Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.845
Filtrar
1.
Cell Rep ; 36(9): 109621, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34469741

RESUMO

Radiotherapy (RT) resistance is a major cause of treatment failure in cancers that use definitive RT as their primary treatment modality. This study identifies the cancer/testis (CT) antigen G antigen (GAGE) as a mediator of radio resistance in cervical cancers. Elevated GAGE expression positively associates with de novo RT resistance in clinical samples. GAGE, specifically the GAGE12 protein variant, confers RT resistance through synemin-dependent chromatin localization, promoting the association of histone deacetylase 1/2 (HDAC1/2) to its inhibitor actin. This cumulates to elevated histone 3 lysine 56 acetylation (H3K56Ac) levels, increased chromatin accessibility, and improved DNA repair efficiency. Molecular or pharmacological disruption of the GAGE-associated complex restores radiosensitivity. Molecularly, this study demonstrates the role of GAGE in the regulation of chromatin dynamics. Clinically, this study puts forward the utility of GAGE as a pre-screening biomarker to identify poor responders at initial diagnosis and the therapeutic potential of agents that target GAGE and its associated complex in combination with radiotherapy to improve outcomes.

2.
Am J Ophthalmol ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509434

RESUMO

PURPOSE: To compare the outcomes of using an internal limiting membrane (ILM) flap and the conventional ILM peel technique for small- or medium-sized full-thickness macular hole (FTMH) repair. DESIGN: Retrospective, interventional case series. METHODS: Eyes with an FTMH ≤ 400 µm that underwent vitrectomy with either a single-layer inverted ILM flap (flap group, 55 eyes) or an ILM peel (peel group, 62 eyes) were enrolled. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) measurements were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. RESULTS: Primary hole closure was achieved in 54 (98%) and 60 (97%) eyes in the flap and peel groups, respectively. The preoperative and postoperative 12-month BCVA were comparable between the groups but were significantly better in the flap than in the peel groups at 1 month (logMAR, mean ± SD, 0.83 ± 0.43 vs. 1.14 ± 0.50, P = 0.001), 3 months (0.58 ± 0.33 vs. 0.82 ± 0.43; P = 0.002), and 6 months (0.56 ± 0.32 vs. 0.72 ± 0.48; P = 0.028). In the flap group, foveal gliosis was less common than the peel group at 1 month (P = 0.030) and restored external limiting membrane and interdigitation zone was more common at 3 months (P = 0.046 and < 0.001, respectively). CONCLUSIONS: Both the single-layer ILM flap and conventional ILM peel techniques closed FTMHs and improved vision. ILM flaps were associated with better visual outcomes up to 6 months postoperatively and should be considered in FTMHs ≤ 400 µm.

3.
J Occup Environ Med ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34510097

RESUMO

OBJECTIVES: The aim of this study is to investigate the change in employment status in survivors with occupational cancers at the time of diagnosis until 2 years. METHODS: In this study, we included 382 occupational cancer workers from Labor Insurance Database. After applying exclusion criteria, 86 workers in 2004-2015 were included. The mean age of cancer workers were 51.38 ±â€Š9.1119 years old and the average salary of industry of NTD 31492 ±â€Š10696. RESULTS: Salary adjustment was the most change in the employment status in cancer survivors. Salary adjustment (37%), 28-45-year-old group (55%), male (30%), and Southern district (34%), had the most workers on day 730. Wholesale and Retail Trade had the most of percentage of cancer survivals remained on workplace. CONCLUSIONS: Change of employment status in cancer survivors are important to decrease the impact of economic burden on society.

