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Dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA1-3. Chromatin complex compositions change during cellular differentiation and ageing, and are expected to be highly heterogeneous among terminally differentiated single cells4-7. Here we introduce the multinucleic acid interaction mapping in single cells (MUSIC) technique for concurrent profiling of multiplex chromatin interactions, gene expression and RNA-chromatin associations within individual nuclei. When applied to 14 human frontal cortex samples from older donors, MUSIC delineated diverse cortical cell types and states. We observed that nuclei exhibiting fewer short-range chromatin interactions were correlated with both an 'older' transcriptomic signature and Alzheimer's disease pathology. Furthermore, the cell type exhibiting chromatin contacts between cis expression quantitative trait loci and a promoter tends to be that in which these cis expression quantitative trait loci specifically affect the expression of their target gene. In addition, female cortical cells exhibit highly heterogeneous interactions between XIST non-coding RNA and chromosome X, along with diverse spatial organizations of the X chromosomes. MUSIC presents a potent tool for exploration of chromatin architecture and transcription at cellular resolution in complex tissues.
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Envelhecimento , Núcleo Celular , Cromatina , Lobo Frontal , RNA , Análise de Célula Única , Idoso , Feminino , Humanos , Masculino , Envelhecimento/genética , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Núcleo Celular/genética , Senescência Celular/genética , Cromatina/genética , Cromatina/metabolismo , Cromossomos Humanos X/genética , Cromossomos Humanos X/metabolismo , Lobo Frontal/metabolismo , Perfilação da Expressão Gênica/métodos , Regiões Promotoras Genéticas , Locos de Características Quantitativas , RNA/genética , RNA/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Análise de Célula Única/métodos , Transcrição GênicaRESUMO
Background: Clinically useful predictors for risk stratification of long-term survival may assist in selecting patients for endovascular abdominal aortic aneurysm (EVAR) procedures. This study aimed to analyze the prognostic significance of peroperative novel systemic inflammatory markers (SIMs), including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), hemoglobin-to-red cell distribution width ratio (HRR), systemic immune-inflammatory index (SIII), and systemic inflammatory response index (SIRI), for long-term mortality in EVAR. Methods: A retrospective analysis was performed on 147 consecutive patients who underwent their first EVAR procedure at the Department of Vascular Surgery, Beijing Hospital. The patients were divided into the mortality group (n = 37) and the survival group (n = 110). The receiver operating characteristic curves were used to ascertain the threshold value demonstrating the most robust connection with mortality. The Kaplan-Meier survival analysis was performed between each SIM and mortality. The relationship between SIMs and survival was investigated using restricted cubic splines and multivariate Cox regression analysis. Results: The study included 147 patients, with an average follow-up duration of 34.28 ± 22.95 months. Deceased patients showed significantly higher NLR (p < 0.001) and reduced HRR (p < 0.001). The Kaplan-Meier estimates of mortality were considerably greater in the higher-NLR group (NLR > 2.77) and lower-HRR group (HRR < 10.64). The hazard ratio (HR) of 0.833 (95% confidence interval (95% CI): 0.71-0.97, p < 0.021) was determined to be statistically significant in predicting death in the multivariable analysis. Conclusions: Preoperative higher-NLR and lower-HRR have been associated with a lower long-term survival rate in abdominal aortic aneurysm (AAA) patients undergoing elective EVAR. Multivariate Cox regression showed that decreased preoperative HRR is an independent risk factor that increases mortality risk following EVAR. SIMs, such as the NLR and HRR, could be used in future clinical risk prediction methodologies for AAA patients undergoing EVAR. However, additional prospective cohort studies are needed to identify these findings.
