RESUMO
Fruit colour is a critical determinant for the appearance quality and commercial value of apple fruits. Viroid-induced dapple symptom severely affects the fruit coloration, however, the underlying mechanism remains unknown. In this study, we identified an apple dimple fruit viroid (ADFVd)-derived small interfering RNA, named vsiR693, which targeted the mRNA coding for a bHLH transcription factor MdPIF1 (PHYTOCHROME-INTERACTING FACTOR 1) to regulate anthocyanin biosynthesis in apple. 5' RLM-RACE and artificial microRNA transient expression system proved that vsiR693 directly targeted the mRNA of MdPIF1 for cleavage. MdPIF1 positively regulated anthocyanin biosynthesis in both apple calli and fruits, and it directly bound to G-box element in the promoter of MdPAL and MdF3H, two anthocyanin biosynthetic genes, to promote their transcription. Expression of vsiR693 negatively regulated anthocyanin biosynthesis in both apple calli and fruits. Furthermore, co-expression of vsiR693 and MdPIF1 suppressed MdPIF1-promoted anthocyanin biosynthesis in apple fruits. Infiltration of ADFVd infectious clone suppressed coloration surrounding the injection sites in apple fruits, while a mutated version of ADFVd, in which the vsiR693 producing region was mutated, failed to repress fruit coloration around the injection sites. These data provide evidence that a viroid-derived small interfering RNA targets host transcription factor to regulate anthocyanin biosynthesis in apple.
RESUMO
The discovery of novel and highly effective P-gp inhibitors is considered to be an effective strategy for overcoming tumor drug resistance. In this paper, a phenotypic screening via a self-constructed synthetic methodology-based library identified a new class of tricyclic spiroindole derivatives with excellent tumor multidrug resistance reversal activity. A stereospecific compound OY-103-B with the best reversal activity was obtained based on a detailed structure-activity relationship study, metabolic stability optimization and chiral resolution. For the VCR-resistant Eca109 cell line (Eca109/VCR), co-administration of 5.0 µM OY-103-B resulted in a reversal fold of up to 727.2, superior to the typical third-generation P-gp inhibitor tariquidar. Moreover, the compound inhibited the proliferation of Eca109/VCR cells in a concentration-dependent manner in plate cloning and flow cytometry. Furthermore, fluorescence substrate accumulation assay and chemotherapeutic drug reversal activity tests demonstrated that OY-103-B reversed tumor drug resistance via P-gp inhibition. In conclusion, this study provides a novel skeleton that inspires the design of new P-gp inhibitors, laying the foundation for the treatment of drug-resistant tumors.
RESUMO
Antibiotic residue stands as a significant ongoing environmental issue, with aquaculture being a major source of annual antibiotic discharge into the ocean. Nevertheless, there is still an incomplete evaluation of antibiotic residues in the Beibu Gulf, an area encompassed by two prominent aquaculture nations, China and Vietnam. The present systematic review and meta-analysis was conducted to examine the presence antibiotic residues in the Beibu Gulf based on published studies. Data were obtained through eight databases up to December 19th, 2023, and were updated on April 15th, 2024. The pooled concentration of antibiotic residues in seawater was 5.90 (ng/L), ranging from 5.73 to 6.06 (ng/L), and was 8.03 (ng/g), ranging from 7.77 to 8.28 (ng/g) in sediments. Fluoroquinolones, tetracyclines, and macrolides were identified as the main antibiotics found in both seawater and sediment samples. The Beibu Gulf showed higher antibiotic levels in its western and northeastern areas. Additionally, the nearshore mangrove areas displayed the highest prevalence of antibiotic residues. It is strongly advised to conduct regular long-term monitoring of antibiotic residues in the Beibu Gulf. Collaborative surveys covering the entire Beibu Gulf involving China and Vietnam are recommended.
