drugs that inhibit corticotroph tumor ACTH secretion and growth. DESIGN: High throughput screen employing a novel "gain of signal" ACTH AlphaLISA assay. SETTING: Academic medical center. PATIENTS: Corticotroph Tumor tissues from patients with CD. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Potent inhibitors of corticotroph tumor ACTH secretion and growth. RESULTS: From a kinase inhibitor library, we identified the dual PI3K/HDAC inhibitor CUDC-907 as a potent inhibitor of murine and human corticotroph tumor ACTH secretion (EC50 1-5nM), and cell proliferation (IC50 5nM). In an in vivo murine corticotroph tumor xenograft model, orally administered CUDC-907 (300mg/kg) reduced corticotroph tumor volume (TV (cm 3), Control 0.17 ± 0.05 vs. CUDC-907 0.07 ± 0.02, p<0.05) by 65% and suppressed plasma ACTH (ACTH (pg/mL) Control 206 ± 27 vs. CUDC-907 47 ± 7, p<0.05) and corticosterone (Corticosterone (ng/mL) Control 180 ± 87 vs. CUDC-907 27 ± 5, p<0.05) levels by 77% and 85% respectively compared to controls. We also demonstrated that CUDC-907 acts through HDAC1/2 inhibition at the POMC transcriptional level combined with its PI3K-mediated inhibition of corticotroph cell viability to reduce ACTH secretion. CONCLUSIONS: Given its potent efficacy in in vitro and in vivo models of CD, combined with proven safety and tolerance in clinical trials, we propose CUDC-907 may be a promising therapy for CD.

15.
Environ Health ; 19(1): 101, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943053

RESUMO

BACKGROUND: Association between fine particulate matter (PM2.5) and hypertensive disorders of pregnancy (HDP) is inconsistent and appears to change in each trimester. We aim to investigate the association of exposure to ambient PM2.5 in early pregnancy with HDP. METHODS: A retrospective cohort study was performed among 8776 women with singleton pregnancy who attended the antenatal clinic before 20 gestational weeks in a tertiary women's hospital during 2014-2015. Land use regression models were used to predict individual levels of PM2.5 exposure. RESULTS: The average PM2.5 concentration during the first 20 gestational weeks ranged from 28.6 to 74.8 µg m- 3 [median, 51.4 µg m- 3; interquartile range, 47.3-57.8 µg m- 3]. A total of 440 (5.0%) women was diagnosed with HDP. The restricted cubic spline showed a positive exposure-response relationship between the PM2.5 concentration and risk of HDP. We observed an association between PM2.5 exposure during the first trimester with HDP (RR = 3.89 per 10 µg m- 3, 95% CI: 1.45-10.43), but not during the second trimester (RR = 0.71 per 10 µg m- 3, 95% CI: 0.40-1.27). Compared with their counterparts, nulliparous women who were exposed to high levels of PM2.5 in the index pregnancy had a higher risk of developing HDP [the relative excess risk due to interaction was 0.92 (0.46-1.38)]. CONCLUSION: Our findings suggest that PM2.5 exposure during the first trimester is associated with the development of HDP. The effect estimate is more obvious for nulliparous women than multiparous women.

16.
J Chin Med Assoc ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32925298

RESUMO

BACKGROUND: This study aimed to evaluate whether the role-play (RP) of real patients by medical students as part of interactive clinical reasoning training can improve medical students' clinical performance. METHODS: A total of 26 medical students volunteered to portray real patients within this program, and were defined as the RP group while the other 72 students were the non-RP group. In the interactive morning meeting, the medical students practiced how to approach the RP student as if they were encountering a real patient. All students were evaluated by mini-clinical evaluation exercises (mini-CEX) before and after this training program. RESULTS: We found that all students had an increased total mini-CEX score after 4-weeks training, especially for interviewing skills. Notably, after training the RP students had significantly elevated total mini-CEX scores (51.23 ± 1.06 vs. 53.12 ± 1.11, p=0.028), and for counselling (7.15 ± 0.14 vs. 7.54 ± 0.18, p=0.015) and overall clinical competence (7.27 ± 0.15 vs. 7.65 ± 0.16, p=0.030). In contrast, the non-RP students had lower scores compared with those in the RP group, as revealed by both the pre- and post-training tests. Moreover, their mini-CEX scores were not improved after training. CONCLUSION: Medical students who were motivated to RP real patients had better performance scores than those who did not. In addition, RP can enhance their counselling skills and clinical competences.

17.
Int Heart J ; 61(5): 1056-1058, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921678

RESUMO

An 84-year-old woman with hypertension, Alzheimer's disease, and chronic kidney disease presented with fever and was diagnosed with corona virus disease 2019 (COVID-19). During the hospitalization, she experienced unexpected sinus bradycardia with prolonged QTc, which was thought to be closely related to the short-term use of hydroxychloroquine (HCQ), an old drug used to treat malaria and autoimmune diseases, but now used against COVID-19. The cardiac side effects of HCQ were rare, seen with short-term and low-dose use. With the COVID-19 pandemic, this case alerts clinicians to be aware of the arrhythmogenic effects of HCQ when it is used as an antiviral drug, especially in patients with preexisting cardiovascular diseases.


