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1.
Biomed J ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35552020

RESUMO

OBJECTIVES: Mouth opening/breathing during sleep is common in patients with obstructive sleep apnea (OSA), which is probably associated with more water loss and higher risk for nocturnal ischemic heart attack. This study aimed to evaluate nocturnal changes in hematocrit/hemoglobin levels and estimated plasma volume loss in OSA patients and its relation to their OSA severity and mouth open/breathing. METHODS: Sixty OSA patients and fifteen healthy controls were enrolled and underwent overnight polysomnography. Mouth status was evaluated via an infrared camera and nasal/mouth airflow. Hematocrit and hemoglobin levels in peripheral venous blood were measured before and after sleep to estimate the change of plasma volume. RESULTS: Compared to controls, OSA patients had a greater nocturnal increase in hematocrit (1.35% vs. 1.0%, p=0.013), hemoglobin (0.50% vs. 0.30%, p=0.002) and more estimated water loss (5.5% vs 3.7% of plasma volume, p<0.013). The extent of increase was correlated to apnea-hypopnea index_the marker of OSA severity (Spearman's ρ=0.332, p=0.004; ρ=0.367, p=0.001 for hematocrit, hemoglobin, respectively), which remained significant after serial multivariate adjustment. OSA patients had more sleep time with mouth open (96.7% vs 26.7% of total sleep time, p<0.001) and time with complete mouth breathing (14.1% vs 2.7%, p<0.001). The extent of mouth breathing was correlated to apnea-hypopnea index (ρ=0.487, p<0.001), nocturnal increase in hematocrit/hemoglobin levels (ρ=0.236, p=0.042; ρ=0.304, p=0.008, respectively) and estimated plasma volume loss (ρ=0.262, p=0.023). CONCLUSIONS: OSA patients had a greater increase in hematocrit/hemoglobin levels after sleep, which is probably linked to more water loss and more sleep time with mouth open/breathing.

2.
Heliyon ; 8(5): e09411, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35607497

RESUMO

Intracellular pH (pHi) is very essential for the function of cells and organisms. Thus, it is of great scientific and technical significance to develop nanosensors for probing pHi. In this work, nitrogen-doped graphene oxide quantum dots (N-GOQDs) with fluorescent efficiency of 54% are prepared. The fluorescent spectrum excited at 340 nm contains two remarkable bands at 430 and 520 nm. Interestingly, when pH value increases from 3.6 to 10.5, the blue band at 430 nm slightly changes, while the green band at 520 nm significantly quenches. The change of fluorescent intensities also can be reflected by the variation of fluorescent color. The dual-emissive N-GOQDs are developed as ratiometric fluorescent probes for pHi, which can avoid the influence of several deviations, such as probe concentration, optical path length, and detector efficiency. As a proof of concept, pHi of Hela cells is monitored successfully. This work demonstrates the construction of nano-biosensors based on N-GOQDs with bright fluorescence, high-stability, and good biocompatibility.

3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(2): 276-285, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35538763

RESUMO

Objective To investigate the relationship between the expression of glutathione peroxidase(GPX)genes and the clinical prognosis in glioma patients,and to construct and evaluate the model for predicting the prognosis of glioma. Methods The clinical information and GPX expression of 663 patients,including 153 patients of glioblastoma(GBM)and 510 patients of low-grade glioma(LGG),were obtained from The Cancer Genome Atlas(TCGA)database.The relationship between GPX expression and patient survival was analyzed.The key GPX affecting the prognosis of glioma was screened out by single- and multi-factor Cox's proportional-hazards regression models and validated by least absolute shrinkage and selection operator(Lasso)regression.Finally,we constructed the model for predicting the prognosis of glioma with the screening results and then used concordance index and calibration curve respectively to evaluate the discrimination and calibration of model. Results Compared with those in the control group,the expression levels of GPX1,GPX3,GPX4,GPX7,and GPX8 were up-regulated in glioma patients(all P<0.001).Moreover,the expression levels of other GPX except GPX3 were higher in GBM patients than in LGG patients(all P<0.001).The Kaplan-Meier curves showed that the progression-free survival of GBM with high expression of GPX1(P=0.013)and GPX4(P=0.040),as well as the overall survival,disease-specific survival,and progression-free survival of LGG with high expression of GPX1,GPX7,and GPX8,was shortened(all P<0.001).GPX7 and GPX8 were screened out as the key factors affecting the prognosis of LGG.The results were further used to construct a nomogram model,which suggested GPX7 was the most important variable.The concordance index of the model was 0.843(95%CI=0.809-0.853),and the calibration curve showed that the predicted and actual results had good consistency. Conclusion GPX7 is an independent risk factor affecting the prognosis of LGG,and the nomogram model constructed with it can be used to predict the survival rate of LGG.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Glioma/diagnóstico , Glutationa Peroxidase/metabolismo , Humanos , Peroxidases , Prognóstico , Modelos de Riscos Proporcionais
4.
Bioorg Chem ; 124: 105800, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35468415

