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1.
PeerJ ; 12: e17027, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38436011

RESUMO

Background: Psoriasis is a chronic immune-mediated inflammatory disease. N6-methyladenosine (m6A) is involved in numerous biological processes in both normal and diseased states. Herein, we aimed to explore the potential role of m6A regulators in the diagnosis of psoriasis and predict molecular mechanisms by which m6A regulators impact psoriasis. Methods: GSE30999 (170 human skin tissue samples) and GSE13355 (180 human skin tissue samples) were downloaded as the training analysis dataset and validation dataset respectively. M6A-related genes were obtained from the literature and their expression levels in GSE30999 samples were measured to identify M6A-related DEGs between psoriasis lesions (LS) and non-lesional lesions (NL). We identified m6A-related DEGs using differential expression analysis and assessed their interactions through correlation analysis and network construction. A logistic regression analysis followed by LASSO optimization was employed to select m6A-related DEGs for the construction of a diagnostic model. The performance of the model was validated using support vector machine (SVM) methodology with sigmoid kernel function and extensive cross-validation. Additionally, the correlation between m6A-related DEGs and immune cell infiltration was analyzed, as well as the association of these DEGs with psoriasis subtypes. Functional analysis of the m6A-related DEGs included the construction of regulatory networks involving miRNAs, transcription factors (TFs), and small-molecule drugs. The m6A modification patterns were also explored by examining the gene expression differences between psoriasis subtypes and their enriched biological pathways. Finally, the expression of significant m6A regulators involved in the diagnostic model was examined by RT-qPCR. Results: In this study, ten optimal m6A-related DEGs were identified, including FTO, IGF2BP2, METTL3, YTHDC1, ZC3H13, HNRNPC, IGF2BP3, LRPPRC, YTHDC2, and HNRNPA2B1. A diagnostic model based on these m6A-related DEGs was constructed, demonstrating high diagnostic accuracy with an area under the curve (AUC) in GSE30999 and GSE13355 of 0.974 and 0.730, respectively. Meanwhile, the expression level of m6A regulators verified by RT-qPCR was consistent with the results in GSE30999. The infiltration of activated mast cells and NK cells was significantly associated with all ten m6A-related DEGs in psoriasis. Among them, YTHDC1, HNRNPC, and FTO were targeted by most miRNAs and were regulated by nine related TFs. Therefore, patients may benefit from dorsomorphin and cyclosporine therapy. Between the two subgroups, 1,592 DEGs were identified, including LRPPRC and METTL3. These DEGs were predicted to be involved in neutrophil activation, cytokine-cytokine receptor interactions, and chemokine signaling pathways. Conclusions: A diagnostic model based on ten m6A-related DEGs in patients with psoriasis was constructed, which may provide early diagnostic biomarkers and therapeutic targets for psoriasis.


Assuntos
Adenina/análogos & derivados , MicroRNAs , Psoríase , Humanos , Psoríase/diagnóstico , Adenosina , Metiltransferases , Proteínas de Ligação a RNA , Dioxigenase FTO Dependente de alfa-Cetoglutarato
2.
Anal Chim Acta ; 1297: 342379, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38438245

RESUMO

Here, 1,3,4-thiadiazole unit was employed as novel excited state intramolecular proton transfer (ESIPT) structure to prepare favorable fluorescent probe. High selectivity and rapid response to Cu2+ was obtained and the settling reaction was also used to recover ESIPT characteristics of probe to achieve sequential detection of H2S. Remarkable color change of solution from colorless to bright yellow and fluorescence emission from green to dark realized the visual detection of Cu2+ by naked eyes and transition of probe into portable fluorescent test strips. As expected, L-E could be utilized to quantitatively sense Cu2+ and H2S in different actual water and food samples including herbs, wine and fruits. The limits of detection for Cu2+ and H2S were as low as 34.5 nM and 38.6 nM. Also, probe L-E achieved real-time, portable, on-site quantitative detection of Cu2+ via a colorimeter and a smartphone platform with limit of detection to 90.3 nM.


