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1.
Molecules ; 29(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38930831

RESUMO

In recent years, researchers have often encountered the significance of the aberrant metabolism of tumor cells in the pathogenesis of malignant neoplasms. This phenomenon, known as the Warburg effect, provides a number of advantages in the survival of neoplastic cells, and its application is considered a potential strategy in the search for antitumor agents. With the aim of developing a promising platform for designing antitumor therapeutics, we synthesized a library of conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones. To gain insight into the determinants of the biological activity of the prepared compounds, we showed that the conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones, which are cytotoxic agents, demonstrate selective activity toward a number of tumor cell lines with glycolysis-inhibiting ability. Moreover, the results of molecular and in silico screening allowed us to identify these compounds as potential inhibitors of the pyruvate kinase M2 oncoprotein, which is the rate-determining enzyme of glycolysis. Thus, the results of our work indicate that the synthesized conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones can be considered a promising platform for designing selective cytotoxic agents against the glycolysis process, which opens new possibilities for researchers involved in the search for antitumor therapeutics among compounds containing piperidone platforms.


Assuntos
Antineoplásicos , Lactonas , Piperidonas , Sesquiterpenos , Humanos , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Lactonas/química , Lactonas/farmacologia , Lactonas/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Piperidonas/farmacologia , Piperidonas/química , Glicólise/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Ensaios de Seleção de Medicamentos Antitumorais
3.
Vopr Pitan ; 93(2): 63-72, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38809800

RESUMO

Chronic systemic inflammation is one of the leading pathogenetic pathways for the development of atherosclerosis in obese patients. In this regard, it seems promising to evaluate the effect of the diet and physical exertion on the proinflammatory activity of monocytes. The purpose of this research was to evaluate the effect of the diet and regular physical trainings on the secretion of monocyte chemotactic factor 1 (MCP-1) by monocytes in obese patients with coronary artery disease. Material and methods. 27 obese participants (body mass index >30 kg/m2) with a confirmed diagnosis of coronary heart disease were recruited. All participants were prescribed with 12 weeks of a specialized diet with a restriction of simple carbohydrates and salt, a 500-kcal daily energy deficit, and with inclusion of cruciferous (200 g per day), seasonal dark berries (70 g per day) and green tea (200 ml per day). The regular assisted physical trainings were also administered. The body composition, blood biochemical parameters and MCP-1 secretion rates in the primary culture of monocytes isolated from blood samples via the immunomagnetic separation method were assessed before and after the intervention. Results. As a result, after the 12-weeks intervention the reliable body weight loss (-4.0%), waist circumference (-4.2%), visceral fat (-5.4%), total cholesterol (-9.8%), LDL-cholesterol (-16.6%) and triglycerides (-26.0%), an improvement in the results of the 6-minute walk test (+10.33%) was achieved, as well as an LPS-stimulated monocytes secretion of MCP-1 decreased by 2.8 times (p=0.005). Conclusion. Overall, the results suggest that diet and regular physical activity in patients with obesity and coronary heart disease may decrease the functional "proinflammatory" activity of monocytes.


Assuntos
Quimiocina CCL2 , Doença das Coronárias , Monócitos , Obesidade , Humanos , Monócitos/metabolismo , Obesidade/dietoterapia , Obesidade/sangue , Obesidade/metabolismo , Obesidade/terapia , Masculino , Quimiocina CCL2/sangue , Quimiocina CCL2/metabolismo , Pessoa de Meia-Idade , Feminino , Doença das Coronárias/dietoterapia , Doença das Coronárias/metabolismo , Doença das Coronárias/sangue , Idoso
4.
Bull Exp Biol Med ; 176(5): 645-648, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38727954

RESUMO

Using the method of dominant lethal mutations, we assessed the frequency of the death of Drosophila melanogaster embryos under combined exposure to ionizing γ-radiation and non-ionizing pulsed magnetic field at various doses and modes of exposure. Mutagenic effect of combined exposure is antagonistic in nature. The antagonism is more pronounced when the following mode of exposure was used: exposure to non-ionizing pulsed magnetic field for 5 h followed by exposure to γ-radiation at doses of 3, 10, and 60 Gy. In case of reverse sequence of exposures, the antagonistic effect was statistically significant after exposure to γ-radiation at doses of 3 and 10 Gy, whereas at a dose of 20 Gy, a synergistic interaction was noted.