Assuntos
Antibacterianos , Monitoramento Ambiental , Água do Mar , Poluentes Químicos da Água , Antibacterianos/análise , Água do Mar/química , Poluentes Químicos da Água/análise , China , Vietnã , AquiculturaRESUMO
Previous studies have indicated a potential connection between plasma levels of Dickkopf-1 (DKK1) and platelet-derived growth factor subunit-B (PDGF-B) with the development of atherosclerosis. However, the causal relationship between DKK1, PDGF-B, and the risk of acute myocardial infarction (AMI) is yet to be established. To address this research gap, we conducted Mendelian randomization (MR) and mediation analyses to investigate the potential mediating role of PDGF-B in the association between DKK1 and AMI risk. Summary statistics for DKK1 (n = 3,301) and PDGF-B (n = 21,758) were obtained from the GWAS meta-analyses conducted by Sun et al. and Folkersen et al., respectively. Data on AMI cases (n = 3,927) and controls (n = 333,272) were retrieved from the UK Biobank study. Our findings revealed that genetic predisposition to DKK1 (odds ratio [OR]: 1.00208; 95% confidence interval [CI]: 1.00056-1.00361; P = 0.0072) and PDGF-B (OR: 1.00358; 95% CI: 1.00136-1.00581; P = 0.0015) was associated with an increased risk of AMI. Additionally, genetic predisposition to DKK1 (OR: 1.38389; 95% CI: 1.07066-1.78875; P = 0.0131) was linked to higher PDGF-B levels. Furthermore, our MR mediation analysis revealed that PDGF-B partially mediated the association between DKK1 and AMI risk, with 55.8% of the effect of genetically predicted DKK1 being mediated through genetically predicted PDGF-B. These findings suggest that genetic predisposition to DKK1 is positively correlated with the risk of AMI, and that PDGF-B partially mediates this association. Therefore, DKK1 and PDGF-B may serve as promising targets for the prevention and treatment of AMI.
Assuntos
Aterosclerose , Infarto do Miocárdio , Humanos , Análise da Randomização Mendeliana , Infarto do Miocárdio/genética , Predisposição Genética para Doença , Proteínas Proto-Oncogênicas c-sis , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Epidemiological investigations have indicated a correlation between elevated plasma levels of Dickkopf-related protein 1 (DKK1) and the presence of atherosclerosis. However, the exact causal relationship of DKK1 with the development of coronary artery disease (CAD) and ischemic stroke (IS) remains unclear. To address this gap, our study aimed to explore their causal association using a two-sample Mendelian randomization (MR) approach. We obtained summary statistics from genome-wide association studies (GWAS) meta-analyses conducted by Folkersen et al. and Nikpay et al., which included data from 21,758 individuals for DKK1 and 42,096 cases of CAD. Additionally, we obtained data from the FinnGen biobank analysis round 5, which included 10,551 cases of IS. Eight MR methods were employed to estimate causal effects and detect directional pleiotropy. Our findings demonstrated that genetic liability to DKK1 was associated with increased risks of CAD (odds ratio [OR]: 1.087; 95% confidence interval [CI]: 1.024-1.154; P = 0.006) and IS (OR: 1.096; 95% CI: 1.004-1.195; P = 0.039). These results establish a causal link between genetic liability to DKK1 and elevated risks of CAD and IS. Consequently, DKK1 may represent a promising therapeutic target for the prevention and treatment of CAD and IS.
RESUMO
The role of RNA N6-methyladenosine (m6A) modification in the regulation of the immune microenvironment in ischaemic cardiomyopathy (ICM) remains largely unclear. This study first identified differential m6A regulators between ICM and healthy samples, and then systematically evaluated the effects of m6A modification on the characteristics of the immune microenvironment in ICM, including the infiltration of immune cells, the human leukocyte antigen (HLA) gene, and HALLMARKS pathways. A total of seven key m6A regulators, including WTAP, ZCH3H13, YTHDC1, FMR1, FTO, RBM15 and YTHDF3, were identified using a random forest classifier. A diagnostic nomogram based on these seven key m6A regulators could effectively distinguish patients with ICM from healthy subjects. We further identified two distinct m6A modification patterns (m6A cluster-A and m6A cluster-B) that are mediated by these seven regulators. Meanwhile, we also noted that one m6A regulator, WTAP, was gradually upregulated, while the others were gradually downregulated in the m6A cluster-A vs. m6A cluster-B vs. healthy subjects. In addition, we observed that the degree of infiltration of the activated dendritic cells, macrophages, natural killer (NK) T cells, and type-17 T helper (Th17) cells gradually increased in m6A cluster-A vs. m6A cluster-B vs. healthy subjects. Furthermore, m6A regulators, including FTO, YTHDC1, YTHDF3, FMR1, ZC3H13, and RBM15 were significantly negatively correlated with the above-mentioned immune cells. Additionally, several differential HLA genes and HALLMARKS signalling pathways between the m6A cluster-A and m6A cluster-B groups were also identified. These results suggest that m6A modification plays a key role in the complexity and diversity of the immune microenvironment in ICM, and seven key m6A regulators, including WTAP, ZCH3H13, YTHDC1, FMR1, FTO, RBM15, and YTHDF3, may be novel biomarkers for the accurate diagnosis of ICM. Immunotyping of patients with ICM will help to develop immunotherapy strategies with a higher level of accuracy for patients with a significant immune response.