RESUMO

Icariside II, a flavonol glycoside, one of the major components of Traditional Chinese Medicine Herba epimedii. In the present study, we found that Icariside II suppressed the proliferation of CRC by inducing cell cycle arrest and apoptosis in vitro and inhibited tumor growth in vivo. The further mechanism investigation showed that Icariside II suppressed the expression of ß-catenin and led to the functional inactivation of Wnt/ß-catenin signaling. Circß-catenin was considered as a promising candidate for mediating the tumorigenesis and the activation of Wnt/ß-catenin signaling in CRC cells. Furthermore, Icariside II has been proven to suppress the biogenesis of circß-catenin via epigenetically targeting DNA methyltransferases (DNMTs) to decrease global DNA methylation levels in CRC cells. Taken together, our results indicated that Icariside II suppressed tumorigenesis by epigenetically silencing the activation of circß-catenin-Wnt/ß-catenin axis in colorectal cancer. More importantly, the information gained from this study suggest that Icariside II may have great potential to be developed as a therapeutic drug for CRC patients.

5.
Small ; 18(18): e2200911, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35363427

RESUMO

Single atom sites (SAS) of FeN4 are clarified as one of the most active components for the oxygen reduction reaction (ORR). Effective strategies by engineering the local coordination environment and site density of FeN4 sites are crucial to further enhance the electrocatalytic ORR performance. Herein, the integration of a second metal of Mn with Fe to construct Fe&Mn/N-C catalysts with enhanced density of FeN4 active sites and modulated electronic structure is reported. The formation of MnN4 centers modulates the local environment of FeN4 sites and reserves more FeN4 embedded in carbon substrate by forming the possible FeN4 -O-MnN4 configurations. Density functional theory calculations demonstrate that the overall energy barrier of ORR is decreased over the FeN4 -O-MnN4 moieties. Therefore, the Fe&Mn/N-C catalyst exhibits enhanced ORR performance both in alkaline and acidic solution (half-wave potentials are 0.904 and 0.781 V). This work provides an effective strategy by modulating the local electronic structure and density of FeN4 active sites to improve the ORR activity and stability through Mn cooperation.


Assuntos
Carbono , Oxigênio , Catálise , Oxigênio/química
6.
Sleep Breath ; 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35460049

RESUMO

PURPOSE: To investigate the impact of sleep quality and chronotype on job burnout among medical residents under standardized residency training (SRT) in a tertiary hospital in Beijing, China. METHODS: Medical residents in the Department of Internal Medicine of Peking Union Medical College Hospital were assessed by Morning and Evening Questionaire-5 (MEQ-5), Pittsburgh sleep quality index (PSQI), and Maslach Burnout Inventory-General Survey (MBI-GS). Factors associated with burnout were analyzed. RESULTS: A total of 142 respondents returned completed questionnaires. Burnout was present in 85 (60%) residents. Prevalence of high emotional exhaustion, high depersonalization, and low personal accomplishment were 51%, 28%, and 18%, respectively. The global PSQI score of residents was 5.9 ± 2.4, and the self-reported sleep duration was 6.2 ± 0.8 h/day. The MEQ-5 distribution skewed towards morningness, with a median score of 14.5 [13.0, 16.3]. Poor daytime function significantly predicted emotional exhaustion and depersonalization. Chronotypes were not associated with any of the burnout components. CONCLUSION: Sleep-related daytime dysfunction was strongly related to burnout. Strategies protecting the sleep of residents should be incorporated into the SRT programs for both efficiency and sustainability considerations.

