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1.
Curr Med Imaging ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38639287

RESUMO

BACKGROUND: Carotid duplex ultrasonography (DUS) is the primary screening tool for carotid artery stenosis, but has low reliability. MHR, which is the ratio of monocytes to high-density lipoprotein cholesterol (HDL-C), can be a marker for the degree and distribution of extracranial and intracranial atherosclerotic stenosis. OBJECTIVE: We determined the diagnostic value of DUS+MHR for internal carotid artery (ICA) stenosis. METHODS: We divided 273 hospitalized patients into non-stenosis (<50%) and ICA stenosis (≥50%) groups based on Digital Subtraction Angiography (DSA). We determined the peak systolic velocity (PSV) in the ICA on DUS, calculated the MHR, and investigated their relationship with ICA stenosis. RESULTS: On DSA, 34.1% (93/273) patients had moderate-to-severe ICA stenosis. DUS and DSA showed low concordance for detecting ICA stenosis (kappa = 0.390). With increasing age, the incidence of moderate-to-severe ICA stenosis increased. PSV, monocyte count, and MHR were significantly greater in the stenosis group than in the non-stenosis group (P < 0.001), while the HDL-C level was significantly lower (P = 0.001). PSV (OR: 1.020, 95% CI: 1.011-1.029, P < 0.001) and MHR (OR: 5.662, 95% CI: 1.945-16.482, P = 0.002) were independent risk factors for ICA stenosis. The area under the receiver operating characteristic curve of PSV+MHR (0.819) was significantly higher than that of PSV or MHR alone (77.42% sensitivity, P = 0.0207; 73.89% specificity, P = 0.0032). CONCLUSION: The combination of ICA PSV on DUS and MHR is better than PSV alone at identifying ICA stenosis and is well-suited to screen high-risk patients.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38608312

RESUMO

Embryonic development is a dynamic process orchestrated by a delicate interplay of biochemical and biophysical factors. While the role of genetics and biochemistry in embryogenesis has been extensively studied, recent research has highlighted the significance of mechanical regulation in shaping and guiding this intricate process. Here, we provide an overview of the current understanding of the mechanical regulation of embryo development. We explore how mechanical forces generated by cells and tissues play a crucial role in driving the development of different stages. We examine key morphogenetic processes such as compaction, blastocyst formation, implantation, and egg cylinder formation, and discuss the mechanical mechanisms and cues involved. By synthesizing the current body of literature, we highlight the emerging concepts and open questions in the field of mechanical regulation. We aim to provide an overview of the field, inspiring future investigations and fostering a deeper understanding of the mechanical aspects of embryo development.