Assuntos
Cardiomiopatias , Isquemia Miocárdica , Humanos , Adenosina , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Proteína do X Frágil da Deficiência Intelectual , Metilação , RNARESUMO
The immune molecular mechanisms involved in ischaemic cardiomyopathy (ICM) have not been fully elucidated. The current study aimed to elucidate the immune cell infiltration pattern of the ICM and identify key immune-related genes that participate in the pathologic process of the ICM. The differentially expressed genes (DEGs) were identified from two datasets (GSE42955 combined with GSE57338) and the top 8 key DEGs related to ICM were screened using random forest and used to construct the nomogram model. Moreover, the "CIBERSORT" software package was used to determine the proportion of infiltrating immune cells in the ICM. A total of 39 DEGs (18 upregulated and 21 downregulated) were identified in the current study. Four upregulated DEGs, including MNS1, FRZB, OGN, and LUM, and four downregulated DEGs, SERP1NA3, RNASE2, FCN3 and SLCO4A1, were identified by the random forest model. The nomogram constructed based on the above 8 key genes suggested a diagnostic value of up to 99% to distinguish the ICM from healthy participants. Meanwhile, most of the key DEGs presented prominent interactions with immune cell infiltrates. The RT-qPCR results suggested that the expression levels of MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 between the ICM and control groups were consistent with the bioinformatic analysis results. These results suggested that immune cell infiltration plays a critical role in the occurrence and progression of ICM. Several key immune-related genes, including the MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 genes, are expected to be reliable serum markers for the diagnosis of ICM and potential molecular targets for ICM immunotherapy.
Assuntos
Cardiomiopatias , Isquemia Miocárdica , Humanos , Nomogramas , Algoritmo Florestas Aleatórias , Isquemia Miocárdica/genética , Biologia Computacional , Lectinas , Peptídeos e Proteínas de Sinalização IntercelularRESUMO
Lipid metabolism plays an essential role in the genesis and progress of acute myocardial infarction (AMI). Herein, we identified and verified latent lipid-related genes involved in AMI by bioinformatic analysis. Lipid-related differentially expressed genes (DEGs) involved in AMI were identified using the GSE66360 dataset from the Gene Expression Omnibus (GEO) database and R software packages. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to analyze lipid-related DEGs. Lipid-related genes were identified by two machine learning techniques: least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE). The receiver operating characteristic (ROC) curves were used to descript diagnostic accuracy. Furthermore, blood samples were collected from AMI patients and healthy individuals, and real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the RNA levels of four lipid-related DEGs. Fifty lipid-related DEGs were identified, 28 upregulated and 22 downregulated. Several enrichment terms related to lipid metabolism were found by GO and KEGG enrichment analyses. After LASSO and SVM-RFE screening, four genes (ACSL1, CH25H, GPCPD1, and PLA2G12A) were identified as potential diagnostic biomarkers for AMI. Moreover, the RT-qPCR analysis indicated that the expression levels of four DEGs in AMI patients and healthy individuals were consistent with bioinformatics analysis results. The validation of clinical samples suggested that 4 lipid-related DEGs are expected to be diagnostic markers for AMI and provide new targets for lipid therapy of AMI.
