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1.
Front Microbiol ; 15: 1391697, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741730

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV exhibits genetic diversity and complexity in terms of immune responses, posing challenges for eradication. The nucleocapsid (N) protein of PRRSV, an alkaline phosphoprotein, is important for various biological functions. This review summarizes the structural characteristics, genetic evolution, impact on PRRSV replication and virulence, interactions between viral and host proteins, modulation of host immunity, detection techniques targeting the N protein, and progress in vaccine development. The discussion provides a theoretical foundation for understanding the pathogenic mechanisms underlying PRRSV virulence, developing diagnostic techniques, and designing effective vaccines.

2.
J Cancer Res Clin Oncol ; 150(5): 234, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710918

RESUMO

BACKGROUND: The pathogenesis and treatment of colorectal cancer (CRC) continue to be areas of ongoing research, especially the benefits of traditional Chinese medicine (TCM) in slowing the progression of CRC. This study was conducted to investigate the effectiveness and mechanism of action of modified Lichong decoction (MLCD) in inhibiting CRC progression. METHODS: We established CRC animal models using azoxymethane/dextran sodium sulfate (AOM/DSS) and administered high, medium, or low doses of MLCD or mesalazine (MS) for 9 weeks to observe MLCD alleviation of CRC. The optimal MLCD dose group was then subjected to metagenomic and RNA sequencing (RNA-seq) to explore the differentially abundant flora and genes in the control, model and MLCD groups. Finally, the mechanism of action was verified using WB, qRT‒PCR, immunohistochemistry and TUNEL staining. RESULTS: MLCD inhibited the progression of CRC, and the optimal effect was observed at high doses. MLCD regulated the structure and function of the intestinal flora by decreasing the abundance of harmful bacteria and increasing that of beneficial bacteria. The differentially expressed genes were mainly associated with the Wnt/ß-catenin pathway and the cell cycle. Molecular biology analysis indicated that MLCD suppressed the Wnt/ß-catenin pathway and the epithelial-mesenchymal transition (EMT), inhibited abnormal cell proliferation and promoted intestinal epithelial cell apoptosis. CONCLUSION: MLCD mitigated the abnormal growth of intestinal epithelial cells and promoted apoptosis, thereby inhibiting the progression of CRC. This inhibition was accomplished by modifying the intestinal microbiota and disrupting the Wnt/ß-catenin pathway and the EMT. Therefore, MLCD could serve as a potential component of TCM prescriptions for CRC treatment.


Assuntos
Neoplasias Colorretais , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Via de Sinalização Wnt , Via de Sinalização Wnt/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Humanos , Masculino , Apoptose/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sulfato de Dextrana , beta Catenina/metabolismo , Modelos Animais de Doenças
3.
Epidemiol Infect ; 152: e75, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634450

RESUMO

This paper retrospectively analysed the prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) in some parts of China. Between January 2013 and December 2019, we collected 4,145 respiratory samples, including pharyngeal swabs and alveolar lavage fluid. The highest PCR-positive rate of M. pneumoniae was 74.5% in Beijing, the highest resistance rate was 100% in Shanghai, and Gansu was the lowest with 20%. The highest PCR-positive rate of M. pneumoniae was 74.5% in 2013, and the highest MRMP was 97.4% in 2019; the PCR-positive rate of M. pneumoniae for adults in Beijing was 17.9% and the MRMP was 10.48%. Among the children diagnosed with community-acquired pneumonia (CAP), the PCR-positive and macrolide-resistant rates of M. pneumoniae were both higher in the severe ones. A2063G in domain V of 23S rRNA was the major macrolide-resistant mutation, accounting for more than 90%. The MIC values of all MRMP to erythromycin and azithromycin were ≥ 64 µg/ml, and the MICs of tetracycline and levofloxacin were ≤ 0.5 µg/ml and ≤ 1 µg/ml, respectively. The macrolide resistance varied in different regions and years. Among inpatients, the macrolide-resistant rate was higher in severe pneumonia. A2063G was the common mutation, and we found no resistance to tetracycline and levofloxacin.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Macrolídeos , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Mycoplasma pneumoniae/efeitos dos fármacos , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/isolamento & purificação , Humanos , China/epidemiologia , Macrolídeos/farmacologia , Estudos Retrospectivos , Criança , Antibacterianos/farmacologia , Pré-Escolar , Adolescente , Adulto , Feminino , Masculino , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/microbiologia , Pneumonia por Mycoplasma/tratamento farmacológico , Pessoa de Meia-Idade , Adulto Jovem , Testes de Sensibilidade Microbiana , Idoso , Lactente , Prevalência , RNA Ribossômico 23S/genética , Idoso de 80 Anos ou mais
4.
FASEB J ; 38(7): e23591, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38572579