7.
Front Psychiatry ; 13: 814828, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295780

RESUMO

Background: The highly heterogeneous pathogenesis of depression and limited response to current antidepressants call for more objective evidence for depression subtypes. Reactive and endogenous depression are two etiologically distinct subtypes associated with different treatment responses. This study aims to explore the potential biomarkers that differentiate reactive and endogenous depressions. Methods: The clinical manifestations and biological indicators of 64 unmedicated mild-to-moderate depression patients (32 reactive depression patients and 32 endogenous depression patients) and 21 healthy subjects were observed. The 24-item Hamilton rating scale for depression (HAMD-24) was used to evaluate the severity of depression. Serum levels of depression-related biological indicators were measured by using the enzyme-linked immunosorbent assay. Results: The NLRP3 level of reactive depression was significantly lower than those of endogenous depression and healthy controls. There was a significant negative correlation between the BDNF level and the HAMD-24 total scores for patients with reactive depression. Conclusion: Our findings suggested the serum NLRP3 and BDNF levels could be potential biomarkers for detecting and evaluating the severity of reactive depression.

8.
J Orthop Translat ; 33: 132-141, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35330943

RESUMO

Background: Osteosarcoma (OS) is a common type of malignant bone tumor in adolescents with high risk of metastasis. However, the clinical management still remains unsatisfactory. Traditional Chinese medicine (TCM) has been widely considered as an alternative treatment, and their extracts have proved to possess great potential for drug discovery. Baicalein (BA), the active pharmaceutical ingredient of rhizoma coptidis, was proved to have anti-tumor properties in OS, but the mechanism remains poorly understood. Methods: The potential anti-cancer effects on cell growth, cell cycle, apoptosis and migration were examined in OS cells. Moreover, the lncRNA-Neighboring Enhancer of FOXA2 (lncRNA-NEF) and Wnt/ß-catenin signaling were detected by qPCR and Western blotting assays. The in vivo effect of GA on tumor growth was investigated using a xenograft mice model. Results: In the present study, BA was found to significantly suppress tumor growth in vitro and in vivo. And it was also found to inhibit the invasion and metastasis as well. As for the mechanism investigation, lncRNA-NEF was obviously upregulated by BA in OS cells, and thus induced the inactivation of Wnt/ß-catenin signaling. Moreover, lncRNA-NEF knockdown partially reversed the BA-induced anti-cancer activities; and successfully compensated the suppressive effect on Wnt/ß-catenin signaling. We therefore suggested that BA induced the inactivation of Wnt/ß-catenin signaling through promoting lncRNA-NEF expression. Conclusions: In conclude, our results demonstrated that BA suppressed tumor growth and metastasis in vitro and in vivo through an lncRNA-NEF driven Wnt/ß-catenin regulatory axis, in which lncRNA-NEF was upregulated by BA, and thus induced the inactivation of Wnt/ß-catenin signaling. The Translational potential of this article: The findings derived from this study validates the anti-cancer activity of BA in OS and provides a novel underlying mechanism, which suggest that BA may be a potential candidate to develop the effective drug for OS patients.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35104228

RESUMO

Most existing graph neural networks (GNNs) are proposed without considering the selection bias in data, i.e., the inconsistent distribution between the training set with the test set. In reality, the test data are not even available during the training process, making selection bias agnostic. Training GNNs with biased selected nodes leads to significant parameter estimation bias and greatly impacts the generalization ability on test nodes. In this article, we first present an experimental investigation, which clearly shows that the selection bias drastically hinders the generalization ability of GNNs, and theoretically proves that the selection bias will cause the biased estimation on GNN parameters. Then to remove the bias in GNN estimation, we propose a novel debiased GNNs (DGNN) with a differentiated decorrelation regularizer. The differentiated decorrelation regularizer estimates a sample weight for each labeled node such that the spurious correlation of learned embeddings could be eliminated. We analyze the regularizer in causal view and it motivates us to differentiate the weights of the variables based on their contribution to the confounding bias. Then, these sample weights are used for reweighting GNNs to eliminate the estimation bias, and thus, help to improve the stability of prediction on unknown test nodes. Comprehensive experiments are conducted on several challenging graph datasets with two kinds of label selection biases. The results well verify that our proposed model outperforms the state-of-the-art methods and DGNN is a flexible framework to enhance existing GNNs.

