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1.
J Exp Clin Cancer Res ; 40(1): 54, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33526068

RESUMO

BACKGROUND: Accumulating evidence has highlighted the importance of negative elongation factor complex member E (NELFE) in tumorigenesis. However, the relationship between NELFE and gastric cancer (GC) remains unclear. This study aimed to explore the expression pattern and specific function of NELFE in GC. METHODS: NELFE expression was evaluated by immunohistochemistry and qRT-PCR in GC tissues, respectively. Cell proliferation, migration and invasion were measured by CCK-8, colony formation, transwell assays, and nude mice model. Bioinformatics analysis was performed to search potential target genes of NELFE, and a Cignal Finder 10-Pathway Reporter Array was used to explore potential signaling pathways regulated by NELFE. Dual-luciferase reporter assays, qRT-PCR and western blotting were conducted to verify their regulatory relationship. The expression correlations among NELFE, ß-catenin and CSNK2B were further explored by immunohistochemistry on consecutive resections. RESULTS: NELFE was significantly overexpressed in GC tissues both in protein and mRNA level and negatively correlated with the prognosis of GC patients. Gain- and loss-of-function experiments showed that NELFE potentiated GC cell proliferation and metastasis in vitro and in vivo. CSNK2B was identified as a downstream effector of NELFE. Wnt/ß-catenin signaling may mediate the regulation of CSNK2B by NELFE. In addition, NELFE, ß-catenin and CSNK2B were all remarkably upregulated in tumor tissues compared with adjacent normal tissues, and their expression levels in GC were positively correlated with each other. CONCLUSION: Our findings reveal a new NELFE-Wnt/ß-catenin-CSNK2B axis to promote GC progression and provide new candidate targets against this disease.

3.
Gerontology ; : 1-8, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33582668

RESUMO

INTRODUCTION: This study aimed to examine whether intraplaque neovascularization (IPN) of carotid plaques, as characterized by contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke recurrence in patients with carotid atherosclerosis. METHODS: We conducted a prospective study of consecutive patients with a recent stroke and at least one atherosclerotic plaque in the carotid artery on the side consistent with symptoms. All patients underwent CEUS after their first admission. IPN was graded on the basis of the presence and location of microbubbles within each plaque. RESULTS: We eventually included 155 patients, all of whom underwent IPN analysis. After a follow-up of 24 months, we recorded 25 (16.1%) stroke recurrences in the whole population. All the recurrences occurred in patients presenting IPN. There was significant difference in the IPN between the 2 groups (p = 0.002). In the final Cox proportional-hazards multivariable models, IPN of grade 2 was independently associated with the risk of stroke recurrence (HR = 4.535; 95% CI: 1.892-10.870; p = 0.001). This association remained after adjusting for the degree of carotid stenosis (HR = 3.491; 95% CI: 1.410-8.646; p = 0.007). CONCLUSIONS: IPN was an independent predictor of stroke recurrence in patients with a recent ischemic stroke and carotid atherosclerosis. In predicting stroke recurrence, IPN may be an earlier indicator than carotid stenosis and may help stratify the risk of stroke recurrence.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33615888

