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1.
Front Psychiatry ; 13: 815678, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573349

RESUMO

Background: At present, there is no established biomarker for the diagnosis of depression. Meanwhile, studies show that acoustic features convey emotional information. Therefore, this study explored differences in acoustic characteristics between depressed patients and healthy individuals to investigate whether these characteristics can identify depression. Methods: Participants included 71 patients diagnosed with depression from a regional hospital in Beijing, China, and 62 normal controls from within the greater community. We assessed the clinical symptoms of depression of all participants using the Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Patient Health Questionnaire (PHQ-9), and recorded the voice of each participant as they read positive, neutral, and negative texts. OpenSMILE was used to analyze their voice acoustics and extract acoustic characteristics from the recordings. Results: There were significant differences between the depression and control groups in all acoustic characteristics (p < 0.05). Several mel-frequency cepstral coefficients (MFCCs), including MFCC2, MFCC3, MFCC8, and MFCC9, differed significantly between different emotion tasks; MFCC4 and MFCC7 correlated positively with PHQ-9 scores, and correlations were stable in all emotion tasks. The zero-crossing rate in positive emotion correlated positively with HAMA total score and HAMA somatic anxiety score (r = 0.31, r = 0.34, respectively), and MFCC9 of neutral emotion correlated negatively with HAMD anxiety/somatization scores (r = -0.34). Linear regression showed that the MFCC7-negative was predictive on the PHQ-9 score (ß = 0.90, p = 0.01) and MFCC9-neutral was predictive on HAMD anxiety/somatization score (ß = -0.45, p = 0.049). Logistic regression showed a superior discriminant effect, with a discrimination accuracy of 89.66%. Conclusion: The acoustic expression of emotion among patients with depression differs from that of normal controls. Some acoustic characteristics are related to the severity of depressive symptoms and may be objective biomarkers of depression. A systematic method of assessing vocal acoustic characteristics could provide an accurate and discreet means of screening for depression; this method may be used instead of-or in conjunction with-traditional screening methods, as it is not subject to the limitations associated with self-reported assessments wherein subjects may be inclined to provide socially acceptable responses rather than being truthful.

2.
JACC CardioOncol ; 4(1): 1-18, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35492830

RESUMO

Rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors have revolutionized melanoma treatment. Approximately half of patients with melanoma harbor a BRAF gene mutation with subsequent dysregulation of the RAF-MEK-ERK signaling pathway. Targeting this pathway with BRAF and MEK blockade results in control of cell proliferation and, in most cases, disease control. These pathways also have cardioprotective effects and are necessary for normal vascular and cardiac physiology. BRAF and MEK inhibitors are associated with adverse cardiovascular effects including hypertension, left ventricular dysfunction, venous thromboembolism, atrial arrhythmia, and electrocardiographic QT interval prolongation. These effects may be underestimated in clinical trials. Baseline cardiovascular assessment and follow-up, including serial imaging and blood pressure assessment, are essential to balance optimal anti-cancer therapy while minimizing cardiovascular side effects. In this review, an overview of BRAF/MEK inhibitor-induced cardiovascular toxicity, the mechanisms underlying these, and strategies for surveillance, prevention, and treatment of these effects are provided.