10.
J Environ Manage ; 303: 113999, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34863591

RESUMO

This paper presents a potential process that can enhance H2 transformation to CH4 and simultaneously upgrading biogas by using hydrogenotrophic methanogens. For the first time, anaerobic granules were developed in upflow anaerobic sludge blanket (UASB) reactor feeding H2/CO2 syngas as the sole substrate and the granule characterization was thoroughly investigated. The results from experiment revealed that the H2 consumption rates of UASB reactor increased from 32.2 mmol L-1·d-1 at H2 feeding rate 0.08 g L-1·d-1 to 132.0 mmol L-1·d-1 at 0.37 g L-1·d-1, indicating that the hydrogenotrophic methanogenesis pathway was stimulated by injection of H2. Abundant cavities and cracks were observed on the surface and cross-section of granules, which greatly facilitated internally transferring H2/CO2 synthesis gas and biogas escape. The abundance of hydrogenotrophic Methanobacterium increased, while Methanosaeta, Methanosarcina, and Methanomassiliicoccus decreased with increasing H2 feeding rate. In general, this paper offers a feasible solution in terms of energy transformation and connecting power to fuel.


Assuntos
Euryarchaeota , Esgotos , Anaerobiose , Biocombustíveis , Reatores Biológicos , Hidrogênio , Metano
11.
Bioresour Technol ; 346: 126525, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34896540

RESUMO

Anaerobic ammonium oxidation (anammox) is a cost-effective nitrogen removal pathway but instinctively generated nitrate limits its application. A novel anammox aggregate reduced the production of nitrate significantly with efficient removal of ammonia and nitrite in this work. The results demonstrated that the internal heterotrophic nitrate removal (IHNAR) pathway exists stably at inner of anammox aggregates, which eliminated 42.31 ± 3.85 % nitrate generated in anammox at without consuming external carbon source. The observed volatile fatty acids (VFAs) and adequate protein, polysaccharide and humic acids in the aggregates verified that the in-situ fermentation supplied sustainably endogenous carbon sources for the IHNAR. The efficient interspecies cooperation between anammox bacteria, heterotrophic denitrifiers and fermentative bacteria was identified, as the intrinsic justification for the obtained sustainability of IHNAR pathway. The findings were expected to provide theoretical guidance for promotions and applications of the anammox process with high-efficiency total nitrogen removal capabilities.


Assuntos
Compostos de Amônio , Nitratos , Anaerobiose , Reatores Biológicos , Carbono , Desnitrificação , Nitrogênio , Oxirredução , Águas Residuárias
12.
Schizophr Res ; 241: 292-297, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35217357

RESUMO

Neurocognitive impairment is a core feature of schizophrenia, and patients with first-episode schizophrenia (FES) are optimal candidates for cognitive remediation, but we do not know enough about the incidence, severity and longitudinal changes in neurocognitive impairment in those with FES. This study aimed to assess the neurocognitive trajectories of patients with FES and to compare the clinical and functional outcomes among those with different trajectories. A total of 562 untreated patients with FES completed a neurocognitive test battery and psychopathological and functional assessment. A total of 373 patients attended the follow-up. Group-based trajectory modelling (GBTM) was applied to identify neurocognitive trajectories. Analysis of variance and chi-square tests were conducted to compare demographic characteristics, multiple neurocognitive domains, and clinical and functional outcomes among the different subgroups. We identified three neurocognitive subgroups: preserved (n = 133), mildly to moderately impaired (n = 187) and severely impaired (n = 53). Neurocognitive function in the two impaired subgroups improved within a year but failed to reach the normal level. The processing speed followed trajectories similar to those of overall cognition. The three subgroups did not significantly differ in antipsychotic usage or clinical remission rate. The severely impaired subgroup had poorer functional outcomes than the preserved subgroup, but the mildly to moderately impaired subgroup did not. Patients with FES followed distinct neurocognitive trajectories during the first year of treatment. Patients with severe neurocognitive impairment have poorer functional outcomes, which require and are more likely to benefit from cognitive remediation. Processing speeding is a potential indicator for screening overall cognition.