RESUMO

CircRNAs are abnormally expressed in various cancers and play an important role in the occurrence and development of cancers. However, their biological functions and the underlying molecular mechanisms in pancreatic cancer (PC) metastasis are incompletely understood. Differentially expressed circRNAs were identified by second-generation transcriptome sequencing in three pairs of PC tissues and adjacent tissues. The expression and prognostic significance of hsa_circ_0007919 were evaluated by qRT-PCR and Kaplan-Meier survival curves. Gain- and loss-of-function assays were conducted to detect the role of hsa_circ_0007919 in PC metastasis in vitro. A lung metastasis model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor metastasis in vivo. Mechanistically, RNA immunoprecipitation and chromatin immunoprecipitation assays were conducted to explore the interplay among hsa_circ_0007919, Sp1, and the THBS1 promoter. hsa_circ_0007919 was significantly upregulated in PC tissues and cells and was correlated with lymph node metastasis, TNM stage, and poor prognosis. Knockdown of hsa_circ_0007919 significantly suppressed the migration and invasion of PC cells in vitro and inhibited tumor metastasis in vivo. However, overexpression of hsa_circ_0007919 exerted the opposite effects. Mechanistically, hsa_circ_0007919 could recruit the transcription factor Sp1 to inhibit THBS1 transcription, thereby facilitating PC metastasis. hsa_circ_0007919 can promote the metastasis of PC by inhibiting THBS1 expression. hsa_circ_0007919 may be a potential therapeutic target in PC.


Assuntos
MicroRNAs , Neoplasias Pancreáticas , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Invasividade Neoplásica/genética , Neoplasias Pancreáticas/genética , RNA Circular/genética , RNA Circular/metabolismo
5.
Eur J Pharmacol ; 974: 176602, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38677538

RESUMO

BACKGROUND: The interleukin (IL) -12 p40 subunit is the common subunit of IL-12 and IL-23. It affects the immune inflammatory response, which may be closely related to cardiac remodeling. In this study, the regulatory effect of IL-12p40 knockout (KO) on cardiac remodeling was investigated, and the underlying mechanism was explored. METHODS AND RESULTS: Mice were subjected to transverse aortic constriction (TAC) to establish a model of cardiac remodeling. First, IL-12p40 was deleted to observe its effects on cardiac remodeling and cardiac inflammation, and the results showed that IL-12p40 deletion reduced both T helper 17 (Th17) and γδT17 cell differentiation, decreased proinflammatory macrophage differentiation, alleviated cardiac remodeling, and relieved cardiac dysfunction in TAC mice. Next, we explored whether IL-17 regulated TAC-induced cardiac remodeling, and the results showed that IL-17 neutralization alleviated proinflammatory macrophage differentiation and cardiac remodeling in IL-12p40 knockout mice and WT mice. Neutralization with cluster of differentiation 4 receptor (CD4) and γδ T-cell receptor (γδTCR) antibodies inhibited pro-inflammatory macrophage polarization and improved cardiac remodeling, and CD4 neutralizing antibody (NAb) had more significant effects. Finally, adoptive transfer of Th17 cells aggravated proinflammatory macrophage differentiation and cardiac remodeling in TAC-treated CD4 KO mice, while neutralization with the IL-12p40 antibody alleviated these pathological changes. CONCLUSION: Mainly Th17 cells but not γδT17 cells secrete IL-17, which mediates IL-12p40, promotes the polarization of proinflammatory macrophages, and exacerbates cardiac remodeling in TAC mice. IL-12p40 may be a potential target for the prevention and treatment of cardiac remodeling.

