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1.
Arch Insect Biochem Physiol ; : e21662, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32027059

RESUMO

Although the Cas9 protein from Streptococcus pyogenes (SpCas9) is the most widely used clustered regularly interspaced short palindromic repeats (CRISPR) variant in genome engineering experiments, it does have certain limitations. First, the stringent requirement for the protospacer adjacent motif (PAM) sequence limits the target DNA that can be manipulated using this method in insects. Second, its complementarity specifications are not very stringent, meaning that it can sometimes cause off-target effects at the target site. A recent study reported that an evolved SpCas9 variant, xCas9(3.7), with preference for various 5'-NG-3' PAM sequences not only has the broadest PAM compatibility but also has much greater DNA specificity and lower genome-wide off-target activity than SpCas9 in mammalian cells. Here we applied the CRISPR/xCas9 system to target the white gene in Drosophila melanogaster, testing the genome-editing efficiency of xCas9 at different PAM sites. On the GGG PAM site, xCas9 showed less activity than SpCas9. For the non-NGG PAM site TGA, xCas9 could produce DNA cleavage and indel-mediated disruption on the target gene. However, for other non-NGG PAM sites, xCas9 showed no activity. These findings show that the evolved Cas9 variant with broad PAM compatibility is functional in Drosophila to induce heritable gene alterations, increasing the targeting range for the applications of genome editing in insects.

2.
FEBS Lett ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32052437

RESUMO

Eukaryotic transcription factors (TFs) coordinate different upstream signals to regulate the expression of their target genes. To unveil this regulatory network in B cell receptor signaling, we developed a computational pipeline to systematically analyze the extracellular signal-regulated kinase (ERK)- and IB kinase (IKK)-dependent transcriptome responses. We combined a bilinear regression method and kinetic modeling to identify the signal-to-TF and TF-to-gene dynamics, respectively. We input a set of time-course experimental data for B cells and concentrated on transcriptional activators. The results show that the combination of TFs differentially controlled by ERK and IKK could contribute divergent expression dynamics in orchestrating the B cell response. Our findings provide insights into the regulatory mechanisms underlying signal-dependent gene expression in eukaryotic cells.

3.
Lab Invest ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949244

RESUMO

Glioblastoma multiforme (GBM) is characterized by highly invasive growth, which leads to extensive infiltration and makes complete tumor excision difficult. Since cytoskeleton proteins are related to leading processes and cell motility, and through analysis of public GBM databases, we determined that an actin-interacting protein, zyxin (ZYX), may involved in GBM invasion. Our own glioma cohort as well as the cancer genome atlas (TCGA), Rembrandt, and Gravendeel databases consistently showed that increased ZYX expression was related to tumor progression and poor prognosis of glioma patients. In vitro and in vivo experiments further confirmed the oncogenic roles of ZYX and demonstrated the role of ZYX in GBM invasive growth. Moreover, RNA-seq and mass-spectrum data from GBM cells with or without ZYX revealed that stathmin 1 (STMN1) was a potential target of ZYX. Subsequently, we found that both mRNA and protein levels of STMN1 were positively regulated by ZYX. Functionally, STMN1 not only promoted invasion of GBM cells but also rescued the invasion repression caused by ZYX loss. Taken together, our results indicate that high ZYX expression was associated with worse prognosis and highlighted that the ZYX-STMN1 axis might be a potential therapeutic target for GBM.

4.
Oncogene ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996785

RESUMO

Aurora B is a serine/threonine kinase that has been implicated in regulating cell proliferation in distinct cancers, including breast cancer. Here we show that Aurora B expression is elevated in basal-like breast cancer (BLBC) compared with other breast cancer subtypes. This high level of expression seems to correlate with poor metastasis-free survival and relapse-free survival in affected patients. Mechanistically, we show that elevated Aurora B expression in breast cancer cells activates AKT/GSK3ß to stabilize Snail1 protein, a master regulator of epithelial-mesenchymal transition (EMT), leading to EMT induction in a kinase-dependent manner. Conversely, Aurora B knock down by short-hairpin RNAs (shRNAs) suppresses AKT/GSK3ß/Snail1 signaling, reverses EMT and reduces breast cancer metastatic potential in vitro and in vivo. Finally, we identified a specific OCT4 phosphorylation site (T343) responsible for mediating Aurora B-induced AKT/GSK3ß/Snail1 signaling and EMT that could be attenuated by Aurora B kinase inhibitor treatment. These findings support that Aurora B induces EMT to promote breast cancer metastasis via OCT4/AKT/GSK3ß/Snail1 signaling. Pharmacologic Aurora B inhibition might be a potential effective treatment for breast cancer patients with metastatic disease.

