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1.
Front Med (Lausanne) ; 8: 719593, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722564

RESUMO

Background: Vogt-Koyanagi-Harada (VKH) disease is a multisystem autoimmune disorder which could induce bilateral panuveitis involving the posterior pole and peripheral fundus. Optical coherence tomography angiography (OCTA) provides several advantages over traditional fluorescence angiography for revealing pathological abnormalities of the retinal vasculature. Until recently, however, the OCTA field of view (FOV) was limited to 6 × 6 mm2 scans. Purpose: This study examined retinal vasculature and choriocapillaris abnormalities across multiple regions of the retina (15 × 9 mm2 wide field, macular, peripapillary regions) among acute and convalescent VKH patients using a novel widefield swept-source OCTA (WSS-OCTA) device and assessed correlations between imaging features and best-corrected visual acuity (BCVA). Methods: Twenty eyes of 13 VHK disease patients in the acute phase, 30 eyes of 17 patients in the convalescent phase, and 30 eyes of 15 healthy controls (HCs) were included in this study. Vascular length density (VLD) in superficial and deep vascular plexuses (SVP, DVP), vascular perfusion density (VPD) in SVP, DVP, and choriocapillaris (CC), and flow voids (FV) in CC were measured across multiple retinal regions via WSS-OCTA (PLEX Elite 9000, Carl Zeiss Meditec Inc., USA) using the 15 × 9 mm2 scan pattern centered on the fovea and quantified by ImageJ. Results: Compared to HCs, acute phase VKH patients exhibited significantly reduced SVP-VLD, SVP-VPD, and CC-VPD across multiple retinal regions (all p < 0.01). Notably, the FV area was more extensive in VKH patients, especially those in the acute phase (p < 0.01). These changes were reversed in the convalescent phase. Stepwise multiple linear regression analysis demonstrated that macular DVP-VLD and macular CC-VPD were the best predictive factors for BCVA in the acute and convalescent VKH groups. Conclusion: The wider field of SS-OCAT provides more comprehensive and detailed images of the microvasculature abnormalities characterizing VKH disease. The quantifiable and layer-specific information from OCTA allows for the identification of sensitive and specific imaging markers for prognosis and treatment guidance, highlighting WSS-OCTA as a promising modality for the clinical management of VKH disease.

2.
Front Public Health ; 9: 745118, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778179

RESUMO

In this study, 223 primary and secondary school teachers in Shandong province were selected to examine the effect of work-family conflict on occupational well-being, using the questionnaire of work-family conflict, occupational well-being and psychological capital as measuring instruments. We further explored the mediating role of psychological capital between work-family conflict and occupational well-being. The obtained data were analyzed using SPSS20.0, AMOS16.0 and M-plus 7.0. Results revealed that (1) Work-family conflict was negatively correlated with the occupational well-being and psychological capital of primary and secondary school teachers, and negatively predicted occupational well-being and psychological capital of primary and secondary school teachers; (2) Psychological capital had a significant positive correlation with the occupational well-being of primary and secondary school teachers, and significantly predicted the occupational well-being of primary and secondary school teachers; (3) Psychological capital of primary and secondary school teachers played a mediating role in work-family conflict and occupational well-being.


Assuntos
Conflito Familiar , Professores Escolares , Estudos Transversais , Humanos , Instituições Acadêmicas , Inquéritos e Questionários
4.
Front Med (Lausanne) ; 8: 727151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604263

