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1.
J Cardiothorac Surg ; 16(1): 121, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933129

RESUMO

BACKGROUND: The overall survival (OS) remains unsatisfactory in patients with esophageal squamous cell carcinoma (ESCC) after extended esophagectomy with two-field lymphadenectomy. Therefore, this retrospective study aimed to identify the risk factors that contribute to the low survival of patients with pT1-3N0M0 ESCC. METHODS: Patients with pT1-3N0M0 ESCC who only underwent R0 esophagectomy with two-field lymphadenectomy in our department from January 2008 to December 2012 were retrospectively enrolled in this study and medical records were reviewed. Postoperative OS, disease-free survival (DFS), recurrence-free survival (RFS), and locoregional recurrence-free survival (LRFS) were analyzed sequentially. RESULTS: This study recruited a total of 488 patients, whose follow-up visits were completed at the end of December 2019. The five-year OS, DFS, RFS and LRFS rates were 62.1, 53.1, 58.3 and 65.6%, respectively. Multivariate Cox analysis identified patient age, site of the lesion, small mediastinal lymph nodes in CT imaging (SLNs in CT), dissected lymph nodes (LNs), and stage of esophageal malignancy as independent risk factors for OS of the patients. Of these factors, the site of the lesion, SLNs in CT and stage of the cancer were determined to be independent factors for DFS, RFS and LRFS. Based on all five factors, the recursive partitioning analysis (RPA) score system was developed to stratify the patients into low-, medium- and high-risk groups, which were found to possess significantly different rates of OS, DFS, RFS and LRFS (p < 0.001). CONCLUSIONS: Several factors were associated with the survival of patients with pT1-3 N0M0 ESCC who underwent extended esophagectomy with two-field lymphadenectomy. These factors contributed to the RPA scoring system, which could stratify the risk of postoperative survival and may expedite the initiation of postoperative adjuvant therapy.

2.
Medicine (Baltimore) ; 100(16): e25532, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33879694

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread almost all regions of the world and caused great loss to the whole body of mankind. Thus, numerous clinical trials were conducted to find specific medicine for COVID-19 recently. However, it remains unanswered whether they are beneficial. OBJECTIVE: This study aimed to evaluate the efficiency and safety of the COVID-19 medicine. METHODS: Studies were determined through searching PubMed, Embase, Cochrane Library, and Medline. The studies of COVID-19 medicine were involved with eligible end points containing mortality, discharge rate, rate of clinical improvement, and rate of serious adverse events. RESULTS: A total of 33 studies involving 37,879 patients were included in our study, whose intervening measures contained three major types of COVID-19 medicine, ACEI/ARB, antiviral medicine, and chloroquine/hydroxychloroquine. Compared to control group, COVID-19 drugs have no distinct effect on mortality (RR, 0.93; 95% CI, 0.79-1.11, P = .43) and discharge rate (RR, 1.06; 95% CI, 0.98-1.14, P = .13). However, antiviral medicine presents the obvious advantage in clinical improvement (RR, 1.11; 95% CI, 1.01-1.23, P < .05). In addition, the serious adverse events rate (RR, 0.75; 95% CI, 0.63-0.88, P < .05) of COVID-19 medicine is lower than control group. CONCLUSION: The results indicated antiviral medicine was potential specific medicine for COVID-19 treatment by improving clinical symptoms, but it failed to increase the discharge rate and reduce mortality. Chloroquine/hydroxychloroquine and ACEI/ARB had no significant effect on treatment of COVID-19, thus they were not recommended for routine medication. Moreover, more trials are needed to find effective drugs to lower the mortality of COVID-19 patients.