4.
BMC Cardiovasc Disord ; 21(1): 446, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535088

RESUMO

OBJECTIVES: Coronary artery disease (CAD) is a common cardiac disease with high morbidity and mortality, and triple-vessel disease (TVD) is a severe type of CAD. This study investigated risk factors for revascularization and in-stent restenosis (ISR) in TVD patients who underwent second-generation drug-eluting stent implantation. METHODS: A retrospective clinical study was conducted, and 246 triple-vessel disease (TVD) patients with 373 vessels after second-generation drug-eluting stent (DES) implantation who received follow-up coronary angiography (CAG) were consequently enrolled. According to the follow-up angiography, patients were categorized into the revascularization group and nonrevascularization group as well as the in-stent restenosis (ISR) group and non-ISR group. Univariate and multivariate logistic regression analyses were used to identify risk factors for revascularization and ISR. Receiver operating characteristic (ROC) curve with area under the curve (AUC) analysis was performed to assess the predictive power of these risk factors. RESULTS: In the median follow-up period of 28.0 (14.0, 56.0) months, 142 TVD patients (57.7%) with 168 vessels underwent revascularization, and ISR occurred in 43 TVD patients (17.5%) with 47 vessels after second-generation DES implantation. Compared to the nonrevascularization group, the revascularization group presented with an increased rate of current smoking and higher levels of TC, LDL-C, HDL-C, non-HDL-c, ApoB, neutrophils, and Hs-CRP as well as a longer follow-up of months but with a lower level of HDL-C. In addition, patients in the ISR group had an older age, longer follow-up (months) and elevated rates of current smoking and stage 4-5 chronic kidney disease (CKD4-5). In multivariate analysis, current smoking and higher non-HDL-c were independent risk factors for revascularization. In addition, older age, current smoking and CKD4-5 were considered independent risk factors for ISR. Importantly, the receiver operating characteristic curve showed that non-HDL-C and age displayed predictive power for revascularization and ISR, respectively. CONCLUSION: Current smoking is an independent risk factor for both revascularization and in-stent restenosis. Higher non-HDL-c is independently related to revascularization; moreover, increased age and CKD4-5 are potential risk factors for ISR in TVD patients after second-generation drug-eluting stent implantation.

5.
Elife ; 102021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477552

RESUMO

DNA double-strand break (DSB) repair by homologous recombination (HR) is thought to be restricted to the S- and G2- phases of the cell cycle in part due to 53BP1 antagonizing DNA end resection in G1-phase and non-cycling quiescent (G0) cells. Here, we show that LIN37, a component of the DREAM transcriptional repressor, functions in a 53BP1-independent manner to prevent DNA end resection and HR in G0 cells. Loss of LIN37 leads to the expression of HR proteins, including BRCA1, BRCA2, PALB2, and RAD51, and promotes DNA end resection in G0 cells even in the presence of 53BP1. In contrast to 53BP1-deficiency, DNA end resection in LIN37-deficient G0 cells depends on BRCA1 and leads to RAD51 filament formation and HR. LIN37 is not required to protect DNA ends in cycling cells at G1-phase. Thus, LIN37 regulates a novel 53BP1-independent cell phase-specific DNA end protection pathway that functions uniquely in quiescent cells.

6.
Blood Adv ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34500472

RESUMO

To advance the use of circulating tumor DNA (ctDNA) applications, their broad clinical validity must be tested in different treatment settings, including targeted therapies. Utilizing the prespecified longitudinal systematic collection of plasma samples in the phase 1/2a LYM1002 trial (NCT02329847), we tested the clinical validity of ctDNA for baseline mutation profiling, residual tumor load quantification, and acquisition of resistance mutations in patients with lymphoma treated with ibrutinib plus nivolumab. Inclusion criterion for this ancillary biological study was the availability of blood collected at baseline and cycle 3 day 1. Overall, 172 ctDNA samples from 67 patients were analyzed using LyV4.0 ctDNA CAncer Personalized Profiling by deep Sequencing assay. Among baseline variants in ctDNA, only TP53 mutations (detected in 25.4% of patients) were associated with shorter progression-free survival; clones harboring baseline TP53 mutations did not disappear during treatment. Molecular response, defined as a >2-log reduction in ctDNA levels after 2 cycles of therapy (28 days), was achieved by 28.6% of patients with relapsed diffuse large B-cell lymphoma who had ≥1 baseline variant and was associated with best response and improved progression-free survival. Clonal evolution occurred frequently during treatment, and 10.3% new mutations were identified after 2 treatment cycles in nonresponders. PLCG2 was the topmost among genes that acquired new mutations. No patients acquired C481S BTK mutations implicated in resistance to ibrutinib in CLL. Collectively, our results provide the proof of concept that ctDNA is useful for noninvasive monitoring of lymphoma treated with targeted agents in the clinical trial setting.