Assuntos
Biologia Computacional , Infarto do Miocárdio , Humanos , Biomarcadores , Coenzima A Ligases/genética , Bases de Dados Factuais , Lipídeos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/genética , Fosfolipases , Fosfolipases A2 do Grupo I/metabolismoRESUMO
The role of m6A in the regulation of the immune microenvironment in atrial fibrillation (AF) remains unclear. This study systematically evaluated the RNA modification patterns mediated by differential m6A regulators in 62 AF samples, identified the pattern of immune cell infiltration in AF and identified several immune-related genes associated with AF. A total of six key differential m6A regulators between healthy subjects and AF patients were identified by the random forest classifier. Three distinct RNA modification patterns (m6A cluster-A, -B and -C) among AF samples were identified based on the expression of 6 key m6A regulators. Differential infiltrating immune cells and HALLMARKS signaling pathways between normal and AF samples as well as among samples with three distinct m6A modification patterns were identified. A total of 16 overlapping key genes were identified by weighted gene coexpression network analysis (WGCNA) combined with two machine learning methods. The expression levels of the NCF2 and HCST genes were different between controls and AF patient samples as well as among samples with the distinct m6A modification patterns. RT-qPCR also proved that the expression of NCF2 and HCST was significantly increased in AF patients compared with control participants. These results suggested that m6A modification plays a key role in the complexity and diversity of the immune microenvironment of AF. Immunotyping of patients with AF will help to develop more accurate immunotherapy strategies for those with a significant immune response. The NCF2 and HCST genes may be novel biomarkers for the accurate diagnosis and immunotherapy of AF.
Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/genética , Metilação , RNA , Redes Reguladoras de Genes , Voluntários SaudáveisRESUMO
Ischemic stroke (IS) is harmful to human health and social development, and there is no medicine available at present. To find the hit compound for treating ischemic stroke, we screened 28 FDA approved nervous system drugs by using an in vitro OGD-induced stroke model. Notably, our in vitro and in vivo studies demonstrated that low-dose sertraline had good neuroprotective activities, while high-dose sertraline showed significant toxicity. Interestingly, the same high-dose sertraline in the control group did not exhibit any obvious toxic effect. Therefore, it is important to modify the structure of sertraline to improve the activity and reduce the toxicity. Stereoisomers of sertraline were first investigated to analyze the influence of stereochemistry on the neuroprotective activities, which showed no obvious difference. Then we evaluated the activity of our previously reported sertraline analogues and found that introducing amide or alkane groups to the amino moiety might be beneficial to enhance the activity and reduce the toxicity. Thus, 10 new analogues were designed, synthesized, and evaluated. Among them, compound OY-201 showed the best safety and neuroprotective activity in both in vitro and in vivo models. Moreover, it exhibited good blood-brain barrier (BBB) permeability, indicating its potential for the development of anti-ischemic stroke drugs.
Assuntos
AVC Isquêmico , Fármacos Neuroprotetores , Acidente Vascular Cerebral , Humanos , Sertralina/farmacologia , Sertralina/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Barreira Hematoencefálica , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/químicaRESUMO
The AP2/ERF family is an important class of transcription factors involved in plant growth and various biological processes. One of the AP2/ERF transcription factors, RAP2.6L, participates in various stresses responses. However, the function of RAP2.6L is largely unknown in apples (Malus domestica). In this study, an apple gene homologous to Arabidopsis AtRAP2.6L, MdERF113, was analyzed by bioinformatic characterization, gene expression analysis and subcellular localization assessment. MdERF113 was highly expressed in the sarcocarp and was responsive to hormonal signals and abiotic stresses. MdERF113-overexpression apple calli were less sensitive to low temperature, drought, salinity, and abscisic acid than wild-type. Subcellular localization revealed that MdERF113 was a nuclear-localized transcription factor, and yeast experiments confirmed that MdERF113 has no autonomous activation activity. Overall, this study indicated that MdERF113 plays a role in regulating plant growth under abiotic conditions.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Malus , Malus/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Fatores de Transcrição/metabolismo , Arabidopsis/metabolismo , Ácido Abscísico/metabolismo , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Filogenia , Secas , Proteínas de Arabidopsis/metabolismoAssuntos