3.
Dis Markers ; 2022: 7785497, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35392494

RESUMO

Objectives: To explore independent risk factors with good and early predictive power for SAP severity and prognosis. Methods: Patients with SAP were enrolled at Central South University Xiangya Hospital between April 2017 and May 2021 and used as the training cohort. From June 2021 to February 2022, all patients with SAP were defined as external patients for validation. Patients were grouped by survival status at a 30-day posthospital admission and then compared in terms of basic information and laboratory tests to screen the independent risk factors. Results: A total of 249 patients with SAP were enrolled in the training cohort. The all-cause mortality rate at a 30-day postadmission was 25.8% (51/198). Blood urea nitrogen (BUN) levels were significantly higher in the mortality group (20.45 [interquartile range (IQR), 19.7] mmol/L) than in the survival group (6.685 [IQR, 6.3] mmol/L; P < 0.001). After propensity score matching (PSM), the BUN level was still higher in the mortality group than in the survival group (18.415 [IQR, 19.555] mmol/L vs. 10.63 [IQR, 6.03] mmol/L; P = 0.005). The area under the curve (AUC) of the receiver operating characteristic curve (ROC) of BUN was 0.820 (95% confidence interval, 0.721-0.870; P < 0.001). The optimal BUN level cut-off for predicting a 30-day all-cause mortality was 10.745 mmol/L. Moreover, patients with SAP were grouped according to BUN levels and stratified according to optimal cut-off value. Patients with high BNU levels were associated with significantly higher rates of invasive mechanical ventilation (before PSM: 61.8% vs. 20.6%, P < 0.001; after PSM: 71.1% vs. 32%, P = 0.048) and a 30-day all-cause mortality (before PSM: 44.9% vs. 6.9%, P < 0.001; after PSM: 60% vs. 34.5%, P = 0.032) than those with low BNU levels before or after PSM. The effectiveness of BUN as a prognostic marker was further validated using ROC curves for the external validation set (n = 49). The AUC of BUN was 0.803 (95% CI, 0.655-0.950; P = 0.011). It showed a good ability to predict a 30-day all-cause mortality in patients with SAP. We also observed similar results regarding disease severity, including the Acute Physiology and Chronic Health Evaluation II score (before PSM: 16 [IQR, 8] vs. 8 [IQR, 6], P < 0.001; after PSM: 18 [IQR, 10] vs. 12 [IQR, 7], P < 0.001), SOFA score (before PSM: 7 [IQR, 5] vs. 3 [IQR, 3], P < 0.001; after PSM: 8 [IQR, 5] vs. 5 [IQR, 3.5], P < 0.001), and mMarshall score (before PSM: 4 [IQR, 3] vs. 3 [IQR, 1], P < 0.001; after PSM: 5 [IQR, 2.5] vs. 3 [IQR, 1], P < 0.001). There was significant increase in intensive care unit occupancy in the high BUN level group before PSM (93.3% vs. 73.1%, P < 0.001), but not after PSM (97.8% vs. 86.2%, P = 0.074). Conclusions: Our results showed that BUN levels within 24 h after hospital admission were independent risk factors for a 30-day all-cause death in patients with SAP.


Assuntos
Pancreatite , Doença Aguda , Nitrogênio da Ureia Sanguínea , Humanos , Pancreatite/diagnóstico , Prognóstico , Curva ROC , Estudos Retrospectivos
4.
Cell Rep ; 39(2): 110622, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35417717

RESUMO

The tumor suppressor p53 is inactivated by over hundreds of heterogenous mutations in cancer. Here, we purposefully selected phenotypically reversible temperature-sensitive (TS) p53 mutations for pharmacological rescue with thermostability as the compound-screening readout. This rational screening identified antiparasitic drug potassium antimony tartrate (PAT) as an agent that can thermostabilize the representative TS mutant p53-V272M via noncovalent binding. PAT met the three basic criteria for a targeted drug: availability of a co-crystal structure, compatible structure-activity relationship, and intracellular target specificity, consequently exhibiting antitumor activity in a xenograft mouse model. At the antimony dose in clinical antiparasitic therapy, PAT effectively and specifically rescued p53-V272M in patient-derived primary leukemia cells in single-cell RNA sequencing. Further scanning of 815 frequent p53-missense mutations identified 65 potential PAT-treatable mutations, most of which were temperature sensitive. These results lay the groundwork for repurposing noncovalent antiparasitic antimonials for precisely treating cancers with the 65 p53 mutations.