7.
Genes Dev ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503990

RESUMO

Double-strand break (DSB) repair choice is greatly influenced by the initial processing of DNA ends. 53BP1 limits the formation of recombinogenic single-strand DNA (ssDNA) in BRCA1-deficient cells, leading to defects in homologous recombination (HR). However, the exact mechanisms by which 53BP1 inhibits DSB resection remain unclear. Previous studies have identified two potential pathways: protection against DNA2/EXO1 exonucleases presumably through the Shieldin (SHLD) complex binding to ssDNA, and localized DNA synthesis through the CTC1-STN1-TEN1 (CST) and DNA polymerase α (Polα) to counteract resection. Using a combinatorial approach of END-seq, SAR-seq, and RPA ChIP-seq, we directly assessed the extent of resection, DNA synthesis, and ssDNA, respectively, at restriction enzyme-induced DSBs. We show that, in the presence of 53BP1, Polα-dependent DNA synthesis reduces the fraction of resected DSBs and the resection lengths in G0/G1, supporting a previous model that fill-in synthesis can limit the extent of resection. However, in the absence of 53BP1, Polα activity is sustained on ssDNA yet does not substantially counter resection. In contrast, EXO1 nuclease activity is essential for hyperresection in the absence of 53BP1. Thus, Polα-mediated fill-in partially limits resection in the presence of 53BP1 but cannot counter extensive hyperresection due to the loss of 53BP1 exonuclease blockade. These data provide the first nucleotide mapping of DNA synthesis at resected DSBs and provide insight into the relationship between fill-in polymerases and resection exonucleases.

8.
Cancer Biomark ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34511486

RESUMO

BACKGROUND: Effective biomarkers for prediction of recurrence of lung adenocarcinoma cancer (LADC) patients are needed to determine treatment strategies post-surgery to improve outcome. OBJECTIVE: This study evaluates the efficacy of carboxypeptidase E (CPE) mRNA including its splice isoforms, CPE-ΔN, as a biomarker for predicting recurrence in adenocarcinoma patients. METHODS: RNA was extracted from resected tumors from 86 patients with different stages of non-small cell LADC. cDNA was synthesized and qRT-PCR carried out to determine the copy numbers of CPE/CPE-ΔN mRNA. Patients were followed for 7 years post-tumor resection to determine recurrence and death. RESULTS: ROC curve analysis showed the overall AUC for CPE/CPE-ΔN copy number was 0.563 in predicting recurrence and 0.563 in predicting death. Kaplan-Meier survival analysis showed statistical difference (p= 0.018), indicating that patients with high CPE/CPE-ΔN copy numbers had a shorter time of disease-free survival and also shorter time to death (p= 0.035). Subgroup analyses showed that association of disease-free survival time with CPE/CPE-ΔN copy number was stronger among stage I and II LADC patients (p= 0.047). CONCLUSIONS: CPE/CPE-ΔN mRNA is a potentially useful biomarker for predicting recurrence and death in LADC patients, especially in identifying patients at high risk of recurrence at early stages I and II.