Assuntos
Corantes Fluorescentes , Tiadiazóis , Vinho , Frutas , Prótons
3.
Lancet Reg Health West Pac ; 45: 101019, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38371948

RESUMO

Background: China's National Essential Public Health Service Package (NEPHSP) aims to promote health for all at the primary health care level and includes a focus on hypertension and type-2 diabetes mellitus (T2DM). However, there are limited contemporary data to quantify the care cascades of hypertension and T2DM in primary health care. Methods: This cross-sectional study involved individual level linkage of routinely collected data from the NEPHSP, health insurance claims and hospital electronic health records, from four diverse regions in China, including Xiling District (central China), Wenchuan County (western), Acheng District and Jiao District (northern). We first compared numbers of people aged ≥35 with a recorded diagnosis of hypertension and T2DM against expected numbers derived from epidemiological data. We then constructed care cascades to assess the percentages (1) enrolled in the NEPHSP, (2) adherent to the follow-up care of NEPHSP, (3) receiving medication treatment, and (4) having hypertension and/or T2DM controlled. Findings: In the four regions, the total numbers of people aged ≥35 diagnosed of hypertension and T2DM from any data source were 149,176 and 50,828, respectively. This was estimated to be 46.0% (95% confidence interval [CI]: 45.8%-46.2%) and 45.6% (95% CI: 45.3%-45.9%) of the expected totals for hypertension and T2DM, respectively. Among those diagnosed, 65.4% (95% CI: 65.1%-65.6%) with hypertension and 66.1% (95% CI: 65.7%-66.5%) with T2DM were enrolled in the NEPHSP, respectively, in which 54.8% (95% CI: 54.5%-55.2%) with hypertension and 64.7% (95% CI: 64.1%-65.2%) with T2DM were adherent to the required services. Among those enrolled, the overall treatment rates were 70.8% (95% CI: 70.6%-71.1%) for hypertension and 82.2% (95% CI: 81.8%-82.6%) for T2DM. Among those treated, a further 80.9% (95% CI: 80.6%-81.2%) with hypertension and 73.9% (95% CI: 73.3%-74.4%) with T2DM achieved control. These results varied considerably across regions, with the northern sites showing relatively higher enrolment rates while the central site had higher control rates. Interpretation: Detection and control rates for hypertension and T2DM are suboptimal in these four regions of China. Further strategies are needed to improve people's enrolment in and adherence to the NEPHSP and strengthen care delivery processes. Of note, our estimations of the diagnosis rates for each region are based on national level large epidemiological data. The interpretation of these data needs caution due to potential bias caused by regional variations. Funding: This study is funded by National Health and Medical Research Council (NHMRC) Global Alliance for Chronic Diseases funding (APP1169757), and National Natural Science Foundation of China (72074065).

4.
Heliyon ; 9(10): e20709, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37876445

RESUMO

The targets and mechanisms of Si-Wu-Tang (SWT) against (Breast cancer) BRCA were identified and a survival model and nomogram was construted by network pharmacology, bioinformatic analysis and in vitro experiments. A total of 72 anti-breast cancer SWT targets were selected, among which eleven genes (MAOA、SQLE、CACNA2D1、GLI1、RORB、ITGB3、TACR1、NR3C2、CA3、RBP4 and PTK6) were used to construct a novel prognostic model of breast cancer. The anti-breast cancer activity of SWT was related to the modulation of the receptor tyrosine kinases signaling pathways. Moreover, two compounds, mairin and senkyunone were found to bind directly to ITGB3 and RORB proteins. Finally, mRNA and protein expression of ITGB3 and RORB was observed to be significantly down-regulated after incubation of MCF-7 cells with SWT. Overall, our results indicated that mairin and senkyunone were the key ingredients present in SWT, and ITGB3 as well as RORB proteins were the major targets affected by SWT. The prognostic model can be used to predict the outcome of BRCA patients.

5.
iScience ; 26(9): 107680, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37680468

RESUMO

Progressive damage of retinal ganglion cells (RGCs) is observed in early diabetic retinopathy. Intracellular Ca2+ overload mediated by Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) is involved in neurodegeneration, whereas glucagon-like peptide-1 (GLP-1) provides neuroprotection. However, whether GLP-1 plays a neuroprotective role in diabetic retinas by modulating VGCCs remains unknown. We found that eye drops of exendin-4, a long-acting GLP-1 receptor (GLP-1R) agonist, prevented the increase of L-type Ca2+ current (ILCa) densities of RGCs induced by 4-week hyperglycemia and promoted RGC survival by suppressing L-type VGCC (L-VGCC) activity in streptozotocin-induced diabetic rats. Moreover, exendin-4-induced suppression of ILCa in RGCs may be mediated by a GLP-1R/Gs/cAMP-PKA/ryanodine/Ca2+/calmodulin/calcineurin/PP1 signaling pathway. Furthermore, exendin-4 functionally improved the light-evoked spiking ability of diabetic RGCs. These results suggest that GLP-1R activation enhances cAMP to PP1 signaling and that PP1 inactivates L-VGCCs by dephosphorylating them, thereby reducing Ca2+ influx, which could protect RGCs against excitotoxic Ca2+ overload.