Assuntos
Neoplasias , Proteína Supressora de Tumor p53 , Animais , Antimônio/metabolismo , Antimônio/farmacologia , Antimônio/uso terapêutico , Antiparasitários , Reposicionamento de Medicamentos , Humanos , Camundongos , Mutação/genética , Neoplasias/genética , Temperatura , Proteína Supressora de Tumor p53/metabolismo
5.
Cancers (Basel) ; 14(5)2022 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-35267526

RESUMO

Immune checkpoint inhibitors have shown great promise, emerging as a new pillar of treatment for cancer; however, only a relatively small proportion of recipients show a durable response to treatment. Strategies that reliably differentiate durably-responding tumours from non-responsive tumours are a critical unmet need. Persistent and durable immunological responses are associated with the generation of memory T cells. Effector memory T cells associated with tumour response to immune therapies are characterized by substantial upregulation of the potassium channel Kv1.3 after repeated antigen stimulation. We have developed a new Kv1.3 targeting radiopharmaceutical, [18F]AlF-NOTA-KCNA3P, and evaluated whether it can reliably differentiate tumours successfully responding to immune checkpoint inhibitor (ICI) therapy targeting PD-1 alone or combined with CLTA4. In a syngeneic colon cancer model, we compared tumour retention of [18F]AlF-NOTA-KCNA3P with changes in the tumour immune microenvironment determined by flow cytometry. Imaging with [18F]AlF-NOTA-KCNA3P reliably differentiated tumours responding to ICI therapy from non-responding tumours and was associated with substantial tumour infiltration of T cells, especially Kv1.3-expressing CD8+ effector memory T cells.

6.
ACS Appl Mater Interfaces ; 14(14): 16669-16677, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35357138

RESUMO

Maintaining the dynamical microwave synchronization between a target and its background is the key to electromagnetical invisibility in real environment. Herein, we introduce an archetypical paradigm for ultraelastic films of graphene-functionalized ionic gel with tunable microwave-absorbing behaviors. Inspired by the local structural changes during the wing-spreading process of vespertilionids, the experimental and finite element simulations have revealed that proper shape changing of 3D wrinkled structure containing ridge walls with moderate impedance is the effective way to minimize reflected wave and promote energy attenuation. An optimal RL value of -43.6 dB and valid regulatory amplitude of 41.5 dB, covering a microwave-absorbing to shielding state, could be reached with only 0.2% weight fraction of the active ingredient RGO filler. The significant regulatory performance is attributed to the competitive effect between intrinsic dielectric attenuation of silicon nitride modified reduced graphene oxide (RGO-SiN), multiscattering of a 3D wrinkled structure, and evolution of the oriented RGO-SiN.

7.
Mol Phylogenet Evol ; 171: 107458, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35351637

RESUMO

The complexity of global biodiversity in the tropical Indochina Peninsula and subtropical China bioregions has fascinated biologists for decades, but little is known about the spatiotemporal patterns in these regions. Accordingly, the aims of present study were to investigate the evolutionary and distribution patterns of Engelhardia in these regions and establish a model for examining biogeographic patterns and geological events throughout the tropical Indochina Peninsula and subtropical China. The effects of geological events occurring in the area between the Indochina Peninsula and subtropical China bioregions on the two trees species (i.e., E. roxburghiana and E. fenzelii) were evaluated. A robust phylogenetic framework of 884 individuals from 79 populations was used to generate time-calibrated cytoplasmic and nuclear phylogenetic frameworks based on cpDNA, nrDNA, and nSSR data, respectively. When considered along with ancestral area reconstructions, the genetic data were also used to assess and reconstruct the species' population genetic structure and diversity. These analyses yielded important information about the (1) historical distribution relationships between the tropical and subtropical flora of China; (2) effects of the East Asian summer monsoon (EASM) on the evolutionary history of Asia's plants; and (3) importance of biogeography in conservation planning. Although cytoplasmic-nuclear discordance indicated cpDNA and nrDNA were subject to distinct evolutionary mechanisms that reflected respective evolutionary histories of the plastid and nuclear genomes of prior demographic and biogeographic events. The tropical elements of Engelhardia occupied the Indochina Peninsula during the early Eocene, whereas the subtropical elements were transformed from the tropical elements during Miocene cooling and the onset of the EASM at the Oligocene-Miocene boundary, intensified during the late Miocene and Pliocene, facilitating the transformation of Engelhardia from the tropical Indochina Peninsula to subtropical China. Demographic history provided insights into prominent planning frameworks in conservation biology, namely that subtropical China functioned as a refugium during past climate oscillations and will continue to serve in this capacity in the future.