9.
J Hazard Mater ; 416: 126222, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492977

RESUMO

Plastic biodegradation by mealworm is regarded as an emerging strategy for plastic disposal. In this study, the polystyrene (PS) and low density polyethylene (LDPE) degradation efficiency by yellow mealworms (Tenebrio molitor larvae) supplemented with bran and the effects of plastics on the gut core microbiome were explored to construct a circular and continuous reactor for plastic biodegradation in the future. The gut microbiome was also investigated with dietary shift to explore the relationship between specific diets and gut microbes. The bran plus plastic (7:1 ratio, w/w) co-diet contributed to the mealworm survival and growth. The formation of -CË­O-/-C-O- groups in the plastic-fed mealworms frass represented the oxidation process of plastic biodegradation in the mealworm gut. The changes in molecular weights (Mw, Mn and Mz) of residual PS and LDPE in mealworms frass compared with that of PS and PE feedstock confirmed the plastic depolymerization and biodegradation. Lactobacillus and Mucispirillum were significantly associated with PE + bran diet compared to bran diet and PE diet, representing the response of mealworm gut microbiome to the bran and plastic mixture was distinguished from either bran or plastics alone. The gut microbiome changed substantially with the diet shift, indicating that microbial community assembly was a stochastic process and diverse plastic-degrading bacteria might occur in the mealworm gut.


Assuntos
Microbioma Gastrointestinal , Tenebrio , Animais , Dieta , Polietileno , Poliestirenos
10.
J Cell Mol Med ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34498380

RESUMO

Oestradiol (E2) is a critical factor for multiple systems' development during the embryonic period. Here, we aimed to investigate the effects of oestradiol on intrahepatic bile duct development, which may allow a better understanding of congenital bile duct dysplasia. DLK+ hepatoblasts were extracted from the C57BL/6CrSlc foetal mice and randomly divided into control group, oestradiol groups (1, 10, 100 nM) and oestradiol (10 nM) + DAPT (inhibitor of Notch signalling; 40 µM) group for in vitro experiments. For in vivo analysis, pregnant mice were divided into control group, oestradiol (intraperitoneal injection of 0.6 mg/kg/day) ± DAPT (subcutaneous injection of 10 mg/kg/day) groups and tamoxifen (gavage administration of 0.4 mg/kg/day) group. The results showed that oestradiol promoted hepatoblast differentiation into cholangiocytes and intrahepatic bile duct development during the embryonic period. Tamoxifen, an antioestrogenic drug, inhibited the above processes. Moreover, oestradiol promoted the expression of Notch signalling pathway-associated proteins and genes both in vitro and in vivo. Notably, DAPT addition inhibited the oestradiol-mediated effects. In conclusion, oestradiol can promote hepatoblast differentiation into cholangiocytes and intrahepatic bile duct development of C57BL/6CrSlc mice during embryonic period via the Notch signalling pathway.

11.
Anal Methods ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34545384

RESUMO

The diffuse growth of glioma cells leads to gliomatosis, which has less cure rate and high mortality. As the severity deepens, the treatment difficulty and mortality of glioma patients gradually increase. Therefore, a rapid and non-invasive diagnostic technique is very important for glioma patients. The target of this study is to classify contract subjects and glioma patients by serum mid-infrared spectroscopy combined with an ensemble learning method. The spectra were normalized and smoothed, and principal component analysis (PCA) was utilized for dimensionality reduction. Particle swarm optimization-support vector machine (PSO-SVM), decision tree (DT), logistic regression (LR) as well as random forest (RF) were used as base classifiers, and AdaBoost integrated learning was introduced. AdaBoost-SVM, AdaBoost-LR, AdaBoost-RF and AdaBoost-DT models were established to discriminate glioma patients. The single classification accuracy of the four models for the test set was 87.14%, 90.00%, 92.00% and 90.86%, respectively. For the purpose of further improving the prediction accuracy, the four models were fused at decision level, and the final classification accuracy of the test set reached 94.29%. Experiments show that serum infrared spectroscopy combined with the ensemble learning method algorithm shows wonderful potential in non-invasive, fast and precise identification of glioma patients, and can also be used for reference in intelligent diagnosis of other diseases.