RESUMO

Purpose: To investigate the involvement of peripapillary zone vascular abnormalities in Behcet's uveitis (BU) and associated visual dysfunction. We evaluated the retinal and choroidal microvascular features in both macular and peripapillary areas of BU patients to identify vascular abnormalities contributing to reduced best-corrected visual acuity (BCVA) using optical coherence tomography angiography (OCTA). Methods: A prospective, observational study was conducted in 24 eyes of 13 patients with BU and 24 eyes of 15 healthy participants as controls. They received a standard eye examination and were recorded by OCTA measurements of macular and peripapillary areas. The vascular densities of superficial capillary plexus (SCP) and deep capillary plexus (DCP), choroidal flow area, radial peripapillary capillary network (RPCN) density, foveal avascular zone (FAZ) area and perimeter, full retinal thickness (FRT), and peripapillary retinal nerve fiber layer thickness (pRNFLT) were measured.Correlations among microvascular, structural, and functional changes were assessed. Results: Our findings uncovered that the vascular density was significantly reduced in the peripapillary zone of BU eyes compared to healthy eyes, especially in the inferior subfield of the RPCN. The vascular densities of SCP and DCP quadrants within the macular zone had no significant difference between BU and control groups except for DCP density of the nasal parafoveal quadrant. Both FAZ area and perimeter were greater but without statistical significance in the BU group. Compared to healthy eyes, the choriocapillaris flow area was smaller while the FRT and pRNFLT were greater in the BU group. Notably, there was a significant correlation between the reduction in RPCN vascular density and decreased BCVA in BU patients. Conclusion: Based on OCTA, vascular changes associated with BU are more prominent in the peripapillary zone than those in the macular zone. The vascular density of the RPCN could serve as a sensitive indicator to monitoring BU pathogenic progression and treatment response using a non-invasively method of OCTA.

5.
Blood Adv ; 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34710216

RESUMO

Secondary myelodysplastic syndromes and acute myeloid leukemia (sMDS/AML) are rare in children/adolescents and have a dismal prognosis. The mainstay therapy is hematopoietic cell transplantation (HCT) but there has been no innovation in cytoreductive regimens. CPX-351, a fixed 5:1 molar ratio of liposomal cytarabine/daunorubicin, has shown favorable safety and efficacy in elderly individuals with sAML and children with relapsed de novo AML. We report the outcomes of seven young patients (six with newly diagnosed sMDS/AML and one with primary MDS/AML) uniformly treated with CPX-351. Five patients had previously received chemotherapy for osteosarcoma, Ewing sarcoma, neuroblastoma, or T-ALL; one had predisposing genomic instability disorder (Cornelia de Lange); and one MDS-related AML and multi-organ failure. The median age at diagnosis of myeloid malignancy was 17 (13-23) years. Patients received 1-3 cycles of CPX-351 (cytarabine 100mg/m2 plus daunorubicin 44mg/m2) on days 1, 3, and 5, resulting in complete morphologic remission without overt toxicity or treatment-related mortality. This approach allowed for adding FLT3 inhibitor as individualized therapy in one patient. Six patients were alive and leukemia-free at 0.5-3.3 years after HCT. One patient died from disease progression before HCT. Concluding, CPX-351 is an effective and well-tolerated regimen for cytoreduction in pediatric sMDS/AML warranting prospective studies.

6.
Addict Behav ; 125: 107142, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34673361

RESUMO

The current study examined the bidirectional relationship between parental psychological control and problematic smartphone use (PSU) in early Chinese adolescence using a two time-points repeated-measures study and explored the role of psychological security and insomnia in the relationship between parental psychological control and subsequent PSU in early adolescence. The sample consisted of 2128 fourth- and fifth-grade students (55.69% male, age = 9 to 13, Mage ± SD = 10.91 ± 0.80) who participated in two measurements and completed questionnaires about parental psychological control, PSU, psychological security and insomnia. The results indicated that: (1) Autoregressive cross-lagged models showed a reciprocal relationship between parental psychological control and PSU severity in early adolescence. (2) Both psychological security and insomnia mediate the link between parental psychological control and subsequent PSU severity. (3) Psychological security and insomnia play serial mediating roles between parental psychological control and subsequent PSU severity. These findings indicate that reducing parental psychological control, boosting psychological security and alleviating insomnia symptoms in adolescents are all conducive to decrease PSU severity in early adolescence.