Assuntos
Antipsicóticos , Transtornos Cognitivos , Esquizofrenia , Antipsicóticos/uso terapêutico , Cognição , Transtornos Cognitivos/diagnóstico , Humanos , Testes Neuropsicológicos , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico
13.
Front Psychiatry ; 12: 763603, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34887790

RESUMO

Background: Herein, we validate the psychometric properties of the Chinese version of the THINC-integrated tool (THINC-it) as a screening tool for cognitive deficits in patients with major depressive disorder. The primary aim of this study is to determine whether cognitive deficits as detected by the THINC-it tool in adults with major depressive disorder (MDD) are associated with workplace productivity and/or psychosocial function. Methods: Subjects aged 18-65 (n = 91) with MDD were evaluated and compared to age-, sex- and education- matched healthy controls (n = 95). Symptoms of cognitive dysfunction, workplace productivity, and psychosocial function were measured using the THINC-it tool, Hamilton Depression Scale (HAMD), Sheehan Disability Scale (SDS), The Work Productivity and Activity Impairment questionnaire- Specific Health Problem (WPAI-SHP). Results: There were significant differences in THINC-it scores (p < 0.01), the average of HAMD total score (p < 0.01) and all aspects of SDS (p < 0.01) between two groups. There were significant differences in the four aspects of WPAI between the two groups in the employed status (p <0.01). THINC-it subjective cognition and SDS total score, SDS work/school, SDS social, SDS family showed significantly correlation (r ranging from 0.255 to 0.386, p <0.01). SDS and THINC-it Objective cognition, THINC-it comprehensive cognition were no correlation between two groups. HAMD total score and SDS total score, SDS social, SDS family showed significantly correlation (r ranging.

14.
Medicine (Baltimore) ; 100(41): e27514, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731138

RESUMO

ABSTRACT: Since its application in medical institutions in China, quality control circle (QCC) has gained achievements in medical care and thus earned more attention from the administrative department of health. This paper focuses on the application of QCC (bone-strength test circle) as a new management concept and tool circle in improving the implementation rate of functional exercise in patients undergoing orthopedic surgery, which further effectively improve the accuracy and compliance of functional exercise in patients undergoing surgery, and further effectively promote the rehabilitation of patients.From July 2018 to November 2018, the management tools and statistical methods of QCC were used to compare the promotion effect of functional exercise execution rate of orthopedic surgery patients before and after QCC activities.The checklist investigated 6 key causes of functional exercise in patients undergoing orthopedic surgery, the operative rate of orthopaedic surgery in all aspects changed significantly. Among them, the factors of inadequate propaganda and education were compared before and after the improvement, which decreased by 71% after the improvement. The incorrect factors of exercise decreased by 69% after improvement, the effect was more obvious, the difference was statistically significant (P < .05). The improvement rate was 59.4%.Through this activity, functional exercise education process and functional exercise paths, and corresponding standards for various orthopedic diseases were established. At the same time, the measures such as health education for patients were strengthened, and the expected goals were effectively achieved.


Assuntos
Exercício Físico/fisiologia , Educação em Saúde/métodos , Procedimentos Ortopédicos/reabilitação , Cooperação do Paciente/estatística & dados numéricos , Lista de Checagem , China/epidemiologia , Humanos , Controle de Qualidade , Melhoria de Qualidade , Estudos Retrospectivos
15.
Front Pharmacol ; 12: 708967, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690755

RESUMO

Gallic acid (3,4,5-trihydroxybenzoic acid; GA), a natural phenolic acid, is abundantly found in numerous natural products. Increasing evidence have demonstrated that GA plays anti-cancer roles in multiple cancers. However, its anti-tumor effects on hepatocellular carcinoma (HCC) and the underlying mechanism remain obscure. In the present study, we found that GA suppressed the in vitro cell viability and metastasis and inhibited the in vivo tumor growth of HCC cells. The underlying mechanism was further to investigate and it was showed that GA suppressed the expression of ß-catenin and led to the functional inactivation of Wnt/ß-catenin signaling. As a kind of significant regulators, the long noncoding RNA molecules (lncRNAs) have attracted widespread attentions for their critical roles in diverse biological process and human diseases. To further identify which lncRNA participated this GA-mediated process, several lncRNAs related to Wnt/ß-catenin signaling were chosen for examination of their expression profiling in the GA-treated HCC cells. Of which, Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) was the most promising candidate. And moreover, MALAT1 was significantly down-regulated by GA. Its overexpression partially reversed the GA-induced the inhibitory effects on cell proliferation and metastasis; and successfully abolished the suppressive effect of GA on Wnt/ß-catenin signaling. In conclusion, our results indicated that GA suppressed tumorigenesis in vitro and in vivo by the MALAT1-Wnt/ß-catenin signaling axis, suggesting that GA has great potential to be developed as a chemo-prevention and chemotherapy agent for HCC patients.