12.
Biomater Sci ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34546259

RESUMO

Correction for 'Recent development of gene therapy for pancreatic cancer using non-viral nanovectors' by Yu Liu et al., Biomater. Sci., 2021, DOI: 10.1039/d1bm00748c.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34480310

RESUMO

Ionic liquids are widely used in many fields due to their extremely tunable nature and exceptional properties. The extensive application of ionic liquids raises great concerns regarding their bioaccumulation potential and adverse effects on organisms. Green plants have a great potential for uptake of persistent xenobiotics from aquatic and terrestrial environment. However, the assimilation and bioaccumulation of 1-tetradecyl-3-methylimidazolium bromide ([C14mim]Br) have not been studied in plants yet. In order to explore the phytoaccumulation of [C14mim]+, ryegrass were exposed to [C14mim]Br with hydroponic experiment. The effects of [C14mim]Br dosages on growth index, chlorophyll content, malondialdehyde (MDA) content, and antioxidant enzyme activity of ryegrass were investigated. The toxic effects of [C14mim]Br on ryegrass growth increased with increasing initial concentration. The high initial concentration treatment resulted in rapid changes in physiological characteristics in ryegrass tissue. [C14mim]+ ions were mainly accumulated in root tissue and partly translocated to the above ground part of ryegrass. [C14mim]+ was observed in the highest concentration (314.35 µg/g in root and 101.42 µg/g in aboveground parts of ryegrass) with 10 mg/L of [C14mim]Br. Our results demonstrated that ryegrass can uptake and accumulate [C14mim]+ and is therefore a suitable species for phytoremediation of trace amount of [C14mim]+ and possibly other ionic liquids.

14.
Plant Biotechnol J ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34498364

RESUMO

Stomatal closure is an important process to prevent water loss in plants response to drought stress, which is finely modulated by ion channels together with their regulators in guard cells, especially the S-type anion channel AtSLAC1 in Arabidopsis. However, the functional characterization and regulation analyses of anion channels in gramineous crops, such as in maize guard cells are still limited. In this study, we identified an S-type anion channel ZmSLAC1 that was preferentially expressed in maize guard cells and involved in stomatal closure under drought stress. We found that two Ca2+ -dependent protein kinases ZmCPK35 and ZmCPK37 were expressed in maize guard cells and localized on the plasma membrane. Lesion of ZmCPK37 resulted in drought-sensitive phenotypes. Mutation of ZmSLAC1 and ZmCPK37 impaired ABA-activated S-type anion currents in maize guard cells, while the S-type anion currents were increased in the guard cells of ZmCPK35- and ZmCPK37-overexpression lines. Electrophysiological characterization in maize guard cells and Xenopus oocytes indicated that ZmCPK35 and ZmCPK37 could activate ZmSLAC1-mediated Cl- and NO3 - currents. The maize inbred and hybrid lines overexpressing ZmCPK35 and ZmCPK37 exhibited enhanced tolerance and increased yield under drought conditions. In conclusion, our results demonstrate that ZmSLAC1 plays crucial roles in stomatal closure in maize, whose activity is regulated by ZmCPK35 and ZmCPK37. Elevation of ZmCPK35 and ZmCPK37 expression levels is a feasible way to improve maize drought tolerance as well as reduce yield loss under drought stress.