7.
Br J Radiol ; 94(1127): 20210682, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34478333

RESUMO

OBJECTIVE: To evaluate the correlation between elastic heterogeneity (EH) and lymphovascular invasion (LVI) in breast cancers and assess the clinical value of using EH to predict LVI pre-operatively. METHODS: This retrospective study consisted of 376 patients with breast cancers that had undergone shear wave elastography (SWE) with virtual touch tissue imaging quantification between June 2017 and June 2018. The EH was determined as the difference between the averaged three highest and three lowest shear wave value. Clinicalpathological parameters including histological type and grades, LVI, axillary lymph node status and molecular markers (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and Ki-67) were reviewed and recorded. Relationship EH and clinicalpathological parameters was investigated respectively. The diagnostic performance of EH in distinguishing LVI or not was analyzed. RESULTS: At multivariate regression analysis, only EH (p = 0.017) was positively correlated with LVI in all tumors. EH (p = 0.003) and Ki-67 (p = 0.025) were positively correlated with LVI in tumors ≤ 2 cm. None of clinicalpathological parameters were correlated with LVI in tumors > 2 cm (p > 0.05 for all). Using EH to predict LVI in tumors ≤ 2 cm, the sensitivity and negative predictive value were 93 and 89% respectively. CONCLUSION: EH has the potential to be served as an imaging biomarker to predict LVI in breast cancer especially for tumors ≤ 2 cm. ADVANCES IN KNOWLEDGE: There was no association between LVI and other most commonly used elastic features such as SWVmean and SWVmax. Elastic heterogeneity is an independent predictor of LVI, so it can provide additional prognostic information for routine preoperative breast cancer assessment.For tumors ≤ 2cm, using EH value higher than 1.36 m/s to predict LVI involvement, the sensitivity and negative predictive value can reach to 93% and 89%, respectively, suggesting that breast cancer with negative EH value was more likely to be absent of LVI.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Técnicas de Imagem por Elasticidade/métodos , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Vasos Linfáticos/diagnóstico por imagem , Adulto , Estudos de Avaliação como Assunto , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Vasos Linfáticos/patologia , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade
8.
Bioorg Chem ; 115: 105271, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34426155

RESUMO

In this study, a novel batch of thiazole-containing mitochondrial targeting agents were designed and synthesized. Four kinds of mitochondrial targeting moieties and six kinds of linkers were designed. Their structures were confirmed by NMR and HR-MS. The screening of antiproliferative activity revealed that most compounds displayed cytotoxicity on HeLa cancer cell. In particular, D1 has an IC50 value of 35.32 µmol·L-1 against HeLa cell. In addition, cellular respiratory activities were also tested on HeLa cancer cells. D1 had a basal oxygen consumption rate of 8.84 pmol·s-1·mL-1. Also, D1 inhibited the mitochondrial respiration of HeLa cell significantly at 5 µmol·L-1, as well as a complete inhibitory of oxygen consumption for cellular ATP coupling. Furthermore, the pKa, logP, and logD under different pH conditions of all the compounds were calculated by the ACD/Percepta-PhysChem Suite, and the results manifested the correlation between physicochemical properties and chemical activity of compounds. The results identify D1 as a promising mitochondria inhibitor and anticancer agent with appropriate physicochemical properties.

10.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(7): 577-584, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34140067

RESUMO

Objective To explore the role of transient receptor potential melastatin 8 (TRPM8) in the expression of airway epithelial-derived cytokines interleukin 25 (IL-25), IL-33 and thymic stromal lymphopoietin (TSLP) in human bronchial epithelial BEAS-2B cells induced by menthol and its related signal transduction mechanism. Methods BEAS-2B cells were treated with 2 mmol/L menthol for 1, 2, 3 and 4 hours. The groups with the higher expression of IL-25, IL-33, TSLP or Ca2+ were chosen to carry out the following experiments. The cells were transfected with siRNA of TRPM8 (si-TRPM8) or negative control siRNA (si-NC) and pretreated with intracellular calcium chelator BAPTA-AM, nuclear factor κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC), and then intervened with menthol. Cell survival rate was measured by CCK-8 assay. The mRNA levels of IL-25, IL-33 and TSLP were detected by real-time quantitative PCR. The protein levels of IL-25, IL-33 and TSLP were detected by ELISA. The intracellular Ca2+ fluorescence intensity was detected by flow cytometry with Fluo-4 AM loading. Western blotting was used to detect the interference efficiency of si-TRPM8 on BEAS-2B cells and its effect on the protein expression of NF-κB p65. Results Compared with the blank control group, the mRNA and protein expression of IL-25, IL-33 and TSLP, the level of Ca2+, and the protein expression of NF-κB p65 were significantly up-regulated in the menthol group. After knock-down of TRPM8, the menthol-induced increases of Ca2+, IL-25, IL-33, TSLP and NF-κB p65 expression were inhibited. Both BAPTA-AM and PDTC could inhibit the high expression of IL-25, IL-33 and TSLP induced by menthol. Conclusion Menthol can induce the secretion of IL-25, IL-33 and TSLP in human BEAS-2B cells by activating TRPM8 which leads to increased Ca2+ concentration and activation of the NF-κB pathway.