6.
Front Cell Dev Biol ; 11: 1166308, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37554306

RESUMO

Tumor Necrosis Factor-alpha (TNF-α) is ubiquitous in the human body and plays a significant role in various physiological and pathological processes. However, TNF-α-induced diseases remain poorly understood with limited efficacy due to the intricate nature of their mechanisms. N6-methyladenosine (m6A) methylation, a prevalent type of epigenetic modification of mRNA, primarily occurs at the post-transcriptional level and is involved in intranuclear and extranuclear mRNA metabolism. Evidence suggests that m6A methylation participates in TNF-α-induced diseases and signaling pathways associated with TNF-α. This review summarizes the involvement of TNF-α and m6A methylation regulators in various diseases, investigates the impact of m6A methylation on TNF-α-induced diseases, and puts forth potential therapeutic targets for treating TNF-α-induced diseases.

7.
Toxins (Basel) ; 15(5)2023 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-37235384

RESUMO

We conducted a comparative analysis to unveil the divergence among venoms from a subset of Old World habu snakes (Protobothrops) in terms of venomic profiles and toxicological and enzymatic activities. A total of 14 protein families were identified in the venoms from these habu snakes, and 11 of them were shared among these venoms. The venoms of five adult habu snakes were overwhelmingly dominated by SVMP (32.56 ± 13.94%), PLA2 (22.93 ± 9.26%), and SVSP (16.27 ± 4.79%), with a total abundance of over 65%, while the subadult P. mangshanensis had an extremely low abundance of PLA2 (1.23%) but a high abundance of CTL (51.47%), followed by SVMP (22.06%) and SVSP (10.90%). Apparent interspecific variations in lethality and enzymatic activities were also explored in habu snake venoms, but no variations in myotoxicity were found. Except for SVSP, the resemblance of the relatives within Protobothrops in other venom traits was estimated to deviate from Brownian motion evolution based on phylogenetic signals. A comparative analysis further validated that the degree of covariation between phylogeny and venom variation is evolutionarily labile and varies among clades of closely related snakes. Our findings indicate a high level of interspecific variation in the venom proteomes of habu snakes, both in the presence or absence and the relative abundance of venom protein families, and that these venoms might have evolved under a combination of adaptive and neutral mechanisms.


Assuntos
Trimeresurus , Animais , Filogenia , Trimeresurus/metabolismo , Serpentes/metabolismo , Venenos de Serpentes , Fosfolipases A2/análise , Proteoma/metabolismo
8.
Lancet Reg Health West Pac ; 31: 100664, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36879777

RESUMO

Background: China launched the primary health care (PHC) system oriented National Essential Public Health Service Package (NEPHSP) in 2009, to combat health challenges including the increasing burden from hypertension and type-2 diabetes (T2DM). In this study, the PHC system was assessed to understand factors influencing the uptake of the NEPHSP for hypertension and T2DM management. Methods: A mixed-methods study was conducted in seven counties/districts from five provinces across the mainland of China. Data included a PHC facility level survey and interviews with policy makers, health administrators, PHC providers, and individuals with hypertension and/or T2DM. The facility survey used the World Health Organisation (WHO) service availability and readiness assessment questionnaire. Interviews were thematically analysed using the WHO health systems building blocks. Findings: A total of 518 facility surveys were collected with over 90% in rural settings (n = 474). Forty-eight in-depth individual interviews and 19 focus-group discussions were conducted across all sites. Triangulating the quantitative and qualitative data found that China's continuous political commitment to strengthening the PHC system led to improvements in workforce and infrastructure. Despite this, many barriers were identified, including insufficient and under-qualified PHC personnel, remaining gaps in medicines and equipment, fragmented health information systems, residents' low trust and utilization of PHC, challenges in coordinated and continuous care, and lack of cross-sectorial collaborations. Interpretation: The study findings provided recommendation for future PHC system strengthening, including improving the quality of NEPHSP delivery, facilitating resource-sharing across health facilities, establishing integrated care systems, and exploring mechanisms for better cross-sectorial engagement in health governance. Funding: The study is supported by National Health and Medical Research Council (NHMRC) Global Alliance for Chronic Disease funding (APP1169757).