Assuntos
Biodiversidade , Plantas , China , DNA de Cloroplastos , Humanos , Indochina , Filogenia , Filogeografia
8.
Front Med ; 16(2): 263-275, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35258762

RESUMO

Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases. Here, to explore the role of the gut microbiome in the host immune responses in COVID-19, we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples. We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones. We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity, such as Enterococcus faecium, Coprococcus comes, Roseburia intestinalis, Akkermansia muciniphila, Bacteroides cellulosilyticus and Blautia obeum. We further analyzed the correlation between the abundance of gut microbes and host responses, and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe, including Coprococcus comes that was positively correlated with CD3+/CD4+/CD8+ lymphocyte counts. In addition, an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells (PBMCs) showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples. Moreover, a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases, including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19. Together, our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.


Assuntos
COVID-19 , Microbioma Gastrointestinal , Clostridiales , Humanos , Imunidade , Leucócitos Mononucleares , SARS-CoV-2
9.
J Psychiatry Neurosci ; 47(2): E86-E98, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35301253

RESUMO

BACKGROUND: Evidence indicates that cytokines are associated with cognitive deficits in schizophrenia; however, the underlying brain-behaviour mechanisms remain unclear. We hypothesized that aberrations in brain structural connectivity mediate the cytokine effect in schizophrenia. METHODS: In this study, we recruited patients with first-episode schizophrenia (n = 75, average illness duration 12.3 months, average medication period 0.6 days) and healthy controls (n = 44) of both sexes. We first conducted whole-blood RNA sequencing to detect differentially expressed genes. We also explored transcriptomic data on the dorsal lateral prefrontal cortices (dlPFC) retrieved from the CommonMind Consortium for gene functional clustering; we measured plasma transforming growth factor ß1 (TGF-ß1) levels by enzyme-linked immunosorbent assay; we acquired high-resolution T 1-weighted MRI data on cortical thickness MRI; and we assessed cognitive function using the validated Chinese version of the MATRICS Consensus Cognitive Battery. We compared these parameters in patients with schizophrenia and controls, and analyzed their associations. RESULTS: Patients with schizophrenia had higher TGF-ß1 at both the mRNA level (log2 fold change = 0.24; adjusted p = 0.026) and the protein level (12.85 ± 6.01 µg/mL v. 8.46 ± 5.15 µg/mL, adjusted p < 0.001) compared to controls. Genes coexpressed with TGFB1 in the dlPFC were less abundant in patients with schizophrenia compared to healthy controls. In patients with schizophrenia, TGF-ß1 protein levels were inversely correlated with cortical thickness, especially of the lateral occipital cortex (r = -0.47, adjusted p = 0.001), and with the MATRICS Consensus Cognitive Battery visual learning and memory domain (r = -0.50, adjusted p < 0.001). We found a complete mediation effect of the thickness of the lateral occipital cortex on the negative relationship between TGF-ß1 and visual cognition (p < 0.05). LIMITATIONS: We did not explore the effect of other blood cytokines on neurocognitive performance and cortical thickness. Participants from the CommonMind Consortium did not all have first-episode schizophrenia and they were not all antipsychotic-naive, so we could not exclude an effect of antipsychotics on TGF-ß1 signalling in the dlPFC. The sample size and cross-sectional design of our study were additional limitations. CONCLUSION: These findings highlighted an association between upregulated blood levels of TGF-ß1 and impairments in brain structure and function in schizophrenia.


