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1.
Artigo em Inglês | MEDLINE | ID: mdl-36636861

RESUMO

BACKGROUND: Proteinuria is a well-known cardiovascular risk factor, but whether it independently increases the risk for atrial fibrillation (AF) in Chinese population is unknown. To address this deficiency, herein, we investigated the association between proteinuria detected using urine dipstick test and the risk of AF. METHODS: This was a prospective cohort study of Kailuan study participants who underwent the 2006-2007 and 2010-2011 health checkups and was free from AF. Participants were classified into four groups based on the level of proteinuria: [-, trace (±), 1+, ≥2+]. The outcome was incident AF as confirmed by 12-lead electrocardiography. RESULTS: During a median of 11.90 years of follow-up, we documented 514 incident AF cases among 60,599 participants. Proteinuria was found in 6302 (10.40%) participants. Relative to participants without proteinuria at the baseline, those with proteinuria (≥2+) had an 83.9% higher risk (95% CI, 1.073-3.154, P = 0.0267) of developing AF, after adjusted for confounding variables. The result was consistent in the sensitivity analysis. Compared to consistently negative proteinuria, the risk of AF significantly increased in the aggravated proteinuria group (HR 1.552, 95% CI 1.140-2.114) and the persistent proteinuria group (HR 2.485, 95% CI 1.414-4.366). Among participants with resolved proteinuria (from positive to negative), the risk of incident AF was not significantly increased compared to those with persistently negative proteinuria (HR 1.300, 95% CI 0.743-2.276). CONCLUSIONS: Proteinuria could be a modifiable risk factor for predicting AF development. Knowing the presence of proteinuria may improve risk stratification for decision-making about AF prevention. This article is protected by copyright. All rights reserved.

2.
Eye Contact Lens ; 49(2): 71-76, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36694310

RESUMO

OBJECTIVES: To investigate the impact of aspheric base curve (BC)-designed orthokeratology (ortho-k) (AOK) lenses on higher-order aberrations (HOA) at different pupil diameters and visual performance. METHODS: This prospective clinical study included subjects randomized to wear spherical BC-designed ortho-k (SOK) or AOK lenses. The Pediatric Refractive Error Profile (PREP) questionnaire was completed before and after 3 months of lens wear. The Strehl ratio (SR) and root mean square of ocular higher-order aberrations (HOAs), spherical aberration (SA), coma, and trefoil were measured under 4-mm, 5-mm, and 6-mm pupil diameters at baseline and 3-month visits. Corneal topography, uncorrected low-contrast (LC) visual acuity (VA), and high-contrast (HC) VA were measured at baseline and at 1 day, 1 week, 1 month, and 3 month follow-ups. RESULTS: Sixty-five participants completed the study. After 3 months with the ortho-k lens, there were no significant differences in ocular HOA, SA, coma, or trefoil between the SOK group and AOK group at 4-mm, 5-mm, and 6-mm pupil diameters (all P>0.05), except for a significant increase in SA in the AOK group (P=0.01). Stratified analyses showed that the AOK group exhibited greater HOA and SA at 5-mm and 6-mm pupil diameters in the lower myopia subgroup and greater SA at 6 mm in the higher myopia subgroup (all P<0.05). There were no significant differences between the groups in SR, HC VA, LC VA, or PREP scores (all P>0.05). CONCLUSION: Aspheric BC-designed ortho-k lenses produced a significantly greater SA than SOK lenses, with more significance at lower diopters, without sacrificing subjective visual performance.

