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Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease characterized by disability and deformity. To better understand ONFH at molecular level and to explore the possibility of early diagnosis, instead of diagnosis based on macroscopic spatial characteristics, a matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) method was developed for ONFH disease for the first time. The most challenging step for ONFH MSI is to deal with human bone tissues which are much harder than the other biological samples studied by the reported MSI studies. In this work, the MSI sectioning method of hard bone tissues was established using tender acids and a series of test criteria. Small-molecule metabolites, such as lipids and amino acids, were detected in bone sections, realizing the in situ detection of spatial distribution of biometabolites. By comparing the distribution of metabolites from different regions of normal femoral head, ONFH bone tissue (ONBT), and adjacent ONFH bone tissue (ANBT), the whole process of femoral head from normal stage to necrosis was monitored and visualized at molecular level. Moreover, this developed MSI method was used for metabolomics study of ONFH. 72 differential metabolites were identified, suggesting that disturbances in energy metabolism and lipid metabolism affected the normal life activities of osteoblasts and osteoclasts. This study provides new perspectives for future pathological studies of ONFH.
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Trichinella spiralis (T. spiralis) muscle larvae (ML) excretory/secretory products (ESPs) are antitumor substances extracted from the culture medium of T. spiralis ML. The ESPs inhibit tumor growth and induce tumor cell apoptosis. To explore the effects of these products on the non-small-cell lung cancer (NSCLC) line A549, logarithmically growing A549 cells were co-cultured with different concentrations of T. spiralis ML ESPs for 24, 36 and 48 h. Our results showed that T. spiralis ML ESPs significantly inhibited A549 cells proliferation, which was dose-and time-dependent. To evaluate the inhibition by T. spiralis ML ESPs of the growth of A549 cells, we assayed their apoptosis and cell-cycle distribution by flow cytometry (FCM). To determine whether ESPs induced apoptosis of A549 cells via the mitochondrial pathway, we evaluated the levels of mitochondrion-related factors by Western blotting. The FCM indicated a clear trend toward apoptosis of A549 cells co-cultured with ESPs for 24 h. The cells were blocked in S-phase. Western blotting revealed that the expression levels of the genes encoding Bax, caspase-3, and caspase-9 increased (compared to a control group), and the Bcl-2 gene expression level decreased. Our results suggest that T. spiralis ML ESPs induce apoptosis of the NSCLC line A549 via the mitochondrial pathway; the cells become arrested in S-phase. This may explain the antineoplastic activity of T. spiralis ML ESPs.
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Células A549/efeitos dos fármacos , Antígenos de Helmintos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proteínas de Helminto/farmacologia , Fase S/efeitos dos fármacos , Trichinella spiralis/química , Células A549/citologia , Análise de Variância , Animais , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/efeitos dos fármacos , Meios de Cultura Livres de Soro , Feminino , Humanos , Larva/química , Camundongos , Trichinella spiralis/imunologiaRESUMO
Human securin is regulatory protein involved in control of the metaphase-anaphase transition and anaphase onset of colorectal cancer. Molecular evidences suggest that the protein is integrated into oncogenic signaling network by binding to SH3-containing proteins through its proline-rich peptides. In this study, we have performed a genome-wide analysis and identification of securin-binding partners in the gene diversity space of human colorectal cancer. The securin-binding potency of SH3-containing proteins found in colorectal cancer was investigated by using bioinformatics modeling and intermolecular assay. With the protocol we were able to predict those high-affinity domain binders of the proline-rich peptides of human securin in a high-throughput manner, and to analyze sequence-specific interaction in the domain-peptide recognition at molecular level. Consequently, a number of putative domain binders with both high affinity and specificity were identified, from which the Src SH3 domain was selected as a case study and tested for its binding activity towards the securin peptides using fluorescence-based analysis. We also designed two peptide mutants that may have potent capability to competitively disrupt securin interaction with its partners. This article is protected by copyright. All rights reserved.
