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1.
Hum Mol Genet ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38723288

RESUMO

microRNAs (miRNAs) are short non-coding RNAs that have been increasingly recognized for their significant roles in the progression of cancer. Distinct miRNAs exhibit diverse functions attributed to variations in their sequences. As a result of possessing highly homologous seed sequences, these miRNAs target overlapping or similar gene sets, thus performing analogous roles. However, different from this sight, our study discovered that miR-135a-5p and miR-135b-5p, despite differing by only one nucleotide, exhibit distinct functional roles. Using non-small cell lung cancer (NSCLC) as a paradigm, our findings unveiled the downregulation of miR-135a-5p and upregulation of miR-135b-5p within NSCLC through TCGA database. Consequently, we further investigated their functional differences in A549 cells. Overexpression of miR-135b-5p enhanced the proliferation and migration capabilities of A549 cells, whereas miR-135a-5p transfection exhibited the opposite effect. We demonstrated that the activation of specific enhancers serves as a crucial mechanism underlying the disparate functions exerted by miR-135a-5p and miR-135b-5p in the context of NSCLC, consequently instigating a shift from inhibition to activation in NSCLC progression. Finally, we validated through animal experiments that miR-135b-5p promoted tumor progression, while miR-135a-5p exerted inhibitory effects on NSCLC development. This study offers a novel perspective for researchers to elucidate functional disparities exhibited by highly homologous miRNAs (miR-135a-5p and miR-135b-5p) in the context of NSCLC, along with the transition from inhibitory to progressive states in NSCLC. This study provides a solid foundation for future investigations into the functional roles of highly homologous miRNAs in pathological situation.

2.
Zhongguo Yi Liao Qi Xie Za Zhi ; 48(2): 179-183, 2024 Mar 30.
Artigo em Chinês | MEDLINE | ID: mdl-38605618

RESUMO

Objective: To introduce a locating device for the entry point of intramedullary nail based on the inertial navigation technology, which utilizes multi-dimensional angle information to assist in rapid and accurate positioning of the ideal direction of femoral anterograde intramedullary nails' entry point, and to verify its clinical value through clinical tests. Methods: After matching the locating module with the developing board, which are the two components of the locating device, they were placed on the skin surface of the proximal femur of the affected side. Anteroposterior fluoroscopy was performed. The developing angle corresponding to the ideal direction of entry point was selected based on the X-ray image, and then the yaw angle of the locating module was reset to zero. After resetting, the locating module was combined with the surgical instrument to guide the insertion angle of the guide wire. The ideal direction of entry point was accurately located based on the angle guidance. By setting up an experimental group and a control group for clinical surgical operations, the number of guide wire insertion times, surgical time, fluoroscopy frequency, and intraoperative blood loss with or without the locating device was recorded. Results: Compared to the control group, the experimental group showed significant improvement in the number of guide wire insertion times, surgical time, fluoroscopy frequency, and intraoperative blood loss, with a statistically significant difference (P<0.01). Conclusion: The locating device can assist doctors in quickly locating the entry point of intramedullary nail, effectively reducing the fluoroscopy frequency and surgical time by improving the success rate of the guide wire insertion with one shot, improving surgical efficiency, and possessing certain clinical value.


Assuntos
Fixação Intramedular de Fraturas , Cirurgia Assistida por Computador , Humanos , Pinos Ortopédicos , Perda Sanguínea Cirúrgica , Fluoroscopia/métodos , Fixação Intramedular de Fraturas/métodos , Cirurgia Assistida por Computador/métodos
3.
J Agric Food Chem ; 72(17): 9599-9610, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38646697