Assuntos
Antivirais/efeitos adversos , Antivirais/uso terapêutico , /tratamento farmacológico , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Resultado do Tratamento
3.
Neurology ; 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33893204

RESUMO

ObjectivesThis study was to develop an appropriate parametric survival model to predict patient's age at onset (AAO) for Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) populations from mainland China.MethodsWe compared the efficiency and performance of six parametric survival analysis methods (exponential, weibull, log-gaussian, gaussian, log-logistic and logistic) based on CAG repeat length at ATXN3 to predict the probability of AAO in the largest cohort of SCA3/MJD patients. A set of evaluation criteria, including -2 log-likelihood statistic, Akaike's information criterion (AIC), Bayesian information criterion (BIC), Nagelkerke R square (Nagelkerke R^2) and Cox-Snell residual plot, were used to indentify the best model.ResultsAmong these six parametric survival models, the logistic model had the lowest -2 log-likelihood (6560.12), AIC (6566.12), BIC (6566.14), and the highest value of Nagelkerke R^2 (0.54), with closest graph to the bisector Cox-Snell residual graph. Therefore, the logistic survival model was the best fit to the studied data. Based on the optimal logistic survival model, we indicated the age-specific probability distribution of AAO according to the CAG repeat size and current age.ConclusionsWe first demonstrated logistic survival model provided the best fit for AAO prediction in SCA3/MJD patients from mainland China. This optimal model can be valuable in clinical and research. However, the rigorous clinical testing and practice of other independent cohorts are needed for its clinical applications. A unified model across multi-ethnic cohorts is worth further exploration by identifying regional differences and significant modifiers in AAO determination.

4.
Oncogene ; 40(12): 2296-2308, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33654199

RESUMO

Lymph node metastasis (LNM), a common metastatic gastric-cancer (GC) route, is closely related to poor prognosis in GC patients. Bone marrow-derived mesenchymal stem cells (BM-MSCs) preferentially engraft at metastatic lesions. Whether BM-MSCs are specifically reprogrammed by LNM-derived GC cells (LNM-GCs) and incorporated into metastatic LN microenvironment to prompt GC malignant progression remains unknown. Herein, we found that LNM-GCs specifically educated BM-MSCs via secretory exosomes. Exosomal Wnt5a was identified as key protein mediating LNM-GCs education of BM-MSCs, which was verified by analysis of serum exosomes collected from GC patients with LNM. Wnt5a-enriched exosomes induced YAP dephosphorylation in BM-MSCs, whereas Wnt5a-deficient exosomes exerted the opposite effect. Inhibition of YAP signaling by verteporfin blocked LNM-GC exosome- and serum exosome-mediated reprogramming in BM-MSCs. Analysis of MSC-like cells obtained from metastatic LN tissues of GC patients (GLN-MSCs) confirmed that BM-MSCs incorporated into metastatic LN microenvironment, and that YAP activation participated in maintaining their tumor-promoting phenotype and function. Collectively, our results show that LNM-GCs specifically educated BM-MSCs via exosomal Wnt5a-elicited activation of YAP signaling. This study provides new insights into the mechanisms of LNM in GC and BM-MSC reprogramming, and will provide potential therapeutic targets and detection indicators for GC patients with LNM.

5.
Metallomics ; 13(4)2021 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-33765153

RESUMO

Hyperaccumulators have exceptional phloem translocation capability for heavy metals. This study aims at quantifying the mobility and accumulation of Ni and Co via the phloem in the model hyperaccumulator Noccaea caerulescens. "Phloem loading capability (PLC)," which is calculated by the "Metal content in phloem sap/Metal content in leaves," was introduced to evaluate the metal phloem mobility, while "Phloem mobility value (PMV)" was used for the normalization of PLC, which sets the PLC of Sr as PMV 0 and that of Rb as 100. The results showed that the PMVs of Ni and Co were 63 and 47, respectively. And the phloem mobility of Rb, Ni, Co, and Sr could be graded as highly mobile, mobile, intermediate, and immobile accordingly. The phloem stream can supply up to 19.1% and 16.0% of the total Ni and Co accumulated in the young leaves, respectively, while for Rb and Sr, the phloem contributes to 29% and 1.4% of the total Rb or Sr, indicating phloem contribution of certain metal is directly linked with its mobility. The results of this study raise the importance of phloem translocation on metal accumulation in shoots and provide insights on the metal cycling process in hyperaccumulators.