3.
Zhen Ci Yan Jiu ; 49(4): 331-340, 2024 Apr 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38649200

RESUMO

OBJECTIVES: To observe whether acupuncture up-regulates chemokine CXC ligand 1 (CXCL1) in the brain to play an analgesic role through CXCL1/chemokine CXC receptor 2 (CXCR2) signaling in adjuvant induced arthritis (AIA) rats, so as to reveal its neuro-immunological mechanism underlying improvement of AIA. METHODS: BALB/c mice with relatively stable thermal pain reaction were subjected to planta injection of complete Freund adjuvant (CFA) for establishing AIA model, followed by dividing the AIA mice into simple AF750 (fluorochrome) and AF750+CXCL1 groups (n=2 in each group). AF750 labeled CXCL1 recombinant protein was then injected into the mouse's tail vein to induce elevation of CXCL1 level in blood for simulating the effect of acupuncture stimulation which has been demonstrated by our past study. In vivo small animal imaging technology was used to observe the AF750 and AF750+CXCL1-labelled target regions. After thermal pain screening, the Wistar rats with stable pain reaction were subjected to AIA modeling by injecting CFA into the rat's right planta, then were randomized into model and manual acupuncture groups (n=12 in each group). Other 12 rats that received planta injection of saline were used as the control group. Manual acupuncture (uniform reinforcing and reducing manipulations) was applied to bilateral "Zusanli" (ST36) for 4×2 min, with an interval of 5 min between every 2 min, once daily for 7 days. The thermal pain threshold was assessed by detecting the paw withdrawal latency (PWL) using a thermal pain detector. The contents of CXCL1 in the primary somatosensory cortex (S1), medial prefrontal cortex, nucleus accumbens, amygdala, periaqueductal gray and rostroventromedial medulla regions were assayed by using ELISA, and the expression levels of CXCL1, CXCR2 and mu-opioid receptor (MOR) mRNA in the S1 region were detected using real time-quantitative polymerase chain reaction. The immune-fluorescence positive cellular rate of CXCL1 and CXCR2 in S1 region was observed after immunofluorescence stain. The immunofluorescence double-stain of CXCR2 and astrocyte marker glial fibrillary acidic protein (GFAP) or neuron marker NeuN or MOR was used to determine whether there is a co-expression between them. RESULTS: In AIA mice, results of in vivo experiments showed no obvious enrichment signal of AF750 or AF750+CXCL1 in any organ of the body, while in vitro experiments showed that there was a stronger fluorescence signal of CXCL1 recombinant protein in the brain. In rats, compared with the control group, the PWL from day 0 to day 7 was significantly decreased (P<0.01) and the expression of CXCR2 mRNA in the S1 region significantly increased in the model group (P<0.05), while in comparison with the model group, the PWL from day 2 to day 7, CXCL1 content, CXCR2 mRNA expression and CXCR2 content, and MOR mRNA expression in the S1 region were significantly increased in the manual acupuncture group (P<0.05, P<0.01). Immunofluorescence stain showed that CXCR2 co-stained with NeuN and MOR in the S1 region, indicating that CXCR2 exists in neurons and MOR-positive neurons but not in GFAP positive astrocytes. CONCLUSIONS: Acupuncture can increase the content of CXCL1 in S1 region, up-regulate CXCR2 on neurons in the S1 region and improve MOR expression in S1 region of AIA rats, which may contribute to its effect in alleviating inflammatory pain.

4.
Elife ; 122024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478405

RESUMO

Previous research has found that prolonged eye-based attention can bias ocular dominance. If one eye long-termly views a regular movie meanwhile the opposite eye views a backward movie of the same episode, perceptual ocular dominance will shift towards the eye previously viewing the backward movie. Yet it remains unclear whether the role of eye-based attention in this phenomenon is causal or not. To address this issue, the present study relied on both the functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) techniques. We found robust activation of the frontal eye field (FEF) and intraparietal sulcus (IPS) when participants were watching the dichoptic movie while focusing their attention on the regular movie. Interestingly, we found a robust effect of attention-induced ocular dominance shift when the cortical function of vertex or IPS was transiently inhibited by continuous theta burst stimulation (cTBS), yet the effect was significantly attenuated to a negligible extent when cTBS was delivered to FEF. A control experiment verified that the attenuation of ocular dominance shift after inhibitory stimulation of FEF was not due to any impact of the cTBS on the binocular rivalry measurement of ocular dominance. These findings suggest that the fronto-parietal attentional network is involved in controlling eye-based attention in the 'dichoptic-backward-movie' adaptation paradigm, and in this network, FEF plays a crucial causal role in generating the attention-induced ocular dominance shift.


Assuntos
Dominância Ocular , Estimulação Magnética Transcraniana , Humanos , Estimulação Magnética Transcraniana/métodos , Atenção/fisiologia , Lobo Frontal/fisiologia , Lobo Parietal/fisiologia , Estimulação Luminosa/métodos
5.
Heliyon ; 10(3): e25797, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38352800

RESUMO

Internal migrants with chronic diseases (IMCDs) are a specific subgroup of the internal migrants, but few studies have focused on health service utilization among this group. Social integration is an essential element in the maintenance of health and well-being in migrants. However, the measurement of social integration remains inconsistent. This study aimed to measure social integration more comprehensively and evaluate the association between social integration and National Basic Public Health Services (NBPHS) utilization among IMCDs in China, thereby providing theoretical support for health promotion among IMCDs. The data of this study were obtained from the China Migrants Dynamic Survey (CMDS) in 2017. A total of 9272 internal migrants who self-reported hypertension and/or type 2 diabetes were included in the analysis. Four factors were extracted through exploratory factor analysis to measure the social integration of IMCDs: psychological identity, community involvement, social security, and sociocultural adaptation. The results show the IMCDs underutilized NBPHS, with 26.80 % stating that they have not used any of the services in the NBPHS. We confirmed the positive association between social integration and NBPHS use among IMCDs. The social integration of IMCDs in developed regions was relatively worse than in developing regions, further exacerbating the underutilization of NBPHS in developed regions. Therefore, targeted government measures and supportive policies are necessary, especially in developed regions, to encourage IMCDs to participate in social organizations and community activities and stimulate their active participation in the NBPHS.