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OBJECTIVES: To investigate the sleep quality in patients with ocular graft-versus-host disease (oGVHD) compared with patients without oGVHD after allogeneic hematopoietic stem cell transplantation (alloHCT) and healthy controls. METHODS: This cross-sectional study analyzed 142 patients after alloHCT including 94 patients with oGVHD and 48 without. Fifty healthy controls were also enrolled. oGVHD was diagnosed according to International Chronic Ocular GVHD Consensus Group (ICOGCG) criteria. Sleep quality was assessed by the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI). Poor sleep quality was defined as CPQSI score greater than 6. RESULTS: Patients after alloHCT demonstrated a significantly higher CPQSI score than those of controls {7.0 [interquartile range (IQR) 5.0-10.0] vs. 5.5 [IQR 4.8-7.0], P =0.002}, especially in the oGVHD subgroup (7.5 [IQR 5.0-11.0] vs. 6.0 [IQR 5.0-8.0], P =0.04) with nearly double prevalence of poor sleep quality (58 [62%] vs. 18 [37%], P =0.006). Poor sleep quality was strikingly correlated with oGVHD diagnosis (adjusted odds ratio [OR]=2.55, 95% confidence interval [CI]: 1.02-6.34, P =0.04) and systemic immunosuppressants (adjusted OR=2.61, 95% CI: 1.32-5.71, P =0.02). Among the ocular parameters, poor sleep quality was significantly associated with higher ICOGCG score (adjusted OR=1.20, 95% CI: 1.03-1.39, P =0.02) and lower tear film break-up time (adjusted OR=0.85, 95% CI: 0.74-0.99, P =0.05). CONCLUSIONS: Poor sleep quality was associated with an increased severity of oGVHD and tear film instability in the long-term alloHCT survivorship.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Transversais , Qualidade do Sono , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/complicações , OlhoRESUMO
BACKGROUND: The potential predictive significance of atherogenic index of plasma (AIP) for cardiovascular outcomes in patients with acute coronary syndrome (ACS) and who have undergone percutaneous coronary intervention (PCI), with low-density lipoprotein-cholesterol (LDL-C) below 1.8mmol/L, has not been well explored. METHODS: The retrospective cohort analysis included 1,133 patients with ACS and LDL-C levels below 1.8mmol/L who underwent PCI. AIP is calculated as log (triglyceride/high-density lipoprotein-cholesterol). Patients were divided into two groups according to the median value of AIP. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), a composite of all-cause death, nonfatal myocardial infarction, ischemic stroke or unplanned repeat revascularization. The association between AIP and the prevalence of MACCE was evaluated using multivariable Cox proportional hazard models. RESULTS: Over a median follow-up of 26 months, the incidence of MACCE was higher in the high AIP group compared to the low AIP group (9.6% vs. 6.0%, P log-rank = 0.020), and the difference was mainly derived from an increased risk of unplanned repeat revascularization (7.6% vs. 4.6%, P log-rank = 0.028). After adjusting for multiple variables, elevated AIP was independently associated with an increased risk of MACCE, regardless of whether AIP was considered a nominal or continuous variable (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.04-2.53 or HR 2.01, 95% CI 1.09-3.73). CONCLUSIONS: The present study demonstrates that AIP is a significant predictor of adverse outcomes in ACS patients undergoing PCI with LDL-C < 1.8mmol/L. These results suggest that AIP may offer supplementary prognostic information for ACS patients with optimally managed LDL-C levels.
