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1.
Nature ; 591(7848): 147-151, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33505025

RESUMO

Many sequence variants have been linked to complex human traits and diseases1, but deciphering their biological functions remains challenging, as most of them reside in noncoding DNA. Here we have systematically assessed the binding of 270 human transcription factors to 95,886 noncoding variants in the human genome using an ultra-high-throughput multiplex protein-DNA binding assay, termed single-nucleotide polymorphism evaluation by systematic evolution of ligands by exponential enrichment (SNP-SELEX). The resulting 828 million measurements of transcription factor-DNA interactions enable estimation of the relative affinity of these transcription factors to each variant in vitro and evaluation of the current methods to predict the effects of noncoding variants on transcription factor binding. We show that the position weight matrices of most transcription factors lack sufficient predictive power, whereas the support vector machine combined with the gapped k-mer representation show much improved performance, when assessed on results from independent SNP-SELEX experiments involving a new set of 61,020 sequence variants. We report highly predictive models for 94 human transcription factors and demonstrate their utility in genome-wide association studies and understanding of the molecular pathways involved in diverse human traits and diseases.


Assuntos
Polimorfismo de Nucleotídeo Único/genética , Técnica de Seleção de Aptâmeros , Máquina de Vetores de Suporte , Fatores de Transcrição/metabolismo , Sítios de Ligação/genética , Doença/genética , Genoma Humano/genética , Humanos , Ligantes , Ligação Proteica
2.
Bioinformatics ; 39(9)2023 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-37647650

RESUMO

MOTIVATION: Single-cell DNA methylation sequencing can assay DNA methylation at single-cell resolution. However, incomplete coverage compromises related downstream analyses, outlining the importance of imputation techniques. With a rising number of cell samples in recent large datasets, scalable and efficient imputation models are critical to addressing the sparsity for genome-wide analyses. RESULTS: We proposed a novel graph-based deep learning approach to impute methylation matrices based on locus-aware neighboring subgraphs with locus-aware encoding orienting on one cell type. Merely using the CpGs methylation matrix, the obtained GraphCpG outperforms previous methods on datasets containing more than hundreds of cells and achieves competitive performance on smaller datasets, with subgraphs of predicted sites visualized by retrievable bipartite graphs. Besides better imputation performance with increasing cell number, it significantly reduces computation time and demonstrates improvement in downstream analysis. AVAILABILITY AND IMPLEMENTATION: The source code is freely available at https://github.com/yuzhong-deng/graphcpg.git.


Assuntos
Epigenoma , Estudo de Associação Genômica Ampla , Metilação de DNA , Bioensaio , Contagem de Células
3.
Int Orthop ; 48(7): 1849-1858, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38627330

RESUMO

PURPOSE: To introduce anterior peri-sacroiliac joint osteotomy (APSJO) through the lateral-rectus approach (LRA) for treating pelvic fracture malunion and nonunion, and to evaluate the safety, feasibility, and potential effectiveness. METHODS: Data of 15 patients with pelvic fracture malunion and nonunion who underwent treatment by APSJO were selected and analyzed. The reduction quality was assessed using the Mears and Velyvis criteria, while the pre-operative and post-operative function was revealed by the Majeed scoring system. The British Medical Research Council (BMRC) grading system was recruited for the evaluation of lumbosacral plexus function. RESULTS: The average operative duration was 264.00 ± 86.75 min, while the intra-operative blood loss was 2000 (600, 3000) mL. Anatomical reduction was complete in three cases, satisfactory in ten cases, and unsatisfactory in two cases. Among the seven patients with lumbosacral plexus injury, the pre-operative Majeed grades were good in two cases, fair in two cases, and poor in three cases, while the post-operative Majeed grades were excellent in three cases, good in three cases, and fair in one case. Muscle strength recovered to M5 in two cases, M4 in three cases, and showed no recovery in two cases. The pre-operative Majeed grades were good in five cases, fair in two cases, and poor in one case of the series without lumbosacral plexus injury, while the post-operative Majeed grades were excellent in seven cases and good in one case. CONCLUSION: APSJO through LRA may be a feasible strategy for treating pelvic fracture malunion and nonunion with promising application.