Assuntos
Drosophila melanogaster , Raios gama , Animais , Drosophila melanogaster/efeitos da radiação , Drosophila melanogaster/genética , Raios gama/efeitos adversos , Radiação Eletromagnética , Relação Dose-Resposta à Radiação , Campos Eletromagnéticos/efeitos adversos , Embrião não Mamífero/efeitos da radiação , Radiação Ionizante , Mutação/efeitos da radiação , Mutagênese/efeitos da radiação
5.
Eur Rev Med Pharmacol Sci ; 28(8): 2988-2995, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38708455

RESUMO

OBJECTIVE: The impact of selenium on autoimmune thyroid disease (AITD) is a subject of ongoing debate. This study aimed to analyze the causal correlations of selenium with autoimmune thyroiditis (AIT), autoimmune hyperthyroidism (AIH), and Graves' disease (GD) by Mendelian randomization (MR). MATERIALS AND METHODS: Single nucleotide polymorphisms related to selenium, AIT, AIH, and GD were sourced from the IEU Open GWAS project and FinnGen. Exposure-outcome causality was assessed using inverse variance weighted, MR-Egger, and weighted median. Horizontal pleiotropy was examined using the MR-Egger intercept, heterogeneity was evaluated with Cochran's Q test, and the robustness of the results was confirmed via leave-one-out sensitivity analysis. RESULTS: The MR analysis revealed that selenium did not exhibit a causal relationship with AIT (OR 0.993, 95% CI 0.786 to 1.108, p=0.432), AIH (OR 1.066, 95% CI 0.976 to 1.164, p=0.154), or GD (OR 1.052, 95% CI 0.984 to 1.126, p=0.138). Moreover, the MR-Egger intercept and Cochran's Q test demonstrated the absence of horizontal pleiotropy or heterogeneity in these results (p>0.05). Sensitivity analysis affirmed the robustness of these results. CONCLUSIONS: This MR analysis concluded that selenium was not linked to AIT, AIH, or GD risk. Therefore, indiscriminate selenium supplementation is not advisable for AITD patients without concurrent selenium deficiency.


Assuntos
Doença de Graves , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Selênio , Tireoidite Autoimune , Humanos , Selênio/administração & dosagem , Tireoidite Autoimune/genética , Doença de Graves/genética , Estudo de Associação Genômica Ampla
6.
Plant Biol (Stuttg) ; 26(4): 602-611, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38634818

RESUMO

Seed coat mucilage plays an important role in promoting seed germination under adversity. Previous studies have shown that Arabidopsis thaliana MYB52 (AtMYB52) can positively regulate seed coat mucilage accumulation. However, the role of Brassica napus MYB52 (BnaMYB52) in accumulation of seed coat mucilage and tolerance to osmotic stress during seed germination remains largely unknown. We cloned the BnaA09.MYB52 coding domain sequence from B. napus cv ZS11, identified its conserved protein domains and elucidated its relationship with homologues from a range of plant species. Transgenic plants overexpressing BnaA09.MYB52 in the A. thaliana myb52-1 mutant were generated through Agrobacterium-mediated transformation and used to assess the possible roles of BnaA09.MYB52 in accumulation of seed coat mucilage and tolerance to osmotic stress during seed germination. Subcellular localization and transcriptional activity assays demonstrated that BnaA09.MYB52 functions as a transcription factor. RT-qPCR results indicate that BnaA09.MYB52 is predominantly expressed in roots and developing seeds of B. napus cv ZS11. Introduction of BnaA09.MYB52 into myb52-1 restored thinner seed coat mucilage in this mutant to levels in the wild type. Consistently, expression levels of three key genes participating in mucilage formation in developing seeds of myb52-1 were also restored to wild type levels by overexpressing BnaA09.MYB52. Furthermore, BnaA09.MYB52 was induced by osmotic stress during seed germination in B. napus, and ectopic expression of BnaA09.MYB52 successfully corrected sensitivity of the myb52-1 mutant to osmotic stress during seed germination. These findings enhance our understanding of the functions of BnaA09.MYB52 and provide a novel strategy for future B. napus breeding.