RESUMO

In the search for novel succinate dehydrogenase inhibitor (SDHI) fungicides to control Rhizoctonia solani, thirty-five novel pyrazole-4-carboxamides bearing either an oxime ether or an oxime ester group were designed and prepared based on the strategy of molecular hybridization, and their antifungal activities against five plant pathogenic fungi were also investigated. The results indicated that the majority of the compounds containing oxime ether demonstrated outstanding in vitro antifungal activity against R. solani, and some compounds also displayed pronounced antifungal activities against Sclerotinia sclerotiorum and Botrytis cinerea. Particularly, compound 5e exhibited the most promising antifungal activity against R. solani with an EC50 value of 0.039 µg/mL, which was about 20-fold better than that of boscalid (EC50 = 0.799 µg/mL) and 4-fold more potent than fluxapyroxad (EC50 = 0.131 µg/mL). Moreover, the results of the detached leaf assay showed that compound 5e could suppress the growth of R. solani in rice leaves with significant protective efficacies (86.8%) at 100 µg/mL, superior to boscalid (68.1%) and fluxapyroxad (80.6%), indicating promising application prospects. In addition, the succinate dehydrogenase (SDH) enzymatic inhibition assay revealed that compound 5e generated remarkable SDH inhibition (IC50 = 2.04 µM), which was obviously more potent than those of boscalid (IC50 = 7.92 µM) and fluxapyroxad (IC50 = 6.15 µM). Furthermore, SEM analysis showed that compound 5e caused a remarkable disruption to the characteristic structure and morphology of R. solani hyphae, resulting in significant damage. The molecular docking analysis demonstrated that compound 5e could fit into the identical binding pocket of SDH through hydrogen bond interactions as well as fluxapyroxad, indicating that they had a similar antifungal mechanism. The density functional theory and electrostatic potential calculations provided useful information regarding electron distribution and electron transfer, which contributed to understanding the structural features and antifungal mechanism of the lead compound. These findings suggested that compound 5e could be a promising candidate for SDHI fungicides to control R. solani, warranting further investigation.


Assuntos
Botrytis , Fungicidas Industriais , Oximas , Doenças das Plantas , Pirazóis , Rhizoctonia , Succinato Desidrogenase , Rhizoctonia/efeitos dos fármacos , Rhizoctonia/crescimento & desenvolvimento , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Succinato Desidrogenase/antagonistas & inibidores , Succinato Desidrogenase/metabolismo , Pirazóis/farmacologia , Pirazóis/química , Relação Estrutura-Atividade , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Oximas/química , Oximas/farmacologia , Botrytis/efeitos dos fármacos , Botrytis/crescimento & desenvolvimento , Simulação de Acoplamento Molecular , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Ascomicetos/efeitos dos fármacos , Ascomicetos/química , Estrutura Molecular , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química
4.
MedComm (2020) ; 5(4): e543, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38585233

RESUMO

High metastatic propensity of osteosarcoma leads to its therapeutic failure and poor prognosis. Although nuclear activation miRNAs (NamiRNAs) are reported to activate gene transcription via targeting enhancer and further promote tumor metastasis, it remains uncertain whether NamiRNAs regulate osteosarcoma metastasis and their exact mechanism. Here, we found that extracellular vesicles of the malignant osteosarcoma cells (143B) remarkably increased the migratory abilities of MNNG cells representing the benign osteosarcoma cells by two folds, which attributed to their high miR-1246 levels. Specially, miR-1246 located in nucleus could activate the migration gene expression (such as MMP1) to accelerate MNNG cell migration through elevating the enhancer activities via increasing H3K27ac enrichment. Instead, MMP1 expression was dramatically inhibited after Argonaute 2 (AGO2) knockdown. Notably, in vitro assays demonstrated that AGO2 recognized the hybrids of miR-1246 and its enhancer DNA via PAZ domains to prevent their degradation from RNase H and these protective roles of AGO2 may favor the gene activation by miR-1246 in vivo. Collectively, our findings suggest that miR-1246 could facilitate osteosarcoma metastasis through interacting with enhancer to activate gene expression dependent on AGO2, highlighting the nuclear AGO2 as a guardian for NamiRNA-targeted gene activation and the potential of miR-1246 for osteosarcoma metastasis therapy.