Assuntos
Mentol , Canais de Cátion TRPM , Citocinas/genética , Células Epiteliais/metabolismo , Humanos , Proteínas de Membrana , Mentol/farmacologia , NF-kappa B/genética , NF-kappa B/metabolismo , Transporte Proteico , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo
11.
Eur J Med Chem ; 222: 113541, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34116326

RESUMO

A series of benzofuran piperidine derivatives were designed, synthesized and evaluated as multifunctional Aß antiaggregant to treat Alzheimer's disease (AD). In vitro results revealed that all of them are very good Aß antiaggregants and some of the compounds are potent acetylcholinesterase (AChE) inhibitors with moderate antioxidant property. Selected compounds were also tested for neuroprotection activity, LDH release, ATP production and inhibitory activity to prevent Aß peptides binding to the cell membrane. The different modifications introduced in the structure of our lead compound 3 (hAChE IC50 = 61 µM and self induced Aß 25-35 aggregation 45.45%), to increase its activity toward AD related targets. The most interesting multifunctional Aß antiaggregants were compounds 3a, 3h and 3i, highlighting 3h as potent Aß antiaggregant and good antiacetylholinesterase inhibitor (self induced Aß 25-35 aggregation 57.71% and hAChE IC50 = 21 µM), with good neuroprotective and antioxidant activity. In addition, these three most promising compounds prevent intracellular reactive oxygen species (ROS) formation and cell apoptosis induced by Aß25-35 peptides in SH-SY5Y cells. Molecular docking studies were also accomplished to understand the binding interaction of these compounds on Aß monomer, Aß fibril and AChE. Based on all data, compounds 3a, 3h and 3i were concluded as potent multifunctional Aß antiaggregant, useful candidate for the treatment of AD.


Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Benzofuranos/farmacologia , Inibidores da Colinesterase/farmacologia , Fármacos Neuroprotetores/farmacologia , Piperidinas/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Benzofuranos/síntese química , Benzofuranos/química , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Relação Dose-Resposta a Droga , Humanos , Modelos Moleculares , Estrutura Molecular , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Piperidinas/síntese química , Piperidinas/química , Agregados Proteicos/efeitos dos fármacos , Agregação Patológica de Proteínas/tratamento farmacológico , Agregação Patológica de Proteínas/metabolismo , Relação Estrutura-Atividade
12.
Bioorg Chem ; 114: 105015, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34139611

RESUMO

Mitochondria are pivotal energy production sources for cells to maintain necessary metabolism activities. Targeting dysfunctional mitochondrial features has been a hotspot for mitochondrial-related disease researches. Investigation with cancerous mitochondrial metabolism is a continuing concern within tumor therapy. Herein, we set out to assess the anti-cancer activities of a novel family of TPP-thiazole derivatives based on our earlier research on mitochondrial targeting agents. Specifically, we designed and synthesized a series of TPP-thiazole derivatives and revealed by the MTT assay that most synthesized compounds effectively inhibited three cancer cell lines (HeLa, PC3 and MCF-7). After structure modifications, we explored the SAR relationships and identified the most promising compound R13 (IC50 of 5.52 µM) for further investigation. In the meantime, we performed ATP production assay to assess the selected compounds inhibitory effect on HeLa cells energy production. The results displayed the test compounds significantly restrained ATP production of cancer cells. Overall, we have designed and synthesized a series of compounds which exhibited significant cytotoxicity against cancer cells and effectively inhibited mitochondrial energy production.