Assuntos
Arabidopsis , Brassica napus , Regulação da Expressão Gênica de Plantas , Germinação , Pressão Osmótica , Proteínas de Plantas , Plantas Geneticamente Modificadas , Sementes , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Arabidopsis/crescimento & desenvolvimento , Germinação/genética , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Brassica napus/genética , Brassica napus/metabolismo , Brassica napus/fisiologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Mucilagem Vegetal/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética
7.
Arch Gerontol Geriatr ; 124: 105442, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38676979

RESUMO

While player-video game interaction appears to affect older adults in gaming, there is limited knowledge regarding the cognitive demands associated with the anticipation of performing a button press, specifically focusing on the input and game elements relation (I/E relation) in game environments. The study aims to investigate the effects of lateral and rotational displacement amplitudes of game elements, triggered by a single button-press, on the cognitive effort of older adults. Both subjective and objective measurement methods were employed to assess these effects. A total of 48 older adults participated in three casual video game tasks encompassing lateral and rotational displacements at varying I/E relations (low, medium, and high). Results obtained from the NASA Task Load Index and electroencephalography (EEG) measurements revealed significant differences between the I/E relations. Specifically, the subjective rating of cognitive demand among older players was significantly impacted by a small rotation angle associated with a button press, leading to increased mental, physical, and temporal demands, along with decreased performance. Surprisingly, the analysis of EEG data, particularly the theta-alpha ratio, revealed significant interaction effects of I/E relations, button press type, and game type on the cognitive demand required during gameplay. These findings offer practical implications and point towards future avenues for developing player-video game interactions that are more cognitively friendly for older players in gaming environments.


Assuntos
Cognição , Eletroencefalografia , Jogos de Vídeo , Humanos , Jogos de Vídeo/psicologia , Idoso , Masculino , Eletroencefalografia/métodos , Feminino , Cognição/fisiologia , Idoso de 80 Anos ou mais , Desempenho Psicomotor/fisiologia
8.
Eur Rev Med Pharmacol Sci ; 28(6): 2272-2287, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38567590

RESUMO

OBJECTIVE: This study aimed to systematically evaluate the efficacy, safety and optimal dose of polyethylene glycol loxenatide (PEX168) for treating type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Clinical trials of PEX168 for T2DM were identified in 8 databases, with a build time limit of January 2023. Included studies were subjected to meta-analysis and trial sequential analysis (TSA). RESULTS: On the efficacy endpoint, the meta-analysis showed that PEX168 100 µg significantly reduced 0.86% glycated hemoglobin type A1c (HbA1c) (MD -0.86, 95% CI -1.02 - -0.70,  p<0.00001), 1.11 mmol/L fasting plasma glucose (FPG) (MD -1.11, 95% CI -1.49 - -0.74, p<0.00001) and 1.91 mmol/L 2h postprandial glucose (PPG) (MD -1.91, 95% CI -3.35 - -0.46, p=0.01) compared with placebo. The TSA showed that all these benefits were conclusive. On safety endpoints, total adverse events (AEs), gastrointestinal (GI) AEs, serious AEs, and hypoglycemia were comparable to placebo for PEX168 100 µg (p>0.05). In the dose comparison, the HbA1c, FPG, and 2h PPG of PEX168 200 µg were comparable to 100 µg (p>0.05), while GI AEs were significantly higher than 100 µg (RR=2.84, 95% CI 1.64-4.93,  p=0.0002). CONCLUSIONS: PEX168 100 µg can significantly lower blood glucose and does not increase the risk of total AEs, GI AEs, and hypoglycemia, which may be a preferred glucagon-like peptide-1 receptor agonist for type 2 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Peptídeos , Polietilenoglicóis , Humanos , Hipoglicemiantes , Hemoglobinas Glicadas , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Glicemia , Hipoglicemia/induzido quimicamente , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas
9.
Zhonghua Nei Ke Za Zhi ; 62(12): 1430-1435, 2023 Dec 01.
Artigo em Chinês | MEDLINE | ID: mdl-38044069