Assuntos
Fraturas Mal-Unidas , Fraturas não Consolidadas , Osteotomia , Ossos Pélvicos , Articulação Sacroilíaca , Humanos , Adulto , Feminino , Masculino , Osteotomia/métodos , Fraturas Mal-Unidas/cirurgia , Fraturas não Consolidadas/cirurgia , Ossos Pélvicos/lesões , Ossos Pélvicos/cirurgia , Pessoa de Meia-Idade , Articulação Sacroilíaca/cirurgia , Articulação Sacroilíaca/lesões , Resultado do Tratamento , Adulto Jovem , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Fraturas Ósseas/cirurgia , Adolescente
4.
J Orthop Traumatol ; 25(1): 32, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926180

RESUMO

BACKGROUND: Lumbar-iliac fixation (LIF) is a common treatment for Tile C1.3 pelvic fractures, but different techniques, including L4-L5/L5 unilateral LIF (L4-L5/L5 ULIF), bilateral LIF (BLIF), and L4-L5/L5 triangular osteosynthesis (L4-L5/L5 TOS), still lack biomechanical evaluation. The sacral slope (SS) is key to the vertical shear of the sacrum but has not been investigated for its biomechanical role in lumbar-iliac fixation. The aim of this study is to evaluate the biomechanical effects of different LIF and SS on Tile C1.3 pelvic fracture under two-legged standing load in human cadavers. METHODS: Eight male fresh-frozen human lumbar-pelvic specimens were used in this study. Compressive force of 500 N was applied to the L4 vertebrae in the two-legged standing position of the pelvis. The Tile C1.3 pelvic fracture was prepared, and the posterior pelvic ring was fixed with L5 ULIF, L4-L5 ULIF, L5 TOS, L4-L5 TOS, and L4-L5 BLIF, respectively. Displacement and rotation of the anterior S1 foramen at 30° and 40° sacral slope (SS) were analyzed. RESULTS: The displacement of L4-L5/L5 TOS in the left-right and vertical direction, total displacement, and rotation in lateral bending decreased significantly, which is more pronounced at 40° SS. The difference in stability between L4-L5 and L5 ULIF was not significant. BLIF significantly limited left-right displacement. The ULIF vertical displacement at 40° SS was significantly higher than that at 30° SS. CONCLUSIONS: This study developed an in vitro two-legged standing pelvic model and demonstrated that TOS enhanced pelvic stability in the coronal plane and cephalad-caudal direction, and BLIF enhanced stability in the left-right direction. L4-L5 ULIF did not further improve the immediate stability, whereas TOS is required to increase the vertical stability at greater SS.


Assuntos
Cadáver , Fixação Interna de Fraturas , Fraturas Ósseas , Vértebras Lombares , Ossos Pélvicos , Sacro , Humanos , Masculino , Ossos Pélvicos/lesões , Fenômenos Biomecânicos , Sacro/lesões , Sacro/cirurgia , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Vértebras Lombares/fisiopatologia , Fraturas Ósseas/cirurgia , Fixação Interna de Fraturas/métodos , Ílio , Pessoa de Meia-Idade , Idoso
5.
Arch Orthop Trauma Surg ; 143(7): 3669-3675, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35852598

RESUMO

OBJECTIVES: This study was aimed to measure the application of W-shaped acetabular angular plate (WAAP) through direct posterior approach (DPA) on the reconstruction of acetabular posterior wall fractures when compared with reconstruction plates. PATIENTS AND METHODS: A retrospective study was performed on patients treated with the WAAP or reconstruction plates via the DPA. The intraoperative data of operative time, blood loss and radiation exposure times were recorded. Radiographs of the pelvis and CT scan were obtained within one week post-operation to assess the reduction quality. The clinical outcome was evaluated by the modified Merle d'Aubigne and Postel score. RESULTS: From May 2016 to October 2019, a total of 41 patients with simple acetabular posterior wall fractures were included in this study, 22 from the WAAP group and 19 from the reconstruction plates group. There were no significant differences between the two group in age, gender, time from injury to operation, cause of injuries, length of incision and follow-up time (P > 0.05). In comparison with the reconstruction plates group, the average operation time of the WAAP group was significantly shorter (46.1 ± 12.7 min vs 59.2 ± 17.4 min, P < 0.05), the average radiation exposure times were significantly less (2.3 ± 0.6 vs 3.6 ± 1.0, P < 0.001), the average blood loss was significantly less (240 ± 98.9 ml vs 301.1 ± 66.6 ml, P < 0.05). According to Matta radiology criteria and the modified Merle d' Aubigne and Postel score, no significant difference was observed between the two group, as for the quality of reduction and function outcomes. CONCLUSION: The application of WAAP through DPA showed satisfactory preliminary clinical outcomes, showing promise to be an alternative technique for the treatment of acetabular posterior wall fractures.