3.
Eur Urol Open Sci ; 47: 3-11, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36601042

RESUMO

Background: Androgen deprivation therapy (ADT) worsens glycaemic control and cardiovascular outcomes. The prognostic value of visit-to-visit HbA1c variability (VVHV) has been unexplored in prostate cancer (PCa) patients receiving ADT. Objective: To explore the effect of ADT on VVHV and the cardiovascular prognostic value of VVHV. Design setting and participants: PCa patients receiving ADT in Hong Kong between January 1, 1993 and March 31, 2021 were included in this retrospective cohort study. Those with fewer than three HbA1c results available within 3 yr after ADT initiation, <6 mo of ADT, missing baseline HbA1c, prior diagnosis of any component of major adverse cardiovascular events (MACEs), and MACEs occurring within 3 yr were excluded. Patients were followed up until September 31, 2021. Outcome measurements and statistical analysis: The outcome was MACEs (composite of heart failure, myocardial infarction, stroke, and cardiovascular mortality). VVHV was calculated from HbA1c levels within 3 yr after and, separately where available, before ADT initiation using coefficient of variation (CV; standard deviation [SD] divided by mean) and average real variability (ARV; average difference between consecutive measurements). Results and limitations: Altogether, 1065 patients were analysed (median age 74.4 yr old [interquartile range 68.3-79.5 yr]). In 709 patients with VVHV available before and after ADT initiation, VVHV increased after ADT initiation (p < 0.001), with 473 (66.2%) and 474 (66.9%) having increased CV and ARV, respectively. Over a median follow-up of 4.3 yr (2.8-6.7 yr), higher VVHV was associated with a higher risk of MACEs (adjusted hazard ratio [per SD] for CV 1.21 [95% confidence interval: 1.02, 1.43], p = 0.029; ARV 1.25 [1.06, 1.48], p = 0.008). Limitations included residual confounding and selection bias. Conclusions: In PCa patients receiving ADT, VVHV increased after ADT initiation. Higher VVHV was associated with an increased risk of MACEs. Patient summary: In prostate cancer patients receiving androgen deprivation therapy (ADT), glycaemic control is less stable after initiating ADT, which was associated with an increased cardiovascular risk.

4.
Ann Noninvasive Electrocardiol ; : e13030, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36628595

RESUMO

BACKGROUND AND OBJECTIVES: Risk stratification in Brugada syndrome remains a difficult problem. Given the male predominance of this disease and their elevated risks of arrhythmic events, affected females have received less attention. It is widely known that symptomatic patients are at increased risk of sudden cardiac death (SCD) than asymptomatic patients, while this might be true in the male population; recent studies have shown that this association might not be significant in females. Over the past few decades, numerous markers involving clinical symptoms, electrocardiographic (ECG) indices, and genetic tests have been explored, with several risk-scoring models developed so far. The objective of this study is to review the current evidence of clinical and ECG markers as well as risk scores on asymptomatic females with Brugada syndrome. FINDINGS: Gender differences in ECG markers, the yield of genetic findings, and the applicability of risk scores are highlighted. CONCLUSIONS: Various clinical, electrocardiographic, and genetic risk factors are available for assessing SCD risk amongst asymptomatic female BrS patients. However, due to the significant gender discrepancy in BrS, the SCD risk amongst females is often underestimated, and there is a lack of research on female-specific risk factors and multiparametric risk scores. Therefore, multinational studies pooling female BrS patients are needed for the development of a gender-specific risk stratification approach amongst asymptomatic BrS patients.

5.
J Chemother ; : 1-8, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36591729

RESUMO

The aim of this study was to assess the cost-effectiveness of pembrolizumab versus chemotherapy for metastatic colorectal cancer (mCRC) patients with mismatch-repair deficiency or microsatellite instability-high (dMMR/MSI-H) in China. A partitioned survival model was constructed to determine the costs and effects of pembrolizumab and chemotherapy based on KEYNOTE-177 trial outcomes data. Health outcomes were measured in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). The Chinese health service system perspective was considered. A willing-to-pay threshold was set at 35,832 USD/QALY, which was three times the gross domestic product (GDP) per capita of China in 2021. We examined the robustness of the model in the one-way and probabilistic sensitivity analysis. Pembrolizumab was associated with better health outcomes than chemotherapy (5.30 vs 3.37 QALYs). Compared with chemotherapy, the pembrolizumab strategy yielded an incremental cost of $16 032.57, which resulted in an ICER of $8285 per QALY. The cost of pembrolizumab and chemotherapy had the largest impact on the ICER. The parameters with less influence on the ICER were utility values of the Post-PFS state. Compared to chemotherapy, pembrolizumab had the economic advantage as the first-line treatment of mCRC patients with dMMR/MSI-H in China.