6.
J Am Heart Assoc ; 13(6): e031283, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38456416

RESUMO

BACKGROUND: Dilated cardiomyopathy (DCM) is the leading cause of heart failure with a poor prognosis. Recent studies suggest that endothelial to mesenchymal transition (EndMT) may be involved in the pathogenesis and cardiac remodeling during DCM development. EDIL3 (epidermal growth factor-like repeats and discoidin I-like domains 3) is an extracellular matrix glycoprotein that has been reported to promote EndMT in various diseases. However, the roles of EDIL3 in DCM still remain unclear. METHODS AND RESULTS: A mouse model of DCM and human umbilical vein endothelial cells were used to explore the roles and mechanisms of EDIL3 in DCM. The results indicated that EndMT and EDIL3 were activated in DCM mice. EDIL3 deficiency attenuated cardiac dysfunction and remodeling in DCM mice. EDIL3 knockdown alleviated EndMT by inhibiting USP10 (ubiquitin specific peptidase 10) dependent Smad4 deubiquitination in vivo and in vitro. Recombinant human EDIL3 promoted EndMT via reinforcing deubiquitination of Smad4 in human umbilical vein endothelial cells treated with IL-1ß (interleukin 1ß) and TGF-ß (transforming growth factor beta). Inhibiting USP10 abolished EndMT exacerbated by EDIL3. In addition, recombinant EDIL3 also aggravates doxorubicin-induced EndMT by promoting Smad4 deubiquitination in HUVECs. CONCLUSIONS: Taken together, these results indicate that EDIL3 deficiency attenuated EndMT by inhibiting USP10 dependent Smad4 deubiquitination in DCM mice.


Assuntos
Cardiomiopatia Dilatada , Animais , Humanos , Camundongos , Proteínas de Ligação ao Cálcio/metabolismo , Cardiomiopatia Dilatada/metabolismo , Moléculas de Adesão Celular/metabolismo , Discoidinas , Fator de Crescimento Epidérmico , Transição Epitelial-Mesenquimal , Células Endoteliais da Veia Umbilical Humana/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Ubiquitina Tiolesterase , Proteases Específicas de Ubiquitina/metabolismo
7.
Front Neurol ; 15: 1355546, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38497043

RESUMO

Objective: To explore the effect of cognitive reserve (CR) on brain volume and cerebrospinal fluid (CSF) in patients with mild cognitive impairment (MCI) and healthy elders (HE). Methods: 31 HE and 50 MCI patients were collected in this study to obtain structural MRI, cognitive function, and composite CR scores. Educational attainment, leisure time, and working activity ratings from two groups were used to generate cognitive reserve index questionnaire (CRIq) scores. The different volumes of brain regions and CSF were obtained using uAI research portal in both groups, which were taken as the regions of interest (ROI), the correlation analysis between ROIs and CRIq scores were conducted. Results: The scores of CRIq, CRIq-leisure time, and CRIq-education in HE group were significantly higher than patients in MCI group, and the montreal cognitive assessment (MoCA) and minimum mental state examination (MMSE) scores were positively correlated with the CRIq, CRIq-education in both groups, and were positively correlated with CRIq-leisure time in MCI group. The scores of auditory verbal learning test (AVLT) and verbal fluency test (VFT) were also positively correlated with CRIq, CRIq-leisure time, and CRIq-education in MCI group, but the score of AVLT was only positively correlated with CRIq in HE group. Moreover, in MCI group, the volume of the right middle cingulate cortex and the right parahippocampal gyrus were negatively correlated with the CRIq, and the volume of CSF, peripheral CSF, and third ventricle were positively correlated with the CRIq-leisure time score. The result of mediation analysis suggested that right parahippocampal gryus mediated the main effect of the relationship between CRIq and MoCA score in MCI group. Conclusion: People with higher CR show better levels of cognitive function, and MCI patients with higher CR showed more severe volume atrophy of the right middle cingulate cortex and the right parahippocampal gyrus, but more CSF at a given level of global cognition.