5.
Comput Biol Med ; 171: 108149, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38401455

RESUMO

Stiffer cages provide sufficient mechanical support but fail to promote bone ingrowth due to stress shielding. It remains challenging for fusion cage to satisfy both bone bridging and mechanical stability. Here we designed a fusion cage based on twist metamaterial for improved bone ingrowth, and proved its superiority to the conventional diagonal-based cage in silico. The fusion process was numerically reproduced via an injury-induced osteogenesis model and the mechano-driven bone remodeling algorithm, and the outcomes fusion effects were evaluated by the morphological features of the newly-formed bone and the biomechanical behaviors of the bone-cage composite. The twist-based cages exhibited oriented bone formation in the depth direction, in comparison to the diagonal-based cages. The axial stiffness of the bone-cage composites with twist-based cages was notably higher than that with diagonal-based cages; meanwhile, the ranges of motion of the twist-based fusion segment were lower. It was concluded that the twist metamaterial cages led to oriented bone ingrowth, superior mechanical stability of the bone-cage composite, and less detrimental impacts on the adjacent bones. More generally, metamaterials with a tunable displacement mode of struts might provide more design freedom in implant designs to offer customized mechanical stimulus for osseointegration.


Assuntos
Próteses e Implantes , Fusão Vertebral , Osteogênese , Vértebras Lombares , Fenômenos Biomecânicos
6.
Sci Rep ; 14(1): 3674, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38351216

RESUMO

As part of supportive therapy, prophylaxis with tiopronin for injection (TI) against common hepatotoxicity complications has often been used. However, methods to prevent hepatotoxicity have not been established. Therefore, our study was aimed to find out the relationship between the periods of TI prophylaxis and post-treatment hepatotoxicity, and evaluated the value of prolonging the duration of TI administration in preventing hepatotoxicity. Hepatotoxicity was detected through liver transaminases, bilirubin, alkaline phosphatase, and clinical features of liver insufficiency. Multivariable logistic regressions were conducted to examine the association of the periods of TI prophylaxis and post-treatment hepatotoxicity. Between January 2022 and March 2023, a total of 452 patients with gynecological cancer were enrolled in the study, of which 93 (20.58%) participants were post-treatment hepatotoxicity positive. TI with different prevention days were no significant difference among participants with or without post-treatment hepatotoxicity in crude model (P > 0.05). The P-value, the odds ratios (OR) and 95% confidence intervals (CI) of participants with TI prophylaxis for 1 day for post-treatment hepatotoxicity were 0.040, 3.534 (1.061-11.765) in fully adjusted model. Past history of hepatotoxicity is a confounding variable, and there was no significant difference for post-treatment hepatotoxicity when stratified by past history of hepatotoxicity (P > 0.05). The study indicate that the periods of TI prophylaxis is not associated with post-treatment hepatotoxicity, suggesting that prolonged the periods of TI prophylaxis might be an invalid method for the prevention of post-treatment hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Tiopronina , Humanos , Testes de Função Hepática , Transaminases , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico
7.
Zhongguo Yi Liao Qi Xie Za Zhi ; 48(1): 15-19, 2024 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-38384211

RESUMO

Different porous structures were studied through finite element analysis and then optimal porous structure was selected for the orthopedic applications. The optimal Voronoi structure was designed and fabricated using 3D printing. The mechanical properties and osseointegration ability were both investigated. The mechanical tests showed that the tensile strength, compressive strength and bending strength of Voronoi structures were obviously higher than that of the human bone, and the modulus of Voronoi structures were similar to human bone. In addition, the animal experimental results exhibited that obvious bone ingrowth was found from Month 1 to Month 6. This study provides some theoretical references for the orthopedic application of porous structures.