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Síndrome Coronariana Aguda , Aterosclerose , Intervenção Coronária Percutânea , Humanos , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/terapia , LDL-Colesterol , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
PURPOSE: To compare the vision-specific and cancer-specific quality of life (QOL) between patients with and without ocular graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplantation (alloHCT). METHODS: This cross-sectional observational study analyzed 142 patients after alloHCT including 94 patients with oGVHD and 48 without. oGVHD was diagnosed according to International Chronic Ocular GVHD Consensus Group (ICOGCG) criteria. QOL was assessed by using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). RESULTS: Compared with non-oGVHD patients, patients with oGVHD had worse vision-specific (NEI VFQ-25: 64.3 ± 20.3 vs. 77.6 ± 19.3, P < 0.001) and cancer-specific (EORTC QLQ-C30: 59.9 ± 20.3 vs. 67.4 ± 17.5, P = 0.03) QOL, as well as impaired cognitive function (72.7 ± 22.1 vs. 82.3 ± 19.0, P = 0.01). The vision-specific QOL was significantly correlated with ICOGCG score (ß = - 1.88, 95%CI: - 3.35 to - 0.41, P = 0.01) and post-alloHCT medical expense (ß = - 5.70, 95%CI: - 10.35 to - 1.05, P = 0.02), while cancer-specific QOL was strikingly correlated with post-alloHCT medical expense (ß = - 9.91, 95%CI: - 14.43 to - 5.39, P < 0.001), frequency of ophthalmic medication (ß = - 0.93, 95%CI: - 1.64 to - 0.21, P = 0.01), education (ß = - 6.97, 95%CI: - 13.31 to - 0.62, P = 0.03), and peripheral blood stem cell use (ß = - 6.42, 95%CI: - 12.59 to - 0.25, P = 0.04). CONCLUSIONS: Patients with oGVHD experienced significant impairment in both vision-specific and cancer-specific QOL including cognitive function when compared with those without after alloHCT. Multidimensional QOL assessment should be included in the long-term alloHCT survivorship care.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Neoplasias , Humanos , Qualidade de Vida/psicologia , Estudos Transversais , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologiaRESUMO
The rational design of the heterogeneous interfaces enables precise adjustment of the electronic structure and optimization of the kinetics for electron/ion migration in energy storage materials. In this work, the built-in electric field is introduced to the iron-based anode material (Fe2O3@TiO2) through the well-designed heterostructure. This model serves as an ideal platform for comprehending the atomic-level optimization of electron transfer in advanced lithium-ion batteries (LIBs). As a result, the core-shell Fe2O3@TiO2 delivers a remarkable discharge capacity of 1342 mAh g-1 and an extraordinary capacity retention of 82.7% at 0.1 A g-1 after 300 cycles. Fe2O3@TiO2 shows an excellent rate performance from 0.1 A g-1 to 4.0 A g-1. Further, the discharge capacity of Fe2O3@TiO2 reached 736 mAh g-1 at 1.0 A g-1 after 2000 cycles, and the corresponding capacity retention is 83.62%. The heterostructure forms a conventional p-n junction, successfully constructing the built-in electric field and lithium-ion reservoir. The kinetic analysis demonstrates that Fe2O3@TiO2 displays high pseudocapacitance behavior (77.8%) and fast lithium-ion reaction kinetics. The capability of heterointerface engineering to optimize electrochemical reaction kinetics offers novel insights for constructing high-performance iron-based anodes for LIBs.
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BACKGROUND: Prophylactic central lymph node dissection (PCND) was a basic consensus for patients with papillary thyroid carcinoma (PTC) in China. However, unilateral or bilateral central lymph node dissection (CND) was still controversial. This study aimed at investigating the safety and long-term benefit for the patients undergone with bilateral central lymph node dissection (BCCD). METHODS: 581 patients were enrolled and divided randomly into the test and control groups according to range of CND. 285 patients were prospectively assigned to undergo thyroid lobectomy plus BCND in the test group, other 296 patients were assigned to undergo thyroid lobectomy plus ipsilateral central lymph node dissection (ICND) in the control group. RESULTS: We found that the numbers of total LN and pN1a in the test group were more than that of the control group (p = 0.002,0.004), but there was no difference in the number of metastasized lymph nodes (p = 0.857) and tumor recurrence (p = 0.308). Additionally, in the aspect of postoperative complication (1 day after surgery), the serum levels of parathyroid hormone in the BCND group were lower than that in the ICND group (P = 0.010), and the numbers of transient laryngeal nerve palsy were more than that(p = 0.033). Meanwhile, we further found that pathological tumor size larger than 1 cm and tumor side lymph node metastasis were independent risk factors for contralateral central lymph node metastasis(p = 0.002,0.001). CONCLUSION: BCND may be an alternative for patients with tumor sizes larger than 1 cm, but it would significantly increase the rate of transient vocal cord palsy, parathyroid auto transplantation and decreased PTH, but the risk of permanent complications was similar to the ICND group.