6.
Neurosurgery ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38334381

RESUMO

BACKGROUND AND OBJECTIVES: Spinal cord stimulation (SCS) is an effective treatment for diabetic peripheral neuropathy. The purpose of this study was to investigate the effectiveness of SCS in the treatment of ischemic diabetic foot ulcers. METHODS: In this retrospective study, the SCS group comprised 102 patients with ischemic diabetic foot who were treated with SCS for foot ulcers and nonhealing wounds due to severe lower limb ischemia. The traditional debridement care (TDC) group comprised 104 patients with ischemic diabetic foot who received only TDC. Strict screening criteria were applied. The assignment of patients to either group depended solely on their willingness to be treated with SCS. Secondary end points were transcutaneous partial pressure of oxygen (PtcO2), ankle-brachial index (ABI), and color Doppler of the lower limb arteries in the feet at 6 months and 12 months after treatment. The primary end point was the amputation. RESULTS: The dorsal foot PtcO2 and ABI of the patients in the SCS group were significantly improved at 6 months and 12 months postoperation (P < .05). The therapeutic efficacy was significantly better than that of the TDC group over the same period of time (P < .05). The degree of vasodilation of the lower limb arteries (ie, femoral, popliteal, posterior tibial, and dorsalis pedis arteries) on color Doppler was higher in the SCS group than in the TDC group (P < .05). The odds ratios for total amputation at 6 and 12 months postoperatively in the SCS group were 0.45 (95% CI, 0.19-1.08) and 0.17 (95% CI, 0.08-0.37), respectively, compared with the TDC group. CONCLUSION: SCS improved symptoms of lower limb ischemia in ischemic diabetic feet and reduced the rate of toe amputation by increasing PtcO2, ABI, and arterial vasodilation in the lower limbs.

7.
Annu Rev Biophys ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424091

RESUMO

The volumes of living cells undergo dynamic changes to maintain the cells' structural and functional integrity in many physiological processes. Minor fluctuations in cell volume can serve as intrinsic signals that play a crucial role in cell fate determination during mechanotransduction. In this review, we discuss the variability of cell volume and its role in vivo, along with an overview of the mechanisms governing cell volume regulation. Additionally, we provide insights into the current approaches used to control cell volume in vitro. Furthermore, we summarize the biological implications of cell volume regulation and discuss recent advances in understanding the fundamental relationship between cell volume and mechanotransduction. Finally, we delve into the potential underlying mechanisms, including intracellular macromolecular crowding and cellular mechanics, that govern the global regulation of cell fate in response to changes in cell volume. By exploring the intricate interplay between cell volume and mechanotransduction, we underscore the importance of considering cell volume as a fundamental signaling cue to unravel the basic principles of mechanotransduction. Additionally, we propose future research directions that can extend our current understanding of cell volume in mechanotransduction. Overall, this review highlights the significance of considering cell volume as a fundamental signal in understanding the basic principles in mechanotransduction and points out the possibility of controlling cell volume to control cell fate, mitigate disease-related damage, and facilitate the healing of damaged tissues. Expected final online publication date for the Annual Review of Biophysics, Volume 53 is May 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

8.
Neurophotonics ; 11(1): 015005, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38298609

RESUMO

Significance: A fleeting flash aligned vertically with an object remaining stationary in the head-centered space would be perceived as lagging behind the object during the observer's horizontal head rotation. This perceptual mislocalization is an illusion named head-rotation-induced flash-lag effect (hFLE). While many studies have investigated the neural mechanism of the classical visual FLE, the hFLE has been hardly investigated. Aim: We measured the cortical activity corresponding to the hFLE on participants experiencing passive head rotations using functional near-infrared spectroscopy. Approach: Participants were asked to judge the relative position of a flash to a fixed reference while being horizontally rotated or staying static in a swivel chair. Meanwhile, functional near-infrared spectroscopy signals were recorded in temporal-parietal areas. The flash duration was manipulated to provide control conditions. Results: Brain activity specific to the hFLE was found around the right middle/inferior temporal gyri, and bilateral supramarginal gyri and superior temporal gyri areas. The activation was positively correlated with the rotation velocity of the participant around the supramarginal gyrus and negatively related to the hFLE intensity around the middle temporal gyrus. Conclusions: These results suggest that the mechanism underlying the hFLE involves multiple aspects of visual-vestibular interactions including the processing of multisensory conflicts mediated by the temporoparietal junction and the modulation of vestibular signals on object position perception in the human middle temporal complex.