16.
Molecules ; 26(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34641281

RESUMO

Upgrading furfural (FAL) to cyclopentanone (CPO) is of great importance for the synthesis of high-value chemicals and biomass utilization. The hydrogenative ring-rearrangement of FAL is catalyzed by metal-acid bifunctional catalysts. The Lewis acidity is a key factor in promoting the rearrangement of furan rings and achieving a high selectivity to CPO. In this work, highly dispersed Pd nanoparticles were successfully encapsulated into the cavities of a Zr based MOF, UiO-66-NO2, by impregnation using a double-solvent method (DSM) followed by H2 reduction. The obtained Pd/UiO-66-NO2 catalyst showed a significantly better catalytic performance in the aforementioned reaction than the Pd/UiO-66 catalyst due to the higher Lewis acidity of the support. Moreover, by using a thermal treatment. The Lewis acidity can be further increased through the creating of missing-linker defects. The resulting defective Pd/UiO-66-NO2 exhibited the highest CPO selectivity and FAL conversion of 96.6% and 98.9%, respectively. In addition, the catalyst was able to maintain a high activity and stability after four consecutive runs. The current study not only provides an efficient catalytic reaction system for the hydrogenative ring-rearrangement of furfural to cyclopentanone but also emphasizes the importance of defect sites.

17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 868-876, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34622608

RESUMO

OBJECTIVE: To define the gene expression characteristics in the peripheral blood of patients with lumbar disc extrusion (LDE) and the effect of nonoperative treatment on the gene expression. METHODS: DNA microarray was used to identify semi-quantitatively the differentially expressed genes (DEGs) in the peripheral blood of patients with LDE and that of the healthy controls and the variation trend of these DEGs after nonoperative treatment. Enrichment analysis was done to reveal the functional characteristics of these DEGs, and network analysis was done to identify key genes that contribute to gene dysregulation. The levels of these key genes were measured by qRT-PCR to examine their expression in LDE patients and the controls, and the effect of nonoperative treatment on the expression level. RESULTS: We identified 153 DEGs in the peripheral blood of LDE patients and healthy controls, including 131 upregulated genes and 22 downregulated genes. Enrichment analysis revealed that most of the DEGs were related to immunity and the inflammatory response. Network analysis revealed that toll-like receptor 4 ( TLR4 ), matrix metallopeptidase 9 ( MMP9) and myeloperoxidase ( MPO), cathelicidin antimicrobial peptide ( CAMP), resistin ( RETN), toll-like receptor 5 ( TLR5) were the key genes in the protein-protein interaction network. These key genes were all enriched into the terms releated to immunity and the inflammatory response. The patients experienced pain relief after nonoperative treatment. Among the 153 DEGs, TLR5 , interleukin 1 receptor antagonist ( IL1 RN) and solute carrier family 8 member A1 ( SLC8 A1) were downregulated after nonoperative treatment. qRT-PCR revealed that the levels of TLR4, MMP9 , MPO, CAMP, RETN, TLR5, IL1 RN and SLC8 A1 in the peripheral blood of the LDE patients were higher than those of the healthy control group ( P<0.05). In addition, TLR5 , IL1 RN and SLC8 A1 expression levels decreased after treatmentin in comparison with the levels before treatment ( P<0.05). CONCLUSION: Gene expression in the peripheral blood of LDE patients was characterized by the dysregulation of immune and inflammatory response-related genes, among which, TLR4, MMP9, MPO, CAMP, RETN and TLR5, the genes relevant to immune and inflammatory response, played a key role in the dysregulation of gene expression in the peripheral blood of LDE patients. The outcome of non-operative treatment may be related to the downregulation of the overexpressed TLR5, IL1 RN and SLC8 A1 in the peripheral blood of patients.