5.
J Cardiothorac Surg ; 15(1): 18, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931858

RESUMO

INTRODUCTION: Lung cancer is the leading causes of cancer-related deaths globally. The most frequent histologic type of lung cancer is non-small-cell lung cancer (NSCLC). NSCLC often undergo epithelial-mesenchymal transition (EMT). The components that control this process are thus promising therapeutic targets. MATERIALS AND METHODS: Gli/EMT protein expression levels were examined by western blot in paired NSCLC patient tissues and NSCLC cell lines. Functional analyses were performed to investigate SHH/Gli signaling and EMT in NSCLC cell lines. MTS cell viability, luciferase reporter, and western blot assays were performed to analyze pathway activity, while wound healing and transwell assays were executed to measure cell migration and invasion. RESULTS: Higher Gli1 expressions were detected in tumor samples than in paired normal tissues. Differential expression of EMT biomarkers and activation of p-AKT were observed in tumor tissues. N-Shh stimulation of cells significantly increased reporter activity in NSCLC cell lines, while Gli-i treatment of transfected cells showed less relative reporter activity. When subjected to both Gli-i and N-Shh treatment, NSCLC cell lines continued to demonstrate decreased Gli transcriptional activity. Gli inhibition is associated with decreased expression level of p-AKT, N-cadherin and Vimentin. Knockdown of both Gli1 and Gli2 showed decreased EMT, migrative and invasive ability. Cells stimulated by N-Shh demonstrated greater mobility. In addition, AKT-i treated cells also demonstrated inhibited EMT activity. CONCLUSIONS: This study provides evidence for aberrant upregulation of the Gli signaling pathway and a strong association between expression of Gli versus AKT and EMT markers in NSCLC.

6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 17-20, 2020 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-31922588

RESUMO

OBJECTIVE: To explore the genetic basis of a pedigree affected with hereditary spherocytosis. METHODS: Peripheral blood samples were collected from 17 members of the pedigree. Genomic DNA of the proband was subjected to next generation sequencing. Candidate variant was validated by co-segregation analysis. pCAS2(c.5798+1G) and pCAS2(c.5798+1A) plasmids were constructed by homologous recombination and transfected into 293T cells. Reverse transcription PCR, TA cloning and Sanger sequencing were used to analyze the effect of candidate variant on splicing. Meanwhile, peripheral blood RNAs were extracted to analyze the effect of candidate variant on splicing in vivo. RESULTS: The proband was found to carry a c.5798+1G>A variant of the SPTB gene. The variant has co-segregated with the phenotype in the pedigree. In vitro and in vivo splicing experiments confirmed that the mutation has significantly affected the splicing, resulting in shift of reading frame and produced a premature termination codon. CONCLUSION: The novel c.5798+1G>A variant of the SPTB gene probably underlies the pathogenesis of hereditary spherocytosis in this pedigree.


Assuntos
Espectrina , Esferocitose Hereditária , Códon sem Sentido/genética , Variação Genética , Células HEK293 , Humanos , Mutação/genética , Linhagem , Plasmídeos , Processamento de RNA , Espectrina/genética , Esferocitose Hereditária/genética , Transfecção
7.
Acad Radiol ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31982342