Tumores do Estroma Gastrointestinal , Jejuno , Humanos , Jejuno/cirurgia , Jejuno/patologia , Ruptura Espontânea , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/cirurgia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , AbdomeRESUMO
BACKGROUND: Pharmacological modulation of cannabinoid 2 receptor (CB2R) is a promising therapeutic strategy for pulmonary fibrosis (PF). Thus, to develop CB2R selective ligands with new chemical space has attracted much research interests. This work aims to discover a novel CB2R agonist from an in-house library, and to evaluate its therapeutic effects on PF model, as well as to disclose the pharmacological mechanism. METHODS: Virtual screening was used to identify the candidate ligand for CB2R from a newly established in-house library. Both in vivo experiments on PF rat model and in vitro experiments on cells were performed to investigate the therapeutic effects of the lead compound and underlying mechanism. RESULTS: A "natural product-like" pyrano[2,3-b]pyridine derivative, YX-2102 was identified that bound to CB2R with high affinity. Intraperitoneal YX-2102 injections significantly ameliorated lung injury, inflammation and fibrosis in a rat model of PF induced by bleomycin (BLM). On one hand, YX-2102 inhibited inflammatory response at least partially through modulating macrophages polarization thereby exerting protective effects. Whereas, on the other hand, YX-2102 significantly upregulated CB2R expression in alveolar epithelial cells in vivo. Its pretreatment inhibited lung alveolar epithelial-to-mesenchymal transition (EMT) in vitro and PF model induced by transforming growth factor beta-1 (TGF-ß1) via a CB2 receptor-dependent pathway. Further studies suggested that the Nrf2-Smad7 pathway might be involved in. CONCLUSION: These findings suggest that CB2R is a potential target for PF treatment and YX-2102 is a promising CB2R agonist with new chemical space.
Assuntos
Agonistas de Receptores de Canabinoides , Fibrose Pulmonar , Animais , Ratos , Fibrose Pulmonar/tratamento farmacológico , Receptores de CanabinoidesRESUMO
A cascade Michael addition/alkylation reaction between 3-chlorooxindoles and α-cyano chalcones catalyzed using a multifunctional quinine-derived aminoindanol-thiourea substance was investigated. A series of spirooxindoles incorporating a densely substituted cyclopropane motif were efficiently obtained with moderate to excellent diastereo- and enantioselectivity and further transformed to products with versatile structural diversity. Density functional theory (DFT) calculations indicated that the tentative intramolecular hydrogen bonds in the chiral catalyst were crucial for the stereocontrol.
Assuntos
Ciclopropanos , Tioureia , Estereoisomerismo , Alquilação , Tioureia/químicaRESUMO
Background: The immune system significantly participates in the pathologic process of atrial fibrillation (AF). However, the molecular mechanisms underlying this participation are not completely explained. The current research aimed to identify critical genes and immune cells that participate in the pathologic process of AF. Methods: CIBERSORT was utilized to reveal the immune cell infiltration pattern in AF patients. Meanwhile, weighted gene coexpression network analysis (WGCNA) was utilized to identify meaningful modules that were significantly correlated with AF. The characteristic genes correlated with AF were identified by the least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithm. Results: In comparison to sinus rhythm (SR) individuals, we observed that fewer activated mast cells and regulatory T cells (Tregs), as well as more gamma delta T cells, resting mast cells, and M2 macrophages, were infiltrated in AF patients. Three significant modules (pink, red, and magenta) were identified to be significantly associated with AF. Gene enrichment analysis showed that all 717 genes were associated with immunity- or inflammation-related pathways and biological processes. Four hub genes (GALNT16, HTR2B, BEX2, and RAB8A) were revealed to be significantly correlated with AF by the SVM-RFE algorithm and LASSO logistic regression. qRT-PCR results suggested that compared to the SR subjects, AF patients exhibited significantly reduced BEX2 and GALNT16 expression, as well as dramatically elevated HTR2B expression. The AUC measurement showed that the diagnostic efficiency of BEX2, HTR2B, and GALNT16 in the training set was 0.836, 0.883, and 0.893, respectively, and 0.858, 0.861, and 0.915, respectively, in the validation set. Conclusions: Three novel genes, BEX2, HTR2B, and GALNT16, were identified by WGCNA combined with machine learning, which provides potential new therapeutic targets for the early diagnosis and prevention of AF.