RESUMO

Objective: To investigate the association between remnant cholesterol (RC) and the risk of diabetic retinopathy (DR) in middle-aged and older individuals with diabetes. Methods: Based on the Shanghai Nicheng Cohort Study database, the data of 1 255 individuals with diabetes aged 55-70 years at baseline (2013-2014) with complete fundus photographs and serum cholesterol data in Nicheng, Shanghai, were analyzed. Multinomial logistic regression models were used to evaluate risk ratios (RRs) and their 95% confidence intervals (CIs) between baseline RC level and incident DR. Results: The median age of the subjects was 61.9 years, and 60.4% were women. After a 4.6-year follow-up, 79 (6.3%) patients developed DR, including 50 (4.0%) mild non-proliferative DR and 29 (2.3%) referable DR (RDR). Multivariable logistic regression showed that each mmol/L increase of RC was associated with a 40% higher risk of RDR (RR=1.40, 95%CI 1.03-1.90). Compared with the lowest tertile of RC (<0.63 mmol/L), the risk of RDR in the highest tertile (≥0.85 mmol/L) increased by 4.59 times (RR=5.59, 95%CI 1.51-20.73). Conclusion: The RC level may help identify individuals at high risk of incident RDR in middle-aged and older Chinese adults with diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Adulto , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Masculino , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Estudos de Coortes , China/epidemiologia , Colesterol , Fatores de Risco
10.
J Nutr Health Aging ; 27(10): 824-832, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37960905

RESUMO

OBJECTIVES: Evidence on the effectiveness of cooking activities as a well-being promotion intervention for older adults with subjective cognitive decline (SCD) and their caregivers is scarce. In view of this, a randomized controlled trial was conducted to examine whether a dyadic cooking-based intervention can improve the subjective health and well-being of older adults with SCD and their caregivers, as well as the cooking competence of the former group. DESIGN: Randomized controlled trial. SETTING: Community. PARTICIPANTS: Sixty pairs of community-dwelling older adults aged 60 years or above with SCD (mean age = 78.4 years) and their caregivers (mean age = 65.3 years) were randomly assigned to the intervention group (N = 30 pairs) and the wait-list control group (N = 30 pairs). INTERVENTION: The intervention was an innovative 5-week (two hours per week) dyadic cooking-based intervention employing procedural learning methods specifically adapted for older adults with SCD. MEASUREMENTS: The outcome measures included 1) a well-being index composed by four indicators: life satisfaction, feeling of happiness, sense of purpose and meaning in life, and perceived health, and 2) cooking competence. RESULTS: For both older adults with SCD and their caregivers, the increases in the well-being index were significantly greater in the intervention group than in the control group (ß = 0.508, 95% CI [0.036, 0.980]). For older adults with SCD, the increases in the cooking competence score were significantly greater in the intervention group than in the control group (ß = 1.629, 95% CI [0.165, 3.071]). CONCLUSION: The dyadic cooking-based intervention resulted in improvements in the cooking competence and well-being of older adults with SCD, as well as the well-being of caregivers.


Assuntos
Cuidadores , Disfunção Cognitiva , Humanos , Idoso , Cuidadores/psicologia , Autoavaliação Diagnóstica , Avaliação de Resultados em Cuidados de Saúde , Culinária
11.
J Nutr Health Aging ; 27(11): 1028-1037, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37997725

RESUMO

OBJECTIVES: Different types of community-based intervention activities may have differential effects in improving the intrinsic capacity (IC) of older people. This study aims to (i) identify subgroups of older people based on their IC impairments, (ii) examine the differential associations between different types of activity participations and change in IC across subgroups, and (iii) assess whether the activity participation patterns of older people align with the way that would benefit them the most. METHODS: Participants were community-dwelling older people aged 60 years or above. They were screened for IC impairments at baseline, and their participation records of different types (cognitive, physical, nutritional, mental, and social) of intervention activities were collected for one year. An aggregated IC score was created based on four IC domains including cognitive (self-rated memory), locomotor (self-rated difficulties in walking), vitality (self-rated weight loss), and psychological (subjective well-being). Cluster analysis was used to group homogenous participants. Mixed-effects regression was used to examine the associations between activity counts (i.e., number of sessions participated) and change in IC. Activity participation patterns were also compared across subgroups. RESULTS: Data were obtained from 7,357 participants (mean age = 74.72 years). Four clusters were identified, including those who were relatively robust (cluster 1, N = 4,380, 59.5%), those who had cognitive decline (cluster 2, N = 2,134, 29.0%), those who had impaired mobility and vitality (cluster 3, N = 319, 4.3%), and those with poor psychological well-being (cluster 4, N = 524, 7.1%). Overall, activity count was associated with IC improvement (ß = 0.073, 95% CI [0.037, 0.108]). However, as regards the cluster-specific results, different types of activities were associated with IC improvement for different specific clusters. For instance, cognitive activity count was associated with IC improvement only for cluster 2 (ß = 0.491, 95% CI [0.258, 0.732]). Notably, none of the activity types were associated with IC improvement for cluster 1. Regarding the activity participation patterns, there were no significant differences across the four clusters (Wilk's Λ = 0.997, F = 1.400, p = .138). CONCLUSIONS AND IMPLICATIONS: IC improvement depended on the activity types and IC status of older people. In view of this, a people-centred and targeted approach should be adopted to maximize the overall benefits of intervention activities.