15.
Thorac Cancer ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34498378

RESUMO

BACKGROUND: Studies regarding the outcomes of salvage lung resections of epidermal growth factor receptor (EGFR)-mutant advanced lung adenocarcinomas (ALAs) following treatment with EGFR tyrosine kinase inhibitors (TKIs) are limited, hence the objective of this study was to investigate such outcomes. METHODS: A total of 29 patients with EGFR-mutant ALA who underwent salvage surgery after EGFR-TKI treatment from October 2013 through January 2019 were enrolled. The patients were divided into two groups according to the surgical indications. Their perioperative parameters and surgical outcomes, including progression-free survival (PFS) and overall survival (OS), were then analyzed. RESULTS: The initial stages of the patients were stage IIIB (seven patients), IVA (17 patients), and IVB (five patients). Their surgical indications included residual tumor (25 patients) and progressive disease (PD) (four patients). They all underwent surgery via minimally invasive approaches and the median follow-up was 33.9 months. Within that follow-up duration, the median PFS after surgery was 36.4 months, and the median OS was still not reached. There were no significant differences in PFS or OS according to the different EGFR-TKIs used, the different durations of EGFR-TKI treatment before surgery, or the different surgical indications. However, the patients presenting with pleural seeding before EGFR-TKI treatment had significantly poorer PFS and OS than the other patients (P < 0.001). CONCLUSIONS: Salvage surgery following EGFR-TKI treatment of ALAs is a safe procedure with acceptable intra- and postoperative results. However, studies involving more cases and longer follow-up periods are needed to clarify its benefits. KEY POINTS: Salvage surgery following EGFR-TKI treatment of ALAs is a safe procedure with acceptable intra- and postoperative results. Our results support the use of surgery following treatment with EGFR-TKIs such as afatinib in advanced lung cancer.

16.
Cancer Nurs ; 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34469358

RESUMO

BACKGROUND: Fatigue, sleep disturbance, and physical inactivity have been increasingly recognized as health issues that negatively affect quality of life (QoL) for children with cancer. Existing studies focus either on children receiving treatment or in survivorship, but not on both populations in a study. This causes difficulty in examining differences of these issues between treatment statuses and identifying associations of these issues with QoL. OBJECTIVE: The aims of this study were to examine differences in fatigue, sleep disturbance, physical activity, and QoL between on- and off-treatment children and to identify their associations with QoL. METHODS: The correlational study was conducted with 100 children with cancer 7 to 12 years old. Descriptive, bivariate, and multivariate regression analyses were used. RESULTS: Participants undergoing treatment had higher degrees of fatigue (P = .002), physical inactivity (P = .004), and QoL distress (P = .001) than those in survivorship. Mean sums (SDs) of sleep disturbance were 47.15 (8.23) and 48.48 (7.13) in the on- and off-treatment groups. Age (P = .000), sex (P = .023), fatigue (P = .000), and sleep disturbance (P = .004) were significantly associated with QoL distress. CONCLUSIONS: This study is unique in that a frame of reference is addressed to gain insight into the distinct developmental issues of school-aged children undergoing cancer treatment and in survivorship. More studies are needed. IMPLICATIONS FOR PRACTICE: Interventions to increase QoL should target children who are younger, male, and have higher levels of fatigue and sleep disturbance. Diagnosis and treatment of sleep disturbance should be considered as part of routine activities.

17.
Int J Artif Organs ; : 3913988211041636, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34474617

RESUMO

An accurate representation of the flow field in blood pumps is important for the design and optimization of blood pumps. The primary turbulence modeling methods applied to blood pumps have been the Reynolds-averaged Navier-Stokes (RANS) or URANS (unsteady RANS) method. Large eddy simulation (LES) method has been introduced to simulate blood pumps. Nonetheless, LES has not been widely used to assist in the design and optimization of blood pumps to date due to its formidable computational cost. The purpose of this study is to explore the potential of the LES technique as a fast and accurate engineering approach for the simulation of rotary blood pumps. The performance of "Light LES" (using the same time and spatial resolutions as the URANS) and LES in two rotary blood pumps was evaluated by comparing the results with the URANS and extensive experimental results. This study showed that the results of both "Light LES" and LES are superior to URANS, in terms of both performance curves and key flow features. URANS could not predict the flow separation and recirculation in diffusers for both pumps. In contrast, LES is superior to URANS in capturing these flows, performing well for both design and off-design conditions. The differences between the "Light LES" and LES results were relatively small. This study shows that with less computational cost than URANS, "Light LES" can be considered as a cost-effective engineering approach to assist in the design and optimization of rotary blood pumps.