9.
IEEE J Biomed Health Inform ; 28(2): 1110-1121, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38055359

RESUMO

Accumulating evidence indicates that microRNAs (miRNAs) can control and coordinate various biological processes. Consequently, abnormal expressions of miRNAs have been linked to various complex diseases. Recognizable proof of miRNA-disease associations (MDAs) will contribute to the diagnosis and treatment of human diseases. Nevertheless, traditional experimental verification of MDAs is laborious and limited to small-scale. Therefore, it is necessary to develop reliable and effective computational methods to predict novel MDAs. In this work, a multi-kernel graph attention deep autoencoder (MGADAE) method is proposed to predict potential MDAs. In detail, MGADAE first employs the multiple kernel learning (MKL) algorithm to construct an integrated miRNA similarity and disease similarity, providing more biological information for further feature learning. Second, MGADAE combines the known MDAs, disease similarity, and miRNA similarity into a heterogeneous network, then learns the representations of miRNAs and diseases through graph convolution operation. After that, an attention mechanism is introduced into MGADAE to integrate the representations from multiple graph convolutional network (GCN) layers. Lastly, the integrated representations of miRNAs and diseases are input into the bilinear decoder to obtain the final predicted association scores. Corresponding experiments prove that the proposed method outperforms existing advanced approaches in MDA prediction. Furthermore, case studies related to two human cancers provide further confirmation of the reliability of MGADAE in practice.


Assuntos
MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , Reprodutibilidade dos Testes , Biologia Computacional/métodos , Neoplasias/genética , Algoritmos
10.
Neurosci Bull ; 40(3): 339-349, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37635196

RESUMO

Previous research has shown that ocular dominance can be biased by prolonged attention to one eye. The ocular-opponency-neuron model of binocular rivalry has been proposed as a candidate account for this phenomenon. Yet direct neural evidence is still lacking. By manipulating the contrast of dichoptic testing gratings, here we measured the steady-state visually evoked potentials (SSVEPs) at the intermodulation frequencies to selectively track the activities of ocular-opponency-neurons before and after the "dichoptic-backward-movie" adaptation. One hour of adaptation caused a shift of perceptual and neural ocular dominance towards the unattended eye. More importantly, we found a decrease in the intermodulation SSVEP response after adaptation, which was significantly greater when high-contrast gratings were presented to the attended eye than when they were presented to the unattended eye. These results strongly support the view that the adaptation of ocular-opponency-neurons contributes to the ocular dominance plasticity induced by prolonged eye-based attention.


Assuntos
Dominância Ocular , Visão Binocular , Visão Binocular/fisiologia , Estimulação Luminosa/métodos , Visão Ocular , Neurônios
11.
Ann Hematol ; 103(1): 163-174, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37817010

RESUMO

The present study aimed to investigate the clinical features, prognosis, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma (ENKTCL). This real-world study retrospectively reviewed 56 newly diagnosed advanced-stage non-nasal type ENKTCL patients from two large-scale Chinese cancer centers in the last 10-15 years and screened 139 newly diagnosed advanced-stage nasal type ENKTCLs admitted during the same period for comparison. The non-nasal type ENKTCLs exhibited significantly higher Ki-67 expression levels compared to nasal type disease (P = 0.011). With a median follow-up duration of 75.03 months, the non-nasal group showed slightly inferior survival outcomes without statistically significant differences compared to the nasal group (median overall survival (OS): 14.57 vs. 21.53 months, 5-year OS: 28.0% vs. 38.5%, P = 0.120). Eastern Cooperative Oncology Group (ECOG) score ≥ 2 (hazard ratio (HR) = 2.18, P = 0.039) and lactic dehydrogenase (LDH) elevation (HR = 2.44, P = 0.012) were significantly correlated with worse OS in the non-nasal group. First-line gemcitabine-based chemotherapy regimens showed a trend toward slightly improved efficacy and survival outcomes compared to non-gemcitabine-based ones in the present cohort of non-nasal ENKTCLs (objective response rate: 91.7% vs. 63.6%, P = 0.144; complete response rate: 50.0% vs. 33.3%, P = 0.502; median progression-free survival: 10.43 vs. 3.40 months, P = 0.106; median OS: 25.13 vs. 9.30 months, P = 0.125), which requires further validation in larger sample size studies. Advanced-stage non-nasal type patients could achieve comparable prognosis with nasal cases after rational therapy. The modified nomogram-revised index (including age, ECOG score, and LDH) and modified international prognostic index (including age, ECOG score, LDH, and number of extranodal involvement) functioned effectively for prognostic stratification in non-nasal type ENKTCLs.