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OBJECTIVE: To evaluate the effect of external fixation compared with dynamic hip screw (DHS) for the treatment of elderly intertrochanteric hip fractures. METHODS: We searched Pubmed, Embase, Cochrane central database (All to December 19th, 2015) for comparative studies relevant to external fixation versus DHS for the management of intertrochanteric hip fractures. Only randomized controlled trial (RCT) were included. We extracted the trial characteristics, intervention details, primary and secondary outcomes. Risk of bias was assessed. Fixed/random effect model was adapted according to the heterogeneity tested by I2 statistic. Sensitivity analysis was conducted and publication bias was assessed. RESULTS: A total of 4 RCTs were retrieved involving 260 patients. Pooled results showed for the primary outcomes of Harris hip score and final mortality, no significant difference was found between external fixation and DHS, however, for the secondary outcomes, external fixation had advantages in the aspects of length of surgery, operative blood loss, blood transfusion and hospital stay while shortcomings in pin-track infection. For other secondary outcomes such as fracture reduction, cut out and varus malunion, no significant difference could be found. CONCLUSIONS: While there was no conclusive evidence, as external fixation with less surgery time, less blood loss and less post-operative pain while no compromise in final functional outcome and mortality compared with DHS, it could be considered as an alternative for the elderly intertrochanteric hip fractures, especially in highrisk patients who could not tolerate routine spinal anesthesia and open surgery.
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Parafusos Ósseos , Fixadores Externos , Fixação Interna de Fraturas/instrumentação , Consolidação da Fratura/fisiologia , Fraturas do Quadril/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Fixação Interna de Fraturas/métodos , Avaliação Geriátrica , Fraturas do Quadril/diagnóstico por imagem , Humanos , Escala de Gravidade do Ferimento , Tempo de Internação , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Resultado do TratamentoRESUMO
The emergence of immune checkpoint inhibitors (ICIs) has heralded a transformative era in the therapeutic landscape of non-small cell lung cancer (NSCLC). While ICIs have demonstrated clinical efficacy in a portion of patients with NSCLC, these treatments concurrently precipitate a spectrum of immune-related adverse events (irAEs), encompassing mild to severe manifestations, collectively posing a risk of significant organ damage. Consequently, there exists an imperative to augment our comprehension of the pathophysiological underpinnings of irAEs and to formulate more efficacious preventive and ameliorative strategies. In this comprehensive review, we delineate the clinical presentation of organ-specific irAEs in patients with NSCLC and provide an in-depth analysis of recent advancements in understanding the mechanisms driving ICI-induced toxicity. Furthermore, we discuss potential strategies and targets for ameliorating these irAEs. Ultimately, this review aims to furnish valuable insights to guide further research endeavours in the context of irAEs in NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversosRESUMO
Tertiary lymphoid structures (TLS) represent the ectopic aggregations of immune cells arising during chronic inflammation or tumor progression. In cancer, TLS are often associated with beneficial clinical outcomes in patients undergoing immunotherapy, underscoring their prognostic and predictive significance. Mature TLS, characterized by germinal centers and areas of T-cell and B-cell aggregation, are considered primary locations for activating and maintaining both humoral and cellular anti-tumor immune effects. Despite their recognized importance, the mechanisms driving the formation of mature TLS in cancer and their influence on the immune response within tumors remain insufficiently understood. Therefore, this review aims to comprehensively explore the structural composition, development mechanisms, maturity impact factors, immunological function, and innovative therapeutic strategies of mature TLS within the tumor microenvironment. The research summarized herein offers novel insights and considerations for therapeutic approaches to promote TLS generation and maturation in patients with cancer, representing a promising avenue for future cancer therapies.