RESUMO

RATIONALE AND OBJECTIVES: We assess the performance of a model combining a deep convolutional neural network and a hand-crafted radiomics signature for predicting KRAS status in patients with colorectal cancer (CRC). MATERIALS AND METHODS: The primary cohort consisted of 279 patients with clinicopathologically confirmed CRC between April 2011 and April 2015. Portal venous phase computed tomographic images were analyzed to extract traditional hand-crafted radiomics features as well as deep learning features. A Wilcoxon rank sum test, the minimum redundancy maximum relevance algorithm, and multivariable logistic regression analysis were used to select features and build a radiomics signature. A combined model was then developed using multivariable logistic regression analysis. An independent validation cohort of 119 patients from May 2015 to April 2016 was used to confirm the combined model's predictive performance. RESULTS: The C-index of hand-crafted radiomics signature's discriminative ability was 0.719 (95% confidence interval, CI: 0.658-0.776) for the primary cohort and 0.720 (95% CI: 0.625-0.813) for the validation cohort. The C-index of the deep radiomics signature's discriminative ability was 0.754 (95% CI: 0.696-0.813) for the primary cohort and 0.786 (95% CI: 0.702-0.863) for the validation cohort. The combined model, which merged the hand-crafted radiomics features and deep radiomics features, achieve a C-index of 0.815 (95% CI: 0.766-0.868) for the primary cohort and 0.832 (95% CI: 0.762-0.905) for the validation cohort. CONCLUSION: This study presents a model that incorporates the hand-crafted and deep radiomics signature, which can be used for individualized preoperative prediction of KRAS mutations in patients with CRC.

8.
Postgrad Med J ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911448

RESUMO

BACKGROUND: We aimed to investigate the association between serum uric acid (SUA) and all-cause or cardiovascular mortality among participants with obesity. METHOD: All participants were included from the 1999 to 2014 National Health and Nutrition Examination Survey with follow-up mortality assessment through 31 December 2015. Cox proportional hazards models were built to estimate adjusted HRs and 95% CIs for mortality according to baseline uric acid in quartiles. Obesity was defined as body mass index ≥30 (kg/m2). Generalised additive model (GAM) and two-piecewise linear regression models were performed to explore any non-linearity in associations. RESULTS: There were 12 637 adults with obesity eligible for analysis. There were 999 (7.91%) all-cause and 147 (1.16%) cardiovascular mortality occurred during the mean follow-up of 98.11 months. Comparing with the lowest quartile of SUA, the highest SUA group did not have significant association with all-cause (HR 1.08, 95% CI 0.76 to 1.52) and cardiovascular mortality (HR 1.63, 95% CI 0.58 to 4.53) after adjusting for various confounding factors. GAM and two-piecewise linear regression model demonstrated a non-linearly relationship between SUA and all-cause mortality, and the corresponding cut-off point was 6.5 mg/dL. However, there is no significant relationship between uric acid and cardiovascular death on both sides of the cut-off value of 6.1 mg/dL. CONCLUSIONS: SUA showed a J-shaped relationship with all-cause mortality, but no significant with cardiovascular mortality in adults with obesity.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31904101

RESUMO

Somatic cell nuclear transfer (SCNT) is a valuable technology tool with various uses in transgenic animals, regenerative medicine, and stem cell research. However, the efficiency of SCNT embryos appears to have poor developmental competency. Environmental issues may adversely affect SCNT embryos in buffalo. Thereafter, the present study aimed to explore the effect of season on the maturation of buffalo oocytes and subsequent developmental capability after parthenogenetic activation and SCNT in buffalo. Buffalo oocytes (n = 6353) were collected from local slaughterhouse at various seasons; spring (March-April), summer (May-August), autumn (September-November), and winter (December-January). A significant increase (p < 0.05) was recorded in the maturation rate (57.07%) at autumn compared with spring, summer, and winter (50.46, 50.93, and 50.66%, respectively). No significant differences were recorded in the fusion and the cleavage rates among all seasons. Blastocyst development rate was higher (p < 0.05) in autumn and winter (16.52 ± 8.45% and 15.98 ± 7.17%, respectively) than in spring and summer (9.47 ± 6.71% and 10.84 ± 6.58%, respectively) seasons. It could be concluded that the season had a significant effect on oocyte development competence which can be used for SCNT in buffalo.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31943644

RESUMO

The sensitivity of conventional thin-film OFET-based sensors is limited by the diffusion of analytes through bulk films and remains the central challenge in sensing technology. Now, for the first time, an ultrasensitive (sub-ppb level) sensor is reported that exploits n-type monolayer molecular crystals (MMCs) with porous two-dimensional structures. Thanks to monolayer crystal structure of NDI3HU-DTYM2 (NDI) and controlled formation of porous structure, a world-record detection limit of NH3 (0.1 ppb) was achieved. Moreover, the MMC-OFETs also enabled direct detection of solid analytes of biological amine derivatives, such as dopamine at an extremely low concentration of 500 ppb. The remarkably improved sensing performances of MMC-OFETs opens up the possibility of engineering OFETs for ultrasensitive (bio)chemical sensing.