Assuntos
Disfunção Cognitiva , Vida Independente , Humanos , Idoso , Disfunção Cognitiva/prevenção & controle , Caminhada
12.
Vopr Pitan ; 92(4): 6-19, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37801450

RESUMO

The oral microbiome is a community of symbiotic, commensal and opportunistic microorganisms, usually present in the form of biofilm, that plays a critical role in maintaining the homeostasis and protective function of the oral cavity. Recently, the study of the human oral microbiome to develop new diagnostic and therapeutic approaches has become a promising new area of the research in the field of personalized medicine. The aim of this review was to generalise and analyse the accumulated data on the relationship between the oral microbiome characteristics and the course of systemic diseases. Material and methods. Literature searches were performed using RSCI, PubMed, Google Scholar, and included original research data published mainly in the last 5 years. Results. The review summarized data on the role of the oral microbiome in the development of a number of systemic diseases, including alimentary diseases. The importance of the major exogenous and endogenous factors that lead to changes in the oral microbiome, including diet, macro- and micronutrient composition of foods, was highlighted. Data were provided on the main types of microorganisms associated with the development and c ourse of a number of somatic diseases, represented mainly by obligate anaerobic periodontal pathogens (Tannerella forsythia, Treponema denticola, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans). The role of the systemic inflammatory response as the main pathogenetic factor of oral dysbiosis has been described. The benefits of periodontal therapy in metabolic disorders such as diabetes mellitus, obesity, and dyslipidemia have been discussed. Promising approaches to correct oral dysbiosis have been presented. Conclusion. The knowledge of the relationships between the oral microbiome composition, the development and characteristics of the course of somatic disease can contribute to the development of new technologies for its prevention and treatment. The change in the structure of the oral microbiome observed in systemic diseases is usually accompanied by a decrease in bacterial diversity and an increase in the number of pathogenic bacteria. Lifestyle modification, dietary therapy, smoking cessation, rational use of antibacterial drugs and treatment of periodontitis play an important role in normalising the structure of the oral microbiome.


Assuntos
Disbiose , Porphyromonas gingivalis , Humanos , Prevotella intermedia , Fusobacterium nucleatum
14.
Artigo em Russo | MEDLINE | ID: mdl-37141523

RESUMO

Sarcopenia is a widespread condition in the elderly people, that occurs as a result of impaired muscle structure and function and is significantly associated with reduced quality and time of life. This review represents current approaches to the diagnosis of sarcopenia with reference to recent European and Asian consensus. They include rules for the evaluation of the main muscle strength and function tests (hand dynamometry, sit-to-stand test, 6-minute walk test, physical performance battery tests, etc.), physical and instrumental methods of muscle mass analysis (densitometry, bioimpedance analysis, magnetic resonance imaging). Furthermore, the pathogenetic relationship between the lack of physical activity and muscle dysfunction in elderly people is broached, including in particular the role of myostatin, interleukin-6, somatotropin and insulin resistance. The article represents possibilities of impact of aerobic, strength and neuromuscular physical exercises on prevention and correction of sarcopenic changes in different age groups based on the analysis of current clinical studies.