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Excisão de Linfonodo/efeitos adversos , Esvaziamento Cervical/efeitos adversos , Complicações Pós-Operatórias , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos ProspectivosRESUMO
BACKGROUND: The associations between the long-term triglyceride-glucose (TyG) index level and variability and clinical outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) have not been well studied. METHODS: A total of 1,694 ACS patients with at least three postbaseline TyG index measurements within 2 years after PCI were included in the present study. The TyG index was defined as ln (fasting triglycerides [mg/dL] × fasting plasma glucose [mg/dL]/2). Multivariable-adjusted Cox proportional hazard models were used to examine the association between baseline and mean TyG index levels and TyG index variability and the risk of major adverse cardiovascular and cerebrovascular events (MACCEs). RESULTS: During the median follow-up of 31 months, the overall incidence of MACCE was 5.9%. Both high baseline and mean TyG index levels were independently associated with an increased risk of MACCEs after adjustment for multiple potential confounders (hazard ratio [HR) 1.76 95% confidence interval [CI] 1.06-2.93; and HR 2.73 95% CI 1.57-4.74). Similarly, higher TyG index variability by successive variation (SD) was well related to a higher prevalence of MACCEs (HR 2.17 95% CI 1.28-3.68). In addition, the mean TyG index level showed a stronger risk prediction for MACCEs than the baseline TyG index level and TyG index-SD (AUCs 0.618 vs 0.566 vs 0.566). CONCLUSIONS: The risk of MACCEs significantly increased with higher baseline and mean TyG index levels, as well as TyG index variability, in patients with ACS undergoing PCI. In particular, the mean TyG index level exhibited the highest predicting ability for MACCEs. Therefore, monitoring the long-term pattern of the TyG index deserves attention in clinical practice.
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Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Humanos , Síndrome Coronariana Aguda/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Triglicerídeos , Glucose , Estudos de CoortesRESUMO
DNA-protein cross-links have broad applications in mapping DNA-protein interactions and provide structural insights into macromolecular structures. However, high-resolution mapping of DNA-interacting amino acid residues with tandem mass spectrometry remains challenging due to difficulties in sample preparation and data analysis. Herein, we developed a method for identifying cross-linking amino residues in DNA-protein cross-links at single amino acid resolution. We leveraged the alkaline lability of ribonucleotides and designed ribonucleotide-containing DNA to produce structurally defined nucleic acid-peptide cross-links under our optimized ribonucleotide cleavage conditions. The structurally defined oligonucleotide-peptide heteroconjugates improved ionization, reduced the database search space, and facilitated the identification of cross-linking residues in peptides. We applied the workflow to identifying abasic (AP) site-interacting residues in human mitochondrial transcription factor A (TFAM)-DNA cross-links. With sub-nmol sample input, we obtained high-quality fragmentation spectra for nucleic acid-peptide cross-links and identified 14 cross-linked lysine residues with the home-built AP_CrosslinkFinder program. Semi-quantification based on integrated peak areas revealed that K186 of TFAM is the major cross-linking residue, consistent with K186 being the closest (to the AP modification) lysine residue in solved TFAM:DNA crystal structures. Additional cross-linking lysine residues (K69, K76, K136, K154) support the dynamic characteristics of TFAM:DNA complexes. Overall, our combined workflow using ribonucleotide as a chemically cleavable DNA modification together with optimized sample preparation and data analysis offers a simple yet powerful approach for mapping cross-linking sites in DNA-protein cross-links. The method is amendable to other chemical or photo-cross-linking systems and can be extended to complex biological samples.
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Aminoácidos , Ribonucleotídeos , DNA , HumanosRESUMO
Porcine pancreas lipase (PPL) was immobilized on magnetic multiwalled carbon nanotubes successfully for the synthesis of substituted 2H-chromenes. The catalytic activity of immobilized PPL was much higher than that of free PPL. Effects of reaction medium, temperature, and enzyme dosage were also investigated. Under optimum reaction conditions (acetylacetone (1 mmol), salicylaldehyde (1 equivalent), methanol (10 equivalent), and immobilized PPL (protein content: 30 mg; 65 °C; DMF 5 mL; 5 H), the immobilized PPL showed an excellent catalytic performance on the synthesis of substituted 2H-chromenes. Moreover, the immobilized PPL exhibited satisfactory thermostability, operational simplicity, and reusability in this reaction.