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Neoplasias , Estruturas Linfoides Terciárias , Microambiente Tumoral , Humanos , Estruturas Linfoides Terciárias/imunologia , Estruturas Linfoides Terciárias/patologia , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/patologia , Microambiente Tumoral/imunologia , Animais , Imunoterapia/métodos , Linfócitos B/imunologia , Linfócitos T/imunologiaRESUMO
Tertiary lymphoid structures (TLSs) are ectopic lymphocyte aggregates formed in non-lymphoid tissues, including cancers, and are loci for the generation of in situ anti-tumor immune responses, which play a crucial role in cancer control. The state of TLS presence in cancer and its composition can significantly impact the treatment response and prognosis of patients. TLSs have the potential to serve as predictive and prognostic biomarkers for cancer. However, the mechanisms underlying TLS formation in cancer and how the essential components of TLSs affect cancer are not fully understood. In this review, we summarized TLS formation in cancer, the value of the TLS in different states of existence, and its key constituents for cancer prediction and prognosis. Finally, we discussed the impact of cancer treatment on TLSs.
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OBJECTIVE: To examine vascular endothelial growth factor (VEGF) protein secretion and expression and explore the osteogenic activity of adipose tissue-derived stem cells (ADSCs) after transfection of human VEGF. METHODS: The ADSCs were isolated from human adipose tissue after the digestion of collagenase.After identification by flow cytometry, the cells were cultured and passaged in nutritive medium. Gene sequence encoding human VEGF mature peptide was obtained by Trizol reagent method from human vascular tissue. Target gene VEGF was connected with bicistronic expression vector containing green fluorescent protein to form pSELECT-GFP zeo-VEGF for transfecting 2nd, 3rd, 4th, 5th generation ADSCs mediated by liposome. The transfection results were verified under fluorescence microscope. VEGF protein secretion by transfected cells was detected by enzyme-linked immunosorbent assay (ELISA). Second-generation transfected ADSCs were cultured under osteogenic conditions.The supernatant levels of alkaline phosphatase (ALP) and osteocalcin (OC) were detected. RESULTS: Liposome-mediated VEGF target gene fragment could transfect ADSCs successfully. ELISA quantitative detection showed that VEGF mRNA expression levels in supernatant of the transfected group was significantly higher than the control group. And there were significant differences. After osteogenic culturing, the detections of ELISA, real-time PCR and Western blot showed that the secretion of ALP and OC of VEGF transfected group was significantly higher than that of empty vector transfected and blank cell groups.And there were significant differences (P < 0.01). CONCLUSION: After transfected by liposome-mediated VEGF target gene fragment, human ADSCs can express biologically active VEGF mRNA in vitro continuously and effectively. Directional differentiation capacity of transfected ADSCs is significantly enhanced.
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Tecido Adiposo/citologia , Células-Tronco/citologia , Fator A de Crescimento do Endotélio Vascular/genética , Diferenciação Celular , Células Cultivadas , Vetores Genéticos , Humanos , Osteogênese , Transfecção , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: To compare the effectiveness of a six-month home-based telerehabilitation based on the Internet-based rehabilitation management system coupled with conventional outpatient care in elderly patients with hip fractures following total hip replacement (THR). METHODS: Elderly patients (aged over 65 years) with first hip fractures who underwent THR between March 2018 and September 2018 in Tianjin Hospital were enrolled in this study. Patients were divided into two groups: telerehabilitation group (n = 43) and telephone group (n = 42). A Internet-based telerehabilitation management system was established and applied on patients in the telerehabilitation group. For patients in the telephone group, the rehabilitation intervention was administered through conventional outpatient care (telephone along with outpatient follow-up). Data from the Harris hip scale (HHS), functional independence measure (FIM), self-rating anxiety scale (SAS), and postoperative complications at 1, 3, and 6 months after surgery were collected and compared between the two groups. RESULTS: A total of 85 elderly patients completed the 6-month follow-up assessment. Results showed that the HHS score was significantly higher in the telerehabilitation group than in the telephone group at 1 month (66.35 ± 4.63 vs 63.48 ± 4.49), 3 months (76.33 ± 4.52 vs 71.81 ± 3.84), and 6 months (84.23 ± 3.13 vs 77.29 ± 4.95) after surgery (P < 0.001). The FIM score was significantly higher in the telerehabilitation group than in the telephone group at 1 month (89.00 ± 5.63 vs 73.35 ± 8.70), 3 months (100.16 ± 4.56 vs 92.81 ± 5.17), and 6 months (111.70 ± 3.13 vs 98.64 ± 5.12) after surgery (P < 0.001). The SAS score was significantly lower in the telerehabilitation group than in the telephone group at 1 month (42.40 ± 3.07 vs 46.21 ± 3.53), 3 months (36.77 ± 2.26 vs 40.24 ± 1.66), and 6 months (29.26 ± 1.63 vs 33.81 ± 2.62) after surgery (P < 0.001). The overall complication rate was significantly lower in the telerehabilitation group than in the telephone group (14% vs 40.5%) (P < 0.05). CONCLUSION: Internet-based rehabilitation management system can not only promote the physical rehabilitation of patients, but also play a positive role in psychological rehabilitation and the prevention of complications, which provides new ideas and methods for clinical rehabilitation.