6.
Curr Med Sci ; 41(1): 39-45, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33582903

RESUMO

Infection-associated hemophagocytic syndrome (IAHS), a severe complication of various infections, is potentially fatal. This study aims to determine whether IAHS occurs in critically ill patients with coronavirus disease 2019 (COVID-19). We conducted a retrospective observational study on 268 critically ill patients with COVID-19 between February 1st, 2020 and February 26th, 2020. Demographics, clinical characteristics, laboratory results, information on concurrent treatments and outcomes were collected. A diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH) was made when the patients had an HScore greater than 169. Histopathological examinations were performed to confirm the presence of hemophagocytosis. Of 268 critically ill patients with confirmed SARS-CoV-2 infection, 17 (6.3%) patients had an HScore greater than 169. All the 17 patients with sHLH died. The interval from the onset of symptom of COVID-19 to the time of a diagnosis of sHLH made was 19 days and the interval from the diagnosis of sHLH to death was 4 days. Ten (59%) patients were infected with only SARS-CoV-2. Hemophagocytosis in the spleen and the liver, as well as lymphocyte infiltration in the liver on histopathological examinations, was found in 3 sHLH autopsy patients. Mortality in sHLH patients with COVID-19 is high. And SARS-CoV-2 is a potential trigger for sHLH. Prompt recognition of IAHS in critically ill patients with COVID-19 could be beneficial for improving clinical outcomes.


Assuntos
/complicações , Linfo-Histiocitose Hemofagocítica/mortalidade , Adulto , Idoso , Estado Terminal , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/etiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Prognóstico , Estudos Retrospectivos
7.
Ann Bot ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33615337

RESUMO

BACKGROUND: The fern Dicranopteris linearis is a hyperaccumulator of rare earth elements (REEs), aluminium (Al) and silicon (Si). However, the physiological mechanisms of tissue-level tolerance to high concentrations of REE and Al, and possible interactions with Si, are currently incompletely known. METHODS: In this study, particle-induced X-ray emission (µPIXE) microprobe with the Maia detector, scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS), and chemical speciation modelling were used to decipher the localisation and biochemistry of REEs, Al and Si in D. linearis during uptake, translocation and sequestration processes. RESULTS: The results show that in the roots more than 80% REEs and Al are in apoplastic fractions, among which the REEs are most significantly co-localised with Si and phosphorus (P) in the epidermis. In the xylem sap, REEs are nearly 100% present as REEH3SiO4  2+, without significant differences between the REEs; while 24-45% Al as Al-citrate, and only 1.7-16% Al as AlH3SiO4  2+. In the pinnules, REEs are mainly concentrated in necrotic lesions and in the epidermis, and REEs and Al are possibly co-deposited within phytoliths (SiO2). Finally, we report that different REEs have similar spatial localisations in the epidermis and exodermis of roots, the necrosis, veins and epidermis of pinnae of D. linearis. CONCLUSIONS: In conclusion, we posit that Si plays a critical role in REEs and Al tolerance within the root apoplast, transport within vascular bundle, and sequestration within the blade of D. linearis.

8.
Biomed Res Int ; 2021: 8571438, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33553432

RESUMO

Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal cancer in China. However, patient survival time after surgery remains unsatisfactory, especially in those who are pN+. This retrospective study determined the value of postoperative adjuvant therapy for patients with pN+ ESCC. From Jan 2008 to Sep 2011, 453 pN+ ESCC patients who underwent R0 resection and survived for at least 1 month were retrospectively enrolled. All patients received surgery. Some patients received surgery alone (SA, n = 131), and others received postoperative chemotherapy (POCT, n = 222), radiotherapy (PORT, n = 57), or sequential chemoradiotherapy (POCRT, n = 43). The follow-up ended on 1 Dec 2019. The 5-year overall survival (OS), disease-free survival (DFS), and locoregional recurrence (LR) were significantly worse in the SA group (15.2%, 13.1%, and 71.6%, all p < 0.05) than in the POCT group (28.0%, 20.8%, and 66.5%), the PORT group (27.4%, 24.4%, and 46.9%), and the POCRT group (42.8%, 35.5%, and 43.0%). Furthermore, compared with the SA group, the median OS and DFS were significantly longer in the POCT, PORT, and POCRT groups (all p < 0.05). PORT and POCRT (but not POCT) also significantly reduced the LR (p < 0.01). Multivariate Cox analysis showed that each type of postoperative therapy was independently associated with improvements in OS, DFS, and LR. Postoperative adjuvant therapy-either POCT, PORT, or POCRT-significantly improved OS and DFS in patients with pN+ ESCC after R0 surgery. PORT and PORCT significantly reduced LR in these patients.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 203-206, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554820