Assuntos
Fraturas Ósseas , Fraturas do Quadril , Fraturas da Coluna Vertebral , Humanos , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Acetábulo/lesões , Estudos Retrospectivos , Fixação Interna de Fraturas/métodos , Resultado do Tratamento , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Fraturas do Quadril/cirurgia
6.
Bioinformatics ; 37(13): 1814-1820, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-33459762

RESUMO

MOTIVATION: Single-cell DNA methylation sequencing detects methylation levels with single-cell resolution, while this technology is upgrading our understanding of the regulation of gene expression through epigenetic modifications. Meanwhile, almost all current technologies suffer from the inherent problem of detecting low coverage of the number of CpGs. Therefore, addressing the inherent sparsity of raw data is essential for quantitative analysis of the whole genome. RESULTS: Here, we reported CaMelia, a CatBoost gradient boosting method for predicting the missing methylation states based on the locally paired similarity of intercellular methylation patterns. On real single-cell methylation datasets, CaMelia yielded significant imputation performance gains over previous methods. Furthermore, applying the imputed data to the downstream analysis of cell-type identification, we found that CaMelia helped to discover more intercellular differentially methylated loci that were masked by the sparsity in raw data, and the clustering results demonstrated that CaMelia could preserve cell-cell relationships and improve the identification of cell types and cell subpopulations. AVAILABILITY AND IMPLEMENTATION: Python code is available at https://github.com/JxTang-bioinformatics/CaMelia. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

7.
Nucleic Acids Res ; 47(13): 6753-6768, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31334813

RESUMO

DNA methylation is an important epigenetic mark but how its locus-specificity is decided in relation to DNA sequence is not fully understood. Here, we have analyzed 34 diverse whole-genome bisulfite sequencing datasets in human and identified 313 motifs, including 92 and 221 associated with methylation (methylation motifs, MMs) and unmethylation (unmethylation motifs, UMs), respectively. The functionality of these motifs is supported by multiple lines of evidence. First, the methylation levels at the MM and UM motifs are respectively higher and lower than the genomic background. Second, these motifs are enriched at the binding sites of methylation modifying enzymes including DNMT3A and TET1, indicating their possible roles of recruiting these enzymes. Third, these motifs significantly overlap with "somatic QTLs" (quantitative trait loci) of methylation and expression. Fourth, disruption of these motifs by mutation is associated with significantly altered methylation level of the CpGs in the neighbor regions. Furthermore, these motifs together with somatic mutations are predictive of cancer subtypes and patient survival. We revealed some of these motifs were also associated with histone modifications, suggesting a possible interplay between the two types of epigenetic modifications. We also found some motifs form feed forward loops to contribute to DNA methylation dynamics.


Assuntos
Metilação de DNA/genética , DNA/genética , Epigênese Genética/genética , Sequência de Bases , Sítios de Ligação , Ilhas de CpG , DNA/metabolismo , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA Metiltransferase 3A , DNA de Neoplasias/genética , Conjuntos de Dados como Assunto , Código das Histonas , Humanos , Estimativa de Kaplan-Meier , Oxigenases de Função Mista/metabolismo , Modelos Genéticos , Neoplasias/genética , Neoplasias/mortalidade , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas/metabolismo , Locos de Características Quantitativas , Análise de Sequência de DNA
8.
BMC Genomics ; 21(1): 364, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32414326

RESUMO

BACKGROUND: The computational prediction of methylation levels at single CpG resolution is promising to explore the methylation levels of CpGs uncovered by existing array techniques, especially for the 450 K beadchip array data with huge reserves. General prediction models concentrate on improving the overall prediction accuracy for the bulk of CpG loci while neglecting whether each locus is precisely predicted. This leads to the limited application of the prediction results, especially when performing downstream analysis with high precision requirements. RESULTS: Here we reported PretiMeth, a method for constructing precise prediction models for each single CpG locus. PretiMeth used a logistic regression algorithm to build a prediction model for each interested locus. Only one DNA methylation feature that shared the most similar methylation pattern with the CpG locus to be predicted was applied in the model. We found that PretiMeth outperformed other algorithms in the prediction accuracy, and kept robust across platforms and cell types. Furthermore, PretiMeth was applied to The Cancer Genome Atlas data (TCGA), the intensive analysis based on precise prediction results showed that several CpG loci and genes (differentially methylated between the tumor and normal samples) were worthy for further biological validation. CONCLUSION: The precise prediction of single CpG locus is important for both methylation array data expansion and downstream analysis of prediction results. PretiMeth achieved precise modeling for each CpG locus by using only one significant feature, which also suggested that our precise prediction models could be probably used for reference in the probe set design when the DNA methylation beadchip update. PretiMeth is provided as an open source tool via https://github.com/JxTang-bioinformatics/PretiMeth.