13.
Bioorg Chem ; 114: 105055, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34144278

RESUMO

Cancer therapy targets specific metabolic pathways or a single gene. This may result in low therapeutic effects due to drug selectivity and drug resistance. Recent studies revealed that the mitochondrial membrane potential and transmembrane permeability of cancerous mitochondria are differed from normal mitochondria. Thus, chemotherapy targeting cancerous mitochondria could be an innovative and competent strategy for cancer therapy. Previously, our work with a novel group of mitochondria targeting small molecules presented promising inhibitory capability toward various cancer cell lines and suppressed adenosine triphosphate (ATP) generation. Therefore, it is critical to understand the anticancer effect and targeting mechanism of these small molecules. This study investigated the inhibitory activity of mitochondria targeting small molecules with human cervical cancer cells - HeLa to further explore their therapeutic potential. HeLa cells were exposed to 10 µM of synthesized compounds and presented elevation in intracellular reactive oxygen species (ROS) level, impaired mitochondrial membrane potential and upregulation of apoptosis as well as necrosis. In vivo, HeLa cell tumor-bearing BALB/c nude mice were treated with mitochondria targeting small molecules for 12 days consecutively. Throughout this chemotherapy study, no deleterious side effects nor the appearance of toxicity was observed. Furthermore, mitochondria targeting small molecules treated groups exhibited significant down-regulation with both tumor volume and tumor weight compared to the Doxorubicin (DOX) treated group. Thus, inhibition of mitochondrial ATP synthesis, activation of intracellular ROS production, down-regulation of mitochondrial membrane potential and upregulation of apoptosis and necrosis rates are the indications of cancer therapy. In this work, we examined the anticancer capability of four mitochondria targeting small molecules in vitro and in vivo, and demonstrated a novel therapeutic approach in cancer therapy with tremendous potential.

14.
Front Cell Dev Biol ; 9: 669696, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34095138

RESUMO

Retinal ischemia is a common pathological event that can result in retinal ganglion cell (RGC) death and irreversible vision loss. The pathogenic mechanisms linking retinal ischemia to RGC loss and visual deficits are uncertain, which has greatly hampered the development of effective treatments. It is increasingly recognized that pyroptosis of microglia contributes to the indirect inflammatory death of RGCs. In this study, we report a regulatory NOD-like receptor, NOD-, LRR- and CARD-containing 5 (NLRC5), as a key regulator on microglial pyroptosis and the retinal ischemia process. Through an in-depth analysis of our recently published transcriptome data, we found that NLRC5 was significantly up-regulated in retina during ischemia-reperfusion injury, which were further confirmed by subsequent detection of mRNA and protein level. We further found that NLRC5 was upregulated in retinal microglia during ischemia, while NLRC5 knockdown significantly ameliorated retinal ischemic damage and RGC death. Mechanistically, we revealed that knockdown of NLRC5 markedly suppressed gasdermin D (GSDMD) cleavage and activation of interleukin-1ß (IL-1ß) and caspase-3, indicating that NLRC5 promotes both microglial pyroptosis and apoptosis. Notably, we found that NLRC5 directly bound to NLRP3 and NLRC4 in inflammasomes to cooperatively drive microglial pyroptosis and apoptosis mediating retinal ischemic damage. Overall, these findings reveal a previously unidentified key contribution of NLRC5 signaling to microglial pyroptosis under ischemia or hypoxia conditions. This NLRC5-dependent pathway may be a novel therapeutic target for treatment of ischemic retinopathy.