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Benzopiranos/química , Enzimas Imobilizadas/química , Lipase/química , Nanotubos de Carbono/química , Animais , Catálise , Estabilidade Enzimática , Temperatura Alta , SuínosRESUMO
KEY MESSAGE: An InDel marker closely linked with a major and stable quantitative trait locus (QTL) on chromosome 4BS, QSnpa.cau-4B, controlling spike number per unit area will benefit wheat yield improvement. Spike number per unit area (SNPA) is an essential yield-related trait, and analyzing its genetic basis is important for cultivar improvement in wheat (Triticum aestivum L.). In this study, we used the F2 population derived from a cross between two wheat accessions displaying significant differences in SNPA to perform quantitative trait locus (QTL) analysis. Through bulked segregant analysis, a major and stable QTL that explained 18.11-82.11% of the phenotypic variation was identified on chromosome 4BS. The QTL interval was validated using F4:5 and F6:7 families and narrowed it to a 24.91-38.36 Mb region of chromosome 4BS according to the 'Chinese Spring' reference genome sequence. In this region, variations in 16 genes caused amino acid changes and three genes were present in only one parent. Among these, we annotated a gene orthologous to TB1 in maize (Zea mays), namely TraesCS4B01G042700, which carried a 44-bp deletion in its promoter in the higher-SNPA parent. An InDel marker based on the insertion/deletion polymorphism was designed and used to diagnose the allelic distribution within a natural population. The frequency of the 44-bp deletion allele associated with higher SNPA was relatively low (13.24%), implying that this favorable allele has not been widely utilized and could be valuable for wheat yield improvement. In summary, we identified a major and stable QTL for SNPA and developed a diagnostic marker for the more-spiked trait, which will be beneficial for molecular-assisted breeding in wheat.
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Cromossomos de Plantas , Genes de Plantas , Locos de Características Quantitativas , Triticum/genética , Alelos , Mapeamento Cromossômico , Cruzamentos Genéticos , Ligação Genética , Marcadores Genéticos , Fenótipo , Melhoramento VegetalRESUMO
Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease that affects exocrine glands. To study the molecular mechanism and identify crucial genes/pathways in pSS pathogenesis, the microarray-based whole-genome gene expression profiles from salivary glands of patients with pSS and non-sicca controls were retrieved. After normalization and subsequent batch effect adjustment, significance analysis of microarrays method was applied to five available datasets, and 379 differentially expressed genes (DEGs) were identified. The 300 upregulated DEGs were enriched in Gene Ontology terms of immune and inflammatory responses, including antigen processing and presentation, interferon-mediated signaling pathway, and chemotaxis. Previously reported pSS-associated genes, including HLA-DRA, TAP2, PRDM1, and IFI16, were found to be significantly upregulated. The downregulated DEGs were enriched in pathways of salivary secretion, carbohydrate digestion and absorption, and starch and sucrose metabolism, implying dysfunction of salivary glands during pathogenesis. Next, a protein-protein interaction network was constructed, and B2M, an upregulated DEG, was shown to be a hub, suggesting its potential involvement in pSS development. In summary, we found the activation of pSS-associated genes in pathogenesis, and provide clues for salivary glands dysfunction. Experimental investigation on the identified DEGs in this study will deepen our understanding on pSS.