Assuntos
Metilação de DNA , Epigenômica/métodos , Modelos Genéticos , Ilhas de CpG/genética , Loci Gênicos/genética , Genoma/genética , Humanos , Modelos Logísticos , Neoplasias/genética , Análise de Sequência de DNA
9.
Med Sci Monit ; 26: e915886, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32163378

RESUMO

BACKGROUND Despite the development of minimally invasive techniques for pelvic fractures, performing minimally invasive surgery for Tile C3 pelvic fractures remains challenging. Thus, we propose use of anterior ring internal fixation combined with sacroiliac screw fixation for Tile C3 pelvic fractures. MATERIAL AND METHODS A normal pelvic finite element model (model 1) was established. Two-screw, three-screw, and four-screw anterior ring internal fixators and plate combined with sacroiliac screw Tile C3 pelvic fracture models (models 2, 3, 4, and 5, respectively) were also established. A vertical load of 600 N was applied on S1. The distribution of displacement and stress in the standing and sitting positions was compared. RESULTS Models 2, 3, 4, and 5 can provide effective fixation. Compared with model 1, in the erect position, the maximum displacement of models 2, 3, 4, and 5 increased by 66.51%, 65.36%, 35.16%, and 35.47% and the maximum stress increased by 201.78%, 130.65%, 100.82%, and 99.03%, respectively. Compared with model 1, in sitting position, the maximum displacement of models 2, 3, 4, and 5 increased by 9.1%, 11.04%, 5.57%, and 8.59% and the maximum stress increased by 157.73%, 118.02%, 98.32%, and 93.16%, respectively. CONCLUSIONS Anterior ring internal fixators combined with sacroiliac screws can effectively fix Tile C3 pelvic fractures.


Assuntos
Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Modelos Biológicos , Ossos Pélvicos/lesões , Articulação Sacroilíaca/cirurgia , Adulto , Fenômenos Biomecânicos , Placas Ósseas , Parafusos Ósseos , Análise de Elementos Finitos , Fixação Interna de Fraturas/instrumentação , Humanos , Masculino , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/cirurgia
10.
BMC Musculoskelet Disord ; 21(1): 147, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131792

RESUMO

BACKGROUND: Pelvic fractures are rare in toddlers but are often associated with other injuries that make treatment difficult. Conservative treatment has been used with moderate success, but it is unclear if surgical correction could confer additional benefits and improve patient outcomes. The purpose of this study was to report authors' experience using the lateral-rectus approach (LRA) for surgical correction of unstable pelvic fractures in two toddlers. METHODS: We retrospectively analyzed the cases of two toddlers with unstable pelvic fractures who underwent surgery through the LRA between April 2016 and October 2018. Patients' characteristics, fracture type, mechanism of injury, Injury Severity Score (ISS), operative time, intra-operative blood loss, and post-operative complications were assessed. Pelvic asymmetry, degree of deformity, Cole scoring criteria and modified Barthel Index (MBI) were used to evaluate radiographic and functional outcomes. RESULTS: Successful surgical treatment was performed using the LRA, external fixation, and sacroiliac screw fixation. Surgery duration was 180 min on average, with an average intra-operative bleeding of 250 ml. There were no iatrogenic nerve injuries or infections. Pelvic asymmetry a week after surgery was 0.5 cm on average and dropped to 0.3 cm on average at the end of the follow-up period. The deformity index of the pelvis dropped from an average of 0.035 a week after surgery to 0.02 at the end of the follow-up period. The mean MBI was 100 in the last follow-up, and Cole scoring criteria categorized both patients as being in excellent condition. All patients achieved radiological bone union without discrepancy in length of the lower limbs. Neither patient had loss of reduction nor evidence of low back pain during the mean follow-up period of 22 months. CONCLUSIONS: Pelvic fracture in toddlers is rare, and surgical treatment requires careful consideration. The lateral-rectus approach was proven as a viable alternative for managing unstable pelvic fractures in toddlers, with minimal blood loss and risk of nerve injury. Furthermore, anterior external fixation and posterior sacroiliac screw fixation would be adequate for this population, with excellent final outcome.


Assuntos
Parafusos Ósseos , Fixadores Externos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Ossos Pélvicos/lesões , Ossos Pélvicos/cirurgia , Pré-Escolar , Feminino , Seguimentos , Fraturas Ósseas/diagnóstico por imagem , Humanos , Lactente , Ossos Pélvicos/diagnóstico por imagem , Estudos Retrospectivos
11.
BMC Musculoskelet Disord ; 21(1): 451, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32650750