Assuntos
Linfoma Extranodal de Células T-NK , Linfoma de Células T , Humanos , Prognóstico , Estudos Retrospectivos , Modelos de Riscos Proporcionais , Células Matadoras Naturais/patologia , Linfoma de Células T/patologia , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Estadiamento de Neoplasias
12.
BMJ Open ; 13(12): e071430, 2023 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-38070927

RESUMO

OBJECTIVES: Early identification of fracture risk in patients with osteoporosis is essential. Machine learning (ML) has emerged as a promising technique to predict the risk, whereas its predictive performance remains controversial. Therefore, we conducted this systematic review and meta-analysis to explore the predictive efficiency of ML for the risk of fracture in patients with osteoporosis. METHODS: Relevant studies were retrieved from four databases (PubMed, Embase, Cochrane Library and Web of Science) until 31 May 2023. A meta-analysis of the C-index was performed using a random-effects model, while a bivariate mixed-effects model was used for the meta-analysis of sensitivity and specificity. In addition, subgroup analysis was performed according to the types of ML models and fracture sites. RESULTS: Fifty-three studies were included in our meta-analysis, involving 15 209 268 patients, 86 prediction models specifically developed for the osteoporosis population and 41 validation sets. The most commonly used predictors in these models encompassed age, BMI, past fracture history, bone mineral density T-score, history of falls, BMD, radiomics data, weight, height, gender and other chronic diseases. Overall, the pooled C-index of ML was 0.75 (95% CI: 0.72, 0.78) and 0.75 (95% CI: 0.71, 0.78) in the training set and validation set, respectively; the pooled sensitivity was 0.79 (95% CI: 0.72, 0.84) and 0.76 (95% CI: 0.80, 0.81) in the training set and validation set, respectively; and the pooled specificity was 0.81 (95% CI: 0.75, 0.86) and 0.83 (95% CI: 0.72, 0.90) in the training set and validation set, respectively. CONCLUSIONS: ML has a favourable predictive performance for fracture risk in patients with osteoporosis. However, most current studies lack external validation. Thus, external validation is required to verify the reliability of ML models. PROSPERO REGISTRATION NUMBER: CRD42022346896.


Assuntos
Osteoporose , Fraturas por Osteoporose , Humanos , Densidade Óssea , Reprodutibilidade dos Testes , Osteoporose/complicações , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Medição de Risco/métodos
13.
Hum Brain Mapp ; 44(18): 6499-6510, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37929783

RESUMO

Amblyopia is a developmental visual disorder that causes substantial visual deficits. Studies using resting-state functional magnetic resonance imaging have disclosed abnormal brain functional connectivity (FC) both across long-range cortical sites and within the visual cortex in amblyopes, which is considered to be related to impaired visual functions. However, little work has examined whether restoring the vision of amblyopes accompanies with an improvement of FC. Here in adult amblyopes and healthy participants, we compared their brain FC before and after an altered-reality adaptation training. Before the training, the voxel-wise FCs of amblyopia patients were substantially weaker than those of healthy control participants both within and across the early visual areas. After the training, visual acuities improved in amblyopes but not in the control participants. The effect kept strengthening in the subsequent month without further adaptation. Importantly, we observed enhanced voxel-wise FC both within and across the early visual areas of amblyopes. Moreover, the enhancement continued for at least 1 month. These results suggest that the effective treatment can improve both the amblyopes' vision and functional connections in the visual cortex.