Assuntos
Antipsicóticos , Esquizofrenia , Antipsicóticos/uso terapêutico , Cognição , Estudos Transversais , Citocinas/genética , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/uso terapêutico
10.
Front Med ; 16(2): 251-262, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35192147

RESUMO

Pathogenic microbes can induce cellular dysfunction, immune response, and cause infectious disease and other diseases including cancers. However, the cellular distributions of pathogens and their impact on host cells remain rarely explored due to the limited methods. Taking advantage of single-cell RNA-sequencing (scRNA-seq) analysis, we can assess the transcriptomic features at the single-cell level. Still, the tools used to interpret pathogens (such as viruses, bacteria, and fungi) at the single-cell level remain to be explored. Here, we introduced PathogenTrack, a python-based computational pipeline that uses unmapped scRNA-seq data to identify intracellular pathogens at the single-cell level. In addition, we established an R package named Yeskit to import, integrate, analyze, and interpret pathogen abundance and transcriptomic features in host cells. Robustness of these tools has been tested on various real and simulated scRNA-seq datasets. PathogenTrack is competitive to the state-of-the-art tools such as Viral-Track, and the first tools for identifying bacteria at the single-cell level. Using the raw data of bronchoalveolar lavage fluid samples (BALF) from COVID-19 patients in the SRA database, we found the SARS-CoV-2 virus exists in multiple cell types including epithelial cells and macrophages. SARS-CoV-2-positive neutrophils showed increased expression of genes related to type I interferon pathway and antigen presenting module. Additionally, we observed the Haemophilus parahaemolyticus in some macrophage and epithelial cells, indicating a co-infection of the bacterium in some severe cases of COVID-19. The PathogenTrack pipeline and the Yeskit package are publicly available at GitHub.


Assuntos
COVID-19 , Humanos , RNA , SARS-CoV-2/genética , Análise de Célula Única/métodos , Transcriptoma
11.
Pharmaceutics ; 14(1)2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35057046

RESUMO

Immune checkpoint inhibitors (ICIs) block checkpoint receptors that tumours use for immune evasion, allowing immune cells to target and destroy cancer cells. Despite rapid advancements in immunotherapy, durable response rates to ICIs remains low. To address this, combination clinical trials are underway assessing whether adjuvants can enhance responsiveness by increasing tumour immunogenicity. CpG-oligodeoxynucleotides (CpG-ODN) are synthetic DNA fragments containing an unmethylated cysteine-guanosine motif that stimulate the innate and adaptive immune systems by engaging Toll-like receptor 9 (TLR9) present on the plasmacytoid dendritic cells (pDCs) and B cells. Here, we have assessed the ability of AlF-mNOTA-GZP, a peptide tracer targeting granzyme B, to serve as a PET imaging biomarker in response to CpG-ODN 1585 in situ vaccine therapy delivered intratumourally (IT) or intraperitoneally (IP) either as monotherapy or in combination with αPD1. [18F]AlF-mNOTA-GZP was able to differentiate treatment responders from non-responders based on tumour uptake. Furthermore, [18F]AlF-mNOTA-GZP showed positive associations with changes in tumour-associated lymphocytes expressing GZB, namely GZB+ CD8+ T cells, and decreases in suppressive F4/80+ cells. [18F]AlF-mNOTA-GZP tumour uptake was mediated by GZB expressing CD8+ cells and successfully stratifies therapy responders from non-responders, potentially acting as a non-invasive biomarker for ICIs and combination therapy evaluation in a clinical setting.