RESUMO

BACKGROUND: Complicated acetabular fractures comprise the most challenging field for orthopedists. The purpose of this study was to develop three-dimensional printed patient-specific (3DPPS) Ti-6Al-4 V plates to treat complicated acetabular fractures involving quadrilateral plate (QLP) disruption and to evaluate their efficacy. METHODS: Fifty patients with acetabular fractures involving QLP disruption were selected between January 2016 and June 2017. Patients were divided into a control group (Group A, 35 patients) and an experimental group (Group B, 15 patients), and were treated by the conventional method of shaping reconstruction plates or with 3DPPS Ti-6AL-4 V plates, respectively. The efficacy of Ti-6AL-4 V plates was evaluated by blood loss, operative time, reduction quality, postoperative residual displacement, and complications. RESULTS: The operative time and blood loss in Group B were reduced compared to Group A, and the difference was statistically significant (P < 0.05). There was no significant difference in reduction quality between the two groups (P > 0.05). Reduction quality in Group B was anatomic in 10 (66.7%), satisfactory in four (26.7%), and poor in one (6.7%). In Group A, they were anatomic in 18 (51.4%), satisfactory in 13 (37.1%), and poor in four (11.4%). Residual displacement in Group B was less than that in Group A, and the difference was statistically significant (P < 0.05). In Group B, one case exhibited loosening of the pubic screw postoperatively. In Group A, there was one case of wound infection, one of deep vein thrombosis (DVT) in the ipsilateral lower limb, one case of traumatic arthritis and two obturator nerve injuries. CONCLUSIONS: The 3DPPS Ti-6AL-4 V plate is a feasible, accurate and effective implant for acetabular fracture treatment.


Assuntos
Fraturas Ósseas , Fraturas do Quadril , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Placas Ósseas , Fixação Interna de Fraturas , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Humanos , Impressão Tridimensional
12.
BMC Genomics ; 20(Suppl 2): 192, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30967120

RESUMO

BACKGROUND: Determination of genome-wide DNA methylation is significant for both basic research and drug development. As a key epigenetic modification, this biochemical process can modulate gene expression to influence the cell differentiation which can possibly lead to cancer. Due to the involuted biochemical mechanism of DNA methylation, obtaining a precise prediction is a considerably tough challenge. Existing approaches have yielded good predictions, but the methods either need to combine plenty of features and prerequisites or deal with only hypermethylation and hypomethylation. RESULTS: In this paper, we propose a deep learning method for prediction of the genome-wide DNA methylation, in which the Methylation Regression is implemented by Convolutional Neural Networks (MRCNN). Through minimizing the continuous loss function, experiments show that our model is convergent and more precise than the state-of-art method (DeepCpG) according to results of the evaluation. MRCNN also achieves the discovery of de novo motifs by analysis of features from the training process. CONCLUSIONS: Genome-wide DNA methylation could be evaluated based on the corresponding local DNA sequences of target CpG loci. With the autonomous learning pattern of deep learning, MRCNN enables accurate predictions of genome-wide DNA methylation status without predefined features and discovers some de novo methylation-related motifs that match known motifs by extracting sequence patterns.


Assuntos
Ilhas de CpG , Metilação de DNA , Aprendizado Profundo , Genoma Humano , Genômica/métodos , Modelos Estatísticos , Análise de Sequência de DNA/métodos , Algoritmos , Epigênese Genética , Humanos , Análise de Regressão
13.
Med Sci Monit ; 24: 7285-7294, 2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30311603

RESUMO

BACKGROUND This study aimed to evaluate outcome following a single lateral rectus abdominis surgical approach for complicated acetabular fractures, involving anterior and posterior columns. MATERIAL AND METHODS From January 2012 to March 2016, 59 patients, including 36 anterior column hemitransverse fractures, 18 two-column fractures, and five T-type complicated acetabular fractures, were treated with a single lateral rectus abdominis approach and fixed by plates and cannulated lag screws. Anterior column fractures were fixed with 3.5 mm reconstruction plates; posterior column fractures were fixed with 6.5 mm cannulated lag screws. The quality of surgical reduction (using the Matta criteria), functional outcome (using the modified Merle d'Aubigné and Postel scoring system), and postoperative complications were assessed with 24-month follow-up. RESULTS Fifty-nine patients (mean age, 45 years; range, 18-64 years) including 39 men and 20 women underwent surgery. Mean intraoperative blood loss was 514.6 ml (range, 150-830 ml) and mean operating time was 86.3 min (range, 42-145 min). Anatomical reduction was good in 40 cases (67.8%), fair in 15 cases (25.4%), and poor in four cases (6.8%). The modified Merle d'Aubigné score was excellent in 39 cases (66.1%), good in 14 cases (23.7%), fair in five cases (8.5%), and poor in one case (1.7%). At follow-up, there were five cases of peritoneal damage, eight cases of obturator nerve dysfunction, and four cases of postoperative traumatic arthritis. CONCLUSIONS The single lateral rectus abdominis surgical approach for the treatment of complicated acetabular fractures was minimally invasive with good anatomical exposure and good outcomes.