RESUMO

OBJECTIVE: To investigate the distribution of Ret-He and RBC in thalassemia and the value of combining HbA2 in the detection of thalassemia among patients with microcytic or hypochromic. METHODS: 145 patients with microcytic or hypochromic outpatient or hospitalization in our hospital from May 2018 to December 2019 were selected and were divided into the thalassemia group(68 cases) and the non-thalassemia group (77 cases), and at the same time, the patients were divided into four groups of the non-anemia, mild anemia, moderate anemia and severe anemia group according to the degree of anemia. The Ret-He, RBC, RDW-CV and HbA2 in patients were detected, and the distribution of these parameters were compared, and the joint detection of Ret-He, RBC and HbA2 about its sensitivity, specific and other indicators of auxiliary diagnosis of thalassemia were analyzed. RESULTS: Among patients with microcytic or hypochromic, according to the anemia grade Ret-He gradually decreased from the non-anemia group to the severe anemia group (P<0.05); while RDW-CV was increased gradually from the mild anemia group to the severe anemia group (P<0.05); both RBC and Ret-He were increased in the thalassemia group as compared with the non- thalassemia group (P<0.05); while RDW-CV was decreased in the thalassemia group as compared with the non-thalassemia group (P<0.05); meanwhile Ret-He in the α-thalassemia group was higher than that in the ß-thalassemia group. ROC curve analysis showed that combined with HbA2, the specificity was 93.51%, the sensitivity was 66.18%, the positive predictive value was 90% and the negative predictive value was 75.189% when Ret-He was truncated with 19.25 pg and RBC was truncated with 4.95×1012/L. CONCLUSION: Among patients with microcytic or hypochromic, the distribution of RBC, Ret-He and RDW-CV was different in the thalassemia group and the non-thalassemia group, and was also affected by the degree of anemia. Combined Ret-He and RBC could improve the diagnostic specificity for thalassemia, which were screened by HbA2 in patients with microcytic or hypochromic.


Assuntos
Anemia Ferropriva , Talassemia alfa , Talassemia beta , Índices de Eritrócitos , Humanos , Proteínas Proto-Oncogênicas c-ret , Curva ROC , Talassemia beta/diagnóstico
10.
Fitoterapia ; 150: 104838, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33515649

RESUMO

Vernoramyosides A-F (1-6), six new Δ7,9(11) stigmastane-type steroid saponins, along with four known analogues (7-10) were isolated from the leaves of Vernonia amygdalina Delile (Compositae). Their structures were determined by the combination of NMR, ECD and HR-ESI-MS data. These compounds all possessed highly oxidized side chain and a γ-lactam or α,ß-unsaturated five-membered lactone ring. All isolates were screened for their activities in reversing resistance in MCF/DOX cells.

11.
J Int Med Res ; 48(12): 300060520977403, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33290111

RESUMO

OBJECTIVE: To analyze the factors contributing to recurrence in patients with pT3N0M0 thoracic esophageal squamous cell carcinoma (ESCC). METHODS: Patients with pT3N0M0 thoracic ESCC who underwent esophagectomy from January 2008 to December 2012 were included retrospectively. The last date of follow-up was 1 December 2016. Multivariate proportional hazard Cox models were used to identify factors associated with total (i.e., any) recurrence (TR), locoregional recurrence (LR), and distant metastasis (DM). RESULTS: A total of 692 patients were included. The median follow-up was 53 months (range: 3-107). The 3- and 5-year TR, LR, and DM rates were 35.8% and 41.0%, 28.7% and 32.1%, and 16.8% and 21.1%, respectively. The Cox analyses showed that the tumor location, number of dissected lymph nodes, and postoperative therapies were significantly associated with LR. The subgroup analysis showed that postoperative therapies could significantly decrease LR in the mediastinum but not in the neck and upper abdomen regions. CONCLUSIONS: The recurrence rate of pT3N0M0 thoracic ESCC patients was high, especially for LR in the mediastinum. Postoperative therapies can significantly reduce the incidence of mediastinal recurrence.