Assuntos
Osseointegração , Próteses e Implantes , Animais , Humanos , Porosidade , Teste de Materiais , Impressão Tridimensional , Titânio/química
8.
Heliyon ; 9(10): e20741, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37842588

RESUMO

Postoperative infections (PI) are a serious complication after esophageal cancer surgery, as they might be correlated with an elevated risk of death. While several reports discuss risk factors for PI in esophageal tumor surgery, there is a limited amount of research on overall postoperative infections. Therefore, investigating the factors that influence PI holds great clinical significance. We retrospectively reviewed surgical data from a cohort of 902 patients diagnosed with esophageal tumors. The study included esophageal cancer patients treated in the Department of Thoracic Surgery at Anyang Tumor Hospital from January to December 2021. Preoperative and operative risk factors for PI were evaluated using univariable and multivariable analyses. The overall incidence of PI was 28.3% (255/902). Multivariable logistic regression analysis revealed that smoking and preoperative hospital stays are significant risk factors for PI after esophageal tumor surgery. Smoking and preoperative hospital stays are identified as risk factors for PI following esophageal tumor surgery. Based on our results, we predict that certain groups of patients may have a higher risk of PI following esophageal tumor surgery. Preventive measures or closely monitor of these patients may be required to reduce the incidence of postoperative PI.

9.
J Agric Food Chem ; 71(24): 9255-9265, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37283465

RESUMO

A series of novel pyrazole-4-carboxamides bearing an ether group were designed and synthesized on the basis of the structure of commercial succinate dehydrogenase inhibitor (SDHI) fungicide flubeneteram via scaffold hopping and evaluated for their antifungal activities against five fungi. The bioassay results showed that most of the target compounds exhibited excellent in vitro antifungal activity against Rhizoctonia solani and some compounds exerted remarkable antifungal activities against Sclerotinia sclerotiorum, Botrytis cinerea, Fusarium graminearum, and Alternaria alternate. Particularly, compounds 7d and 12b displayed outstanding antifungal activity against R. solani, with an EC50 value of 0.046 µg/mL, far superior to that of boscalid (EC50 = 0.741 µg/mL) and fluxapyroxad (EC50 = 0.103 µg/mL). Meanwhile, compound 12b also presented a broader fungicidal spectrum than other compounds. Moreover, in vivo anti-R. solani results showed that compounds 7d and 12b could significantly inhibit the growth of R. solani in rice leaves with excellent protective and curative efficacies. In addition, the results of the succinate dehydrogenase (SDH) enzymatic inhibition assay showed that compound 7d generated significant SDH inhibition, with an IC50 value of 3.293 µM, which was about 2 times better than that of boscalid (IC50 = 7.507 µM) and fluxapyroxad (IC50 = 5.991 µM). Furthermore, scanning electron microscopy (SEM) analysis indicated that compounds 7d and 12b significantly destroyed the typical structure and morphology of R. solani hyphae. The molecular docking study revealed that compounds 7d and 12b could embed into the binding pocket of SDH and form hydrogen bond interactions with TRP173 and TRY58 at the activity site of SDH, which was in line with fluxapyroxad, indicating that they had a similar mechanism of action. These results demonstrated that compounds 7d and 12b could be promising candidates of SDHI fungicides, which deserved further investigation.


Assuntos
Antifúngicos , Fungicidas Industriais , Antifúngicos/farmacologia , Antifúngicos/química , Relação Estrutura-Atividade , Éter , Succinato Desidrogenase , Simulação de Acoplamento Molecular , Fungicidas Industriais/química , Rhizoctonia , Pirazóis/farmacologia , Pirazóis/química
10.
J Biomech Eng ; 145(9)2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37144887