15.
BMC Geriatr ; 21(1): 292, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33957882

RESUMO

BACKGROUND: This study aimed to investigate the associations of sarcopenia and its defining components with cognitive function in community-dwelling oldest old (over 80 years old) in China. METHODS: Sarcopenia was diagnosed by the 2019 Asian Working Group for Sarcopenia (AWGS) criteria. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA). Logistic and linear regression models were used to explore the associations of sarcopenia and its defining components with risk of mild cognitive impairment (MCI), and performance on multiple cognitive domains among 428 adults aged 80 years and older. RESULTS: The overall prevalence of sarcopenia was 35.5%, with 40.34% for men and 32.14% for women. The prevalence of MCI was higher among sarcopenic oldest old than non-sarcopenic oldest old (28.95% vs. 17.39%, p = 0.005). Multivariate logistic regression analyses showed that sarcopenia [odds ratio (OR) = 1.86, 95% confidence interval (CI): 1.04-3.33], low handgrip strength (HS) [OR = 2.33, 95% CI: 1.40-3.87] and slow gait speed (GS) [OR = 2.31, 95% CI: 1.13-4.72] were significantly and independently associated with risk of MCI. Multivariate linear regression analyses showed that low HS was associated with worse performance in global cognitive function, visuospatial and executive function, naming and delayed recall. CONCLUSIONS: Sarcopenia, low HS and low GS was significantly associated with MCI in community-dwelling oldest old. The associations between sarcopenia and its defining components with different cognitive subdomains could be further explored in the future.


Assuntos
Sarcopenia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Cognição , Estudos Transversais , Feminino , Avaliação Geriátrica , Força da Mão , Humanos , Vida Independente , Masculino , Prevalência , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia
16.
BMC Geriatr ; 21(1): 336, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039260

RESUMO

BACKGROUND: The Pittsburgh Fatigability Scale (PFS) was developed to capture fatigue and demand in a single tool, filling a gap that no validated questionnaire existed to measure perceived fatigability. Since fatigability is a more sensitive measure of a person's susceptibility to fatigue, we validated the simplified-Chinese version of the PFS among Chinese community-dwelling older adults. METHODS: This cross-sectional study was conducted in an urban community in Beijing between November 2018 and July 2019. The PFS was translated into simplified-Chinese by the translation, retro-translation method. Internal consistency of the Physical subscale of the PFS was evaluated by Cronbach's alpha. Convergent validity and discriminant validity were evaluated against physical performance measures (i.e., Short Physical Performance Battery & Timed Up and Go Test) and daily living performance (i.e., Barthel Index & Instrumental activity of daily living). RESULTS: Our study included 457 participants, including 182 men (39.8%) and 275 women (60.2%). The age range of the included participants was 61-96 years (mean = 84.8 years, SD = 5.8 years). The simplified-Chinese version of PFS Physical scores showed strong internal consistency (Cronbach's alpha = 0.81). Higher PFS Physical scores were associated with worse physical performance, and daily living performance (|correlation coefficient| range: 0.36-0.56, p < .001). Age- and sex-adjusted PFS Physical scores had moderate to good overall discrimination for correctly classifying people by their physical performance and daily living performance (AUCs range 0.70-0.87, p < .001). CONCLUSIONS: The PFS simplified-Chinese version is a valid instrument to assess perceived physical fatigability in Chinese-speaking older adults with good convergent validity. Thus, the PFS, with low cost and greater feasibility, is a desired tool to measure fatigability in large population studies.


Assuntos
Fadiga , Equilíbrio Postural , Idoso , Idoso de 80 Anos ou mais , Pequim , China , Estudos Transversais , Fadiga/diagnóstico , Fadiga/epidemiologia , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários , Estudos de Tempo e Movimento
17.
Chem Rev ; 121(8): 5042-5092, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33792299