Assuntos
Doenças Musculares , Sarcopenia , Humanos , Idoso , Sarcopenia/terapia , Sarcopenia/diagnóstico , Força Muscular/fisiologia , Exercício Físico , Músculo Esquelético
15.
Bull Exp Biol Med ; 174(5): 670-673, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37043061

RESUMO

The frequency of D. melanogaster embryonic death was estimated using the method of dominant lethal mutations after exposure to ionizing γ-radiation and non-ionizing pulsed magnetic field. γ-Radiation had a dose-dependent mutational effect on D. melanogaster. A pronounced increase in embryonic death was observed starting from a dose of 3 Gy and reaches a plateau at 60 Gy due to the maximum death of eggs. When D. melanogaster was exposed to pulsed magnetic field, the effect did not depend on the exposure time; a statistically significant genotoxic effect was detected after 5-h exposure.


Assuntos
Drosophila melanogaster , Radiação Ionizante , Animais , Relação Dose-Resposta à Radiação , Mutação , Raios gama
16.
Zhonghua Er Ke Za Zhi ; 61(5): 446-452, 2023 May 02.
Artigo em Chinês | MEDLINE | ID: mdl-37096265

RESUMO

Objective: To summarize the clinical data and prognosis of children with Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) common genes. Methods: This was a retrospective cohort study.Clinical data of 56 children with Ph-like ALL common gene cases (Ph-like ALL positive group) treated from January 2017 to January 2022 in the First Affiliated Hospital of Zhengzhou University, Henan Children's Hospital, Henan Cancer's Hospital and Henan Provincial People's Hospital were collected, 69 children with other high-risk B cell acute lymphoblastic leukemia (B-ALL) at the same time and the same age were selected as the negative group. The clinical characteristics and prognosis of two groups were analyzed retrospectively. Comparisons between groups were performed using Mann-Whitney U test and χ2 test. Kaplan-Meier method was used for survival curve, Log-Rank test was used for univariate analysis, and the Cox regression model was used for multivariate prognosis analysis. Results: Among 56 Ph-like ALL positive patients, there were 30 males and 26 females, and 15 cases were over 10 years old. There were 69 patients in Ph-like ALL negative group. Compared with the negative group, the children in positive group were older (6.4 (4.2, 11.2) vs. 4.7 (2.8, 8.4) years), and hyperleukocytosis (≥50×109/L) was more common (25% (14/56) vs. 9% (6/69)), the differences were statistically significant (both P<0.05). In the Ph-like ALL positive group, 32 cases were positive for IK6 (1 case was co-expressed with IK6 and EBF1-PDGFRB), 24 cases were IK6-negative, of which 9 cases were CRLF2 positive (including 2 cases with P2RY8-CRLF2, 7 cases with CRLF2 high expression), 5 cases were PDGFRB rearrangement, 4 cases were ABL1 rearrangement, 4 cases were JAK2 rearrangement, 1 case was ABL2 rearrangement and 1 case was EPOR rearrangement. The follow-up time of Ph-like ALL positive group was 22 (12, 40) months, and 32 (20, 45) months for negative group. The 3-year overall survival (OS) rate of positive group was significantly lower than the negative group ((72±7) % vs. (86±5) %, χ2=4.59, P<0.05). Compared with the 24 IK6-negative patients, the 3-year event free survival (EFS) rate of 32 IK6 positive patients was higher, the difference was statistically significant ((88±9) % vs. (65±14) %, χ2=5.37, P<0.05). Multivariate Cox regression analysis showed that the bone marrow minimal residual disease (MRD) not turning negative at the end of first induction (HR=4.12, 95%CI 1.13-15.03) independent prognostic risk factor for patient with Ph-like ALL common genes. Conclusions: Children with Ph-like ALL common genes were older than other high-risk B-ALL patients at diagnosis, with high white blood cells and lower survival rate. The bone marrow MRD not turning negative at the end of first induction were independent prognostic risk factor for children with Ph-like ALL common gene.