RESUMO

Porous cages with lower global stiffness induce more bone ingrowth and enhance bone-implant anchorage. However, it's dangerous for spinal fusion cages, which usually act as stabilizers, to sacrifice global stiffness for bone ingrowth. Intentional design on internal mechanical environment might be a promising approach to promote osseointegration without undermining global stiffness excessively. In this study, three porous cages with different architectures were designed to provide distinct internal mechanical environments for bone remodeling during spinal fusion process. A design space optimization-topology optimization based algorithm was utilized to numerically reproduce the mechano-driven bone ingrowth process under three daily load cases, and the fusion outcomes were analyzed in terms of bone morphological parameters and bone-cage stability. Simulation results show that the uniform cage with higher compliance induces deeper bone ingrowth than the optimized graded cage. Whereas, the optimized graded cage with the lowest compliance exhibits the lowest stress at the bone-cage interface and better mechanical stability. Combining the advantages of both, the strain-enhanced cage with locally weakened struts offers extra mechanical stimulus while keeping relatively low compliance, leading to more bone formation and the best mechanical stability. Thus, the internal mechanical environment can be well-designed via tailoring architectures to promote bone ingrowth and achieve a long-term bone-scaffold stability.


Assuntos
Osseointegração , Fusão Vertebral , Porosidade , Osteogênese , Próteses e Implantes , Fusão Vertebral/métodos , Titânio
11.
Int J Mol Sci ; 24(8)2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37108431

RESUMO

Leaf senescence reduces the photosynthetic capacity of leaves, thus significantly affecting the growth, development, and yield formation of cotton. Melatonin (MT) is a multipotent substance proven to delay leaf senescence. However, its potential mechanism in delaying leaf senescence induced by abiotic stress remains unclear. This study aimed to explore the effect of MT on delaying drought-induced leaf senescence in cotton seedlings and to clarify its morphological and physiological mechanisms. Drought stress upregulated the leaf senescence marker genes, destroyed the photosystem, and led to excessive accumulation of reactive oxygen species (ROS, e.g., H2O2 and O2-), thus accelerating leaf senescence. However, leaf senescence was significantly delayed when 100 µM MT was sprayed on the leaves of the cotton seedlings. The delay was embodied by the increased chlorophyll content, photosynthetic capacity, and antioxidant enzyme activities, as well as decreased H2O2, O2-, and abscisic acid (ABA) contents by 34.44%, 37.68%, and 29.32%, respectively. MT significantly down-regulated chlorophyll degradation-related genes and senescence marker genes (GhNAC12 and GhWRKY27/71). In addition, MT reduced the chloroplast damage caused by drought-induced leaf senescence and maintained the integrity of the chloroplast lamellae structure under drought stress. The findings of this study collectively suggest that MT can effectively enhance the antioxidant enzyme system, improve photosynthetic efficiency, reduce chlorophyll degradation and ROS accumulation, and inhibit ABA synthesis, thereby delaying drought-induced leaf senescence in cotton.


Assuntos
Melatonina , Melatonina/farmacologia , Melatonina/metabolismo , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Senescência Vegetal , Secas , Peróxido de Hidrogênio/metabolismo , Clorofila/metabolismo , Folhas de Planta/metabolismo , Plântula/metabolismo
12.
Sci Rep ; 13(1): 6010, 2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-37045891

RESUMO

Diffusion MRI is a complex technique, where new discoveries and implementations occur at a fast pace. The expertise needed for data analyses and accurate and reproducible results is increasingly demanding and requires multidisciplinary collaborations. In the present work we introduce Reproducible Tract Profiles 2 (RTP2), a set of flexible and automated methods to analyze anatomical MRI and diffusion weighted imaging (DWI) data for reproducible tractography. RTP2 reads structural MRI data and processes them through a succession of serialized containerized analyses. We describe the DWI algorithms used to identify white-matter tracts and their summary metrics, the flexible architecture of the platform, and the tools to programmatically access and control the computations. The combination of these three components provides an easy-to-use automatized tool developed and tested over 20 years, to obtain usable and reliable state-of-the-art diffusion metrics at the individual and group levels for basic research and clinical practice.