Assuntos
Betacoronavirus , Bradicardia/induzido quimicamente , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Pneumonia Viral/tratamento farmacológico , Idoso de 80 Anos ou mais , Feminino , Humanos , Pandemias
18.
Nat Commun ; 11(1): 4489, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895384

RESUMO

We report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific extracellular vesicle (EV) purification system for early detection of HCC by performing digital scoring on the purified EVs. Earlier detection of HCC creates more opportunities for curative therapeutic interventions. EVs are present in circulation at relatively early stages of disease, providing potential opportunities for HCC early detection. We develop an HCC EV purification system (i.e., EV Click Chips) by synergistically integrating covalent chemistry-mediated EV capture/release, multimarker antibody cocktails, nanostructured substrates, and microfluidic chaotic mixers. We then explore the translational potential of EV Click Chips using 158 plasma samples of HCC patients and control cohorts. The purified HCC EVs are subjected to reverse-transcription droplet digital PCR for quantification of 10 HCC-specific mRNA markers and computation of digital scoring. The HCC EV-derived molecular signatures exhibit great potential for noninvasive early detection of HCC from at-risk cirrhotic patients with an area under receiver operator characteristic curve of 0.93 (95% CI, 0.86 to 1.00; sensitivity = 94.4%, specificity = 88.5%).


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer/métodos , Vesículas Extracelulares/genética , Neoplasias Hepáticas/diagnóstico , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Química Click/instrumentação , Química Click/métodos , Química Computacional , Simulação por Computador , Diagnóstico Diferencial , Dimetilpolisiloxanos/química , Progressão da Doença , Detecção Precoce de Câncer/instrumentação , Feminino , Células Hep G2 , Humanos , Dispositivos Lab-On-A-Chip , Biópsia Líquida/instrumentação , Biópsia Líquida/métodos , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Pessoa de Meia-Idade , Nanoestruturas/química , Nanofios/química , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Mensageiro/isolamento & purificação , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa/instrumentação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
19.
Environ Res ; 191: 110125, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32861722

RESUMO

Benzo[a]pyrene (BaP), a model compound of polycyclic aromatic hydrocarbon known to impair reproductive functions of vertebrates, while the data is scarce in marine invertebrates. To investigate the toxic effects of BaP on invertebrates reproduction, we exposed male scallop (Chlamys farreri) to BaP (0, 0.38 and 3.8 µg/L) throughout three stages of reproductive cycle (early gametogenesis stage, late gametogenesis stage and ripe stage). The results demonstrated that BaP decreased the gonadosomatic index and mature sperms counts in a dose-dependent manner. Significant changes in sex hormones contents and increased 17ß-estradiol/testosterone ratio suggested that BaP produced the estrogenic endocrine effects in male scallops. In support of this view, we confirmed that BaP significantly altered transcripts of genes along the upstream PKA and PKC mediated signaling pathway like fshr, lhcgr, adcy, PKA, PKC, PLC and NR5A2. Subsequently, the expressions of genes encoding downstream steroidogenic enzymes (e.g., 3ß-HSD, CYP17 and 17ß-HSD) were impacted, which corresponded well with hormonal alterations. In addition, BaP suppressed transcriptions of spermatogenesis-related genes, including ccnd2, SCP3, NRF1 and AQP9. Due to different functional demands, these transcript profiles involved in spermatogenesis exhibited a stage-specific expression pattern. Furthermore, histopathological analysis determined that BaP significantly inhibited testicular development and maturation in male scallops. Overall, the present findings indicated that, playing as an estrogenic-like chemical, BaP could disrupt the steroidogenesis pathway, impair spermatogenesis and caused histological damages, thereby inducing reproductive toxicities with dose- and stage-specific effects in male scallops. And the adverse outcomes might threaten the stability of bivalve populations and destroy the function of marine ecosystems in the long term.

20.
Stroke Vasc Neurol ; 5(3): 270-278, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32792457

RESUMO

AIM: Cerebrovascular disease is the leading cause of death and disability in China, causing a huge burden among patients and their families. Hence, stroke prevention is critical, especially in the high-risk population. Here, we present the evidence-based guideline suitable for the Chinese population. METHODS: Literature search of PubMed and Cochrane library (from January 1964 to June 2019) was done. After thorough discussion among the writing group members, recommendations were listed and summarised. This guideline was reviewed and discussed by the fellow writing committees of the Chinese Stroke Association's Stroke. RESULTS: This evidence-based guideline was written in three parts: controlling the risk factors of stroke, utilisation of antiplatelet agents and assessing the risks of first-ever stroke. All recommendations were listed along with the recommending classes and levels of evidence. CONCLUSIONS: This guideline provides recommendations for primary prevention of cerebrovascular disease among high-risk population in China. Controlling related risk factors, appropriately using antiplatelet agents, assessing the risk of developing first-ever stroke should help reduce the rate of cerebrovascular disease in China.


Assuntos
Transtornos Cerebrovasculares/prevenção & controle , Medicina Baseada em Evidências/normas , Neurologia/normas , Inibidores da Agregação de Plaquetas/uso terapêutico , Prevenção Primária/normas , Comportamento de Redução do Risco , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/epidemiologia , China/epidemiologia , Consenso , Avaliação da Deficiência , Humanos , Inibidores da Agregação de Plaquetas/efeitos adversos , Recuperação de Função Fisiológica , Medição de Risco , Fatores de Risco , Resultado do Tratamento
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