12.
Dig Dis Sci ; 67(2): 667-675, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33570682

RESUMO

OBJECTIVE: It is still uncertain what effects pulmonary artery catheter (PAC)-guided resuscitation has on outcomes for patients with severe acute pancreatitis (SAP). Therefore, we aimed to investigate the effect of PAC on hospital mortality in patients with SAP. METHODS: We collected the data of patients with a diagnosis of SAP from January 10, 2017, to July 30, 2019. Patients were divided into a PAC group and a control group. The primary outcome measured was the day-28 mortality. Secondary outcomes included day-90 mortality, duration of ICU and hospital stay, ventilation days, usage of renal support and vasoactive agents, incidences of acute abdominal compartment syndrome, infusion volumes, and fluid balance and hemodynamic characteristics measured by the PAC. Kaplan-Meier analysis was applied to estimate survival outcomes. Complications related to PAC were also analyzed. RESULTS: There was no significant difference between the PAC group and the control group for day-28 mortality (22.7% vs. 30%, odds ratio, 0.69; 95% CI 0.31-1.52; P = 0.35). The duration of ICU stay in the PAC group was shorter (P = 0.00), and the rate of dependence on renal support treatment was lower in the PAC group than in the control group (P = 0.03). There was no difference in other secondary outcomes and no significant difference in the survival curve between the two groups (log-rank P = 0.72, X2 = 0.13). However, SAP patients inserted PAC within 24 h ICU admission showed that duration of renal support therapy in PAC patients within 24 h ICU admission (mean days, 1.60; standard deviation, 0.14) was shorter than those with 24-72 h ICU admission (mean days, 2.94; standard deviation, 0.73; P = 0.03). The organ failure rates (1 organ, 2 organs and 3 organs) were all lower in PAC patients within 24 h ICU admission than with 24-72 h ICU admission (P = 0.02, P = 0.02, P = 0.048, respectively). CONCLUSION: In patients with severe acute pancreatitis, PAC-guided fluid resuscitation shortened the duration of ICU stay, and patients in the PAC group had a lower rate of dependence on renal support, while no benefit in terms of mortality was observed. However, SAP patients inserted PAC within 24 h ICU admission showed shorter duration of renal support therapy and lower organ failure rates than those with 24-72 h ICU admission, indicating that early use of PAC, especially within 24 h, might be better for SAP patients.


Assuntos
Cateterismo de Swan-Ganz , Duração da Terapia , Hidratação/métodos , Monitorização Hemodinâmica/métodos , Mortalidade Hospitalar , Pancreatite/terapia , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/terapia , Adulto , Gerenciamento Clínico , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Terapia de Substituição Renal/estatística & dados numéricos , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/fisiopatologia , Índice de Gravidade de Doença
13.
Eur J Clin Invest ; 52(1): e13673, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34435353

RESUMO

BACKGROUND: The researches on the associations between different candidate genes and obstructive sleep apnea (OSA) are inconsistent. Here, we performed a comprehensive qualitative and quantitative analysis to estimate the contribution of variants from candidate genes to the risk of OSA. METHODS: Qualitative analysis was conducted to find the relationships for all included genes. Then, quantitative analysis of both allele models and genotype models was applied to evaluate the risk variants for OSA. Furthermore, a similar analysis was performed in different ethnic groups. RESULTS: We included 152 publications containing 75 genes for qualitative analysis. Among them, we included 93 articles containing 28 variants from 16 genes for quantitative analysis. Through allele models, we found 10 risk variants for OSA (rs1801133 of MTHFR, ɛ4 of ApoE, -1438G/A of 5-HT2A, -308G/A of TNF-α, Pro1019Pro of LEPR, rs1130864 and rs2794521 of CRP, D/I of ACE, LPR and VNTR of 5-HTT) with the ORs of 1.21-2.07 in global population. We found that the variant of ɛ2 of ApoE could uniquely decrease the risk of OSA in the East Asian subgroup, while the other 6 variants, including ɛ4 in ApoE, -308G/A in TNF-α, Pro1019Pro in LEPR, D/I in ACE, LPR and VNTR in 5-HTT, could increase the risk of OSA. As for the European subpopulation, we only found that -308G/A in TNF-α could increase the risk for OSA. CONCLUSIONS: Eleven variants from the candidate genes are associated with the risk of OSA, which also show ethnicity differences in East Asian and European subgroups.