Assuntos
Acetábulo/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Acetábulo/lesões , Adolescente , Adulto , Perda Sanguínea Cirúrgica , Placas Ósseas , Parafusos Ósseos , Feminino , Fixação Interna de Fraturas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Reto do Abdome/cirurgia , Resultado do Tratamento
14.
Bioinformatics ; 32(12): 1773-8, 2016 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-26883487

RESUMO

MOTIVATION: DNA methylation signatures in rheumatoid arthritis (RA) have been identified in fibroblast-like synoviocytes (FLS) with Illumina HumanMethylation450 array. Since <2% of CpG sites are covered by the Illumina 450K array and whole genome bisulfite sequencing is still too expensive for many samples, computationally predicting DNA methylation levels based on 450K data would be valuable to discover more RA-related genes. RESULTS: We developed a computational model that is trained on 14 tissues with both whole genome bisulfite sequencing and 450K array data. This model integrates information derived from the similarity of local methylation pattern between tissues, the methylation information of flanking CpG sites and the methylation tendency of flanking DNA sequences. The predicted and measured methylation values were highly correlated with a Pearson correlation coefficient of 0.9 in leave-one-tissue-out cross-validations. Importantly, the majority (76%) of the top 10% differentially methylated loci among the 14 tissues was correctly detected using the predicted methylation values. Applying this model to 450K data of RA, osteoarthritis and normal FLS, we successfully expanded the coverage of CpG sites 18.5-fold and accounts for about 30% of all the CpGs in the human genome. By integrative omics study, we identified genes and pathways tightly related to RA pathogenesis, among which 12 genes were supported by triple evidences, including 6 genes already known to perform specific roles in RA and 6 genes as new potential therapeutic targets. AVAILABILITY AND IMPLEMENTATION: The source code, required data for prediction, and demo data for test are freely available at: http://wanglab.ucsd.edu/star/LR450K/ CONTACT: wei-wang@ucsd.edu or gfirestein@ucsd.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Artrite Reumatoide , Metilação de DNA , Ilhas de CpG , Fibroblastos , Genoma Humano , Humanos , Análise de Sequência com Séries de Oligonucleotídeos
15.
Calcif Tissue Int ; 100(4): 392-401, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28185033

RESUMO

Saikosaponin-A (SA), a class of native compound with numerous biological activities, may exert protective effect against postmenopausal bone loss. However, it remains unknown whether SA regulates the osteogenic differentiation of bone marrow stromal cells (BMSCs) in the treatment and prevention of osteoporosis. In this study, BMSCs were treated with various concentrations of SA to stimulate osteogenic differentiation over a 14-day period. Additionally, a canonical ovariectomized (OVX) mouse model was used to evaluate the effect of 3-month SA treatment in preventing postmenopausal osteoporosis. In vitro, we found that SA promotes alkaline phosphatase activity/staining and Alizarin red assay, stimulated the expression of osteogenic markers, i.e., runt-related transcription factor 2 (Runx2), osterix, osteopontin, and osteocalcin (OCN) in BMSCs. In vivo, the trabecular number, trabecular thickness, and trabecular bone mineral density of the distal femoral metaphysis were significantly increased in OVX mice treated intraperitoneally with SA for 3 months compared with OVX mice that not treated with SA. Moreover, the expression of Runx2 and OCN in OVX + SA mice was significantly increased than that in OVX mice. Finally, we found that SA activated the WNT/ß-catenin pathway and the expression of several downstream genes including T-cell factor-1 and lymphoid enhancer factor-1. Inhibition of WNT/ß-catenin pathway by Dickkopf-related protein 1 blocked the positive role of SA on osteogenesis. Therefore, SA promoted the osteogenic differentiation of BMSCs through WNT/ß-catenin signaling.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Osteogênese/efeitos dos fármacos , Saponinas/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Células da Medula Óssea/citologia , Feminino , Células-Tronco Mesenquimais/citologia , Camundongos Endogâmicos C57BL , Ácido Oleanólico/farmacologia , Fatores de Transcrição/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Via de Sinalização Wnt/fisiologia , beta Catenina/metabolismo
16.
Genomics ; 107(4): 132-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26921858

RESUMO

The Infinium HumanMethylation450 BeadChip array, referred as 450K array hereinafter, has been widely adopted as an affordable technique to determine DNA methylation. Tens of thousands of data have been generated on diverse cell types and patient tissues, which have provided great insight into understanding the crucial roles of epigenetic modifications in many biological processes and diseases. The limitation of this technique is its coverage, which measures methylation levels of about 450,000 CpGs, accounting for about 1.6% of all CpGs in the human genome. In the present study we developed and compared computational models to significantly expand the coverage of Illumina 450K (~11 folds). Using the whole genome bisulfite sequencing and Illumina 450K data in the human H1 embryonic stem cell, we showed that the predicted and measured methylation levels were well correlated. Our proposed model showed superior prediction accuracies compared to the existing methods on the same dataset. When applied to predict the DNA methylome on other cells, our proposed model achieved comparable performance in cross-validations, which indicates the generalizibility of the method. Our method would thus be invaluable to maximize the usage of the existing data.