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Biomarcadores/análise , Regulação da Expressão Gênica , Síndrome de Sjogren/genética , Síndrome de Sjogren/patologia , Transcriptoma , Estudos de Casos e Controles , Perfilação da Expressão Gênica , Humanos , Metanálise como Assunto , Prognóstico , Mapas de Interação de Proteínas , Glândulas Salivares/citologia , Glândulas Salivares/metabolismo , Transdução de SinaisAssuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Correção Endovascular de Aneurisma , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Procedimentos Endovasculares/efeitos adversos , Resultado do Tratamento , Implante de Prótese Vascular/efeitos adversos , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: The study aims to evaluate the clinic feasibility of rapid parathyroid hormone (PTH) detection and nano-carbon technology in preoperative diagnosis and localization of parathyroid adenoma. METHODS: With the guidance of ultrasound, the operator performed the parathyroid puncture and tested the PTH value by using a PTH test kit, and then injected nano-carbon into parathyroid adenoma as a marker to observe whether the parathyroid adenoma was stained black during the final operation. Meanwhile, a part of excised specimen was made into homogenate and detected rapidly again by using the PTH test kit. The remaining was confirmed by intraoperative frozen pathological examination. RESULT: The sensitivity (12/12) of preoperative diagnosis was significantly higher than that of ultrasound (6/12), magnetic resonance imaging (7/12), and MIBI (9/12). During the operation, we found that the inner part of the parathyroid adenoma was stained black, and the PTH value of the specimen homogenate confirmed as parathyroid adenoma was more than 3000 pg/mL. CONCLUSION: This novel technology, as a very positive method for localization of parathyroid adenoma, plays an important role in guaranteeing the surgical reliability of parathyroid adenoma with help of nano-carbon technology.
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Adenoma/diagnóstico por imagem , Biópsia por Agulha Fina/métodos , Glândulas Paratireoides/diagnóstico por imagem , Hormônio Paratireóideo/análise , Neoplasias das Paratireoides/diagnóstico por imagem , Adenoma/patologia , Adulto , Carbono/uso terapêutico , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nanomedicina , Nanopartículas/uso terapêutico , Glândulas Paratireoides/patologia , Neoplasias das Paratireoides/patologia , Ultrassonografia , Adulto JovemRESUMO
OBJECTIVE: To study the feasibility of gas-liquid mixing tumescent solution for creating a working space (WS) in endoscopic thyroidectomy (ET). MATERIALS AND METHODS: A prospective study was performed on 186 patients with thyroid tumor who had undergone ET via chest and breast approach. Patients were randomly divided into 2 groups to receive traditional tumescent solution as group A and modified tumescent solution (gas-liquid mixing tumescent solution) as group B. This study compares the following surgical outcome parameters between the 2 groups, including changes of blood pressure, heart rate, and oxygen saturation before and after creating a WS, time for creating a WS, operative time, hemorrhage volume for creating a WS, overall hemorrhage volume, overall postoperative drainage volume, postoperative pain score, postoperative hospitalization, number of retrieved lymph nodes, total serum calcium, serum parathyroid hormone, and cases of transient and permanent recurrent laryngeal nerve palsy. RESULTS: No postoperative bleeding, permanent recurrent laryngeal nerve palsy, incision and surgical site infection, air embolism, flap injury occurred in both groups. The mean time for creating a WS and the whole operation in group B was significantly shorter than that in group A ( P < .05). There were no statistically significant differences in both groups in terms of other observation index ( P > .05). CONCLUSION: The clinical application of gas-liquid mixing tumescent solution can effectively reduce the time for creating a WS and whole operative time, and worthy of being widely used in ET as a safe and effective technique.
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Endoscopia/métodos , Tireoidectomia/métodos , Adolescente , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Adulto JovemRESUMO
OBJECTIVE: To study application of needlescopic assisted hemithyroidectomy and central neck dissection using bilateral breast approach. METHODS: Totally 145 cases of papillary thyroid cancer patients received endoscopic hemithyroidectomy in Fujian Medical University Union Hospital were randomized to needle assisted endoscopic group (NE group, n=81) and conventional endoscopic group (CE group, n=64). The average age of the patients was 35.9 years and 11 patients were male.All patients underwent hemithyroidectomy and central neck dissection through bilateral breast approach, the NE group additional used the MiniLap-assisted intraoperation.The operative time, postoperative complications and cosmetic results were analyzed by t-test and χ(2) test. RESULTS: The operation time of thyroid gland in NE and CE Group was (42±7) min and (31±7) min(t=9.082, P=0.000), respectively. The operation time of central neck dissection was (33±6) min and (26±3) min (t=9.050, P=0.000), respectively.There were 4 cases occurs transient recurrent laryngeal nerve paralysis in CE group and no case occur in NE group(χ(2)=5.206, P=0.036). There was no significant different in other postoperative complications and cosmetic results. CONCLUSIONS: Hemithyroidectomy and central neck dissection using bilateral breast approach and needlescopic assisted technique isa safe and reliable approach, with high cosmetic effect. Application needle assistive devices can shorten the operation time while no significant increase trauma in patients, it will makes endoscopic thyroid surgery easier to promote.