8.
Front Immunol ; 15: 1380517, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38515746

RESUMO

As a canonical cytoplasmic DNA sensor, cyclic GMP-AMP synthase (cGAS) plays a key role in innate immunity. In recent years, a growing number of studies have shown that cGAS can also be located in the nucleus and plays new functions such as regulating DNA damage repair, nuclear membrane repair, chromosome fusion, DNA replication, angiogenesis and other non-canonical functions. Meanwhile, the mechanisms underlying the nucleo-cytoplasmic transport and the regulation of cGAS activation have been revealed in recent years. Based on the current understanding of the structure, subcellular localization and canonical functions of cGAS, this review focuses on summarizing the mechanisms underlying nucleo-cytoplasmic transport, activity regulation and non-canonical functions of cGAS in the nucleus. We aim to provide insights into exploring the new functions of cGAS in the nucleus and advance its clinical translation.


Assuntos
DNA , Nucleotidiltransferases , Nucleotidiltransferases/genética , Imunidade Inata , Citosol , Citoplasma
9.
Microorganisms ; 12(3)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38543603

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious and pathogenic infectious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). It manifests as reproductive disorders in sows and respiratory disorders in piglets. PRRSV infects swine herds with symptoms such as abortions, stillbirths, and mummified fetuses in gestating sows. Piglets mainly experience abdominal respiration and respiratory symptoms. To date, the prevention of PRRS relies primarily on vaccination and the implementation of various preventive and control measures. Swine deaths caused by PRRS have resulted in significant economic losses to the pig industry worldwide. Non-structural protein 10 (NSP10) has helicase and adenosine triphosphatase (ATPase) activities that unwind DNA and RNA and play important roles in viral replication and transcription. Hence, it can be potentially used to develop novel reagents for the detection of PPRSV. This article reviews genetic variations, interaction with viral and host proteins, effects on PRRSV replication, immunomodulation, apoptosis, and viral virulence of NSP10, with the aim of providing a theoretical basis for the prevention and control of PRRS and drug development in the future.

10.
Molecules ; 29(5)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38474582

RESUMO

Graphene quantum dots (GQDs) possess the photosensitive absorption for photoelectrochemical hydrogen evolution owing to special band structures, whereas they usually confront with photo-corrosion or undesired charge recombination during photoelectrochemical reactions. Hence, we establish the heterojunction between GQDs and MoSe2 sheets via a hydrothermal process for improved stability and performance. Photoanodic water splitting with hydrogen evolution boosted by the heteroatom doped N,S-GQDs/MoSe2 heterojunction has been attained due to the abundant active sites, promoted charge separation and transfer kinetics with reduced energy barriers. Diphasic 1T and 2H MoSe2 sheet-hybridized quantum dots contribute to the Schottky heterojunction, which can play a key role in expedited carrier transport to inhibit accumulative photo-corrosion and increase photocurrent. Heteroatom dopants lead to favored energy band matching, bandgap narrowing, stronger light absorption and high photocurrent density. The external quantum efficiency of the doped heterojunction has been elevated twofold over that of the non-doped pristine heterojunction. Modification of the graphene quantum dots and MoSe2 heterojunction demonstrate a viable and adaptable platform toward photoelectrochemical hydrogen evolution processes.

11.
MedComm (2020) ; 5(3): e491, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38463394

RESUMO

Hypertensive vascular remodeling is defined as the changes in vascular function and structure induced by persistent hypertension. Maresin-1 (MaR1), one of metabolites from Omega-3 fatty acids, has been reported to promote inflammation resolution in several inflammatory diseases. This study aims to investigate the effect of MaR1 on hypertensive vascular remodeling. Here, we found serum MaR1 levels were reduced in hypertensive patients and was negatively correlated with systolic blood pressure (SBP). The treatment of MaR1 reduced the elevation of blood pressure and alleviated vascular remodeling in the angiotensin II (AngII)-infused mouse model. In addition, MaR1-treated vascular smooth muscle cells (VSMCs) exhibited reduced excessive proliferation, migration, and phenotype switching, as well as impaired pyroptosis. However, the knockout of the receptor of MaR1, leucine-rich repeat-containing G protein-coupled receptor 6 (LGR6), was seen to aggravate pathological vascular remodeling, which could not be reversed by additional MaR1 treatment. The mechanisms by which MaR1 regulates vascular remodeling through LGR6 involves the Ca2+/calmodulin-dependent protein kinase II/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway. Overall, supplementing MaR1 may be a novel therapeutic strategy for the prevention and treatment of hypertension.