18.
J Nucl Med ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475235

RESUMO

This prospective non-randomized, multicenter clinical trial was performed to investigate efficacy and safety of 131I-labeled metuximab in adjuvant treatment of unresectable hepatocellular carcinoma. Methods: Patients were assigned to treatment with transcatheter arterial chemoembolization (TACE) combined with 131I-metuximab or TACE alone. The primary outcome was overall tumor recurrence. The secondary outcomes were safety and overall survival. Results: The median time to tumor recurrence was 6 months in the TACE+131I-metuximab group (n = 160) and 3 months in the TACE group (n = 160) (hazard ratio, 0.55; 95% confidence interval, 0.43 to 0.70; P < 0.001). The median overall survival was 28 months in the TACE+131I-metuximab group and 19 months in the TACE group (hazard ratio, 0.62; 95% confidence interval, 0.47 to 0.82; P = 0.001). Conclusion: TACE+131I-metuximab showed a greater anti-recurrence benefit, significantly improved the 5-year survival of patients with advanced hepatocellular carcinoma, and was well tolerated by patients.

19.
Placenta ; 114: 100-107, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34509037

RESUMO

INTRODUCTION: In this study we examined the hypothesis that a hypoxic intrauterine environment causes mitochondrial dysfunction of trophoblasts in fetal growth restriction (FGR). METHODS: The mtDNA content, mRNA levels of mitochondrial encoded genes (ND6, COX I), mitochondrial membrane proteins (COX I, COX IV and VDAC), HIF-1α and BINP3 (mitophagy receptor) protein levels were examined in FGR placentas and normal placentas. The mitochondrial function (ATP production and mitochondrial membrane potential-ΔΨm) and above related proteins were further examined in hypoxic HTR-8/SVneo cells induced by cobalt chloride (CoCl2). Mitophagy and its regulating mechanism under hypoxia in FGR was also investigated. RESULTS: Compared with normal controls, both FGR placentas and CoCl2-treated trophoblast cells demonstrated statistically lower mtDNA content, reduced mRNAs of mitochondrial encoding genes, and decreased mitochondrial membrane proteins, accompanied by increased HIF-1α. Mitochondrial functions were impaired as demonstrated by decreased ATP production, and, reduced ΔΨm in CoCl2-treated cells. Meanwhile, mitophagy was markedly enhanced as indicated by increased LC3 fluorescent puncta in mitochondria of hypoxic trophoblastic cells. The upregulated BINP3 expression was demonstrated in FGR placentas as well as in hypoxic trophoblastic cells. DISCUSSION: We demonstrated that hypoxic conditions lead to impaired mitochondrial function in trophoblasts in FGR. Reduced mtDNA may be associated with enhanced mitophagy via activating HIF-1α/BINP3 signalling pathway, that may, in turn, affect nutrition and energy transfer to the growth-restricted fetus.

20.
IEEE Trans Cybern ; PP2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520384

RESUMO

Generating various goal-oriented movements via the flexible muscle model of the musculoskeletal system as fast and accurately as possible is a pressing problem, which is also the basis of most human adaptive behaviors, such as reaching, catching, interception, and pointing. This article focuses on the adaptive motion generation of fast goal-oriented motion on the musculoskeletal system by implementing the speed-accuracy tradeoff (SAT) in a hierarchical motion learning framework. First, we introduce Fitts' Law into the modified basal ganglia circuit-inspired iterative decision-making model for achieving dynamic and adaptive decision making. Then, as a time constraint, the decision is decomposed into a series of supervised terms by the proposed striatal FSI-SPN interneuron circuit-inspired velocity modulator to implement the tradeoff smoothly on the musculoskeletal system. Finally, an improved policy gradient algorithm is suggested to generate the muscle excitations of the modulated motion via the proposed muscle co-contraction policy, which promotes general cooperation between flexor and extensor muscles. In experiments, a redundant musculoskeletal arm model is trained to perform the adaptive quick pointing movements. By combining the muscle co-contraction policy with SAT, our algorithm shows the most efficient training and the best performance in the adaptive motion generation among the other three popular reinforcement learning algorithms on the musculoskeletal model.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...