9.
Chem Commun (Camb) ; 59(11): 1485-1488, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36655734

RESUMO

Perovskite materials passivated by chiral ligands have recently shown unique chiroptical activity with promising optoelectronic applications. However, the ligands have been limited to chiral amines. Here, chiral phosphate molecules have been exploited to synthesize CsPbBr3 nanoplatelets. The nanoplatelets showed a distinct circular dichroism signal and maintained their chiroptical properties after purification with anti-solvent.

10.
Opt Express ; 30(13): 22986-22998, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-36224988

RESUMO

In this paper, a novel cyclic mode converter (CMC) is proposed and fabricated to implement cyclic mode permutation (CMP) on-chip for differential mode delay and mode-dependent loss elimination in the mode division multiplexing (MDM) transmission system. Cascaded by three optimally designed mode converters that do not affect the non-target modes, the proposed CMC can realize the conversion of any input mode among the TE0/TE1/TM0/TM1 modes. The three-dimensional finite-difference time-domain (3D-FDTD) simulation results show that the insertion loss of our device is less than 0.59 dB, and the crosstalk of each mode is lower than -15 dB under the range of 1500-1600 nm. The flat spectral response of this CMC is maintained even in the presence of fabrication errors up to±10 nm, showing great robustness. The experimental results also prove that at the center wavelength of 1550 nm the measured insertion loss of each mode is below 2.22 dB, and the crosstalk of each mode is lower than -15 dB. The proposed CMC provides a new idea for effectively reducing link damage in the MDM transmission system.

11.
Biomater Sci ; 10(13): 3647-3656, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35670464

RESUMO

One of the main challenges in applying the immune checkpoint blockade to treat colorectal cancer (CRC) is the immunosuppressive tumor microenvironment. Owing to its excellent cancer cell killing ability and immune activation, mild photothermal therapy (PTT) has shown bright promise to sensitize tumors to immune checkpoint inhibition through turning the immunologically "cold" tumors into "hot" ones. Herein, a mild photothermal effect-assisted theragnostic nanodrug (MnO2@MPDA-PEG NPs) is developed by incorporating MnO2 into PEGylated-mesoporous polydopamine nanoparticles (MPDA-PEG NPs). The presence of PEG endows the theragnostic nanodrug with high biostability. After accumulation in colorectal tumor, the theragnostic nanodrug responds to the tumor microenvironment, leading to the simultaneous release of Mn2+ which serves as a magnetic resonance imaging (MRI) contrast agent for tumor imaging. The released Mn2+ could also promote mild photothermal treatment-induced immune response, including the maturation of BMDC cells. In vivo antitumor studies on a CT26 model demonstrate that MnO2@MPDA-PEG NPs could be a promising dual-imaging theragnostic nanodrug to potentiate the systemic antitumor immunities.


Assuntos
Neoplasias Colorretais , Nanopartículas , Linhagem Celular Tumoral , Neoplasias Colorretais/terapia , Meios de Contraste , Humanos , Imunoterapia , Indóis , Compostos de Manganês , Óxidos , Fototerapia/métodos , Polímeros , Microambiente Tumoral
12.
J Chem Phys ; 156(15): 154701, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35459297

RESUMO

Changing the excitation wavelength is a simple but effective strategy to modulate the photophysical cha racteristics of colloidal quantum dots (QDs) near plasmonic nanostructures. It has been observed that the photoluminescence (PL) decay of QDs near plasmonic nanostructures differs when the excitation wavelength is varied, but the exact mechanism is still unclear today. Here, we studied the excitation wavelength dependence of the PL decay of CdSe/CdS core/shell QDs near plasmonic gold nanoparticles at the single QD level. With the aid of statistical science, we demonstrated that the PL decay of a single QD near gold nanoparticles is generally faster when the QD is excited spectrally close to the localized surface plasmon resonance of gold nanoparticles. This excitation wavelength dependence is mainly caused by the varied proportion of photons coming from biexciton emission, which is the result of different local electric field enhancement by gold nanoparticles upon excitation.