Assuntos
Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Masculino , Feminino , Humanos , Criança , Prognóstico , Estudos Retrospectivos , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Neoplasia Residual
18.
Phys Rev Lett ; 130(14): 146101, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37084444

RESUMO

Because of the half-filled t_{2g}-electron configuration, the BO_{6} octahedral distortion in a 3d^{3} perovskite system is usually very limited. In this Letter, a perovskitelike oxide Hg_{0.75}Pb_{0.25}MnO_{3} (HPMO) with a 3d^{3} Mn^{4+} state was synthesized by using high pressure and high temperature methods. This compound exhibits an unusually large octahedral distortion enhanced by approximately 2 orders of magnitude compared with that observed in other 3d^{3} perovskite systems like RCr^{3+}O_{3} (R=rare earth). Essentially different from centrosymmetric HgMnO_{3} and PbMnO_{3}, the A-site doped HPMO presents a polar crystal structure with the space group Ama2 and a substantial spontaneous electric polarization (26.5 µC/cm^{2} in theory) arising from the off-center displacements of A- and B-site ions. More interestingly, a prominent net photocurrent and switchable photovoltaic effect with a sustainable photoresponse were observed in the current polycrystalline HPMO. This Letter provides an exceptional d^{3} material system which shows unusually large octahedral distortion and displacement-type ferroelectricity violating the "d^{0}-ness" rule.

19.
J Frailty Aging ; 12(2): 126-133, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36946709

RESUMO

Although integrated care has been considered a key strategy in reforming health systems around the world, it seems hard to realise in practice, particularly in the part of medical social integration. Worse still, little is known about the capacity of social care professionals who implement it, or their perceived roles and responsibilities, as well as the barriers and facilitators that stakeholders from the health and social sectors identify as factors affecting the ICOPE implementation process. Therefore, the present study was performed to probe into these issues. Data were collected from an online survey based on the WHO ICOPE scorecard (N = 34), and focus groups with policy makers, managers, health and social care professionals (N = 47). Inductive analyses were performed in accordance with the service and system levels within the WHO ICOPE implementation framework. While the findings from the scorecard survey highlight the gap in actualizing the ICOPE approach within the existing social services and care structures, we found support for a model of integrated care underpinned by the WHO ICOPE approach. Factors that may hinder and facilitate ICOPE implementation include workforce capacity-building, coordinated networks and partnerships, and financial mechanisms. This finding can help inform subsequent actions that further support health and social care advancement and collaboration, and the implementation of the ICOPE approach.


Assuntos
Prestação Integrada de Cuidados de Saúde , Saúde Global , Políticas , Humanos , Hong Kong , Apoio Social , Organização Mundial da Saúde
20.
J Nutr Health Aging ; 27(3): 174-181, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36973922

RESUMO

OBJECTIVES: Intrinsic capacity (IC) declines progressively with age, thereby increasing the risk of disability. However, it is less known whether IC trajectories are associated with disability. This study aims to identify the different patterns of IC trajectories in older people, and examine their determinants and associations with Instrumental Activities of Daily Living (IADL). DESIGN: Cohort study. SETTING: Community centres in different regions in Hong Kong. PARTICIPANTS AND MEASUREMENTS: Longitudinal data from community-dwelling older people aged 60 years or above (n = 1371) collected between 2016 and 2021 was analysed. Their mean age was 74.5 years, and 78.7% of them were female. Repeated measurements of a set of 14 self-reported items were used to generate IC scores at four time points using a bi-factor model. Latent class growth analysis was performed to identify classes with distinct IC trajectories. The association between class membership and IADL disability was then examined using logistic regression. RESULTS: Three distinct IC trajectories were identified. The 1st class included those with the highest level of baseline IC and the least declining trajectory, whereas the 3rd class was composed by those with the lowest level of baseline IC and the most declining trajectory. Older age, female gender, lower perceived financial adequacy, living in public or subsidized housing, and chronic diseases were associated with the 3rd class. After adjusting for demographic factors, socioeconomic status, and the number of chronic diseases, the 1st class was more likely to preserve IADL when compared against the 2nd class, with OR being 3.179 (95% CI: 2.152-4.793), whereas for the 3rd class, the OR was 0.253 (95% CI: 0.178-0.359). CONCLUSION: Monitoring IC trajectories is of relevance to clinical practice, as it helps shift the focus from treating acute episodes of illness to preserving the functional ability of older people.


Assuntos
Atividades Cotidianas , Pessoas com Deficiência , Humanos , Feminino , Idoso , Masculino , Estudos de Coortes , Vida Independente , Doença Crônica
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