12.
Sensors (Basel) ; 24(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38475058

RESUMO

Time series anomaly detection is very important to ensure the security of industrial control systems (ICSs). Many algorithms have performed well in anomaly detection. However, the performance of most of these algorithms decreases sharply with the increase in feature dimension. This paper proposes an anomaly detection scheme based on Graph Attention Network (GAT) and Informer. GAT learns sequential characteristics effectively, and Informer performs excellently in long time series prediction. In addition, long-time forecasting loss and short-time forecasting loss are used to detect multivariate time series anomalies. Short-time forecasting is used to predict the next time value, and long-time forecasting is employed to assist the short-time prediction. We conduct a large number of experiments on industrial control system datasets SWaT and WADI. Compared with most advanced methods, we achieve competitive results, especially on higher-dimensional datasets. Moreover, the proposed method can accurately locate anomalies and realize interpretability.

13.
Lung Cancer ; 189: 107472, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38320371

RESUMO

OBJECTIVES: The Lepidic Component (LP) identifies a subgroup with an excellent prognosis for lung adenocarcinoma (LUAD). Our research aimed to propose an improved pathological T (pT) stage for LUAD based on LP. MATERIALS AND METHODS: Totally, 3335 surgical patients with pathological stage I LUAD were incorporated. Factors affecting survival were investigated by analyzing recurrence-free survival (RFS) and overall survival (OS) using the Kaplan-Meier method and Cox regression analyses. Subgroup analysis based on Lepidic Ratio (LR) was further evaluated. The net benefit from the modified pT category (pTm) was assessed using the Area Under the time-dependent Receiver Operating Curve (AUC), Harrell's Concordance Index (C-index), Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI). RESULTS: The presence of LP (LP+) was identified in 1425 (42.7 %) patients, indicating a significantly better RFS (P < 0.001) and OS (P < 0.001) than those without LP, and similar results were reproduced in pT1a-pT2a subcategory (P < 0.050 for all). Multivariable Cox analysis revealed LP+ as an independent prognostic factor for both RFS (HR, 0.622; P < 0.001) and OS (HR, 0.710; P = 0.019). However, lepidic ratio (LR) was not independently associated with both RFS and OS for LP+ patients. The 5-year RFS and OS rates between T1a (LP-) and T1b (LP+), T1b (LP-) and T1c (LP+), and T1b (LP-) and T2a (LP+) were comparable (P > 0.050 for all). After modification, compared with current 8th edition pT stage system (pT8), pTm independently predicted RFS and OS, and AUCs, c-index, NRI, and IDI analysis all demonstrated pTm holds better discrimination performances than pT8 for LUAD prognosis. CONCLUSION: LP can be an additional down-staged T descriptor for pathological stage I LUAD and improve the survival predictive performance of reclassification.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Área Sob a Curva
14.
Food Chem ; 443: 138611, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38309025

RESUMO

The effects of rice bran rancidity-induced protein oxidation and heating time on the stability of rice bran protein fibril aggregates (RBPFA)-high internal phase Pickering emulsions (HIPPEs) were investigated. The optimal conditions for RBPFA-HIPPEs were 8 mg/mL RBPFA with an oil phase volume fraction of 75 %. Moderate oxidation (rice bran stored for 3 d) and moderate heating (8 h) enhanced the wettability, flexibility, diffusion rate, and adsorption rate of RBPFA, meanwhile, the rheological properties of RBPFA-HIPPEs increased. RBPFA-HIPPEs could be stably stored for 50 d at 25 °C. Moderate oxidized and moderate heated RBPFA-stabilized HIPPEs could remain stable after heat treatment and could be re-prepared after freeze-thaw (3 cycles). Additionally, the stability of RBPFA-HIPPEs was significantly related to the structural characteristics and interfacial properties of RBPFA. Overall, moderate oxidation and moderate heating enhanced the storage, thermal, and freeze-thaw stability of RBPFA-HIPPEs by improving the interfacial properties of RBPFA.