13.
Neurosci Bull ; 38(6): 622-636, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35278196

RESUMO

Glucagon-like peptide-1 (GLP-1) is expressed in retinal neurons, but its role in the retina is largely unknown. Here, we demonstrated that GLP-1 or the GLP-1 receptor (GLP-1R; a G protein-coupled receptor) agonist exendin-4 suppressed γ-aminobutyric acid receptor (GABAR)-mediated currents through GLP-1Rs in isolated rat retinal ganglion cells (GCs). Pre-incubation with the stimulatory G protein (Gs) inhibitor NF 449 abolished the exendin-4 effect. The exendin-4-induced suppression was mimicked by perfusion with 8-Br-cAMP (a cAMP analog), but was eliminated by the protein kinase A (PKA) inhibitor Rp-cAMP/KT-5720. The exendin-4 effect was accompanied by an increase in [Ca2+]i of GCs through the IP3-sensitive pathway and was blocked in Ca2+-free solution. Furthermore, when the activity of calmodulin (CaM) and CaM-dependent protein kinase II (CaMKII) was inhibited, the exendin-4 effect was eliminated. Consistent with this, exendin-4 suppressed GABAR-mediated light-evoked inhibitory postsynaptic currents in GCs in rat retinal slices. These results suggest that exendin-4-induced suppression may be mediated by a distinct Gs/cAMP-PKA/IP3/Ca2+/CaM/CaMKII signaling pathway, following the activation of GLP-1Rs.


Assuntos
Peptídeo 1 Semelhante ao Glucagon , Células Ganglionares da Retina , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Exenatida/metabolismo , Exenatida/farmacologia , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Ratos , Receptores de GABA/metabolismo , Células Ganglionares da Retina/fisiologia , Transdução de Sinais
14.
Vaccines (Basel) ; 11(1)2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36679878

RESUMO

Objective: To analyze the differences in efficacy and safety of different types of novel coronavirus pneumonia (COVID-19) vaccines in different age groups (young adults and elderly). Methods: Randomized controlled trials (RCTs) on COVID-19 vaccine in PubMed, Embase, Web of Science, and Cochrane library were searched by computer, and eight eligible studies were analyzed. Meta-analysis was performed using Stata 16.0 and RevMan5.4 software. Results: The mean geometric titer (GMT) of the virus in the elderly was significantly higher than that in the placebo group (SMD = 0.91, 95% CI (0.68, 1.15), p < 0.01), presenting no obvious difference compared with the young adults (SMD = 0.19, 95% CI (0.38, 0.01), p = 0.06). Meanwhile, the effect of multiple vaccinations was better than that of single vaccination (SMD = 0.83, 95% CI (0.33, 1.34), p < 0.01). However, the number of adverse events (AEs) in the elderly was lower than that in the young adults (OR = 0.35, 95% CI (0.29, 0.42), p < 0.01). Conclusions: The immunization effect of COVID-19 vaccine in the elderly is obvious, especially after multiple vaccinations, and the incidence of AEs in the elderly is low, which proves that the vaccination of the elderly is safe and effective.

15.
ACS Appl Mater Interfaces ; 13(50): 59892-59903, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34890203

RESUMO

The electrochemical oxidation of small organic molecules (SOMs) such as methanol and glucose is a critical process and has relevant applications in fuel cells and sensors. A key challenge in SOM oxidation is the poisoning of the surface by carbon monoxide (CO) and other partially oxidized intermediates, which is attributed to the presence of Pt-Pt pair sites. A promising pathway for overcoming this challenge is to develop catalysts that selectively oxidize SOMs via "direct" pathways that do not form CO as a primary intermediate. In this report, we utilize an ambient, template-based approach to prepare PtAu alloy nanowires with tunable compositions. X-ray photoelectron spectroscopy measurements reveal that the surface composition matches that of the bulk composition after synthesis. Monte Carlo method simulations of the surface structure of PtAu alloys with varying coverage of oxygen adsorbates and varying degrees of oxygen adsorption strength reveal that oxygen adsorption under electrochemical conditions enriches the surface with Pt and a large fraction of Pt-Pt sites remain on the surface even with the Au content of up to 50%. Electrochemical properties and the catalytic performance measurements of the PtAu nanowires for the oxidation of methanol and glucose reveal that the mechanistic pathways that produce CO are suppressed by the addition of relatively small quantities of Au (∼10%), and CO formation can be completely suppressed by 50% Au. The suppression of CO formation with small quantities of Au suggests that the presence of Pt-Au pair sites may be more important in determining the mechanism of SOM oxidation rather than Pt-Pt pair site density.