RESUMO

BACKGROUND: Calcineurin inhibitors (CNIs) are vital immunosuppressive therapies in the management of inflammatory conditions. A long-term consequence is nephrotoxicity. In the kidneys, the primary, catalytic calcineurin (CnA) isoforms are CnAα and CnAß. While the renal phenotype of CnAα-/- mice substantially mirrors CNI-induced nephrotoxicity, the mechanisms downstream of CnAa are poorly understood. HYPOTHESIS: Since NADPH oxidase-2 (Nox2)-derived oxidative damage is implicated in CNI-induced nephrotoxicity, we hypothesized that CnAα inhibition drives Nox2 upregulation and promotes oxidative stress. EXPERIMENTAL DESIGN: To test the hypothesis, Nox2 regulation was investigated in kidneys from CnAα-/-, CnAß-/- and WT littermate mice. To identify the downstream mediator of CnAα, NFAT and NFκB regulation was examined. To test if Nox2 is transcriptionally regulated via a NFκB pathway, CnAα-/- and WT renal fibroblasts were treated with the NFκB inhibitor, caffeic acid phenethyl ester. RESULTS: Our findings showed that CsA treatment induced Nox2 upregulation and oxidative stress. Further, Nox2 upregulation and elevated ROS generation occurred only in CnAα-/- mice. In these mice, NFκB but not NFAT activity was increased. In CnAα-/- renal fibroblasts, NFκB inhibition prevented Nox2 upregulation and ROS generation. CONCLUSIONS: These findings indicate that 1) CnAα loss stimulates Nox2 upregulation, 2) NFκB is a novel CnAα-regulated transcription factor and 3) NFκB mediates CnAα-induced Nox2 and ROS upregulation. SIGNIFICANCE: Our results demonstrate that CnAα plays a key role in Nox2 and ROS generation. Further, these novel findings provide evidence of divergent CnA isoform signaling pathways. Finally, this study advocates for CnAα-sparing CNIs, ultimately circumventing the CNI nephrotoxicity.

5.
Nutrition ; 86: 111156, 2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33601124

RESUMO

OBJECTIVES: We investigated whether measurement of muscle quantity/quality has additional predictive value for postoperative complications and long-term survival after gastrectomy for gastric cancer in patients with probable sarcopenia, as defined by the new European Working Group on Sarcopenia in Older People 2 consensus. METHODS: We conducted a prospective study of patients who underwent a radical gastrectomy for gastric cancer between August 2014 and June 2019. Muscle strength was measured using a handgrip dynamometer. Computed tomography images at the third lumbar vertebra level were used to assess muscle quantity and quality by the measuring cross-sectional muscle area and mean muscle attenuation, respectively. Probable sarcopenia was defined by low muscle strength. Sarcopenia was diagnosed by additional low muscle quantity or quality. Clinical outcomes were obtained by prospective data collection and follow up. RESULTS: Probable sarcopenia was identified in 419 patients, including 285 patients with sarcopenia. Patients with sarcopenia had a higher incidence of postoperative complications, higher costs, longer length of postoperative hospital stay, and worse overall survival (OS) and disease-free survival (DFS) compared with patients with low muscle strength only. The multivariate logistic analysis showed that sarcopenia and hypoproteinemia were independent risk factors for postoperative complications in patients with probable sarcopenia. Moreover, multivariate Cox analyses showed that sarcopenia remained an independent risk factor for OS and DFS in patients with probable sarcopenia. CONCLUSIONS: The measurement of muscle quantity/quality has additional predictive value for postoperative complications, OS, and DFS after gastrectomy for gastric cancer in patients with probable sarcopenia.

6.
Am J Clin Nutr ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33471054

RESUMO

BACKGROUND: Few population-based studies have evaluated the influence of long-term diet on the gut microbiome, and data among Asian populations are lacking. OBJECTIVE: We examined the association of long-term diet quality, comprising 8 food groups (fruit, vegetables, dairy, fish/seafood, nuts/legumes, refined grains, red meat, and processed meat), with gut microbiome among Chinese adults. METHODS: Included were 1920 men and women, enrolled in 2 prospective cohorts (baseline 1996-2006), who remained free of cardiovascular diseases, diabetes, and cancer at stool collection (2015-2018) and had no diarrhea or antibiotic use in the last 7 d before stool collection. Microbiome was profiled by 16S rRNA sequencing. Long-term diet was assessed by repeated surveys at baseline and follow-ups (1996-2011), with intervals of 5.2 to 20.5 y between dietary surveys and stool collection. Associations of dietary variables with microbiome diversity and composition were evaluated by linear or negative binomial hurdle models, adjusting for potential confounders. False discovery rate (FDR) <0.1 was considered significant. RESULTS: The mean ± SD age at stool collection was 68 ± 1.5 y. Diet quality was positively associated with microbiome α-diversity (P = 0.03) and abundance of Firmicutes, Actinobacteria, Tenericutes, and genera/species within these phyla, including Coprococcus, Faecalibacterium/Faecalibacterium prausnitzii, Bifidobacterium / Bifidobacterium adolescentis, and order RF39 (all FDRs <0.1). Significant associations were also observed for intakes of dairy, fish/seafood, nuts/legumes, refined grains, and processed meat, including a positive association of dairy with Bifidobacterium and inverse associations of processed meat with Roseburia /Roseburia faecis. Most associations were similar, with or without adjustment for BMI and hypertension status or excluding participants with antibiotic use in the past 6 mo. CONCLUSION: Among apparently healthy Chinese adults, long-term diet quality is positively associated with fecal microbiome diversity and abundance of fiber-fermenting bacteria, although magnitudes are generally small. Future studies are needed to examine if these bacteria may mediate or modify diet-disease relations.