12.
J Immunol Res ; 2020: 8873261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294469

RESUMO

Stroke is a cerebrovascular disease that results in decreased blood flow. Although Panax notoginseng (PN), a Chinese herbal medicine, has been proven to promote stroke recovery, its molecular mechanism remains unclear. In this study, middle cerebral artery occlusion (MCAO) was induced in rats with thrombi generated by thread and subsequently treated with PN. After that, staining with 2,3,5-triphenyltetrazolium chloride was employed to evaluate the infarcted area, and electron microscopy was used to assess ultrastructural changes of the neurovascular unit. RNA-Seq was performed to determine the differential expressed genes (DEGs) which were then verified by qPCR. In total, 817 DEGs were identified to be related to the therapeutic effect of PN on stroke recovery. Further analysis by Gene Oncology analysis and Kyoto Encyclopedia of Genes and Genomes revealed that most of these genes were involved in the biological function of nerves and blood vessels through the regulation of neuroactive live receptor interactions of PI3K-Akt, Rap1, cAMP, and cGMP-PKG signaling, which included in the 18 pathways identified in our research, of which, 9 were reported firstly that related to PN's neuroprotective effect. This research sheds light on the potential molecular mechanisms underlying the effects of PN on stroke recovery.

13.
Aging (Albany NY) ; 122020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33232267

RESUMO

The dominantly inherited spinocerebellar ataxias (SCAs) are a large class of neurodegenerative diseases. Transcranial magnetic stimulation has been used to evaluate the function of the pyramidal tract, and central motor conduction time (CMCT) is one index used to detect pyramidal tract dysfunction. We conducted a comprehensive search of PubMed, Embase and Web of Science. Eight eligible studies were included in the meta-analysis. For upper limb CMCT, the mean difference (95% confidence interval (CI)) between the combined SCA group and the control group was 2.24 [1.76-2.72], while the mean differences (95% CIs) between the subtypes and the control group were as follows: 4.43 [3.58-5.28] for SCA1, 0.25 [-0.15,0.65] for SCA2, 1.04 [-0.37,2.46] for SCA3 and 0.49 [-0.29,1.28] for SCA6. Additionally, SCA1 significantly differed from SCA2 and SCA3 in terms of CMCT (P=0.0006 and P=0.010, respectively). We also compared lower limb CMCT between the SCA2 and control groups. The mean difference (95% CI) was 6.58 [4.49-8.67], which was clearly statistically significant. The differences in CMCT values among different subtypes suggests diverse pathological mechanisms. In general, CMCT is a promising objective index to judge the severity of disease deserving further investigation.

14.
Neurosci Lett ; : 135510, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33221475

RESUMO

OBJECTIVE: This study aimed to investigate factors modulating spinocerebellar ataxia type 3 (SCA3) phenotype severity besides the expanded CAG repeats (ExpCAG) of ATXN3. METHODS: Data regarding CAG trinucleotide repeats, age at onset (AO), duration, age, sex, transmitting parent, and scale scores of SCA3 patients were collected. Multiple linear regression analysis was performed to identify influential independent variables. Age, AO, ExpCAG, and duration were considered control variables to analyze the correlation between independent variables and scale scores. RESULTS: Duration, age, and ExpCAG were screened as influential independent variables (P = 0.000). Age had the greatest impact on multiple linear regression models (P<5E-8). ExpCAG and SARA/ICARS/INAS/Barthel index were not correlated (P > 0.05); considering only age as the control, ExpCAG was slightly-to-moderately correlated with all aforementioned scores except INAS (P < 0.05). Age and all scores, except INAS, were positively correlated (P < 0.05); considering duration, AO, or ExpCAG as controls, their correlations did not change significantly. On controlling age, AO was negatively correlated with all scores (P < 0.05), except for the Barthel index (P > 0.05). Furthermore, the interaction model revealed that the interaction between age, duration, and ExpCAG was significantly associated with SCA3 disease severity (P < 0.05). CONCLUSION: Age is a potentially important modifier of SCA3 phenotype severity, through the interaction between ExpCAG and aging factors.