RESUMO

Polymer networks are complex systems consisting of molecular components. Whereas the properties of the individual components are typically well understood by most chemists, translating that chemical insight into polymer networks themselves is limited by the statistical and poorly defined nature of network structures. As a result, it is challenging, if not currently impossible, to extrapolate from the molecular behavior of components to the full range of performance and properties of the entire polymer network. Polymer networks therefore present an unrealized, important, and interdisciplinary opportunity to exert molecular-level, chemical control on material macroscopic properties. A barrier to sophisticated molecular approaches to polymer networks is that the techniques for characterizing the molecular structure of networks are often unfamiliar to many scientists. Here, we present a critical overview of the current characterization techniques available to understand the relation between the molecular properties and the resulting performance and behavior of polymer networks, in the absence of added fillers. We highlight the methods available to characterize the chemistry and molecular-level properties of individual polymer strands and junctions, the gelation process by which strands form networks, the structure of the resulting network, and the dynamics and mechanics of the final material. The purpose is not to serve as a detailed manual for conducting these measurements but rather to unify the underlying principles, point out remaining challenges, and provide a concise overview by which chemists can plan characterization strategies that suit their research objectives. Because polymer networks cannot often be sufficiently characterized with a single method, strategic combinations of multiple techniques are typically required for their molecular characterization.

18.
Transplant Cell Ther ; 27(7): 611.e1-611.e12, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33895404

RESUMO

Early prediction and intervention are known to be critical for acute graft-versus-host disease (aGVHD) prevention and treatment. Significant progress has been made in the development of human plasma biomarkers for the risk stratification of aGVHD severity. Whether donor-derived immune cells may predict the occurrence of severe aGVHD early after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains poorly understood. The objective of this retrospective study was to evaluate the results of allo-HSCT in pediatric patients with different counts and frequencies of dendritic cell (DC) subsets at engraftment in pediatric patients at the Children's Hospital of Soochow University. A total of 45 patients as a discovery cohort were enrolled from March 2018 to December 2018 at the hospital. The validation cohort (30 patients) was enrolled from December 2019 to May 2020. Plasma samples collected from 2016 to 2018 were used for testing ST2 and Reg3α in pediatric patients undergoing allo-HSCT. Patients with grade II-IV aGVHD (n = 18; termed severe aGVHD) showed 3- and 6-fold fewer frequency and numbers, respectively, of plasmacytoid dendritic cells (pDCs) in the peripheral blood (PB) at the engraftment time than patients with grade 0-I aGVHD (n = 27; termed no/mild aGVHD). Using a receiver operating characteristic curve analysis, we identified the threshold of pDC level at 0.3 cell/µL as a cutoff to evaluate the difference in patients with high (>0.3 cell/µL) versus low (<0.3 cell/µL) pDC counts. Of these 45 patients, 21 (46.7%) had a high number of pDCs and 24 (53.3%) had low pDCs. The patients with low pDCs at the time of engraftment had a significantly higher probability of developing severe aGVHD (P < .05). The sensitivity of distinguishing severe aGVHD from no/mild aGVHD was 75%, and the specificity was 94%. In addition, the low pDC patients had higher transplantation-related mortality compared with the high pDC patients (12.5% versus 0%). Using an additional cohort of 30 allo-HSCT patients, we validated this observation. Our findings demonstrate that donor pDC count in PB at the time of engraftment is a valuable biomarker for predicting severe aGVHD in pediatric patients undergoing allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Criança , Células Dendríticas , Doença Enxerto-Hospedeiro/diagnóstico , Humanos , Prognóstico , Estudos Retrospectivos
19.
Front Oncol ; 11: 614420, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33796456