7.
Cell Death Dis ; 12(1): 90, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462197

RESUMO

Oxaliplatin resistance undermines its curative effects on cancer and usually leads to local recurrence. The oxidative stress induced DNA damage repair response is an important mechanism for inducing oxaliplatin resistance by activating autophagy. ELISA is used to detect target genes expression. TMT-based quantitative proteomic analysis was used to investigate the potential mechanisms involved in NORAD interactions based on GO analysis. Transwell assays and apoptosis flow cytometry were used for biological function analysis. CCK-8 was used to calculate IC50 and resistance index (RI) values. Dual-luciferase reporter gene assay, RIP and ChIP assays, and RNA pull-down were used to detect the interaction. Autophagy flux was evaluated using electron microscope and western blotting. Oxidative stress was enhanced by oxaliplatin; and oxaliplatin resistance gastric cancer cell showed lower oxidative stress. TMT labeling showed that NORAD may regulate autophagy flux. NORAD was highly expressed in oxaliplatin-resistant tissues. In vitro experiments indicate that NORAD knockdown decreases the RI (Resistance Index). Oxaliplatin induces oxidative stress and upregulates the expression of NORAD. SGC-7901 shows enhanced oxidative stress than oxaliplatin-resistant cells (SGC-7901-R). NORAD, activated by H3K27ac and CREBBP, enhanced the autophagy flux in SGC-7901-R to suppress the oxidative stress. NORAD binds to miR-433-3p and thereby stabilize the ATG5- ATG12 complex. Our findings illustrate that NORAD, activated by the oxidative stress, can positively regulate ATG5 and ATG12 and enhance the autophagy flux by sponging miR-433-3p. NORAD may be a potential biomarker for predicting oxaliplatin resistance and mediating oxidative stress, and provides therapeutic targets for reversing oxaliplatin resistance.

8.
Science ; 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514629

RESUMO

Recently, a new SARS-CoV-2 lineage called B.1.1.7 (variant of concern: VOC 202012/01) emerged in the United Kingdom that was reported to spread more efficiently and faster than other strains. This variant has an unusually large number of mutations with 10 amino acid changes in the spike protein, raising concerns that its recognition by neutralizing antibodies may be affected. Here, we tested SARS-CoV-2-S pseudoviruses bearing either the Wuhan reference strain or the B.1.1.7 lineage spike protein with sera of 40 participants who were vaccinated in a previously reported trial with the mRNA-based COVID-19 vaccine BNT162b2. The immune sera had slightly reduced but overall largely preserved neutralizing titers against the B.1.1.7 lineage pseudovirus. These data indicate that the B.1.1.7 lineage will not escape BNT162b2-mediated protection.