6.
Cell Oncol (Dordr) ; 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36593375

RESUMO

PURPOSE: Cancer testis antigens (CTAs) are optimal tumor diagnostic markers and involved in carcinogenesis. However, colorectal cancer (CRC) related CTAs are less reported with impressive diagnostic capability or relevance with tumor metabolism rewiring. Herein, we demonstrated CRC-related CTA, Protamine 1 (PRM1), as a promising diagnostic marker and involved in regulation of cellular growth under nutrient deficiency. METHODS: Transcriptomics of five paired CRC tissues was used to screen CRC-related CTAs. Capability of PRM1 to distinguish CRC was studied by detection of clinical samples through enzyme linked immunosorbent assay (ELISA). Cellular functions were investigated in CRC cell lines through in vivo and in vitro assays. RESULTS: By RNA-seq and detection in 824 clinical samples from two centers, PRM1 expression were upregulated in CRC tissues and patients` serum. Serum PRM1 showed impressive accuracy to diagnose CRC from healthy controls and benign gastrointestinal disease patients, particularly more sensitive for early-staged CRC. Furthermore, we reported that when cells were cultured in serum-reduced medium, PRM1 secretion was upregulated, and secreted PRM1 promoted CRC growth in culture and in mice. Additionally, G1/S phase transition of CRC cells was facilitated by PRM1 protein supplementation and overexpression via activation of PI3K/AKT/mTOR pathway in serum deficient medium. CONCLUSIONS: In general, our research presented PRM1 as a specific CRC antigen and illustrated the importance of PRM1 in CRC metabolism rewiring. The new vulnerability of CRC cells was also provided with the potential to be targeted in future. Diagnostic value and grow factor-like biofunction of PRM1 A represents the secretion process of PRM1 regulated by nutrient deficiency. B represents activation of PI3K/AKT/mTOR pathway of secreted PRM1.

7.
Adv Sci (Weinh) ; : e2205395, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36594618

RESUMO

Breast cancer is now the most frequently diagnosed malignancy, and metastasis remains the leading cause of death in breast cancer. However, little is known about the dynamic changes during the evolvement of dissemination. In this study, 65 968 cells from four patients with breast cancer and paired metastatic axillary lymph nodes are profiled using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. A disseminated cancer cell cluster with high levels of oxidative phosphorylation (OXPHOS), including the upregulation of cytochrome C oxidase subunit 6C and dehydrogenase/reductase 2, is identified. The transition between glycolysis and OXPHOS when dissemination initiates is noticed. Furthermore, this distinct cell cluster is distributed along the tumor's leading edge. The findings here are verified in three different cohorts of breast cancer patients and an external scRNA-seq dataset, which includes eight patients with breast cancer and paired metastatic axillary lymph nodes. This work describes the dynamic metabolic evolvement of early disseminated breast cancer and reveals a switch between glycolysis and OXPHOS in breast cancer cells as the early event during lymph node metastasis.

8.
Circ Arrhythm Electrophysiol ; 16(1): e011453, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36595630

RESUMO

BACKGROUND: Macroscopic T wave alternans (macro-TWA) often heralds the onset of Torsades de Pointes in patients with QT prolongation. However, the mechanisms underlying macro-TWA remain unclear. We examined the cellular and ionic basis for macro-TWA in rabbits with left ventricular hypertrophy (LVH). METHODS: The renovascular hypertension model was used to induce LVH in rabbits. Action potentials were simultaneously recorded from epicardium and endocardium together with a transmural ECG and isometric contractility in arterially perfused left ventricular wedges. Late sodium current (INa-L) was recorded in single-isolated left ventricular myocytes with the whole cell patch-clamp technique. RESULTS: Macro-TWA and accompanied mechanical alternans occurred spontaneously in 8 of 33 LVH rabbits (P<0.05, versus 0/15 in controls) and were induced by an INa-L enhancer ATX-II at 1 to 3 nM in additional 7. Macro-TWA and mechanical alternans occurred discordantly, that is, that longer QT interval and larger T wave were associated with weaker isometric contvractility. Alternating early afterdepolarizations in the endocardium caused macro-TWA in 12 of 15 LVH rabbits and, therefore, early afterdepolarization-dependent R-from-T extrasystoles and Torsades de Pointes always originated from the beats with longer QT and larger T wave during macro-TWA. INa-L density was significantly larger in LVH myocytes than that of control myocytes. Macro-TWA, mechanical alternans, R-from-T extrasystoles, and Torsades de Pointes were all abolished by INa-L blocker ranolazine or mexiletine. CONCLUSIONS: LVH enhances INa-L density and promotes alternating early afterdepolarizations in the left ventricular endocardium that manifest as macro-TWA with discordant mechanical alternans. INa-L blockade abolishes macro-TWA, mechanical alternans, early afterdepolarization-dependent R-from-T extrasystoles, and Torsades de Pointes.