Assuntos
Ilhas de CpG , Metilação de DNA , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Células-Tronco Embrionárias/citologia , Epigênese Genética , Genoma Humano , Humanos , Modelos Logísticos , Máquina de Vetores de Suporte
17.
Zhonghua Wai Ke Za Zhi ; 53(9): 700-3, 2015 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-26654151

RESUMO

OBJECTIVE: To study the clinical effect and surgical operating points of pararectus approach for the internal fixation of acetabular both-column fractures with concurrent displaced quadrilateral plate fractures. METHODS: From January 2012 to December 2013, in the Third Affiliated Hospital of Southern Medical University, 15 patients with acetabular both-column fractures and displaced quadrilateral plate fractures were surgically managed through the pararectus approach. There were 11 male and 4 female patients, with an average age of 40 years (from 19 to 61 years). According to Judet-Letournel classification, there were 9 anterior column plus posterior hemitransverse fractures, 6 both-column fractures, 8 cases involving the pelvic fracture. All these fractures were treated through the pararectus approach, in the horizontal position with general anesthesia. The pre-bended plate was placed in interior pelvic ring to fix the anterior wall, anterior column and quadrilateral plate in direct sight. Then, the posterior column was exposed and fixed with antegrade lag screw. Patients were followed up in 4 weeks, 12 weeks, 6 months, 1 year after the operation, and the anteroposterior radiograph of pelvis and the X-ray examination of the fractured hip was performed. RESULTS: All the 15 cases underwent the operation successfully. Postoperative X-ray and CT exams showed excellent and good reduction of anterior column, posterior column and quadrilateral plate, with none surgical complication occurred. According to the Matta radiological evaluation postoperatively, reduction of acetabular fracture was rated as excellent in 9 cases, good in 3 cases and poor in 3 cases. The rate of excellent and good was 12/15. After 8 to 18 months' follow-up (median follow-up time was 14 months), all the patients gained bone union. According to the modified Merle D'Aubigne and Postel scoring system, 9 cases were excellent, 4 were good, and 2 were fair. The rate of excellent and good was 13/15. CONCLUSIONS: Surgical management of acetabular fractures through the pararectus approach can provide adequate exposure of reducing and fixing both-column acetabular fractures with concurrent displaced quadrilateral plate fractures, which has a good effect in clinical application.


Assuntos
Acetábulo/patologia , Acetábulo/cirurgia , Placas Ósseas , Fixação Interna de Fraturas/métodos , Adulto , Anestesia Geral , Parafusos Ósseos , Feminino , Fraturas do Quadril/patologia , Fraturas do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Ossos Pélvicos/patologia , Ossos Pélvicos/cirurgia , Período Pós-Operatório , Fraturas da Coluna Vertebral , Resultado do Tratamento , Adulto Jovem
18.
Orthop Surg ; 15(10): 2523-2531, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37620863

RESUMO

OBJECTIVE: As conventional plates require repeated pre-bending during surgery with poor matching, this study aimed to explore the design and application of an acetabular integrative anatomical plate (AIAP) via the lateral-rectus approach (LRA) in fresh complex acetabular fractures for the good reduction and fixation. METHODS: We designed an AIAP based on the anatomical morphology of the Chinese people. From March 2016 to September 2021, 178 patients with fresh complex acetabular fractures treated with an AIAP via the LRA were retrospectively analyzed. All patients were treated by the LRA under general anesthesia in a supine position. The fragments were well reduced and fixed by AIAPs. The operation time and intraoperative blood loss were recorded. All patients underwent reexamination of pelvic X-rays and CT scans and were followed up for over 1 year postoperatively. The reduction quality of fracture was evaluated according to the Matta criteria. The postoperative functional recovery was evaluated by modified Merle d'Aubigne-Postel scoring system. Statistics were analyzed by SPSS 25.0 (SPSS Inc., Chicago, IL, USA). RESULTS: All 178 patients went through the operation successfully. The time from injury to operation ranged from 5 to 21 days (8.7 ± 2.6 days). The operation time ranged from 35 to 150 min (75 ± 29 min). The intraoperative blood loss was from 250 to 1400 ml (440 ± 153 ml). According to the Matta score, the fracture reduction was evaluated as excellent in 131 cases, good in 31 cases, and poor in 16 cases, with an overall excellent and good rate of 91%. Four patients suffered wound fat liquefaction and healed after fresh dressing. All patients were followed up for 1 to 5 years without wound infection. All fractures were healed. At the last follow-up, the modified Merle d'Aubigne-Postel score results were evaluated as excellent in 125 cases, good in 26 cases, and fair in 27 cases, with an overall excellent and good rate of 84.8%. Postoperative complications included six cases of traumatic arthritis of the hips and two cases of femoral head necrosis. CONCLUSION: The LRA with an AIAP can help expose, reduce, and fix anterior and posterior columns as well as the quadrilateral area of the acetabulum, which is capable of improving the reduction quality of complex acetabular fractures and shortening surgical time and blood loss, thus reaching a good clinical efficacy.