9.
J Sci Food Agric ; 101(2): 379-387, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32623727

RESUMO

Tea is the one of the most popular non-alcoholic caffeinated beverages in the world. Tea is produced from the tea plant (Camellia sinensis (L.) O. Kuntze), which is known to accumulate fluoride. This article systematically analyzes the literature concerning fluoride absorption, transportation and fluoride tolerance mechanisms in tea plants. Fluoride bioavailability and exposure levels in tea infusions are also reviewed. The circulation of fluoride within the tea plantation ecosystems is in a positive equilibrium, with greater amounts of fluoride introduced to tea orchards than removed. Water extractable fluoride and magnesium chloride (MgCl2 ) extractable fluoride in plantation soil are the main sources of absorption by tea plant root via active trans-membrane transport and anion channels. Most fluoride is readily transported through the xylem as F- /F-Al complexes to leaf cell walls and vacuole. The findings indicate that tea plants employ cell wall accumulation, vacuole compartmentalization, and F-Al complexes to co-detoxify fluoride and aluminum, a possible tolerance mechanism through which tea tolerates higher levels of fluoride than most plants. Furthermore, dietary and endogenous factors influence fluoride bioavailability and should be considered when exposure levels of fluoride in commercially available dried tea leaves are interpreted. The relevant current challenges and future perspectives are also discussed. © 2020 Society of Chemical Industry.

10.
Int J Cancer ; 148(1): 77-89, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32638381

RESUMO

Evidence from animal models suggests that dietary fatty acids have both anticancer and tumor-promoting effects. Whether dietary fatty acids are associated with colorectal cancer (CRC) in humans remains inconclusive. We investigated associations between dietary fatty acids and risk of CRC among 59 986 men who participated in the Shanghai Men's Health Study (SMHS), an ongoing population-based prospective cohort study. We identified 876 incident CRC cases in the SMHS during a mean follow-up of 9.8 years. Associations between dietary fatty acid intake and CRC risk were evaluated by Cox proportional hazard regression analyses. Consumption of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) was not significantly associated with CRC risk. Multivariate hazard ratios (HRs) and respective 95% confidence intervals (CIs) for Quartile 4 vs Quartile 1 were 0.92 (0.74-1.14; Ptrend = 0.47) for SFA, 0.95 (0.79-1.16; Ptrend = 0.74) for MUFA and 1.18 (0.95-1.46; Ptrend = 0.21) for PUFA. No significant associations were found for total n-6 PUFA or total n-3 PUFA. Additionally, we performed a meta-analysis to summarize results from the present study and 28 reports from 26 additional cohorts, which supported the overall null association between dietary fatty acid intake and CRC risk among men. Docosahexanoic acid and eicosapentaenoic acid were associated with 11% to 12% reduced risk, and linoleic acid a 19% increased risk, of CRC in the meta-analysis of combined sexes. In conclusion, this population-based prospective study and meta-analysis of cohort studies found little evidence that dietary fatty acid intake was associated with risk of CRC in men.

11.
Plant Physiol Biochem ; 158: 65-75, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33296847

RESUMO

Tea plant (Camellia sinensis (L.) O. Kuntze) is known to accumulate high concentrations of fluoride (F) in its leaves; however, the underlying mechanism of F accumulation remains unclear. The main objective of this study was to investigate the homeostatic self-defense mechanisms of tea leaves to F supplementation (0, 5, 20, and 50 mgL-1) by metabolomics and ionomics. We identified a total of 96 up-regulated and 40 down-regulated metabolites in tea leaves treated with F. Of these different compounds, minor polypeptides, carbohydrates and amino acids played valuable roles in the F-tolerating mechanism of tea plant. After F treatments, the concentrations of sodium (Na), ferrum (Fe), manganese (Mn), and molybdenum (Mo) were significantly increased in tea leaves, whereas the aluminum (Al) was decreased. These findings suggest that the ionic balance and metabolites are attributable to the development of F tolerance, providing new insight into tea plant adaptation to F stress.