Assuntos
Oryza , Emulsões/química , Agregados Proteicos , Adsorção , Oxirredução , Tamanho da Partícula
15.
Spine J ; 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38316364

RESUMO

BACKGROUND CONTEXT: With the aging population, osteoporosis, which leads to poor fusion, has become a common challenge for lumbar surgery. In addition, most people with osteoporosis are elderly individuals with poor surgical tolerance, and poor bone quality can also weaken the stability of internal fixation. PURPOSE: This study compared the fixation strength of the bilateral traditional trajectory screw structure (TT-TT), the bilateral cortical bone trajectory screw structure (CBT-CBT), and the hybrid CBT-TT (CBT screws at the cranial level and TT screws at the caudal level) structure under different bone mineral density conditions. STUDY DESIGN: A finite element (FE) analysis study. METHODS: Above all, we established a healthy adult lumbar spine model. Second, under normal and osteoporotic conditions, three transforaminal lumbar interbody fusion (TLIF) models were established: bilateral traditional trajectory (TT-TT) screw fixation, bilateral cortical bone trajectory (CBT-CBT) screw fixation, and hybrid cortical bone trajectory screw and traditional trajectory screw (CBT-TT) fixation. Finally, a 500-N compression load with a torque of 10 N/m was applied to simulate flexion, extension, lateral bending, and axial rotation. We compared the range of motion (ROM), adjacent disc stress, cage stress, and posterior fixation stress of the different fusion models. RESULTS: Under different bone mineral density conditions, the range of motion of the fusion segment was significantly reduced. Compared to normal bone conditions, the ROM of the L4-L5 segment, the stress of the adjacent intervertebral disc, the surface stress of the cage, and the maximum stress of the posterior fixation system were all increased in osteoporosis. Under most loads, the ROM and surface stress of the cage and the maximum stress of the posterior fixation system of the TT-TT structure are the lowest under normal bone mineral density conditions. However, under osteoporotic conditions, the fixation strength of the CBT-CBT and CBT-TT structures are higher than that of the TT-TT structures under certain load conditions. At the same time, the surface stress of the intervertebral fusion cage and the maximum stress of the posterior fixation system for the two structures are lower than those of the TT-TT structure. CONCLUSION: Under normal bone mineral density conditions, transforaminal lumbar interbody fusion combined with TT-TT fixation provides the best biomechanictability. However, under osteoporotic conditions, CBT-CBT and CBT-TT structures have higher fixed strength compared to TT-TT structures. The hybrid CBT-TT structure exhibits advantages in minimal trauma and fixation strength. Therefore, this seems to be an alternative fixation method for patients with osteoporosis and degenerative spinal diseases. CLINICAL SIGNIFICANCE: This study provides biomechanical support for the clinical application of hybrid CBT-TT structure for osteoporotic patients undergoing TLIF surgery.

16.
FASEB J ; 38(5): e23513, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38421300

RESUMO

Targeting cardiac remodeling is regarded as a key therapeutic strategy for heart failure. Kielin/chordin-like protein (KCP) is a secretory protein with 18 cysteine-rich domains and associated with kidney and liver fibrosis. However, the relationship between KCP and cardiac remodeling remains unclear. Here, we aimed to investigate the role of KCP in cardiac remodeling induced by pressure overload and explore its potential mechanisms. Left ventricular (LV) KCP expression was measured with real-time quantitative PCR, western blotting, and immunofluorescence staining in pressure overload-induced cardiac remodeling in mice. Cardiac function and remodeling were evaluated in wide-type (WT) mice and KCP knockout (KO) mice by echocardiography, which were further confirmed by histological analysis with hematoxylin and eosin and Masson staining. RNA sequence was performed with LV tissue from WT and KO mice to identify differentially expressed genes and related signaling pathways. Primary cardiac fibroblasts (CFs) were used to validate the regulatory role and potential mechanisms of KCP during fibrosis. KCP was down-regulated in the progression of cardiac remodeling induced by pressure overload, and was mainly expressed in fibroblasts. KCP deficiency significantly aggravated pressure overload-induced cardiac dysfunction and remodeling. RNA sequence revealed that the role of KCP deficiency in cardiac remodeling was associated with cell division, cell cycle, and P53 signaling pathway, while cyclin B1 (CCNB1) was the most significantly up-regulated gene. Further investigation in vivo and in vitro suggested that KCP deficiency promoted the proliferation of CFs via P53/P21/CCNB1 pathway. Taken together, these results suggested that KCP deficiency aggravates cardiac dysfunction and remodeling induced by pressure overload via P53/P21/CCNB1 signaling in mice.