16.
Oxid Med Cell Longev ; 2021: 9930187, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745427

RESUMO

Ulcerative colitis (UC) is a common chronic nonspecific intestinal inflammation of unknown etiology associated with a low cure rate and a high relapse rate. Hair follicle mesenchymal stem cells (HF-MSCs) are a class of pluripotent stem cells that have differentiation potential and strong proliferation ability. Nuclear factor red system related factor (Nrf-2) is a key factor in the oxidative stress response. Dextran sulfate sodium- (DSS-) induced rat UC models closely mimic human UC in terms of symptoms and histological changes. Animals were divided into five groups, including a healthy group and UC model rats treated with normal saline, Nrf-2, HF-MSCs, or Nrf-2-expressing HF-MSC group. Based on the expression of intestinal stem cells, inflammatory factors, anti-inflammatory factors, and disease activity index scores, Nrf-2-expressing HF-MSCs had the most obvious therapeutic effect under the same treatment regimen. This study provided a new potential clinical treatment option for ulcerative colitis.


Assuntos
Colite Ulcerativa/prevenção & controle , Sulfato de Dextrana/toxicidade , Folículo Piloso/química , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Citocinas/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/química , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
17.
Mol Ther Nucleic Acids ; 26: 828-848, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34729251

RESUMO

Myocardial infarction (MI) is defined as cardiomyocyte death in a clinical context consistent with ischemic insult. MI remains one of the leading causes of morbidity and mortality worldwide. Although there are a number of effective clinical methods for the diagnosis and treatment of MI, further investigation of novel biomarkers and molecular therapeutic targets is required. Circular RNAs (circRNAs), novel non-coding RNAs, have been reported to function mainly by acting as microRNA (miRNA) sponges or binding to RNA-binding proteins (RBPs). The circRNA-miRNA-mRNA (protein) regulatory pathway regulates gene expression and affects the pathological mechanisms of various diseases. Undoubtedly, a more comprehensive understanding of the relationship between MI and circRNA will lay the foundation for the development of circRNA-based diagnostic and therapeutic strategies for MI. Therefore, this review summarizes the pathophysiological process of MI and various approaches to measure circRNA levels in MI patients, tissues, and cells; highlights the significance of circRNAs in the regulation MI pathogenesis and development; and provides potential clinical insight for the diagnosis, prognosis, and treatment of MI.

18.
BMC Cancer ; 21(1): 1246, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34798858

RESUMO

BACKGROUND: Atypical tumor response patterns during immune checkpoint inhibitor therapy pose a challenge to clinicians and investigators in immuno-oncology practice. This study evaluated tumor burden dynamics to identify imaging biomarkers for treatment response and overall survival (OS) in advanced gastrointestinal malignancies treated with PD-1/PD-L1 inhibitors. METHODS: This retrospective study enrolled a total of 198 target lesions in 75 patients with advanced gastrointestinal malignancies treated with PD-1/PD-L1 inhibitors between January 2017 and March 2021. Tumor diameter changes as defined by immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) were studied to determine treatment response and association with OS. RESULTS: Based on the best overall response, the tumor diameter ranged from - 100 to + 135.3% (median: - 9.6%). The overall response rate was 32.0% (24/75), and the rate of durable disease control for at least 6 months was 30.7% (23/75, one (iCR, immune complete response) or 20 iPR (immune partial response), or 2iSD (immune stable disease). Using univariate analysis, patients with a tumor diameter maintaining a < 20% increase (48/75, 64.0%) from baseline had longer OS than those with ≥20% increase (27/75, 36.0%) and, a reduced risk of death (median OS: 80 months vs. 48 months, HR = 0.22, P = 0.034). The differences in age (HR = 1.09, P = 0.01), combined surgery (HR = 0.15, P = 0.01) and cancer type (HR = 0.23, P = 0.001) were significant. In multivariable analysis, patients with a tumor diameter with a < 20% increase had notably reduced hazards of death (HR = 0.15, P = 0.01) after adjusting for age, combined surgery, KRAS status, cancer type, mismatch repair (MMR) status, treatment course and cancer differentiation. Two patients (2.7%) showed pseudoprogression. CONCLUSIONS: Tumor diameter with a < 20% increase from baseline during therapy in gastrointestinal malignancies was associated with therapeutic benefit and longer OS and may serve as a practical imaging marker for treatment response, clinical outcome and treatment decision making.