12.
Chin J Traumatol ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33323319

RESUMO

Iatrogenic femoral artery pseudoaneurysm (IFAP) caused by invasive procedures is one of the common complications for endovascular interventions. We present a case of a young male patient with a complex IFAP as a result of iatrogenic femoral artery puncture. The defective femoral artery was repaired with combined bovine pericardial tube and autologous great saphenous vein grafts. Computed tomography angiography showed the grafts were still patent one year after the surgery.

13.
Clin Nutr ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33223117

RESUMO

BACKGROUND: Few studies have comprehensively analyzed the correlations among body composition parameters, muscle strength, and physical performance, as well as the influence of these factors on the postoperative complications and survival after radical gastrectomy for gastric cancer. METHODS: A prospective study was conducted including patients who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral fat area (VFA), subcutaneous fat area (SFA) was obtained by measurement of preoperative computed tomography (CT) images. Grip strength and 6-m gait speed were measured to assess muscle strength and physical performance before surgery. RESULTS: There was a positive correlation between SMI and SMD, as well as between SFA and VFA. SMD negatively correlated with SFA and VFA. SMI had a positive correlation with VFA, but showed minimal correlation with SFA and visceral to subcutaneous fat ratio (VSR). Grip strength and gait speed were both positively correlated with SMI and SMD, but showed minimal correlation with SFA, VFA and VSR. SMI and grip strength independently predicted postoperative complications, rather than SMD or gait speed. Whereas SMD and gait speed had independent predictive value for overall survival (OS) and/or disease-free survival (DFS), rather than SMI or grip strength. VSR independently predicted postoperative complications, rather than VFA or SFA alone. Low SFA was an independent risk factor for OS and DFS. High VFA was associated with worse survival in overweight patients (body mass index, BMI ≥25), but was associated with better survival in non-overweight patients (BMI <25). High SFA did not significantly influence survival in overweight patients, but was associated with better survival in non-overweight patients. CONCLUSION: There is an extensive and complex correlation among body composition parameters, grip strength, and gait speed in patients with operable gastric cancer. A comprehensive analysis of these parameters has significant predictive value for postoperative complications and survival.

14.
Mycopathologia ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184749

RESUMO

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) constantly develops in asthmatics, which has not been fully investigated. OBJECTIVES: This study aimed to investigate serum differentially expressed proteins (DEPs) between ABPA and asthma using the new approach isobaric tags by relative and absolute quantitation (iTRAQ). METHODS: Each 16 serum samples from ABPA or asthmatic subjects were pooled and screened using iTRAQ. After bioinformatic analysis, five candidate DEPs were validated in the enlarged serum samples from additional 21 ABPA, 31 asthmatic and 20 healthy subjects using ELISA. A receiver operating characteristic (ROC) curve was used to estimate the diagnostic power of carnosine dipeptidase 1 (CNDP1). RESULTS: A total of 29 DEPs were screened out between ABPA and asthmatic groups. Over half of them were enriched in proteolysis and regulation of protein metabolic process. Further verification showed serum levels of immunoglobulin heavy constant gamma 1, α-1-acid glycoprotein 1, corticosteroid-binding globulin and vitronectin were neither differentially altered between ABPA and asthma nor consistent with the proteomic analysis. Only serum CNDP1 was significantly decreased in ABPA patients, compared with asthmatics and healthy controls (P < 0.01 and P < 0.05). The ROC analysis determined 10.73 ng/mL as the cutoff value of CNDP1, which could distinguish ABPA among asthmatics (AUC 0.770, 95%CI 0.632-0.875, P < 0.001). CONCLUSIONS: This study firstly identified serological DEPs between ABPA and asthma using the new technique iTRAQ. Serum CNDP1 might assist the differential diagnosis of ABPA from asthma and serve as a new pathogenetic factor in fungal colonization and sensitization.