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Artroplastia de Quadril , Fraturas do Quadril , Telerreabilitação , Idoso , Humanos , Artroplastia de Quadril/reabilitação , Telerreabilitação/métodos , Recuperação de Função Fisiológica , Resultado do Tratamento , Fraturas do Quadril/cirurgiaRESUMO
OBJECTIVE: Osteoporosis is a common complex and polygenic disease in postmenopausal women, which is characterized by a decrease in bone mineral density (BMD). The osteoprotegerin (OPG) is an important candidate gene in the pathogenesis of osteoporosis. The aim of this study was to investigate the association between single-nucleotide polymorphisms (SNPs) in the OPG gene and BMD. METHODS: OPG gene polymorphisms and BMD were analyzed in 352 Chinese postmenopausal women. BMD was quantified at the lumbar spine (L2-4), femoral neck, and total hip. RESULTS: Through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods, an allelic variant corresponding to the GâA mutations at position 23276 in exon 3 of the OPG gene could be detected. The association between g.23276 G>A polymorphisms and BMD was analyzed, and a significant association was found between g.23276 G>A and spine BMD. The mean of genotype GG was significantly higher than those of genotype GA and AA. There was no significant difference in neck hip BMD and total hip BMD among different genotypes. CONCLUSIONS: These findings suggested that g.23276 G>A genotypes in the OPG gene were associated with spine BMD in Chinese postmenopausal women. The A-allele was associated with lower BMD and an increased risk for osteoporosis.
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Densidade Óssea/fisiologia , Predisposição Genética para Doença , Osteoporose Pós-Menopausa/genética , Osteoprotegerina/genética , Polimorfismo de Nucleotídeo Único , Pós-Menopausa/fisiologia , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/metabolismoRESUMO
Purpose: The purpose of this study was to identify which of the risk factors would contribute to the contralateral fracture in very elderly patients after intramedullary nail fixation. Methods: Clinical data of 227 intertrochanteric fracture patients aged 80 years or older were retrospectively reviewed. Intramedullary nails (IMNs) were used on all of the patients. Potential risk factors for contralateral hip refractures were determined using univariate and logistic regression analyses. Results: Contralateral hip refractures occurred in 11 patients (4.84%). Univariate analysis revealed that age, gender, body mass index, fracture classification, hematocrit, D-dimer, and CRP level were not associated with contralateral fractures (P > 0.05). However, neurological diseases, cardiovascular disease, and visual impairments were significantly associated with contralateral fractures (P < 0.05). Multivariate analysis further revealed that neurological diseases (OR 4.25, P = 0.044) and visual impairments (OR 5.42, P = 0.015) were independent risk factors associated with contralateral refractures. Conclusion: To prevent contralateral refractures, more attention should be paid to elderly intertrochanteric fracture patients with underlying neurological disease and visual impairments.