Assuntos
Encéfalo , Substância Branca , Encéfalo/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Algoritmos
13.
Neuroimage ; 262: 119558, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-35973564

RESUMO

The "primary" or "first-order relay" nuclei of the thalamus feed the cerebral cortex with information about ongoing activity in the environment or the subcortical motor systems. Because of the small size of these nuclei and the high specificity of their input and output pathways, new imaging protocols are required to investigate thalamocortical interactions in human perception, cognition and language. The goal of the present study was twofold: I) to develop a reconstruction protocol based on in vivo diffusion MRI to extract and measure the axonal fiber tracts that originate or terminate specifically in individual first-order relay nuclei; and, II) to test the reliability of this reconstruction protocol. In left and right hemispheres, we investigated the thalamocortical/corticothalamic axon bundles linking each of the first-order relay nuclei and their main cortical target areas, namely, the lateral geniculate nucleus (optic radiation), the medial geniculate nucleus (acoustic radiation), the ventral posterior nucleus (somatosensory radiation) and the ventral lateral nucleus (motor radiation). In addition, we examined the main subcortical input pathway to the ventral lateral posterior nucleus, which originates in the dentate nucleus of the cerebellum. Our protocol comprised three components: defining regions-of-interest; preprocessing diffusion data; and modeling white-matter tracts and tractometry. We then used computation and test-retest methods to check whether our protocol could reliably reconstruct these tracts of interest and their profiles. Our results demonstrated that the protocol had nearly perfect computational reproducibility and good-to-excellent test-retest reproducibility. This new protocol may be of interest for both basic human brain neuroscience and clinical studies and has been made publicly available to the scientific community.


Assuntos
Tálamo , Substância Branca , Corpos Geniculados , Humanos , Vias Neurais , Reprodutibilidade dos Testes , Núcleos Talâmicos , Tálamo/diagnóstico por imagem , Núcleos Ventrais do Tálamo , Substância Branca/diagnóstico por imagem
14.
Signal Transduct Target Ther ; 7(1): 91, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35304437

RESUMO

Currently, there is no effective drugs for treating clinically COVID-19 except dexamethasone. We previously revealed that human identical sequences of SARS-CoV-2 promote the COVID-19 progression by upregulating hyaluronic acid (HA). As the inhibitor of HA synthesis, hymecromone is an approved prescription drug used for treating biliary spasm. Here, we aimed to investigate the relation between HA and COVID-19, and evaluate the therapeutic effects of hymecromone on COVID-19. Firstly, HA was closely relevant to clinical parameters, including lymphocytes (n = 158; r = -0.50; P < 0.0001), C-reactive protein (n = 156; r = 0.55; P < 0.0001), D-dimer (n = 154; r = 0.38; P < 0.0001), and fibrinogen (n = 152; r = 0.37; P < 0.0001), as well as the mass (n = 78; r = 0.43; P < 0.0001) and volume (n = 78; r = 0.41; P = 0.0002) of ground-glass opacity, the mass (n = 78; r = 0.48; P < 0.0001) and volume (n = 78; r = 0.47; P < 0.0001) of consolidation in patient with low level of hyaluronan (HA < 48.43 ng/mL). Furthermore, hyaluronan could directly cause mouse pulmonary lesions. Besides, hymecromone remarkably reduced HA via downregulating HAS2/HAS3 expression. Moreover, 89% patients with hymecromone treatment had pulmonary lesion absorption while only 42% patients in control group had pulmonary lesion absorption (P < 0.0001). In addition, lymphocytes recovered more quickly in hymecromone-treated patients (n = 8) than control group (n = 5) (P < 0.05). These findings suggest that hymecromone is a promising drug for COVID-19 and deserves our further efforts to determine its effect in a larger cohort.