Assuntos
Estudos de Associação Genética , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/genética , Humanos , Medição de Risco
14.
Sci Total Environ ; 806(Pt 3): 151203, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34710420

RESUMO

Exotic plant invasion is an urgent issue occurring in the biosphere, which can be stimulated by environmental nitrogen (N) loading. However, the allocation and assimilation of soil N sources between leaves and roots remain unclear for plants in invaded ecosystems, which hampers the understanding of mechanisms behind the expansion of invasive plants and the co-existence of native plants. This work established a new framework to use N concentrations and isotopes of soils, roots, and leaves to quantitatively decipher intra-plant N allocation and assimilation among plant species under no invasion and under the invasion of Chromolaena odorata and Ageratina adenophora in a tropical ecosystem of SW China. We found that the assimilation of N derived from both soil ammonium (NH4+) and nitrate (NO3-) were higher in leaves than in roots for invasive plants, leading to higher leaf N levels than native plants. Compared with the same species under no invasion, most native plants under invasion showed higher N concentrations and NH4+ assimilations in both leaves and roots, and increases in leaf N were higher than in root N for native plants under invasion. These results inform that preferential N allocation, dominated by NH4+-derived N, to leaves over roots as an important N-use strategy for plant invasion and co-existence in the studied tropical ecosystem.


Assuntos
Ecossistema , Nitrogênio , Isótopos , Nitrogênio/análise , Folhas de Planta/química , Raízes de Plantas/química , Solo
15.
Research (Wash D C) ; 2021: 9812523, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34888525

RESUMO

Mitochondrial dysfunction is commonly detected in individuals suffering from Parkinson's disease (PD), presenting within the form of excessive reactive oxygen species (ROS) generation as well as energy metabolism. Overcoming this dysfunction within brain tissues is an effective approach to treat PD, while unluckily, the blood-brain barrier (BBB) substantially impedes intracerebral drug delivery. In an effort to improve the delivery of efficacious therapeutic drugs to the brain, a drug delivery platform hydrogel (MAG-NCs@Gel) was designed by complexing magnolol (MAG)-nanocrystals (MAG-NCs) into the noninvasive thermosensitive poly(N-isopropylacrylamide) (PNIPAM) with self-gelation. The as-prepared MAG-NCs@Gel exhibited obvious improvements in drug solubility, the duration of residence with the nasal cavity, and the efficiency of brain targeting, respectively. Above all, continuous intranasal MAG-NCs@Gel delivery enabled MAG to cross the BBB and enter dopaminergic neurons, thereby effectively alleviating the symptoms of MPTP-induced PD. Taking advantage of the lower critical solution temperature (LCST) behavior of this delivery platform increases its viscoelasticity in nasal cavity, thus improving the efficiency of MAG-NCs transit across the BBB. As such, MAG-NCs@Gel represented an effective delivery platform capable of normalizing ROS and adenosine triphosphate (ATP) in the mitochondria of dopaminergic neurons, consequently reversing the mitochondrial dysfunction and enhancing the behavioral skills of PD mice without adversely affecting normal tissues.

16.
Front Med ; 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34958450

RESUMO

Runt-related transcription factor 1 (RUNX1) is an essential regulator of normal hematopoiesis. Its dysfunction, caused by either fusions or mutations, is frequently reported in acute myeloid leukemia (AML). However, RUNX1 mutations have been largely under-explored compared with RUNX1 fusions mainly due to their elusive genetic characteristics. Here, based on 1741 patients with AML, we report a unique expression pattern associated with RUNX1 mutations in AML. This expression pattern was coordinated by target repression and promoter hypermethylation. We first reanalyzed a joint AML cohort that consisted of three public cohorts and found that RUNX1 mutations were mainly distributed in the Runt domain and almost mutually exclusive with NPM1 mutations. Then, based on RNA-seq data from The Cancer Genome Atlas AML cohort, we developed a 300-gene signature that significantly distinguished the patients with RUNX1 mutations from those with other AML subtypes. Furthermore, we explored the mechanisms underlying this signature from the transcriptional and epigenetic levels. Using chromatin immunoprecipitation sequencing data, we found that RUNX1 target genes tended to be repressed in patients with RUNX1 mutations. Through the integration of DNA methylation array data, we illustrated that hypermethylation on the promoter regions of RUNX1-regulated genes also contributed to dysregulation in RUNX1-mutated AML. This study revealed the distinct gene expression pattern of RUNX1 mutations and the underlying mechanisms in AML development.