Assuntos
Ambliopia , Córtex Visual , Adulto , Humanos , Ambliopia/diagnóstico por imagem , Ambliopia/terapia , Córtex Visual/diagnóstico por imagem , Encéfalo , Mapeamento Encefálico , Resultado do Tratamento
14.
Front Pediatr ; 11: 1272052, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38027259

RESUMO

Objective: To evaluate whether the patent ductus arteriosus (PDA) can serve as a predictive factor for inpatient outcomes in congenital diaphragmatic hernia (CDH) patients. Methods: A retrospective cohort study was conducted on 59 CDH patients at the Capital Institute of Pediatrics from January 2020 to August 2022. Echocardiography was performed at least three times: within 2-3 h after birth, pre-operatively, and post-operatively of CDH surgery. Based on the direction of the PDA shunt in the first echocardiogram, patients were classified into three groups: left-to-right shunting or closed PDA (L-R), bi-directional shunting, and right-to-left shunting (R-L). Results: The mortality rate was 15.3% (9/59), with all non-survivors having R-L shunting and group mortality of 39.1% (9/23). The direction of the PDA shunt was significantly associated with the duration of ventilation and length of hospital stay (p < 0.05). Decreased PDA diameter or pre-operative shunting direction change towards L-R or bi-directional shunting were associated with higher survival rates, while increased PDA diameter or continuous R-L shunting were associated with higher mortality rates. Pre-operative PDA shunt direction, PDA size after birth and before surgery, gestational age of diagnosis, and shortening fraction before surgery were significantly correlated with patient outcomes. The direction of the preoperative PDA shunt was the most relevant factor among these relationships (p = 0.009, OR 20.6, CI 2.2∼196.1). Conclusion: Our findings highlight the importance of monitoring changes in PDA shunt directionality and diameter in the early stage after birth, as these parameters may serve as valuable predictors of patient outcomes.

15.
iScience ; 26(10): 107813, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37810211

RESUMO

Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury from SARS-CoV-2 or other causes across 7 cohorts. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGEhi myeloid cells express features consistent with suppressor cell functionality, including low HLA-DR and high PD-L1. Sustained EN-RAGE program expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers. IL-6 upregulated many EN-RAGE program genes in monocytes in vitro. IL-6 signaling blockade by tocilizumab in a placebo-controlled clinical trial led to rapid normalization of EN-RAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.

16.
iScience ; 26(9): 107597, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37664617

RESUMO

High interleukin (IL)-6 levels are associated with greater COVID-19 severity. IL-6 receptor blockade by tocilizumab (anti-IL6R; Actemra) is used globally for the treatment of severe COVID-19, yet a molecular understanding of the therapeutic benefit remains unclear. We characterized the immune profile and identified cellular and molecular pathways modified by tocilizumab in peripheral blood samples from patients enrolled in the COVACTA study, a phase 3, randomized, double-blind, placebo-controlled trial of the efficacy and safety of tocilizumab in hospitalized patients with severe COVID-19. We identified markers of inflammation, lymphopenia, myeloid dysregulation, and organ injury that predict disease severity and clinical outcomes. Proteomic analysis confirmed a pharmacodynamic effect for tocilizumab and identified novel pharmacodynamic biomarkers. Transcriptomic analysis revealed that tocilizumab treatment leads to faster resolution of lymphopenia and myeloid dysregulation associated with severe COVID-19, indicating greater anti-inflammatory activity relative to placebo and potentially leading to faster recovery in patients hospitalized with COVID-19.

17.
Prev Med Rep ; 35: 102378, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37662871

RESUMO

Osteoporosis is a prevalent chronic disease that often goes unnoticed in postmenopausal women. Early identification of risk factors for osteoporosis in postmenopausal women is essential. This study aimed to develop predictive models for osteoporosis-related factors among postmenopausal women in the U.S. and explore the influencing factors. In this cross-sectional study, we included 4417 postmenopausal women from the NHANES (2009-2010, 2013-2014, and 2017-2020). Through multiple regression analysis, we found that age, minutes of sedentary activity, prednisone or cortisone usage, arthritis, bone loss around teeth, and trouble sleeping were risk factors for osteoporosis after menopause. Conversely, height, BMI, and age at the last menstrual period were identified as protective factors. The findings from the Bayesian network analysis indicated that several factors influenced osteoporosis, including age, BMI, bone loss around teeth, prednisone or cortisone usage, arthritis, and age at the last menstrual period. On the other hand, minutes of sedentary activity and height might have indirect effects, while trouble sleeping may not have a significant impact. Both logistic regression and Bayesian network models demonstrated good predictive capabilities in predicting osteoporosis among postmenopausal women. In addition, Bayesian networks offer a more intuitive depiction of the intricate network risk mechanism between diseases and factors.