11.
Sci Total Environ ; 708: 134596, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31780158

RESUMO

In this study, the effects of nitrogen and phosphorus supply on biodiesel production from Scenedesmus obliquus with glucose as the carbon source were investigated. It was found that sufficient phosphorus could further improve biodiesel production under nitrogen starvation. S. obliquus was cultivated in soybean processing wastewater. The removal efficiencies of carbon oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP) after 8-day cultivation were 72%, 95%, and 54%, respectively. Moreover, the fatty acid productivity after eight-day cultivation reached as high as 99.3 mg·L-1·d-1, which was 1.15 times higher than the highest efficiency using a glucose culture. This result was due to two naturally-formed stages occurring with sufficient phosphorus: nitrogen sufficiency stage for biomass and nitrogen starvation stage for lipid accumulation. It verified the conclusion of the roles of nitrogen and phosphorus obtained in the glucose culture and provided an economic and environmentally friendly choice for biodiesel production with efficient soybean wastewater treatment.

12.
Parasitol Res ; 119(2): 637-647, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31823007

RESUMO

The trichomonad species Tetratrichomonas buttreyi and Pentatrichomonas hominis have been reported in the bovine digestive tract in only a few studies, and the prevalence and pathogenicity of these two protists in cattle herds remain unknown. In this study, the prevalence of T. buttreyi and P. hominis in yellow cattle, dairy cattle, and water buffalo in Anhui Province, China, was determined with a PCR analysis of the small subunit ribosomal RNA genes. The overall infection rates for T. buttreyi and P. hominis were 8.1% and 5.4%, respectively. Double infections were found in 15 (1.6%) samples from four farms. The prevalence of P. hominis in cattle with abnormal feces was significantly higher than that in cattle with normal feces (χ2 = 13.0, p < 0.01), and the prevalence of T. buttreyi in the northern region of Anhui Province was also significantly higher than that in the mid region (χ2 = 16.6, p < 0.01). Minor allelic variations were detected in the T. buttreyi isolates from cattle in this study, as in other hosts in previous studies. Morphological observations, together with the PCR analysis, demonstrated that the trichomonads isolated in this study were P. hominis. The presence of T. buttreyi and P. hominis indicated that cattle are natural hosts of these two trichomonads and could be a potential source of P. hominis infections in humans and other animal hosts.

13.
Radiology ; 294(2): 329-339, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31793849

RESUMO

Background American College of Radiology contrast agent-enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) was developed to improve the accuracy of hepatocellular carcinoma (HCC) diagnosis at contrast agent-enhanced US. However, to the knowledge of the authors, the diagnostic accuracy of the system in characterization of liver nodules 20 mm or smaller has not been fully evaluated. Purpose To evaluate the diagnostic accuracy of CEUS LI-RADS in diagnosing HCC in liver nodules 20 mm or smaller in patients at risk for HCC. Materials and Methods Between January 2015 and February 2018, consecutive patients at risk for HCC presenting with untreated liver nodules 20 mm or less were enrolled in this retrospective double-reader study. Each nodule was categorized according to the CEUS LI-RADS and World Federation for Ultrasound in Medicine and Biology (WFUMB)-European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) criteria. Diagnostic performance of CEUS LI-RADS and WFUMB-EFSUMB characterization was evaluated by using tissue histologic analysis, multiphase contrast-enhanced CT and MRI, and imaging follow-up as reference standard and compared by using McNemar test. Results The study included 175 nodules (mean diameter, 16.1 mm ± 3.4) in 172 patients (mean age, 51.8 years ± 10.6; 136 men). The sensitivity of CEUS LR-5 versus WFUMB-EFSUMB criteria in diagnosing HCC was 73.3% (95% confidence interval [CI]: 63.8%, 81.5%) versus 88.6% (95% CI: 80.9%, 94%), respectively (P < .001). The specificity of CEUS LR-5 versus WFUMB-EFSUMB criteria was 97.1% (95% CI: 90.1%, 99.7%) versus 87.1% (95% CI: 77%, 94%), respectively (P = .02). No malignant lesions were found in CEUS LR-1 and LR-2 categories. Only two nodules (of 41; 5%, both HCC) were malignant in CEUS LR-3 category. The incidences of HCC in CEUS LR-4, LR-5, and LR-M were 48% (11 of 23), 98% (77 of 79), and 75% (15 of 20), respectively. Two of 175 (1.1%) histologic analysis-confirmed intrahepatic cholangiocarcinomas were categorized as CEUS LR-M by CEUS LI-RADS and misdiagnosed as HCC by WFUMB-EFSUMB criteria. Conclusion The contrast-enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) algorithm was an effective tool for characterization of small (≤20 mm) liver nodules in patients at risk for hepatocellular carcinoma (HCC). Compared with World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology criteria, CEUS LR-5 demonstrated higher specificity for diagnosing small HCCs with lower sensitivity. Published under a CC BY 4.0 license. See also the editorial by Crocetti in this issue.