Assuntos
Perfilação da Expressão Gênica , Regulação para Baixo , Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos
18.
Onco Targets Ther ; 14: 4859-4865, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34584426

RESUMO

BACKGROUND: The standard treatment for advanced gastric/gastroesophageal junction cancer (AGC/GEJC) is palliative chemotherapy combined with targeted therapy. The SOX regimen (S-1 plus oxaliplatin) is recommended as neoadjuvant or palliative first-line chemotherapy in Asian patients. Apatinib, an oral VEGFR tyrosine kinase inhibitor, is associated with additional survival benefit as third- or subsequent-line therapy. However, the median overall survival time of AGC/GEJC is only 8-11 months in the West and 13-17 months in East Asia/Japan, even with the application of anti-angiogenic agents. Hence, the multimodal and individual management of patients is challenging standards to improve prognosis, including the preferential use of low-dose anti-angiogenic drugs and immunotherapy, as well as the application of multi-disciplinary treatment (MDT)-directed conversion therapy. METHODS/DESIGN: This single-center study was designed to combine low-dose apatinib with camrelizumab plus the SOX regimen in diagnosed potentially resectable and initially unresectable AGC/GEJC. This a prospective, open-label, single-arm, dose escalation and extension phase Ib clinical trial, conducted in Jiangsu Province Hospital, beginning from June 2020. All patients will first receive this combined regimen (3 weeks/cycle) for at most eight cycles, then apatinib and camrelizumab in maintenance therapy until disease progression, intolerable toxicity, death, a maximum 2 years of treatment or discontinuation for any reason. Follow-up and evaluation will be carried out regularly. If surgery is allowed by MDT discussions, oral apatinib will be discontinued during the last preoperative cycle. The primary endpoints are the objective response rate and maximum tolerated dose according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) and the Common Terminology Criteria for Adverse Events (CTCAE) criteria (version 5.0). DISCUSSION: This study will assess the response and side effects of AGC/GEJC patients in the use of low-dose apatinib combined with camrelizumab and the SOX regimen, and this combined therapy is expected to be a feasible and optimized first-line treatment option. In addition, this study will provide robust evidence and novel ideas for conversion therapy. TRIAL REGISTRATION: ChiCTR.gov.cn: ChiCTR2000034109.

19.
Psychiatry Res ; 305: 114202, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34536696

RESUMO

BACKGROUND: Inflammation and cognition are related to major depressive disorder (MDD), but the role in treatment response remains unclear. In this study, we investigated correlation between inflammatory cytokines and cognition in MDD patients treated with antidepressant medication. METHODS: The participants were 149 MDD patients. Cytokines before therapy, cognitive assessments and severity of depression before and after therapy were tested. Logistic regression was used to explore underlying risks treatment response. RESULTS: There were significant differences in smoking, alcohol drinking, and Stroop Color Test(SCT), Stroop Color-Word Test (SCWT), and Continuous Performance Test(CPT) scores between response group (RG) and non-response group (NRG) at baseline. Performance of patients in RG improved more in Brief Assessment of Cognition in Schizophrenia (BACS), Color Trial Test-I (CTT-I), SCT and SCWT after treatment. Levels of baseline IL-18 were associated with baseline learning and memory, and executive function. Treatment response was associated with drinking, performance of CPT and SCT. CONCLUSION: MDD patients with different treatment responses have different cognitive defects, especially in speed of processing and executive function. Expression of cytokines is associated with cognition and may influence treatment response. Better speed of processing and executive function, and poorer attention at baseline may respond better to antidepressant treatment.


Assuntos
Transtorno Depressivo Maior , Antidepressivos/uso terapêutico , Cognição/fisiologia , Citocinas , Transtorno Depressivo Maior/psicologia , Função Executiva , Humanos
20.
Front Artif Intell ; 4: 697856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490421

RESUMO

Knowledge Graphs (KGs) such as Freebase and YAGO have been widely adopted in a variety of NLP tasks. Representation learning of Knowledge Graphs (KGs) aims to map entities and relationships into a continuous low-dimensional vector space. Conventional KG embedding methods (such as TransE and ConvE) utilize only KG triplets and thus suffer from structure sparsity. Some recent works address this issue by incorporating auxiliary texts of entities, typically entity descriptions. However, these methods usually focus only on local consecutive word sequences, but seldom explicitly use global word co-occurrence information in a corpus. In this paper, we propose to model the whole auxiliary text corpus with a graph and present an end-to-end text-graph enhanced KG embedding model, named Teger. Specifically, we model the auxiliary texts with a heterogeneous entity-word graph (called text-graph), which entails both local and global semantic relationships among entities and words. We then apply graph convolutional networks to learn informative entity embeddings that aggregate high-order neighborhood information. These embeddings are further integrated with the KG triplet embeddings via a gating mechanism, thus enriching the KG representations and alleviating the inherent structure sparsity. Experiments on benchmark datasets show that our method significantly outperforms several state-of-the-art methods.

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