18.
Psychogeriatrics ; 23(6): 1027-1035, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37717947

RESUMO

BACKGROUND: In this study, the long-term trajectories of depressive symptoms in a 7-year prospective survey cohort of Chinese older adults were explored. Additionally, the study examined whether there was an independent association between scores on the Short Physical Performance Battery (SPPB) and the different trajectories of depressive symptoms. METHODS: A total of 2177 elderly individuals had their depressive symptoms assessed based on the Center for Epidemiological Studies-Depression (CES-D) scale in the years 2011, 2013, 2015, and 2018. In addition, their demographic characteristics, chronic diseases, and lifestyle factors were also assessed. The trajectories of depressive symptoms were analysed using the group-based trajectories analysis model. Furthermore, the relationship between the objectively measured SPPB scores and the long-term trajectory of depressive symptoms was explored using multinomial logistic regression. RESULTS: The group-based trajectory analysis model categorized the trajectories of depressive symptoms across four waves into four groups: persistent low depressive symptoms, increasing depressive symptoms, decreased depressive symptoms, and persistent high depressive symptoms. After controlling for confounding factors, it was observed that a higher baseline SPPB score was associated with an increased likelihood of persistent high depressive symptoms, OR (95% CI) = 0.724 (0.644, 0.814), for the persistent high depressive symptoms versus the persistent low depressive symptoms. CONCLUSIONS: Low levels of SPPB score are associated with persistent high depressive symptoms in older adults. Conversely, improving physical performance as measured by the SPPB can help reduce the risk of major depressive disorder and persistent depressive disorder in the elderly.


Assuntos
Depressão , Transtorno Depressivo Maior , Humanos , Idoso , Depressão/diagnóstico , Depressão/epidemiologia , Estudos Prospectivos , População do Leste Asiático , Doença Crônica , Desempenho Físico Funcional , Estudos Longitudinais
19.
Neuromodulation ; 26(7): 1424-1432, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37610397

RESUMO

OBJECTIVE: We aimed to compare the effects of spinal cord stimulation (SCS) with those of endovascular revascularization on the treatment of diabetic foot ulcers. MATERIALS AND METHODS: A total of 104 patients with diabetic foot ulcers who met the inclusion criteria were retrospectively analyzed and classified to the SCS treatment group (n = 46) and endovascular revascularization treatment group (n = 46). The quality-of-life scores (Quality of Life Scale for Patients with Liver Cancer v2.0), visual pain analog scale score, lower limb skin temperature, lower limb arterial ultrasound results, and lower extremity electromyography results were analyzed to compare the efficacy of the two treatments for diabetic foot ulcers in the two groups before surgery and six months after surgery. RESULTS: A total of 92 patients (men: 73.9%, mean age: 66.51 ± 11.67 years) completed the six-month postoperative follow-up period. The patients in the SCS treatment group had a higher quality-of-life score (25.54% vs 13.77%, p < 0.05), a larger reduction in pain scores (69.18% vs 37.21%, p < 0.05), and a larger reduction in foot temperature (18.56% vs 7.24%, p < 0.05) than those of the endovascular revascularization treatment group at six months after surgery. The degree of vasodilation in the lower limbs on color Doppler arterial ultrasound and the nerve conduction velocity were higher in the SCS treatment group than in the endovascular revascularization treatment group at six months after surgery (p < 0.05). CONCLUSION: SCS was more effective than endovascular revascularization in improving quality of life, relieving pain, improving lower limb skin temperature, increasing lower limb blood flow, and improving nerve conduction in patients with diabetic foot ulcers at six months after surgery.


Assuntos
Diabetes Mellitus , Pé Diabético , Estimulação da Medula Espinal , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Pé Diabético/cirurgia , Estudos Retrospectivos , Qualidade de Vida , Dor , Isquemia/terapia , Resultado do Tratamento
20.
Sci Data ; 10(1): 545, 2023 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-37604823

RESUMO

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.


Assuntos
Povo Asiático , Encéfalo , Humanos , Encéfalo/diagnóstico por imagem , China , Data Warehousing , Bases de Dados Factuais , Neurociências
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