Assuntos
Tratamento Farmacológico da COVID-19 , Ácido Hialurônico , Animais , Humanos , Himecromona/metabolismo , Himecromona/farmacologia , Camundongos , Prescrições , SARS-CoV-2
15.
EBioMedicine ; 76: 103861, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35124429

RESUMO

BACKGROUND: Since late 2019, SARS-CoV-2 infection has resulted in COVID-19 accompanied by diverse clinical manifestations. However, the underlying mechanism of how SARS-CoV-2 interacts with host and develops multiple symptoms is largely unexplored. METHODS: Bioinformatics analysis determined the sequence similarity between SARS-CoV-2 and human genomes. Diverse fragments of SARS-CoV-2 genome containing Human Identical Sequences (HIS) were cloned into the lentiviral vector. HEK293T, MRC5 and HUVEC were infected with laboratory-packaged lentivirus or transfected with plasmids or antagomirs for HIS. Quantitative RT-PCR and chromatin immunoprecipitation assay detected gene expression and H3K27ac enrichment, respectively. UV-Vis spectroscopy assessed the interaction between HIS and their target locus. Enzyme-linked immunosorbent assay evaluated the hyaluronan (HA) levels of culture supernatant and plasma of COVID-19 patients. FINDINGS: Five short sequences (24-27 nt length) sharing identity between SARS-CoV-2 and human genome were identified. These RNA elements were highly conserved in primates. The genomic fragments containing HIS were predicted to form hairpin structures in silico similar to miRNA precursors. HIS may function through direct genomic interaction leading to activation of host enhancers, and upregulation of adjacent and distant genes, including cytokine genes and hyaluronan synthase 2 (HAS2). HIS antagomirs and Cas13d-mediated HIS degradation reduced HAS2 expression. Severe COVID-19 patients displayed decreased lymphocytes and elevated D-dimer, and C-reactive proteins, as well as increased plasma hyaluronan. Hymecromone inhibited hyaluronan production in vitro, and thus could be further investigated as a therapeutic option for preventing severe outcome in COVID-19 patients. INTERPRETATION: HIS of SARS-CoV-2 could promote COVID-19 progression by upregulating hyaluronan, providing novel targets for treatment. FUNDING: The National Key R&D Program of China (2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101), and the National Natural Science Foundation of China (31872814, 32000505).


Assuntos
Redes Reguladoras de Genes/genética , Genoma Humano , Ácido Hialurônico/metabolismo , RNA Viral/genética , SARS-CoV-2/genética , Antagomirs/metabolismo , Proteínas Argonautas/genética , Sequência de Bases , COVID-19/patologia , COVID-19/virologia , Linhagem Celular , Progressão da Doença , Elementos Facilitadores Genéticos/genética , Humanos , Hialuronan Sintases/genética , Hialuronan Sintases/metabolismo , Ácido Hialurônico/sangue , MicroRNAs/genética , RNA Viral/química , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade , Regulação para Cima
16.
Zhongguo Yi Liao Qi Xie Za Zhi ; 46(1): 68-75, 2022 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-35150111

RESUMO

Physiological parameter monitoring is essential to medical staff to evaluate, diagnose and treat patients in neonatal intensive care unit (NICU). Monitoring in NICU includes basic vital signal monitoring and functional monitoring. Basic vital signal monitoring (including ECG, respiration, SpO2, blood pressure, temperature) is advanced and focus on study of usability, continuity and anti-interference. Functional monitoring (including respiratory function, circulatory function, cerebral function) still focus on study of monitoring precision and reliability. Meanwhile, video monitoring and artifact intelligence have presented well performance on improving monitoring precision and anti-interference. In this article, the main parameters and relevant measurement technology for monitoring critical neonates were described.