Assuntos
Glicoproteínas , Insuficiência Cardíaca , Peptídeos e Proteínas de Sinalização Intercelular , Deficiência de Proteína , Animais , Camundongos , Proteína Supressora de Tumor p53/genética , Ciclina B1 , Remodelação Ventricular , Transdução de Sinais
17.
Phys Med Biol ; 69(7)2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38224617

RESUMO

Objective.In the realm of utilizing artificial intelligence (AI) for medical image analysis, the paradigm of 'signal-image-knowledge' has remained unchanged. However, the process of 'signal to image' inevitably introduces information distortion, ultimately leading to irrecoverable biases in the 'image to knowledge' process. Our goal is to skip reconstruction and build a diagnostic model directly from the raw data (signal).Approach. This study focuses on computed tomography (CT) and its raw data (sinogram) as the research subjects. We simulate the real-world process of 'human-signal-image' using the workflow 'CT-simulated data- reconstructed CT,' and we develop a novel AI predictive model directly targeting raw data (RCTM). This model comprises orientation, spatial, and global analysis modules, embodying the fusion of local to global information extraction from raw data. We selected 1994 patients with retrospective cases of solid lung nodules and modeled different types of data.Main results. We employed predefined radiomic features to assess the diagnostic feature differences caused by reconstruction. The results indicated that approximately 14% of the features had Spearman correlation coefficients below 0.8. These findings suggest that despite the increasing maturity of CT reconstruction algorithms, they still introduce perturbations to diagnostic features. Moreover, our proposed RCTM achieved an area under the curve (AUC) of 0.863 in the diagnosis task, showcasing a comprehensive superiority over models constructed from secondary reconstructed CTs (0.840, 0.822, and 0.825). Additionally, the performance of RCTM closely resembled that of models constructed from original CT scans (0.868, 0.878, and 0.866).Significance. The diagnostic and therapeutic approach directly based on CT raw data can enhance the precision of AI models and the concept of 'signal-to-image' can be extended to other types of imaging. AI diagnostic models tailored to raw data offer the potential to disrupt the traditional paradigm of 'signal-image-knowledge', opening up new avenues for more accurate medical diagnostics.


Assuntos
Inteligência Artificial , Radiologia , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Algoritmos , Processamento de Imagem Assistida por Computador/métodos
19.
Clin Chest Med ; 45(1): 15-24, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38245363

RESUMO

Diagnosis of sarcoidosis depends on a compatible clinical and imaging presentation, histologic finding of non-necrotizing granulomatous inflammation, and exclusion of alternative causes of granulomatous diseases. This study has reviewed the diagnostic algorithms and approaches of sarcoidosis.


Assuntos
Sarcoidose Pulmonar , Sarcoidose , Humanos , Sarcoidose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/patologia , Sarcoidose/diagnóstico , Sarcoidose/patologia , Diagnóstico por Imagem , Biópsia/métodos
20.
J Cancer ; 15(3): 796-808, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38213729

RESUMO

Background: Most of the current research on prognostic model construction for non-small cell lung cancer (NSCLC) only involves in bulk RNA-seq data without integration of single-cell RNA-seq (scRNA-seq) data. Besides, most of the prognostic models are constructed by predictive genes, ignoring other predictive variables such as clinical features. Methods: We obtained scRNA-seq data from GEO database and bulk RNA-seq data from TCGA database. We construct a prognostic model through the Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression. Furthermore, we performed ESTIMATE, CIBERSORT, immune checkpoint-related analyses and compared drug sensitivity using pRRophetic method judged by IC50 between different risk groups. Results: 14 tumor-related genes were extracted for model construction. The AUC for 1-, 3-, and 5 years overall survival prediction in TCGA and three validation cohorts were almost higher than 0.65, some of which were even higher than 0.7, even 0.8. Besides, calibration curves suggested no departure between model prediction and perfect fit. Additionally, immune-related and drug sensitivity results revealed potential targets and strategies for treatment, which can provide clinical guidance. Conclusion: We integrated traditional bulk RNA-seq and scRNA-seq data, along with predictive clinical features to develop a prognostic model for patients with NSCLC. According to the constructed model, patients in different groups can follow precise and individual therapeutic schedules based on immune characteristics as well as drug sensitivity.

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