17.
Ann Med ; 53(1): 2178-2193, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34913774

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are good candidates as biomarkers for Lung cancer (LC). The aim of this article is to figure out the diagnostic value of both single and combined miRNAs in LC. METHODS: Normative meta-analysis was conducted based on PRISMA. We assessed the diagnostic value by calculating the combined sensitivity (Sen), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) and the area under the curve (AUC) of single and combined miRNAs for LC and specific subgroups. RESULTS: A total of 80 qualified studies with a total of 8971 patients and 10758 controls were included. In non-small cell lung carcinoma (NSCLC), we involved 20 single-miRNAs and found their Sen, Spe and AUC ranged from 0.52-0.81, 0.66-0.88, and 0.68-0.90, respectively, specially, miR-19 with the maximum Sen, miR-20 and miR-10 with the highest Spe as well as miR-17 with the maximum AUC. Additionally, we detected miR-21 with the maximum Sen of 0.74 [95%CI: 0.62-0.83], miR-146 with the maximum Spe and AUC of 0.93 [95%CI: 0.79-0.98] and 0.89 [95%CI: 0.86-0.92] for early-stage NSCLC. We also identified the diagnostic power of available panel (miR-210, miR-31 and miR-21) for NSCLC with satisfying Sen, Spe and AUC of 0.82 [95%CI: 0.78-0.84], 0.87 [95%CI: 0.84-0.89] and 0.91 [95%CI: 0.88-0.93], and furtherly constructed 2 models for better diagnosis. CONCLUSIONS: We identified several single miRNAs and combined groups with high diagnostic power for NSCLC through pooled quantitative analysis, which shows that specific miRNAs are good biomarker candidates for NSCLC and further researches needed.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Área Sob a Curva , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo
18.
Case Rep Surg ; 2021: 7430752, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34840849

RESUMO

Several thoracic vasculature variations were observed in an 81-year-old male cadaver during routine dissection. These included 5 common trunks of posterior intercostal arteries, a descending branch of the right vertebral artery, and atypical neurovascular relationships within intercostal spaces. On the right side, two common trunks of posterior intercostal arteries were observed supplying the 4th-7th intercostal spaces and 9th-11th intercostal spaces, respectively. There was also a small accessary branch supplying the 9th intercostal space. The first three posterior intercostal spaces on the right were supplied by a descending branch of the vertebral artery. On the left side, three common trunks of posterior intercostal arteries were encountered, supplying intercostal spaces 3-5, 6-7, and 11 plus the subcostal space. An atypical neurovascular relationship was observed in the right 6th intercostal space, as well as the left 2nd, 3rd, and 6th intercostal spaces. This is the first case report that presents 5 common trunks of posterior intercostal arteries, as well as common trunks in conjunction with other arterial variation in the posterior thoracic wall. These variations carry a high level of clinical significance and may be helpful in guiding decision-making related to surgical procedures related to the posterior thoracic cavity and spine.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34845717

RESUMO

Most variations of the abdominal blood supply are related to branching of the celiac trunk and superior mesenteric artery. This case details a remarkable variation in the branching pattern of the left colic artery (LCA) observed during routine cadaveric dissection of an 84-year-old male donor. An anomalous common trunk, originating from the common hepatic artery, gave rise to three branches: 1) an accessory posterior pancreaticoduodenal artery to the head of the pancreas and adjacent duodenum, 2) the dorsal pancreatic artery anastomosing with branches of the splenic artery, and 3) the LCA. The LCA descended between the splenic vein and superior mesenteric artery to supply the left colic flexure and form a collateral route with the middle colic artery by contributing to the marginal artery of Drummond. Knowledge of this variation is clinically relevant for surgical and radiological procedures in the abdomen.

20.
Signal Transduct Target Ther ; 6(1): 405, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795208

RESUMO

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent ß-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non ß0/ß0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.


Assuntos
Transfusão de Eritrócitos , Talidomida/administração & dosagem , Talassemia beta/terapia , Adolescente , Adulto , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Talidomida/efeitos adversos
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