RESUMO
BACKGROUND: The immune system plays a vital role in the pathological process of ischaemic stroke. However, the exact immune-related mechanism remains unclear. The current research aimed to identify immune-related key genes associated with ischaemic stroke. METHODS: CIBERSORT was utilized to reveal the immune cell infiltration pattern in ischaemic stroke patients. Meanwhile, a weighted gene coexpression network analysis (WGCNA) was utilized to identify meaningful modules significantly correlated with ischaemic stroke. The characteristic genes correlated with ischaemic stroke were identified by the following two machine learning methods: the support vector machine-recursive feature elimination (SVM-RFE) algorithm and least absolute shrinkage and selection operator (LASSO) logistic regression. RESULTS: The CIBERSORT results suggested that there was a decreased infiltration of naive CD4 T cells, CD8 T cells, resting mast cells and eosinophils and an increased infiltration of neutrophils, M0 macrophages and activated memory CD4 T cells in ischaemic stroke patients. Then, three significant modules (pink, brown and cyan) were identified to be significantly associated with ischaemic stroke. The gene enrichment analysis indicated that 519 genes in the above three modules were mainly involved in several inflammatory or immune-related signalling pathways and biological processes. Eight hub genes (ADM, ANXA3, CARD6, CPQ, SLC22A4, UBE2S, VIM and ZFP36) were revealed to be significantly correlated with ischaemic stroke by the LASSO logistic regression and SVM-RFE algorithm. The external validation combined with a RTâqPCR analysis revealed that the expression levels of ADM, ANXA3, SLC22A4 and VIM were significantly increased in ischaemic stroke patients and that these key genes were positively associated with neutrophils and M0 macrophages and negatively correlated with CD8 T cells. The mean AUC value of ADM, ANXA3, SLC22A4 and VIM was 0.80, 0.87, 0.91 and 0.88 in the training set, 0.85, 0.77, 0.86 and 0.72 in the testing set and 0.87, 0.83, 0.88 and 0.91 in the validation samples, respectively. CONCLUSIONS: These results suggest that the ADM, ANXA3, SLC22A4 and VIM genes are reliable serum markers for the diagnosis of ischaemic stroke and that immune cell infiltration plays a crucial role in the occurrence and development of ischaemic stroke.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/genética , Redes Reguladoras de Genes , Humanos , AVC Isquêmico/genética , Acidente Vascular Cerebral/genética , Máquina de Vetores de Suporte , Enzimas de Conjugação de UbiquitinaRESUMO
BACKGROUND: The objective of this study is to investigate the preparation of a navigation template via a computer-aided design (CAD) and 3D printing (3DP) in order to improve the effectiveness of Tönnis triple osteotomy in older children with developmental dysplasia of the hip (DDH). METHOD: Thirty-eight older children who received Tönnis triple osteotomy were included in this study. Among them, 20 were categorized as the 3DP navigation template group (3DP group), and the remaining 18 were categorized as the conventional surgery group (CS group). Data, including preoperative and postoperative pelvic sharp angle (SA), lateral center-edge angle (LCEA), acetabular roof angle (ARA), acetabular head index (AHI), crossover sign (COS), ischial spine sign (ISS), operation time (OT), intraoperative blood loss (IBL), and number of radiation exposures (NORE) were recorded for both groups. In addition, the therapeutic effect was evaluated at the last follow-up, according to the McKay criteria and Severin's criteria. RESULTS: In the 3DP and CS groups, the mean OT was 126.6 ± 17.6 min and 156.0 ± 18.6 min, respectively; the mean IBL was 115.0 ± 16.9 ml and 135.7 ± 26.5 ml, respectively; the NORE were 3.3 ± 0.8 times and 8.6 ± 1.3 times, respectively. There were significant differences in the OT, IBL, and NORE between the two groups (P = 0.03, 0.05, < 0.001, respectively). At the last follow-up, the 3DP and CS groups displayed SA of 41.8 ± 2.3° and 42.6 ± 3.1°, respectively; LCEA of 35.6 ± 4.2° and 37.1 ± 2.8°, respectively; ARA of 6.9 ± 1.8° and 9.8 ± 2.6°, respectively; and AHI of 86.6 ± 4.1% and 84.3 ± 2.8%, respectively; COS(+) of 5 hips and 4 hips, respectively; ISS(+) of 6 hips and 7 hips. We observed no statistical differences in the SA, LCEA, ARA, AHI, COS and ISS between the two groups (P = 0.918, 0.846, 0.643, 0.891, 0.841, 0.564, respectively). According to the McKay criteria, the 3DP group had 10 excellent, 6 good, and 4 general hips, whereas, the CS group had 12 excellent, 4 good, and 2 general hip. There was no statistical difference between the two groups (P = 0.698). In 3DP group the postoperative Severin's grading included 13 hips in grade I, 4 in grade II, 3 in grade III. Alternately, in the CS group, the postoperative Severin's grading included 11 hips in grade I, 5 in grade II, 2 in grade III. The Severin 's criteria also showed no statistical difference between the two groups (P = 0.945). CONCLUSIONS: Base on our analysis, our CAD-3DP-fabricated navigation template assisted Tönnis triple osteotomy in older DDH children, it reduced operation time and number of radiation exposures. However, no significant differences in radiological assessment and functional outcomes were observed when an experienced surgeon performs the surgery. Therefore, Surgeons who have less experience in triple osteotomy profit more from the application of this technology.