15.
Nat Commun ; 11(1): 5738, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33159087

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

16.
New Phytol ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33089895

RESUMO

Rice (Oryza sativa) is a short-day (SD) plant originally having strong photoperiod sensitivity (PS), with SDs promoting and long days (LDs) suppressing flowering. Although the evolution of PS in rice has been extensively studied, there are few studies that combine the genetic effects and underlying mechanism of different PS gene combinations with variations in PS. We created a set of isogenic lines among the core PS-flowering genes Hd1, Ghd7 and DTH8 using CRISPR mutagenesis, to systematically dissect their genetic relationships under different day-lengths. We investigated their monogenic, digenic, and trigenic effects on target gene regulation and PS variation. We found that Hd1 and Ghd7 have the primary functions for promoting and repressing flowering, respectively, regardless of day-length. However, under LD conditions, Hd1 promotes Ghd7 expression and is recruited by Ghd7 and/or DTH8 to form repressive complexes that collaboratively suppress the Ehd1-Hd3a/RFT1 pathway to block heading, but under SD conditions Hd1 competes with the complexes to promote Hd3a/RFT1 expression, playing a tradeoff relationship with PS flowering. Natural allelic variations of Hd1, Ghd7 and DTH8 in rice populations have resulted in various PS performances. Our findings reveal that rice PS flowering is controlled by crosstalk of two modules - Hd1-Hd3a/RFT1 in SD conditions and (Hd1/Ghd7/DTH8)-Ehd1-Hd3a/RFT1 in LD conditions - and the divergences of these genes provide the basis for rice adaptation to broad regions.

17.
Nat Commun ; 11(1): 5350, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093442

RESUMO

Sociality is among the most important motivators of human behaviour. However, the neural mechanisms determining levels of sociality are largely unknown, primarily due to a lack of suitable animal models. Here, we report the presence of a surprising degree of general sociality in Drosophila. A newly-developed paradigm to study social approach behaviour in flies reveal that social cues perceive through both vision and olfaction converged in a central brain region, the γ lobe of the mushroom body, which exhibite activation in response to social experience. The activity of these γ neurons control the motivational drive for social interaction. At the molecular level, the serotonergic system is critical for social affinity. These results demonstrate that Drosophila are highly sociable, providing a suitable model system for elucidating the mechanisms underlying the motivation for sociality.


Assuntos
Comportamento Animal/fisiologia , Drosophila melanogaster/fisiologia , Comportamento Social , Animais , Animais Geneticamente Modificados , Encéfalo/fisiologia , Sinais (Psicologia) , Drosophila melanogaster/genética , Feminino , Humanos , Masculino , Motivação/fisiologia , Corpos Pedunculados/fisiologia , Rede Nervosa/fisiologia , Sensação/fisiologia , Neurônios Serotoninérgicos/fisiologia
18.
Cytokine ; 136: 155294, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32950810

RESUMO

Increasing evidence shows that inflammation plays critical roles in the tumorigenesis of bladder cancer. Fibroblast growth factor 12 (FGF12), a kind of inflammatory cytokine, is located in the region of 3q28 that has been demonstrated to be a bladder cancer risk locus by genome wide association study (GWAS). In this study, we aimed to investigate the association of GWAS signal rs710521 and rs884309 and rs1464938 in the promoter of FGF12 with the risk of bladder transitional cell carcinoma (TCC). The polymorphisms were analyzed by using a Taqman assay in 331 TCC patients and 516 age-, gender-, and ethnicity-matched controls. The expression levels of FGF12 mRNA were examined in TCC and non-cancerous normal tissues by using quantitative real-time PCR and the luciferase activity was determined by using the Dual-Luciferase Assay System. The rs1464938 AA genotype and A allele were associated with a significantly increased risk of TCC (AA vs. GG: adjusted OR = 2.54, 95% CI, 1.49-4.35, P < 0.001; AA vs. AG/GG: adjusted OR = 2.25, 95% CI, 1.36-3.71, P = 0.002; A vs. G: adjusted OR = 1.44, 95% CI, 1.15-1.80, P = 0.001, respectively). Haplotype analysis showed that rs884309G- rs1464938A haplotype was associated with an increased risk of TCC (OR = 1.61, 95% CI, 1.23-2.11, P = 0.001). Functional analysis showed that the rs1464938 AG/AA genotypes exhibited higher levels of FGF12 mRNA in TCC tissues and the rs1464938 A allele enhanced FGF12 promoter activity (P < 0.05). These findings suggest that the rs1464938 A allele at the 3q28 locus contribute to the development of TCC by regulating FGF12 expression levels.