Assuntos
Respiração , Sinais Vitais , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Monitorização Fisiológica , Reprodutibilidade dos Testes , Tecnologia
17.
Zhongguo Yi Liao Qi Xie Za Zhi ; 46(6): 602-606, 2022 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-36597383

RESUMO

OBJECTIVE: To improve the accuracy of detection of arrhythmia in patients with atrial fibrillation (AF) and to enable the scientific management and assessment of AF, a comprehensive management tool for AF is proposed, which is helpful for medical staff to systematically evaluate and manage patients with AF. METHODS: A professional view of atrial fibrillation (AF View) was designed to unify the statistical information of AF event, and display the statistical distribution data of AF events and trend data of other physiological parameters or characteristics such as heart rate, blood pressure and ST value during the patient monitoring period in a centralized manner. A multi-dimensional summary information was obtained from AF View. In addition, the monitoring period and monitoring parameters or characteristics in the AF View can be adjusted so as to obtain the summary information under different periods and parameters or characteristics, and get the condition of AF of the patient. RESULTS: Accurate detection and comprehensive management of AF were achieved. CONCLUSIONS: The application of AF comprehensive management proposed in this study is helpful for medical staff to know the condition of AF patients in real time and adjust the treatment plan in time.


Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Relevância Clínica , Frequência Cardíaca
18.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(6): 662-669, 2021 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-34862781

RESUMO

Physiological parameters monitoring is essential to direct medical staff to evaluate, diagnose and treat critical patients quantitatively. ECG, blood pressure, SpO2, respiratory rate and body temperature are the basic vital signs of patients in the ICU. The measuring methods are relatively mature at present, and the trend is to be wireless and more accurate and comfortable. Hemodynamics, oxygen metabolism and microcirculation should be taken seriously during the treatment of acute critical patients. The related monitoring technology has made significant progress in recent years, the trend is to reduce the trauma and improve the accuracy and usability. With the development of machine vision and data fusion technology, the identification of patient behavior and deterioration has become hot topics. This review is focused on current parameters monitoring technologies, aims to provide reference for future related research.


Assuntos
Unidades de Terapia Intensiva , Saturação de Oxigênio , Humanos , Monitorização Fisiológica , Tecnologia , Sinais Vitais
19.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(5): 585-590, 2021 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-34628778

RESUMO

OBJECTIVE: The patient monitors were used to explore the alarm actuality in a ICU and NICU to investigate the awareness and reaction of medical staff to alarms. METHODS: A series of surveys and interviews were taken to acquire clinicians' feelings and attitudes to monitoring alarms. The researchers were scheduled to track the alarms with annotations, and collect the alarm data of patient monitors using central monitoring system. RESULTS: A total of 235 387 and 67 783 alarms occurred in ICU and NICU respectively. The average alarm rate was about 142 alarms/patient-day in ICU and 96 alarms/patient-day in NICU. CONCLUSIONS: There remains alarm fatigue in ICU and NICU, the main reason is the large number of false alarms and clinically irrelevant alarms. In addition, patient monitor is still in the level of threshold alarms or combined alarms, the data integrity and intelligence level need to be improved in future.


Assuntos
Alarmes Clínicos , Unidades de Terapia Intensiva Neonatal , Eletrocardiografia , Humanos , Recém-Nascido , Monitorização Fisiológica
20.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(4): 450-453, 2021 Jul 30.
Artigo em Chinês | MEDLINE | ID: mdl-34363377

RESUMO

OBJECTIVE: The patient monitors were used to explore the alarm fatigue in a cardiac care unit and to investigate the awareness and reaction of nurse to alarms. METHODS: A semi-structured survey was taken to acquire nurses' feeling and knowledge about monitoring alarm. Three full-time researchers were scheduled to track the alarms with annotations, and analyze the alarm data of 12 patient monitors using central monitoring system. RESULTS: A total of 72 310 unique alarms occurred in the 67-day study period. About 75.7% of them were physiological alarms and less than 10% of medium-low alarms were false positives. The average alarm rate was 128 alarms/patient-day. CONCLUSIONS: There remains alarm fatigue in CCU, the alarm accuracy has improved than the past by applying new technologies. In some cases, clinicians will pay more attention to trend alarm and combination alarm.


Assuntos
Alarmes Clínicos , Arritmias Cardíacas , Eletrocardiografia , Humanos , Monitorização Fisiológica , Inquéritos e Questionários
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