Assuntos
Displasia do Desenvolvimento do Quadril , Luxação Congênita de Quadril , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Adolescente , Idoso , Criança , Displasia do Desenvolvimento do Quadril/diagnóstico por imagem , Displasia do Desenvolvimento do Quadril/cirurgia , Luxação Congênita de Quadril/diagnóstico por imagem , Luxação Congênita de Quadril/cirurgia , Humanos , Osteotomia/efeitos adversos , Impressão Tridimensional , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The immune system plays a vital role in the pathophysiology of acute myocardial infarction (AMI). However, the exact immune related mechanism is still unclear. This research study aimed to identify key immune-related genes involved in AMI. METHODS: CIBERSORT, a deconvolution algorithm, was used to determine the proportions of 22 subsets of immune cells in blood samples. The weighted gene co-expression network analysis (WGCNA) was used to identify key modules that are significantly associated with AMI. Then, CIBERSORT combined with WGCNA were used to identify key immune-modules. The protein-protein interaction (PPI) network was constructed and Molecular Complex Detection (MCODE) combined with cytoHubba plugins were used to identify key immune-related genes that may play an important role in the occurrence and progression of AMI. RESULTS: The CIBERSORT results suggested that there was a decrease in the infiltration of CD8 + T cells, gamma delta (γδ) T cells, and resting mast cells, along with an increase in the infiltration of neutrophils and M0 macrophages in AMI patients. Then, two modules (midnightblue and lightyellow) that were significantly correlated with AMI were identified, and the salmon module was found to be significantly associated with memory B cells. Gene enrichment analysis indicated that the 1,171 genes included in the salmon module are mainly involved in immune-related biological processes. MCODE analysis was used to identify four different MCODE complexes in the salmon module, while four hub genes (EEF1B2, RAC2, SPI1, and ITGAM) were found to be significantly correlated with AMI. The correlation analysis between the key genes and infiltrating immune cells showed that SPI1 and ITGAM were positively associated with neutrophils and M0 macrophages, while they were negatively associated with CD8 + T cells, γδ T cells, regulatory T cells (Tregs), and resting mast cells. The RT-qPCR validation results found that the expression of the ITGAM and SPI1 genes were significantly elevated in the AMI samples compared with the samples from healthy individuals, and the ROC curve analysis showed that ITGAM and SPI1 had a high diagnostic efficiency for the recognition of AMI. CONCLUSIONS: Immune cell infiltration plays a crucial role in the occurrence and development of AMI. ITGAM and SPI1 are key immune-related genes that are potential novel targets for the prevention and treatment of AMI.