19.
Mov Disord ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32991004

RESUMO

BACKGROUND: In polyglutamine (polyQ) disease, the investigation of the prediction of a patient's age at onset (AAO) facilitates the development of disease-modifying intervention and underpins the delay of disease onset and progression. Few polyQ disease studies have evaluated AAO predicted by machine-learning algorithms and linear regression methods. OBJECTIVE: The objective of this study was to develop a machine-learning model for AAO prediction in the largest spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) population from mainland China. METHODS: In this observational study, we introduced an innovative approach by systematically comparing the performance of 7 machine-learning algorithms with linear regression to explore AAO prediction in SCA3/MJD using CAG expansions of 10 polyQ-related genes, sex, and parental origin. RESULTS: Similar prediction performance of testing set and training set in each models were identified and few overfitting of training data was observed. Overall, the machine-learning-based XGBoost model exhibited the most favorable performance in AAO prediction over the traditional linear regression method and other 6 machine-learning algorithms for the training set and testing set. The optimal XGBoost model achieved mean absolute error, root mean square error, and median absolute error of 5.56, 7.13, 4.15 years, respectively, in testing set 1, with mean absolute error (4.78 years), root mean square error (6.31 years), and median absolute error (3.59 years) in testing set 2. CONCLUSION: Machine-learning algorithms can be used to predict AAO in patients with SCA3/MJD. The optimal XGBoost algorithm can provide a good reference for the establishment and optimization of prediction models for SCA3/MJD or other polyQ diseases. © 2020 International Parkinson and Movement Disorder Society.

20.
Ann Neurol ; 88(6): 1132-1143, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32939785

RESUMO

OBJECTIVE: A recessive biallelic repeat expansion, (AAGGG)exp , in the RFC1 gene has been reported to be a frequent cause of late-onset ataxia. For cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), the recessive biallelic (AAGGG)exp genotype was present in ~92% of cases. This study aimed to examine whether the pentanucleotide repeat (PNR) was related to multiple system atrophy (MSA), which shares a spectrum of symptoms with CANVAS. METHODS: In this study, we screened the pathogenic (AAGGG)exp repeat and 5 other PNRs in 104 Chinese sporadic adult-onset ataxia of unknown aetiology (SAOA) patients, 282 MSA patients, and 203 unaffected individuals. Multiple molecular genetic tests were used, including long-range polymerase chain reaction (PCR), repeat-primed PCR (RP-PCR), Sanger sequencing, and Southern blot. Comprehensive clinical assessments were conducted, including neurological examination, neuroimaging, nerve electrophysiology, and examination of vestibular function. RESULTS: We identified biallelic (AAGGG)exp in 1 SAOA patient and 3 MSA patients. Additionally, 1 MSA patient had the (AAGGG)exp /(AAAGG)exp genotype with uncertain pathogenicity. We also described the carrier frequency for different PNRs in our cohorts. Furthermore, we summarized the distinct phenotypes of affected patients, suggesting that biallelic (AAGGG)exp in RFC1 could be associated with MSA and should be screened routinely in the MSA diagnostic workflow. INTERPRETATION: Our results expanded the clinical phenotypic spectrum of RFC1-related disorders and raised the possibility that MSA might share the same genetic background as CANVAS, which is crucial for re-evaluating the current CANVAS and MSA diagnostic criteria. ANN NEUROL 2020;88:1132-1143.

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