15.
Aging (Albany NY) ; 12(22): 23337-23350, 2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33197886

RESUMO

Growing evidence suggests that microbes can influence the onset of cancer and its consequent development. By researching samples from patients afflicted by cervical cancer, we aimed to explore the associated dynamics and prognostic value of intratumoral levels of F. nucleatum. We used qPCR to analyze tumor tissues obtained from 112 cervical cancer patients in order to characterize the levels and influences of intratumoral levels of the F. nucleatum. Especially for recurrent tissues, there was a distinct observation of higher levels of F. nucleatum in cervical cancer. Patients with high burdens of F. nucleatum intratumoral infiltration exhibited correspondingly poor rates of both overall survival and progression-free survival. Measures of the levels of F. nucleatum were found to have been reliable independent prognostic factors that could predict rates of PFS for afflicted patients (HR = 4.8, 95%CI = 1.2-18.6, P = 0.024). Notably, the levels of F. nucleatum were positively correlated with tumor differentiation. Cancer cells from patients with relatively high levels of F. nucleatum were observed to possess the characteristics of cancer stem cells (CSCs). We propose that F. nucleatum might be one potential cervical cancer diagnostic and prognostic biomarker, and these findings will help to provide a sound rationale and merit for further study of this bacterium.

16.
JNCI Cancer Spectr ; 4(5): pkaa028, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33215060

RESUMO

Background: To address the US Food and Drug Administration's recent safety concern on robotic surgery procedures, we compared short- and long-term mortality for stage I non-small cell lung cancer (NSCLC) patients treated by robotic-assisted thoracoscopic surgical lobectomy (RATS-L) vs video-assisted thoracoscopic surgical lobectomy (VATS-L). Methods: From the National Cancer Database, we identified 18 908 stage I NSCLC patients who underwent RATS-L or VATS-L as the primary operation from 2010 to 2014. Cox proportional hazards models were used to estimate hazard ratios (HRs) for short- and long-term mortality using unmatched and propensity score-matched analyses. All statistical tests were 2-sided. Results: Patients treated by RATS-L had higher 90-day mortality than those with VATS-L (6.6% vs 3.8%, P = .03) if conversion to open thoracotomy occurred. After excluding first-year observation, multiple regression analyses showed RATS-L was associated with increased long-term mortality, compared with VATS-L, in cases with tumor size 20 mm or less: hazard ratio (HR) = 1.33 (95% confidence interval [CI] = 1.15 to 1.55), HR = 1.36 (95% CI = 1.17 to 1.58), and HR = 1.33 (95% CI = 1.11 to 1.61) for unmatched, N:1 matched, and 1:1 matched analyses, respectively, in the intention-to-treat analysis. Among patients without conversion to an open thoracotomy, the respective hazard ratios were 1.19 (95% CI = 1.10 to 1.29), 1.19 (95% CI = 1.10 to 1.29), and 1.17 (95% CI = 1.06 to 1.29). Similar associations were observed when follow-up time started 18 or 24 months postsurgery. No statistically significant mortality difference was found for patients with tumor size of greater than 20 mm. These associations were not related to case volume of VATS-L or RATS-L performed at treatment institutes. Conclusions: Patients with small (≤20 mm) stage I NSCLC treated with RATS-L had statistically significantly higher long-term mortality risk than VATS-L after 1 year postsurgery.

17.
Medicine (Baltimore) ; 99(46): e22988, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181662

RESUMO

The aim of this study is to investigate the feasibility and advantages of the da Vinci robotic system with the "3 + 2" mode (3 robotic arms and 2 assistants) in radical gastrectomy for gastric cancer.The clinical data of 65 patients who underwent da Vinci robotic gastrectomy with the "3 + 2" mode from July 2016 to October 2019 were grouped into an observation group. An additional 65 patients who underwent robotic gastrectomy under the classic mode during the same period were grouped into a control group. The short-term surgical outcomes were compared between 2 different groups.Compared with the control group, the observation group had a significantly shorter operative time (176.18 ±â€Š15.49 vs 203.85 ±â€Š12.77 minutes, P < .001) and lower operation costs ($2761.19 ±â€Š$191.91 vs $3690.91 ±â€Š$162.82; P < .001). No statistical differences in other outcomes were observed (P > .05).We show that robotic gastrectomy with "3 + 2" mode is a safe and beneficial surgical procedure in new robotic surgery institutions.