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Carcinoma/cirurgia , Endoscopia/instrumentação , Esvaziamento Cervical , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adulto , Mama , Carcinoma Papilar , Feminino , Humanos , Masculino , Agulhas , Duração da Cirurgia , Complicações Pós-Operatórias , Câncer Papilífero da TireoideRESUMO
Mitochondrial DNA (mtDNA) plays a key role in mitochondrial and cellular functions. mtDNA is maintained by active DNA turnover and base excision repair (BER). In BER, one of the toxic repair intermediates is 5'-deoxyribose phosphate (5'dRp). Human mitochondrial DNA polymerase γ has weak dRp lyase activities, and another known dRp lyase in the nucleus, human DNA polymerase ß, can also localize to mitochondria in certain cell and tissue types. Nonetheless, whether additional proteins have the ability to remove 5'dRp in mitochondria remains unknown. Our prior work on the AP lyase activity of mitochondrial transcription factor A (TFAM) has prompted us to examine its ability to remove 5'dRp residues in vitro. TFAM is the primary DNA-packaging factor in human mitochondria and interacts with mitochondrial DNA extensively. Our data demonstrate that TFAM has the dRp lyase activity with different DNA substrates. Under single-turnover conditions, TFAM removes 5'dRp residues at a rate comparable to that of DNA polymerase (pol) ß, albeit slower than that of pol λ. Among the three proteins examined, pol λ shows the highest single-turnover rates in dRp lyase reactions. The catalytic effect of TFAM is facilitated by lysine residues of TFAM via Schiff base chemistry, as evidenced by the observation of dRp-lysine adducts in mass spectrometry experiments. The catalytic effect of TFAM observed here is analogous to the AP lyase activity of TFAM reported previously. Together, these results suggest a potential role of TFAM in preventing the accumulation of toxic DNA repair intermediates.
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DNA Polimerase beta , Liases , Fósforo-Oxigênio Liases , Humanos , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Liases/metabolismo , Lisina , DNA Polimerase beta/metabolismo , Reparo do DNA , DNA Polimerase gama/metabolismo , DNA Mitocondrial/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição , Proteínas Mitocondriais/metabolismoRESUMO
BACKGROUND: Insulin resistance (IR) is closely linked to cardiometabolic diseases. Preventing and improving IR in nondiabetic populations is critically important. We aimed to investigate the relationship between Life's Essential 8 (LE8), the latest tool from the American Heart Association quantifying cardiovascular health, and IR among nondiabetic populations in the United States. METHODS AND RESULTS: This cross-sectional study used data on 11 246 nondiabetic adults aged ≥20 years from the 2005 to 2018 the National Health and Nutrition Examination Survey. The LE8 score was classified into 2 subscale scores: health factor score and health behavior score. IR was measured by homeostasis model assessment of insulin resistance (HOMA-IR). Weighted logistic and linear regression models analyzed associations among the LE8 score, health behavior score, health factor score, and IR. Restricted cubic spline models assessed dose-response relationships. Adjusted subgroup analyses and inverse probability of treatment weighting method also evaluated the LE8-IR relationship. Of the 11 246 participants, 4860 (43.2%) had IR. The mean LE8 score was 70.07 (95% CI, 69.57-70.58). In fully adjusted models, higher LE8 scores were associated with lower IR odds (odds ratio per 10-unit increase, 0.57 [95% CI, 0.54-0.61]). Nonlinear LE8-IR dose-response was observed. Similar patterns were seen for health behavior and health factor subscores, with stronger IR correlations for health factors. The inverse LE8-IR association was significantly more pronounced among White participants and those with higher education, higher income, and without hypertension, cardiovascular disease, or chronic kidney disease. Significant negative LE8-IR associations persisted after inverse probability of treatment weighting. CONCLUSIONS: LE8 and subscale scores are negatively associated with IR in a nonlinear relationship. Promoting optimal cardiovascular health adherence may improve IR in nondiabetic populations.