Assuntos
Síndrome do QT Longo , Torsades de Pointes , Animais , Coelhos , Bradicardia , Arritmias Cardíacas , Ventrículos do Coração , Síndrome do QT Longo/diagnóstico , Complexos Cardíacos Prematuros/complicações , Eletrocardiografia , Potenciais de Ação/fisiologia
9.
Nat Commun ; 14(1): 130, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36624140

RESUMO

Catastrophically mechanical failure of soft self-healing materials is unavoidable due to their inherently poor resistance to crack propagation. Here, with a model system, i.e., soft self-healing polyurea, we present a biomimetic strategy of surpassing trade-off between soft self-healing and high fracture toughness, enabling the conversion of soft and weak into soft yet tough self-healing material. Such an achievement is inspired by vascular smooth muscles, where core-shell structured Galinstan micro-droplets are introduced through molecularly interfacial metal-coordinated assembly, resulting in an increased crack-resistant strain and fracture toughness of 12.2 and 34.9 times without sacrificing softness. The obtained fracture toughness is up to 111.16 ± 8.76 kJ/m2, even higher than that of Al and Zn alloys. Moreover, the resultant composite delivers fast self-healing kinetics (1 min) upon local near-infrared irradiation, and possesses ultra-high dielectric constants (~14.57), thus being able to be fabricated into sensitive and self-healing capacitive strain-sensors tolerant towards cracks potentially evolved in service.


Assuntos
Fraturas Ósseas , Humanos , Hidrogéis , Modelos Biológicos
11.
BMC Cardiovasc Disord ; 23(1): 23, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36646993

RESUMO

BACKGROUND: To evaluate the long-term outcome after re-attempt CTO-PCI. METHODS: This is a retrospective cohort study that included 113 re-attempt CTO-PCI patients who were consecutively registered from January 2019 to December 2020 at Beijing Anzhen Hospital's Center of Coronary Artery Disease. All patients were divided into two groups based on procedural success or failure. The primary endpoint was major adverse cardiac events (MACE), a composite of all-cause mortality, myocardial infarction and target vessel revascularization (TVR). The secondary endpoint was angina after PCI. RESULTS: Overall, the successful re-attempt CTO-PCI was archived in 77 patients, the failed CTO-PCI was performed in 36 patients. After a median follow-up of 21.7 months (interquartile range: 10.9-26.0), the incidence of the primary outcome was significantly lower in the success group [14.2% vs. 38.9%, adjusted hazard ratio (HR) 0.351, 95% CI 0.134-0.917, P = 0.033], mainly driven by the reduction of TVR (9.1% vs. 30.6%, adjusted HR 0.238, 95% CI: 0.078-0.72, P = 0.011). Furthermore, patients who had successful re-attempt CTO-PCI had a lower risk of angina after PCI (27.3% vs.61.1%, adjusted HR 0.357, 95% CI 0.167-0.76, P = 0.008). The risk factors of TVR in the patients with successful re-attempt CTO-PCI were stent length > 100 mm (adjusted HR 21.805, 95% CI 1.765-269.368, P = 0.016) and J-CTO score > 3(adjusted HR: 9.733, 95% CI:1.533-61.797, P = 0.016). CONCLUSIONS: For the patients with previous CTO-PCI failure, a successful re-attempt CTO-PCI was associated with significantly lower MACE, which was primarily driven by a lower TVR rate. More complex CTO lesions and longer stents were the independent predictors of TVR after successful CTO-PCI.


Assuntos
Oclusão Coronária , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/cirurgia , Estudos Retrospectivos , Fatores de Risco , Angina Pectoris/etiologia , Doença Crônica , Resultado do Tratamento , Angiografia Coronária/efeitos adversos
12.
Epilepsia Open ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650667