14.
J Trace Elem Med Biol ; 58: 126438, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31760326

RESUMO

BACKGROUND: Observational studies have suggested that selenium levels might associate with the risk of cardio-metabolic diseases, but how circulating selenium is related to dyslipidemia remains inconclusive. OBJECTIVES: To investigate the association of circulating selenium levels with lipid profiles and dyslipidemia among US adults. METHODS: Using the data collected from the National Health and Nutrition Examination Survey (NHANES 1999-2006), we performed multivariate logistic regression to examine the association of circulating selenium levels (in quartiles) with total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and atherogenic index (AI). RESULTS: We included 2903 adults (49.3 % male) (average age: 61.9) for analysis. Circulating selenium had non-linear association with TC, LDL-C, HDL-C, and AI (all p < 0.05). When comparing with the lowest quartile, subjects with the highest quartile of circulating selenium (>147.00 µg/L) had the higher odds of elevated TG (OR: 1.75, 95% CI = 1.14, 2.68), TC (OR: 2.47, 95% CI = 1.62, 3.76), LDL-C (OR: 2.52, 95% CI = 1.60, 3.96), non-HDL-C (OR: 2.17, 95% CI = 1.41, 3.33), AI (OR: 1.20, 95% CI = 0.73, 1.97) and low-HDL-C (OR: 2.10, 95% CI = 1.19, 3.72). Similar patterns were observed in subgroup analysis. CONCLUSIONS: Higher circulating selenium levels had non-linear association with lipid profiles and the increased odds of dyslipidemia.

15.
Postgrad Med J ; 96(1132): 73-78, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31488620

RESUMO

BACKGROUND: The prognostic value of serum uric acid (SUA) for incident acute coronary syndrome (ACS) in hypertensive subjects is uncertain. Therefore, the present study examined the association between SUA and incident ACS in a large cohort of Chinese hypertensive adults. METHODS: This was a retrospective cohort study, which enrolled 5473 Chinese community-dwelling hypertensive patients from 1 January 2012 to 31 December 2012. Study outcomes were ACS events, and patients were followed until 31 December 2016. Cox regression analyses were conducted to determine adjusted HRs and 95% CIs for baseline SUA tertiles (low, middle and high group) and for men and women separately. RESULTS: A total of 5473 participants were included in the analysis (median follow-up was 4.5 years). Participants were divided into tertiles based on SUA levels. During follow-up, 9 (0.49%), 14 (0.77%) and 25 (1.37%) patients developed ACS in the lowest, middle and highest tertiles, respectively. When compared with the lowest tertile of SUA, the highest tertile of SUA was associated with ACS risk in all subjects and in men and women separately (HR: 2.62, 95% CI 1.14 to 7.01, p=0.0233; 2.15, 95% CI 1.08 to 6.04, p=0.021, and 3.49, 95% CI 1.25 to 7.74, p=0.017, respectively). CONCLUSIONS: Higher SUA levels were independently associated with an elevated risk of ACS incidence. The relationship between SUA levels and ACS in hypertensive patients was J-shaped.