Assuntos
Neoplasias Gastrointestinais , Inibidores de Checkpoint Imunológico/uso terapêutico , Critérios de Avaliação de Resposta em Tumores Sólidos , Carga Tumoral , Adulto , Fatores Etários , Análise de Variância , Reparo de Erro de Pareamento de DNA , Feminino , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/imunologia , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Genes ras , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
19.
Front Psychol ; 12: 680614, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484037

RESUMO

OBJECTIVES: The sudden outbreak of the novel coronavirus disease (COVID-19) plunged healthcare workers (HCWs) into warfare. This study aimed to determine the prevalence of burnout and the factors associated with it among frontline HCWs fighting COVID-19. METHODS: A cross-sectional survey was conducted among frontline HCWs fighting against the COVID-19 in Wuhan, Harbin, and Shenzhen during the period from February 18 to March 4. Finally, HCWs were recruited using cluster sampling, 1,163 HCWs were included in the final analysis. Burnout was measured using a 22-item Maslach Burnout Inventory scale (MBI scale). RESULTS: Of the participants, 48.6% suffered from burnout, and 21.8% showed a high degree of burnout. Doctors (b = 3.954, P = 0.011) and nurses (b = 3.067, P = 0.042) showed higher emotional exhaustion (EE) than administrators. Participants who worked continuously for more than 8 h a day (b = 3.392, P = 0.000), those who were unable to eat three regular daily meals (b = 2.225, P = 0.008), whose daily water intake was no more than 800 ml (b = 3.007, P = 0.000), who slept for no more than 6 h (b = 1.609, P = 0.036), and who were infected or had colleagues who were infected with COVID-19 (b = 4.182, P = 0.000) experienced much higher levels of EE, while those who could adhere to infection control procedures (b = -5.992, P = 0.000), who were satisfied with their hospital's infection control measures(b = -3.709, P = 0.001), and who could receive sufficient psychological crisis intervention (b = -1.588, P = 0.039) reported lower levels of EE. CONCLUSION: The study reveals that burnout is prevalent among frontline HCWs and that the known factors associated with burnout, such as workload, and the factors directly associated with COVID-19, such as having insufficient protection, can affect burnout symptoms in frontline HCWs. Synergized and comprehensive interventions should be targeted at reducing its occurrence among frontline HCWs fighting COVID-19.

20.
BMJ Open ; 11(7): e048493, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272223

RESUMO

OBJECTIVE: The purposes of this study were to evaluate the rate of workplace violence in county hospitals in China and its impact on healthcare workers and to explore the relationship between hospital violence, coping styles and anxiety to provide effective procedures for reducing anxiety among healthcare workers. METHODS: The study used stratified sampling to select 1200 healthcare workers from 30 county hospitals in China to conduct a questionnaire survey. Of these, 1030 were valid questionnaires, and the effective response rate was 85.83%. We collected demographic characteristics of our participants and administered the following scales to them: Workplace Violence, Trait Coping Style, Self-rating Anxiety. Data were statistically analysed. RESULTS: The results showed that 67.28% of healthcare workers in county hospitals in China had experienced workplace violence in the previous 12 months, with prevalent verbal violence (66.12%) followed by physical violence (15.24%). Workplace violence in hospitals was negatively related to positive coping (r=-0.091, p<0.01) but positively related to negative coping (r=0.114, p<0.001) and anxiety (r=0.298, p<0.001). Positive and negative coping was negatively (r=-0.085, p<0.01) and positively (r=0.254, p<0.001) associated with anxiety respectively. Positive and negative coping influenced both hospital workplace violence and anxiety in healthcare workers who were victims of violence. Compared with positive coping, the mediating effect of negative coping was stronger (95% CI -0.177 to -0.006). CONCLUSIONS: The incidence of workplace violence among healthcare workers in county-level hospitals in China is relatively high, and there is a correlation between hospital violence, coping styles and anxiety. Positive and negative coping play a mediating role in the impact of hospital violence on healthcare workers' anxiety. Therefore, hospital administrators should actively promote healthcare workers' transition to positive coping strategies and minimise the negative impact of anxiety on them.


Assuntos
Violência no Trabalho , Adaptação Psicológica , Ansiedade/epidemiologia , China , Estudos Transversais , Pessoal de Saúde , Hospitais , Humanos , Inquéritos e Questionários
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