RESUMO

Background: Aberrant expression of CD123 (IL-3Rα) was observed in various hematological malignancies including acute lymphoblastic leukemia (ALL), which is the most common malignancy in childhood. Although widely used for minimal residual disease (MRD) monitoring, the prognostic value of CD123 has not been fully characterized in pediatric B-ALL. This retrospective study aims to evaluate the association between the CD123 expression of leukemic blasts and the outcomes of the pediatric B-ALL patients. Methods: A total of 976 pediatric B-ALL, including 328 treated with CCLG-ALL-2008 protocol and 648 treated with CCCG-ALL-2015 protocol, were recruited in this retrospective study. CD123 expression was evaluated by flow cytometry. Patients with >50, 20-50, or <20% of CD123 expressing blasts were grouped into CD123high, CD123low, and CD123neg, respectively. The correlation between CD123 expression and the patients' clinical characteristics, overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were studied statistically. Results: Of 976 pediatric B-ALL, 53.4% from the CCLG-ALL-2008 cohort and 49.2% from the CCCG-ALL-2015 cohort were CD123high. In the CCLG-ALL-2008 cohort, CD123high was significantly associated with chromosome hyperdiploidy (p < 0.0001), risk stratification (p = 0.004), and high survival rate (p = 0.005). By comparing clinical outcomes, patients with CD123high displayed favorable prognosis, with a significantly better OS (p = 0.005), EFS (p = 0.017), and RFS (p = 0.045), as compared to patients with CD123low and CD123neg. The prognostic value of CD123 expression was subsequently confirmed in the CCCG-ALL-2015 cohort. Univariate and multivariate cox regression model analysis showed that high CD123 expression was independently associated with favorable EFS (OR: 0.528; 95% CI: 0.327 to 0.853; p = 0.009) in this cohort. In patients without prognosis-defining genomic abnormalities, high CD123 expression strongly indicated superior survival rates and was identified as an independent prognosis factor for EFS and RFS in both cohorts. Conclusions: A group of B-ALL lacks prognosis-defining genomic aberrations, which proposes a challenge in risk stratification. Our findings revealed that high CD123 expression of leukemic blasts was associated with favorable clinical outcomes in pediatric B-ALL and CD123 could serve as a promising prognosis predictor, especially in patients without prognosis-defining genetic aberrations.

20.
Front Oncol ; 11: 641195, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33912456

RESUMO

Objective: Data regarding direct comparison of contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) and Computed Tomography/Magnetic Resonance Imaging (CT/MR) LI-RADS in diagnosis of non-hepatocelluar carcinoma (non-HCC) malignancies remain limited. Our study aimed to compare the diagnostic performance of the CEUS LI-RADS version 2017 and CT/MRI LI-RADS v2018 for diagnosing non-HCC malignancies in patients with risks for HCC. Materials and Methods: In this retrospective study, 94 liver nodules pathologically-confirmed as non-HCC malignancies in 92 patients at risks for HCC from January 2009 to December 2018 were enrolled. The imaging features and the LI-RADS categories on corresponding CEUS and CT/MRI within 1 month were retrospectively analyzed according to the ACR CEUS LI-RADS v2017 and ACR CT/MRI LI-RADS v2018 by two radiologists in consensus for each algorithm. The sensitivity of LR-M category, inter-reader agreement and inter-modality agreement was compared between these two standardized algorithms. Results: Ninety-four nodules in 92 patients (mean age, 54 years ± 10 [standard deviation] with 65 men [54 years ± 11] and 27 women [54 years ± 8]), including 56 intrahepatic cholangiocarcinomas, 34 combined hepatocellular cholangiocarcinomas, two adenosquamous carcinomas of the liver, one primary hepatic neuroendocrine carcinoma and one hepatic undifferentiated sarcoma were included. On CEUS, numbers of lesions classified as LR-3, LR-4, LR-5 and LR-M were 0, 1, 10 and 83, and on CT/MRI, the corresponding numbers were 3, 0, 14 and 77. There was no significant difference in the sensitivity of LR-M between these two standardized algorithms (88.3% of CEUS vs 81.9% of CT/MRI, p = 0.210). Seventy-seven lesions (81.9%) were classified as the same LI-RADS categories by both standardized algorithms (five for LR-5 and 72 for LR-M, kappa value = 0.307). In the subgroup analysis for ICC and CHC, no significant differences were found in the sensitivity of LR-M category between these two standardized algorithms (for ICC, 94.6% of CEUS vs 89.3% of CT/MRI, p = 0.375; for CHC, 76.5% of CEUS vs 70.6% of CT/MRI, p = 0. 649). Conclusion: CEUS LI-RADS v2017 and CT/MRI LI-RADS v2018 showed similar value for diagnosing non-HCC primary hepatic malignancies in patients with risks.

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