16.
Photochem Photobiol ; 96(1): 124-138, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31483870

RESUMO

Herbal extracts including asiatic acid (AA) have become popular candidates of anti-photoaging agents due to their anti-inflammatory and antioxidant properties and minimal side effect. Nevertheless, low bioavailability due to poor solubility limits their practical application. In this study, a highly bioavailable form of AA called AAGS (compounded by asiatic acid and glucosamine) was investigated for its anti-photoaging effect using both in vitro and in vivo models along with UVB irradiation. The results showed that AAGS alleviated UVB-induced cell proliferation inhibition by reducing G2 phase arrest and cell apoptosis rate as well as the gene expressions of P53, BAX, CASPASE 3 and CASPASE 9, but enhancing BCL-2 expression. It also reduced the production of reactive oxygen species along with increased gene expression of GPX-1 and downregulated the gene expression of IL-1ß, IL-6, IL-8, IL-17 and TNF-α compared to nontreated cells. In vivo results demonstrated the antiphotodamaging effects by restoring skin thickness, collagen content and reducing MMPs expression, which are also supported by reduced MMPs gene expression and enhanced collagen I and TGF-ß1 gene expression in vitro. Thus, AAGS may become a potential anti-photoaging agent for topical use due to its capability of self-assembling into a water gel.

17.
Postgrad Med ; : 1-5, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31829063

RESUMO

Background: Ischemic stroke is a major public health problem and a main cause of death in China. However, how resting heart rate may associate with ischemic stroke among patients with hypertension remains unclear.Objective: To investigate the association between resting heart rate and ischemic stroke among elderlies with hypertension in China.Methods: We conducted a retrospective study of elderlies with hypertension who aged ≥60 years and were free from a stroke at baseline. Resting heart rate at baseline was treated as both continuous and categorical variable. Hazard ratios for ischemic stroke were estimated by multivariate Cox proportional hazards models.Results: A total of 3071 elderlies with hypertension [1369 (44.6%) men, an average age of 71.3 ± 7.1 years] were enrolled, and 182 cases of ischemic stroke occurred during a mean follow-up period of 5.5 years. Multivariate Cox regression showed that every 10 bpm increment in resting heart rate elevated the risk of ischemic stroke by 21% (95%CI: 1.05, 1.73; P = 0.018). After adjusting for confounders, resting heart rate ≥90 bpm significantly associated with the risk of ischemic stroke (HR: 1.35, 95% CI = 1.16, 2.78) when using the resting heart rate <60 bpm as a referent. Subgroup analysis showed that the relation between resting heart rate and risk of ischemic stroke was seem to be stronger in female (HR: 1.32 vs 1.11), those with uncontrolled hypertension (HR: 1.32 vs 1.12), people with combined diabetes and hypertension (HR: 1.31 vs 1.12), people with overweight (HR: 1.39 vs 1.02) and those who aged >75 (HR: 1.33 vs 1.11). Smoothing spline plots suggested the optimal resting heart rate for the lowest risk of ischemic stroke was between 60 and 80 bpm.Conclusions: In Chinese elderly hypertensive patients, elevated resting heart rate was an independent predictor of ischemic stroke, and the optimal resting heart rate was around 70 bpm.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31454555

RESUMO

BACKGROUND: This research was designed to investigate patient-reported and doctor-reported reasons for the discontinuation of pharmacological treatment in Chinese patients with major depressive disorder (MDD), which was part of the National Survey on Symptomatology of Depression (NSSD) from 2014 to 2015. METHODS: This cross-sectional study included 649 patients who had discontinued antidepressant medications and 711 patients who had remained on them, selected from a group of 3516 candidates who have had at least one depressive episode. Differences in the two groups' sociodemographic factors, clinical characteristics, medication use, and self-reported reasons for drug discontinuation were compared via Student's t-test or chi-square test. Logistic regression analysis was then used to determine the association of all non-subjective dichotomous and ordinal categorical variables, including the additional 63 items of our physician-evaluated symptomatic assessment, with drug compliance. RESULTS: Compared to the spontaneous drug discontinuation (SDD) group, the drug adherence (DA) group had significantly lower rates of the following: family history of mental disease (9.0% vs 13.6%), highest level of education achieved being post-graduate or above (1.6% vs 4.7%), smoking (5.8% vs 9.7%), and other health problems (33.9% vs 42.4%) (p's < 0.05). On the other hand, first-episode depression (48.5% vs 21.9%) and taking of mood stabilizer(s) (8.3% vs 5.6%) were higher in the former group than in the latter (p's < 0.05). Logistic Regression Analysis showed that five symptoms, such as depressed mood, were correlated positively with SDD, while another six symptoms, such as psychomotor retardation, were correlated negatively with it. The receiver operating characteristic (ROC) curve of this model yielded an area under the curve (AUC) of 0.701 (95% CI, 0.673-0.729). Notably, there were three main reasons given by patients in the DA group as to why they discontinued their medication(s): (1) concern about long-term side effects (36.1%), (2) no perceived need for taking said medication(s) long-term (34.2%), and (3) believing oneself to have been cured completely (30.0%). CONCLUSIONS: The aforementioned factors may affect patient compliance and elicit maladaptive thinking even from patients with good educational backgrounds, increasing the risk of drug discontinuation. Compliance of pharmacological treatment might be improved by increasing clarification and elucidation of different symptom clusters to the patient and combating the main reasons for drug discontinuation.