Assuntos
Perfilação da Expressão Gênica , Infarto do Miocárdio , Linfócitos T CD8-Positivos/metabolismo , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Humanos , Macrófagos/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Mapas de Interação de ProteínasRESUMO
Background: Upstream transcription factor 1 (USF1) single-nucleotide polymorphisms (SNPs) are significantly associated with serum lipid levels in several different ethnic groups or populations, but their association with lipid levels and the risk of early-onset coronary artery disease (EOCAD) has not been reported in Han populations of southern China. Methods: Six USF1 SNPs (rs3737787, rs2774276, rs2516839, rs2516838, rs1556259, and rs2516837) were genotyped by next-generation sequencing (NGS) techniques in 686 control subjects and 728 patients with EOCAD. Results: The genotypic and allelic frequencies of the USF1 rs3737787 SNP were significantly different between the control and EOCAD groups. The subgroup analysis identified that the rs3737787T allele was related to a decreased risk of EOCAD, whereas the rs3737787C-rs2774276G-rs2516839A and rs3737787C-rs2774276G-rs2516839G haplotypes were related to an increased risk of EOCAD in men, and the rs3737787C-rs2774276G-rs2516839A and rs3737787T-rs2774276C-rs2516839A haplotypes were correlated with an increased risk of EOCAD in women (p < 0.05-0.01). Male rs3737787T allele carriers had lower low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) concentrations than the rs3737787T allele non-carriers (p < 0.01). The interactions of rs3737787 with alcohol consumption and rs2516839 with smoking affected serum TC and LDL-C levels in men, whereas the interaction of rs3737787 with alcohol consumption affected serum high-density lipoprotein cholesterol (HDL-C) levels and the rs2516839-smoking interaction affected serum TC levels in women (p I < 0.001). The expression levels of the USF1 mRNA, interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) were significantly lower in controls than in patients with EOCAD, and rs3737787T allele carriers displayed lower IL-1ß, TNF-α, IL-6, and USF1 mRNA expression levels than the rs3737787T allele non-carriers. In addition, IL-1ß, TNF-α, and IL-6 expression levels were significantly positively correlated with USF1 mRNA levels (p < 0.01). Conclusion: Sex-specific correlations were identified between the USF1 rs3737787T allele with blood lipid levels and the risk of EOCAD. The USF1 rs3737787T allele affects the risk of EOCAD by modulating serum lipid levels and the expression of inflammatory factors, including IL-1ß, TNF-α, and IL-6.
RESUMO
OBJECTIVE: To identify types of acetabular dysplasia, select the most suitable acetabular plasty, and analyze indications and efficacy of three types of acetabular plasty in treating dislocation of hip joint in children with cerebral palsy by 3D printing technology. METHODS: From July 2019 to December 2019, 7 children with cerebral palsy with hip dislocation were treated with acetabular plasty assisted by 3D printing technology, including 3 males and 4 females, aged from 3 from 8 years old;3 patients on the left side, 2 patients on the right side, and 2 patients on both sides. Subluxation of hip joint occurred in 2 patients and dislocation of hip joint occurred in 5 patients. Preoperative full-length CT scan of pelvis and femur was performed in all children. The types of acetabular dysplasia were determined by 3D printing reconstruction technology, and the results were presented as follows:2 anterior hips, 2 anterior outer hips, 1 outer upper hip, 2 posterior hips, 1 posterior outer hip, and 1 hip without dysplasia(with no acetabular plasty). Pemberton, Dega and San Diego surgery simulations were performed on the 8 hips respectively to find the most suitable and the suitable operations were then conducted. Migration percentage (MP), acetabular index (AI) and cenal-edge angle (CEA), Shenton line, and gross motor function classification system(GMFCS) between preoperative and last follow-up were compared and complications were recorded. RESULTS: The wound healed well after operation and no complication occurred. Seven patients were followed up for 18 to 24 months. The 8 hips were underwent soft tissue release for the first stage+proximal femoral varus and rotation reduction osteotomy+hip reduction+acetabular plasty;1 hip was underwent soft tissue release for the first stage+proximal femoral varus removal and rotation reduction osteotomy +hip reduction. MP decreased from 58% to 100% preoperatively to 0 to 17.9% at the latest follow-up. AI decreased from 25.0° to 47.6° preoperatively to 11.1° to 25.3° at the latest follow-up. CEA increased from 0° preoperatively to 21.1° to 48.5° at the latest follow-up. Shenton's lines changed from interrupted ones to continuous ones. The GMFCS grade of 5 cases decreased by 1 grade, and 2 cases showed no change. CONCLUSION: There is diversity for the hip dislocation of hip in children with cerebral palsy of acetabular dysplasia present type. Accurate judgments could be made with the help of 3D printing reconstruction techniques. There are differences between scopes of applications for three kinds of acetabulum keratoplasty. 3D printing technology could be helpful to choose the most suitable operation method and estimate the treatment effect. Thus the individualized and accurate treatment for hip dislocation in children with cerebral palsy can be gained with 3D printing technology.