Assuntos
Fraturas Ósseas , Fraturas do Quadril , Fraturas da Coluna Vertebral , Humanos , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Acetábulo/lesões , Estudos Retrospectivos , Perda Sanguínea Cirúrgica , Fixação Interna de Fraturas/métodos , Fraturas do Quadril/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Resultado do Tratamento
19.
Orthop Surg ; 15(9): 2300-2308, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37430470

RESUMO

OBJECTIVE: Anterior dislocation of the sacroiliac joint (ADSIJ) is caused by strong violence, and because of its low morbidity, there are no standardized diagnostic and therapeutical guidelines at this moment. This study aims to explore the surgical techniques and preliminary outcomes of the lateral-rectus approach (LRA) for treating ADSIJ. METHODS: A retrospective study was conducted of 15 patients with ADSIJ from January 2016 to January 2021. The patients' age ranged from 1.8 years old to 57 years old (37 ± 18 years old). All patients underwent open reduction and internal fixation (ORIF) through the LRA. Eight patients were combined with lumbosacral plexus injury and underwent neurolysis during operation. Patients' fracture type, mechanism of injury, associated injuries, operation time and intraoperative bleeding volume were accessed by reviewing medical history. Quality of fracture reduction was evaluated with the Matta score. At 1-year follow-up, the functional rehabilitation was evaluated by the Majeed rehabilitation criteria. For those with lumbosacral plexus injury, the neuromotor function was evaluated using muscle strength grading proposed by the British Medical Research Council (BMRC) and recovery was recorded. RESULTS: All 15 patients underwent the operation successfully. The surgical time ranged from 70 to 220 min (126 ± 42 min), and the intraoperative blood loss ranged from 180 to 2000 mL (816 ± 560 mL). Eighty percent of the cohort (12/15) were rated as excellent and good in the Matta score for fracture reduction quality after operation without surgical incision-related complications. At 1-year follow-up, the overall excellent and good rate was 73.3% (11/15) according to the Majeed criteria, the neuromotor function recovered completely in six cases and partially in two cases according to the BMRC muscle strength grading, and the recovery of sensory function was evaluated as excellent in six cases, good in one case and poor in one case, with an overall excellent and good rate of 87.5%. CONCLUSION: The LRA can well expose the surrounding structures of the sacroiliac joint from the front, which helps surgeons reduce and fix the anterior dislocation of the sacroiliac joint under direct vision and effectively decompress the entrapment of the lumbosacral plexus to achieve better clinical efficacy.


Assuntos
Fraturas Ósseas , Luxações Articulares , Ossos Pélvicos , Humanos , Lactente , Fraturas Ósseas/cirurgia , Fixação Interna de Fraturas/métodos , Articulação Sacroilíaca/cirurgia , Estudos Retrospectivos , Ossos Pélvicos/cirurgia , Parafusos Ósseos , Resultado do Tratamento , Luxações Articulares/cirurgia
20.
Health Care Sci ; 2(1): 36-44, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38939740

RESUMO

Objectives: This study aimed to investigate the symmetry of the Chinese pelvis. Methods: Computed tomography scan images of each of 50 Chinese pelvises were converted to 3D models and the left sides of the pelvises were reflected on Mimics software. Then, the reflected left side model was aligned with the right side using the closest point algorithm function of Geomagic software to perform symmetry analysis. The volume and surface area of either side of the pelvises were also calculated. The mean standard deviation (SD), the mean percentage of permissible deviations within the ±2 mm range, the percentage differences in volume and surface area were measured to compare pelvic symmetry. In addition, the distribution of pelvic bilateral symmetry associated with both age and sex were compared. Results: The mean SD was 1.15 ± 0.16 mm and the mean percentage of permissible deviations was 90.82% ± 4.67%. The deviation color maps showed that the specific areas of asymmetry were primarily localized to major muscle or ligament attachment sites and the sacroiliac joint surfaces. There was no significant difference between the bilateral sides of the pelvis in either volume or surface area. Additionally, no difference in any indexes was exhibited in relation to sex and age distribution. Conclusion: Our results demonstrated that the pelvis has high bilateral symmetry, which confirmed the potential of using contralateral pelvic models to create fully patient-specific and custom-made pelvic implants applicable for the treatment of fracture and bony destruction.

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