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Resistência à Insulina , Inquéritos Nutricionais , Humanos , Resistência à Insulina/fisiologia , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Estados Unidos/epidemiologia , Comportamentos Relacionados com a Saúde , Doenças Cardiovasculares/epidemiologia , Fatores de Risco , Medição de Risco , Idoso , Adulto JovemRESUMO
INTRODUCTION: Breast cancer has become the most common cancer worldwide. Various types of mindfulness-based interventions (e.g., mindfulness-based cognitive therapy, mindfulness-based stress reduction) have been conducted in different delivery methods (including face to face and internet delivered) to help patients with breast cancer mitigate their depression. However, at present, there are no studies that compare the effectiveness of all these types and deliveries of mindfulness-based interventions. Therefore, this protocol aims to conduct a systematic review and network meta-analysis to assess the effectiveness of various types and deliveries of mindfulness-based interventions in mitigating depression in patients with breast cancer. METHODS: This protocol is according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The electronic databases, including PubMed, Web of Science, the Cochrane Library, Embase, Google Scholar, The China National Knowledge Infrastructure and OpenGrey, will be comprehensively retrieved for related randomised controlled trials (RCTs) from inception to December 2023. Two reviewers will independently assess the risk of bias using the Cochrane Risk of Bias Tool for Randomised Trials 2.0 (RoB 2.0). The network meta-analysis will be performed using the STATA V.16.0, and the assessment of heterogeneity, inconsistency, publication bias, evidence quality, subgroup analyses and sensitivity analyses will be conducted. ETHICS AND DISSEMINATION: This protocol does not require approval from an ethics committee as it is based on previous research findings. The results will be disseminated via peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42024495996.
Assuntos
Neoplasias da Mama , Depressão , Atenção Plena , Metanálise em Rede , Revisões Sistemáticas como Assunto , Feminino , Humanos , Neoplasias da Mama/terapia , Neoplasias da Mama/psicologia , Depressão/terapia , Depressão/etiologia , Atenção Plena/métodos , Projetos de PesquisaRESUMO
Purpose: Papillary thyroid cancer (PTC) stands as one of the most prevalent types of thyroid cancers, characterized by a propensity for in-situ recurrence and distant metastasis. The high mobility group protein (HMGB1), a conserved nuclear protein, plays a pivotal role in carcinogenesis by stimulating tumor cell growth and migration. Nevertheless, the underlying mechanism driving aberrant HMGB1 expression in PTC necessitates further elucidation. Materials and methods: Our study unraveled the impact of low and overexpression of USP15 on the proliferation, invasion, and metastasis of PTC cells. Through a comprehensive array of molecular techniques, we uncovered the intricate relationship between HMGB1 and USP15 in the progression of PTC. Results: In this study, we identified USP15, a deubiquitinase in the ubiquitin-specific proteases family, as a true deubiquitylase of HMGB1 in PTC. USP15 was shown to interact with HMGB1 in a deubiquitination activity-dependent manner, deubiquitinating and stabilizing HMGB1. USP15 depletion significantly decreased PTC cell proliferation, migration, and invasion. In addition, the effects induced by USP15 depletion could be rescued by further HMGB1 overexpression. But when HMGB1 is knocked down, even overexpression of USP15 could not promote the progression of PTC cells. Conclusion: In essence, our discoveries shed light on the previously uncharted catalytic role of USP15 as a deubiquitinating enzyme targeting HMGB1, offering a promising avenue for potential therapeutic interventions in the management of PTC.