19.
J Affect Disord ; 260: 349-360, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521873

RESUMO

BACKGROUND: Symptomatology differences of major depressive disorder (MDD) in psychiatric and general hospitals in China leads to possible misdiagnosis. Looking at the symptomatology of first-visit patients with MDD in different mental health services, and identifying predictors of health-seeking behavior using machine learning may help to improve diagnostic accuracy. METHODS: 1500 patients first diagnosed with MDD were recruited from 16 psychiatric hospitals and 16 general hospitals across China. Socio-demographic characteristics, causal attribution, symptoms of depression within and outside Diagnostic and Statistical Manual of Mental Disorders (DSM) framework were collected using a self-made questionnaire. A predictive model of 62 variables was established using Random forest, symptom frequencies of patients in general hospitals and psychiatric hospitals were compared. RESULTS: The machine learning approach revealed that symptoms were strong predictors of health-seeking behavior among patients with MDD. General hospitals patients had higher frequencies of suicidal ideation (χ2=15.230, p<0.001), psychosis (χ2=14.264, p<0.001), weight change (all p<0.001), hypersomnia (χ2=25.940, p<0.001), and a tendency of denying emotional/cognitive symptoms compared with psychiatric hospitals patients. LIMITATIONS: Stigma and preference bias were not measured. Severity of current depressive episodes was not assessed. Data of previous episode(s) was not presented. CONCLUSIONS: Symptom evaluation targeting specific patient population in different hospitals is crucial for diagnostic accuracy. Suicide prevention reliant on collaboration between general hospitals and psychiatric hospitals is required in the future construction of Chinese mental health system.

20.
J Biomed Mater Res A ; 108(1): 69-80, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31496042

RESUMO

Polylactic-co-glycolic acid (PLGA) is one of the most promising synthetic materials for tissue engineering due to its excellent biocompatibility, good mechanical properties, and tunable biodegradation time. However, the accumulation of PLGA degradative products could cause significant host inflammatory response, a microenvironment favoring tissue fibrosis that is mainly mediated by M1 subtype macrophage. Drug loading is an emerging technology to modify electrospun nanofibers, and asiaticoside (AS) was demonstrated as an anti-inflammatory drug. This study investigated the potential effect of AS incorporating into PLGA electrospun nanofibers on modulating host inflammatory response. The results showed that AS co-electrospun with PLGA nanofibers could significantly reduce the infiltration of inflammatory cells at the implantation site as opposed to the site of regular PLGA nanofibers. In particular, immunohistochemistry demonstrated decreased M1 macrophage infiltration whereas increased M2 macrophage infiltration in the implantation site of AS-PLGA nanofibers when compared to the PLGA implantation site. In vitro study also revealed that culture of human fibroblasts on PLGA nanofibers resulted in significantly enhanced gene expression of inflammatory cytokines when compared to non-seeded fibroblasts, but these genes were significantly downregulated when seeded on AS-PLGA. Furthermore, culture of macrophage on AS-PLGA led to upregulated M2 marker gene expression and downregulated M1 marker gene expression. Collectively, these results indicate that, AS might be an ideal drug for loading into electrospun polymer nanofibers and thus favoring for tissue regeneration via mediating macrophage polarization.

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