Assuntos
Gastrectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Gástricas/cirurgia , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Resultado do Tratamento
18.
Int J Neurosci ; : 1-14, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208009

RESUMO

BACKGROUND: Cognitive decline is one of the greatest concerns for patients with Parkinson's disease (PD) and their care partners. Repetitive transcranial magnetic stimulation (rTMS) is a nonpharmacological treatment option used to improve cognitive function in PD, but its efficacy is unclear. We performed a meta-analysis to determine whether rTMS improves cognition in PD patients. METHODS: Eligibility criteria (PICOS) were as follows: (1) 'P': The patients participating were diagnosed with idiopathic PD; (2) 'I': Intervention using rTMS; (3) 'C': Sham stimulation as control; (4) 'O': The outcome of the study included cognitive evaluations; (5) 'S': The study adopted randomized controlled design. The standardized mean difference (SMD) of change of score was applied to measure efficacy, and we used Version 2 of the Cochrane tool to assess risk of bias. RESULTS: Twelve studies met the inclusion criteria. Compared with sham-controlled group, the pooled result showed a non-significant short-term effect of rTMS on global cognition (SMD: -0.15, 95% CI: -0.59 to 0.29, I 2 = 36.7%), executive function (SMD: 0.03, 95% CI: -0.21 to 0.26, I 2 = 0.0%), and attention and working memory (SMD: 0.05, 95% CI: -0.25 to 0.35, I 2 = 0.0%). Long-term outcomes were either shown to be statistically nonsignificant. CONCLUSIONS: Based on a limited number of studies, rTMS fails to improve cognition in PD. We call for additional high-quality randomized controlled trials with adequate sample sizes to determine the efficacy of rTMS.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33144283

RESUMO

BACKGROUND: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. METHODS: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e. inverse-variance meta-analysis, co-localization, and M-values), and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. RESULTS: Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10-5). We found seven loci associated with risk for both cancers (PBonferroni < 2.4 × 10-9). In addition, four novel sub-genome wide regions at 7p22.2, 7q22.1, 9p12 and 11q13.3 were identified (P < 5 × 10-7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines, and expression quantitative trait loci (eQTL) data highlighted candidate target genes for further investigation. CONCLUSION: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. IMPACT: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33247368

RESUMO

PURPOSE: Long intergenic non-coding RNAs (lincRNAs) are increasingly recognized as important regulators for pathogenesis and/or prognosis of breast cancer, including triple-negative breast cancer (TNBC) subtype. However, few previous studies used RNA-sequencing (RNA-Seq) technology, and none included an independent replication. METHODS: To systematically evaluate the association between expression of lincRNAs and TNBC survival, we examined lincRNA expression profiles in TNBC tissues using RNA-Seq data for 200 TNBC patients from the Shanghai Breast Cancer Survival Study (SBCSS) and Southern Community Cohort Study (SCCS). RESULTS: Twenty-five lincRNAs were found to be associated with overall survival (P < 0.05 and no significant heterogeneity across studies at Q statistic P > 0.1), and 61 lincRNAs were associated with disease-free survival (DFS). Among these, two lincRNAs (LINC01270 and LINC00449) were significantly associated with both worse overall survival and DFS and were expressed at significantly higher levels in tumor tissues compared with adjacent normal breast tissues (log2[Fold Change] > 0.5 and FDR < 0.05). We further evaluated the potential functions of LINC01270 and LINC00449 using in vitro functional experiments and found that siRNA-mediated knockdown of LINC01270 and LINC00449 expression significantly decreased cell viability, colony formation and cell migration ability in TNBC cells (P < 0.05). CONCLUSIONS: Evidence from observational studies and in vitro experiments indicates that LINC00449 and LINC01270 may be prognostic biomarkers for TNBC.

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