RESUMO

OBJECTIVE: Performing long-term video-electroencephalographic monitoring (LTVEM) to obtain the ictal electroencephalogram (EEG) is important for presurgical evaluation. This study aimed to investigate the safety and efficacy of our protocol developed at Peking University First Hospital (PUFH) for rapid withdrawal of anti-seizure medications (ASMs) during LTVEM to induce seizures in children with drug-resistant epilepsy (DRE) exhibiting non-daily seizures. METHODS: Children with DRE who followed the PUFH protocol for rapid withdrawal of ASMs during LTVEM between 2018 and 2021 were enrolled. The occurrence of seizures, number of ASMs withdrawn, seizure onset time after ASM tapering initiation, changes in interictal epileptiform discharge (IED), and adverse events were evaluated during LTVEM. RESULTS: Among 80 children evaluated in this study, seizures were induced successfully in 72 (90%) children. Furthermore, no change in IED sites was observed in these 72 children following the initiation of ASM tapering while 2 children exhibited secondary bilateral tonic-clonic seizures. The median time from ASM tapering initiation to the onset of the first seizure was found to be 3 days (2-4), while the median number of ASMs withdrawn was 2 (1-2). Finally, 66 children (91.7%) had habitual seizures while 6 children had non-habitual seizure semiology. SIGNIFICANCE: The PUFH protocol can be used for the rapid withdrawal of ASMs during LTVEM in children with DRE. Using this protocol, ictal EEG patterns can be obtained in a relatively short time for most patients with fewer adverse effects during LTVEM, which may provide meaningful electro-clinical information for presurgical evaluation.

13.
Int J Biol Sci ; 19(2): 484-501, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36632457

RESUMO

Silent information regulator 1 (SIRT1), a highly conserved NAD+-dependent deacetylase, is a cellular regulator that has received extensive attention in recent years and regarded as a sensor of cellular energy and metabolism. The accumulated evidence suggests that SIRT1 is involved in the development of endocrine and metabolic diseases. In a variety of organisms, SIRT1 regulates gene expression through the deacetylation of histone, transcription factors, and lysine residues of other modified proteins including several metabolic and endocrine signal transcription factors, thereby enhancing the therapeutic effects of endocrine and metabolic diseases. These evidences indicate that targeting SIRT1 has promising applications in the treatment of endocrine and metabolic diseases. This review focuses on the role of SIRT1 in endocrine and metabolic diseases. First, we describe the background and structure of SIRT1. Then, we outline the role of SIRT1 in endocrine and metabolic diseases such as hyperuricemia, diabetes, hypertension, hyperlipidemia, osteoporosis, and polycystic ovarian syndrome. Subsequently, the SIRT1 agonists and inhibitors in the above diseases are summarized and future research directions are proposed. Overall, the information presents here may highlight the potential of SIRT1 as a future biomarker and therapeutic target for endocrine and metabolic diseases.


Assuntos
Doenças Metabólicas , Sirtuína 1 , Humanos , Sirtuína 1/metabolismo , Fatores de Transcrição/metabolismo , Histonas , Doenças Metabólicas/genética
14.
Bioact Mater ; 24: 387-400, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36632503

RESUMO

Bone marrow-derived mesenchymal stem cell (MSC) is one of the most actively studied cell types due to its regenerative potential and immunomodulatory properties. Conventional cell expansion methods using 2D tissue culture plates and 2.5D microcarriers in bioreactors can generate large cell numbers, but they compromise stem cell potency and lack mechanical preconditioning to prepare MSC for physiological loading expected in vivo. To overcome these challenges, in this work, we describe a 3D dynamic hydrogel using magneto-stimulation for direct MSC manufacturing to therapy. With our technology, we found that dynamic mechanical stimulation (DMS) enhanced matrix-integrin ß1 interactions which induced MSCs spreading and proliferation. In addition, DMS could modulate MSC biofunctions including directing MSC differentiation into specific lineages and boosting paracrine activities (e.g., growth factor secretion) through YAP nuclear localization and FAK-ERK pathway. With our magnetic hydrogel, complex procedures from MSC manufacturing to final clinical use, can be integrated into one single platform, and we believe this 'all-in-one' technology could offer a paradigm shift to existing standards in MSC therapy.

15.
BMC Cardiovasc Disord ; 23(1): 34, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36653770

RESUMO

BACKGROUND: Impaired left ventricular function is an independent predictor of adverse clinical outcomes in patients with aortic stenosis. The aim of this study is to evaluate the short-term changes of echocardiographic parameters, New York Heart Association (NYHA) class and B-type natriuretic peptide (BNP) level and adverse events amongst patients with heart failure (HF) after transcatheter aortic valve replacement (TAVR) procedure. METHODS: This was a retrospective cohort study conducted at affiliated Yantai Yuhuangding Hospital of Qingdao University between September 2017 and September 2022. TAVR cases were stratified into three groups [heart failure with reduced ejection fraction (HFrEF), heart failure with mildly reduced ejection fraction (HFmrEF), heart failure with preserved ejection fraction (HFpEF)] by left ventricular ejection fraction (LVEF). Baseline characteristics, changes in echocardiographic parameters (1 week and 1 month), BNP (1 month), and NYHA class (6 months) post-TAVR were compared across the three groups. Meanwhile, we observed the adverse events of the patients after TAVR. RESULTS: A total of 96 patients were included, of whom 15 (15.6%) had HFrEF, 15 (15.6%) had HFmrEF, and 66 (68.8%) had HFpEF. Compared to the HFpEF subgroup, patients in the HFrEF subgroup were younger (p < 0.05), and with a higher BNP (p < 0.05). The left ventricular end-diastolic dimension (LVEDD) in HFrEF group decreased significantly after TAVR. HFmrEF and HFrEF patients showed significant improvements in LVEF after TAVR. The pulmonary artery systolic pressure (PASP), aortic valve peak gradient (AVPG) and aortic valve peak gradient (Vmax) decreased significantly 1 month after TAVR in all three groups compared to the baseline (all p < 0.05). BNP significantly reduced in HFrEF group compared to HFpEF patients after TAVR (p < 0.05). The majority of patients experienced an improvement at least one NYHA class in all three groups 6 months post-TAVR. There is no significant increase in the risk of adverse events in the HFrEF group. CONCLUSIONS: Patients who underwent TAVR achieved significant improvements in BNP, NYHA class, LVEDD, LVEF, and PASP across the three HF classes, with a more rapid and pronounced improvement in the HFrEF and HFmrEF groups. Complication rates were low in the different HF groups. There is no significant increase in the risk of periprocedural complications in the HFrEF and HFmrEF groups.


Assuntos
Estenose da Valva Aórtica , Insuficiência Cardíaca , Substituição da Valva Aórtica Transcateter , Humanos , Idoso , Função Ventricular Esquerda , Volume Sistólico , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Prognóstico , Estudos Retrospectivos , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia
16.
Artigo em Inglês | MEDLINE | ID: mdl-36662834

RESUMO

The synaptic properties of memristors have been widely studied. However, researchers are still committed to solving various challenges, including the study of highly reliable memristors with comprehensive synaptic functions and memristors that simulate highly complex neurological learning rules. In this work, we report a CeO2/Nb-SrTiO3 heterojunction memristor whose conductance could be gradually tuned under both positive and negative pulse trains. Due to the gradual conductance switching behavior and the high switching ratio (105), the CeO2/Nb-SrTiO3 heterojunction memristor could dutifully mimic biosynaptic functions, including excitatory/inhibitory postsynaptic current (EPSC/IPSC), paired-pulse facilitation and depression (PPF/PPD), spike amplitude-dependent plasticity (SADP), spike duration-dependent plasticity (SDDP), spike rate-dependent plasticity (SRDP), paired/triplet spiking-time-dependent plasticity (STDP), and Bienenstock-Cooper-Munro (BCM) rules. Moreover, a convolutional neural network based on the memristors is constructed to identify the electrocardiogram (ECG) data sets to realize the diagnosis of diseases with a recognition accuracy of 93%. Besides, the recognition accuracy of the handwriting digit reaches 96%. These studies broaden the research scope of high-level synaptic behavior and lay a foundation for the future full synaptic memristor networks.

17.
Sci Total Environ ; 868: 161543, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36640876

RESUMO

There is a great need for timely monitoring and rapid water quality assessment to control the algal blooms that often occur in eutrophic lakes. While algal cell density (ACD) is a critical indicator of algal growth, field monitoring is laborious and time-consuming, and rapid assessment of algal blooms based on ACD is often not possible. To address the limitations of conventional ACD detection, we proposed a soft sensor approach that uses surrogate indicators to simulate ACD in machine learning models. We conducted a case study using monitoring data from Chaohu Lake collected between 2016 and 2019. We found that ensemble learning models, especially extreme gradient boosting (XGBoost), outperformed traditional machine learning algorithms by comparing various machine learning algorithms. Also, considering the influence of input variable selection on model performance, we combined the results of different filter methods in the multi-stage variable selection process. Finally, we screened out seven key variables out of the 43 initial candidate variables, including dissolved oxygen (DO), chlorophyll-a (Chl-a), Secchi disk depth (SD), pH, permanganate index (CODMn), week of the year (WOY), and wind velocity (WV). Their inclusion substantially improved data accessibility and supported the development of a rapid simulation model. The final model was capable of reliable spatiotemporal generalization, with an overall R2 value of 0.761. On the theoretical side, our study makes a new attempt to simulate ACD values in a eutrophic lake. For practical purposes, the soft sensor can facilitate the rapid assessment of bloom conditions, which helps the local administration with emergency prevention and control.

18.
Biomed Res Int ; 2023: 1277258, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36644162

RESUMO

In this study, the expression of Cripto-1 and the role of macrophage polarization in immune response after allogeneic transfusion were analyzed by constructing a mouse model of allogeneic transfusion. In order to analyze the effects of miR-449a on the PI3K/AKT/NF-κB signaling pathway and the expression of downstream related regulatory factors under normal and abnormal conditions, we adopt in vitro and in vivo experiments separately. The molecular mechanism of PI3K/AKT/NF-κB signaling pathway was analyzed by blocking or activating gene expression and western blotting. Experiment in vitro has confirmed that inhibition of miR-449a increased the protein expression of Cripto-1. In vivo experiments confirmed that allogeneic transfusion reduced the expression of Cripto-1, which further inhibited NF-κB signaling pathway through AKT/PI3K phosphorylation, regulated macrophage polarization, inhibited M1 polarization of macrophages, promoted M2 polarization, and thus affected immune response of the body.


Assuntos
Transplante de Células-Tronco Hematopoéticas , MicroRNAs , Animais , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/genética , Macrófagos/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , MicroRNAs/metabolismo
19.
Nat Cell Biol ; 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36646788

RESUMO

Impairment of the circadian clock is linked to cancer development. However, whether the circadian clock is modulated by oncogenic receptor tyrosine kinases remains unclear. Here we demonstrated that receptor tyrosine kinase activation promotes CK2-mediated CLOCK S106 phosphorylation and subsequent disassembly of the CLOCK-BMAL1 dimer and suppression of the downstream gene expression in hepatocellular carcinoma (HCC) cells. In addition, CLOCK S106 phosphorylation exposes its nuclear export signal to bind Exportin1 for nuclear exportation. Cytosolic CLOCK acetylates PRPS1/2 K29 and blocks HSC70-mediated and lysosome-dependent PRPS1/2 degradation. Stabilized PRPS1/2 promote de novo nucleotide synthesis and HCC cell proliferation and liver tumour growth. Furthermore, CLOCK S106 phosphorylation and PRPS1/2 K29 acetylation are positively correlated in human HCC specimens and with HCC poor prognosis. These findings delineate a critical mechanism by which oncogenic signalling inhibits canonical CLOCK transcriptional activity and simultaneously confers CLOCK with instrumental moonlighting functions to promote nucleotide synthesis and tumour growth.

20.
Cancer Med ; 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647331

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly established cancer therapeutics, but they are associated with new-onset diabetes mellitus (DM). Such risks have not been adequately quantified, and between-class and -sex differences remain unexplored. METHODS: This was a prospective cohort study of cancer patients receiving any ICI in Hong Kong between 2013 and 2021. Patients with known DM were excluded. Due to few patients using other ICIs, only programmed cell death 1 inhibitors (PD-1i) and programmed death ligand 1 inhibitors (PD-L1i) were compared, alongside between-sex comparison. When comparing PD-1i against PD-L1i, patients with the use of other ICIs or both PD-1i and PD-L1 were further excluded. Inverse probability treatment weighting (IPTW) was used to minimize between-group covariate imbalances. RESULTS: Altogether, 3375 patients were analyzed (65.2% males, median age 62.2 [interquartile range 53.8-69.5] years old). Over a median follow-up of 1.0 [0.4-2.4] years, new-onset DM occurred in 457 patients (13.5%), with a 3-year risk of 14.5% [95% confidence interval 13.3%, 15.8%]. IPTW achieve acceptable covariate balance between sexes, and between PD-1i (N = 622) and PD-L1i (N = 2426) users. Males had significantly higher risk of new-onset DM (hazard ratio 1.35 [1.09, 1.67], p = 0.006), while PD-1i and PD-L1i users did not have significantly different risks (hazard ratio vs PD-L1i 0.81 [0.59, 1.11], p = 0.182). These were consistent in those with at least 1 year of follow-up, and on competing risk regression. CONCLUSION: Users of ICI may have a substantial risk of new-onset DM, which may be higher in males but did not differ between PD-1i and PD-L1i.

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