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OBJECTIVE: To investigate the effects of home-based telerehabilitation based on the Internet-based rehabilitation management system on hip function, activities of daily living and somatic integrative ability of elderly postoperative hip fracture patients. METHODS: From June 2020 to November 2020, we recruited 58 elderly postoperative hip fracture patients and randomly assigned them to the telephone group (n = 29) and the telerehabilitation group (n = 29). Both groups received routine discharge instructions, and the former received telephone follow-up after discharge, while the latter received remote rehabilitation based on the Internet-based rehabilitation management system. The Harris hip score (HHS), functional independence measure (FIM), timed up-and-go test (TUG), and short physical performance battery (SPPB) were used to evaluate the patients' hip function, activities of daily living, and overall somatic ability. RESULTS: There was no significant difference between the baseline data of the two groups before the intervention (P > 0.05); no matter after hip replacement or internal fixation, the HHS score and FIM score of both groups increased gradually with the postoperative time, and the scores in the telerehabilitation group were higher than those in the telephone group at 1 and 3 months after the intervention, and the difference was significant (P < 0.05); for patients after hip replacement, the TUG and SPPB scores in the telerehabilitation group were better than those in the telephone group at 3 months after the intervention, and the difference was significant (P < 0.05). CONCLUSIONS: The Internet-based rehabilitation management system applied to postoperative home rehabilitation of elderly hip fracture patients can improve the functional recovery of the hip joint and enhance the ability to perform activities of daily living and somatic integration to a certain extent. This seems to provide an effective option for conducting home rehabilitation.
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Fraturas do Quadril , Telerreabilitação , Atividades Cotidianas , Idoso , Envelhecimento , Fraturas do Quadril/cirurgia , Humanos , Recuperação de Função Fisiológica , Resultado do TratamentoRESUMO
Achieving automatic classification of femur trochanteric fracture from the edge computing device is of great importance and value for remote diagnosis and treatment. Nevertheless, designing a highly accurate classification model on 31A1/31A2/31A3 fractures from the X-ray is still limited due to the failure of capturing the scale-variant and contextual information. As a result, this paper proposes a deep scale-variant (DSV) network with a hybrid and progressive (HP) loss function to aggregate more influential representations of the fracture regions. More specifically, the DSV network is based on the ResNet and integrated with the designed scale-variant (SV) layer and HP loss, where the SV layer aims to enhance the representation ability to extract the scale-variant features, and HP loss is intended to force the network to condense more contextual clues. Furthermore, to evaluate the effect of the proposed DSV network, we carry out a series of experiments on the real X-ray images for comparison and evaluation, and the experimental results demonstrate that the proposed DSV network could outperform other classification methods on this classification task.
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Fraturas do Quadril , Fêmur/diagnóstico por imagem , Fraturas do Quadril/diagnóstico por imagem , Humanos , Radiografia , Raios XRESUMO
Osteoarthritis (OA) acts as the most common type of degenerative joint disease. Long noncoding RNA (lncRNA) has been identified to regulate the apoptosis and proliferation of chondrocyte. However, the deepgoing mechanism involved in the regulation is still unclear. This research aims to investigate the role and molecular mechanism by which lncRNA LINC00511 regulates the OA biology. Functionally, the functional experiments found that LINC00511 expression was upregulated in the IL-1ß-stimulated chondrocyte (ATDC5). Knockdown of LINC00511 facilitated proliferation, and repressed the apoptosis and extracellular matrix (ECM) synthesis of chondrocyte. Mechanically, LINC00511 functioned as sponge of miR-150-5p and then interacted with the 3'-UTR of transcription factor (SP1). In turn, transcription factor SP1 bound with the promoter region of LINC00511 and thus upregulated LINC00511 expression. In conclusion, our findings highlight the function and prognostic value of LINC00511/miR-150-5p/SP1 feedback loop in OA and extend the importance of lncRNA epigenetics in OA biology.
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Apoptose , Proliferação de Células , Condrócitos/metabolismo , Osteoartrite/genética , Regiões 3' não Traduzidas , Animais , Linhagem Celular , Condrócitos/fisiologia , Retroalimentação Fisiológica , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoartrite/metabolismo , Regiões Promotoras Genéticas , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismoRESUMO
OBJECTIVE: To compare the clinical therapeutic effect of transverse cancellous lag screw (TCLS) fixations and ordinary cannulated screw (OCS) fixations for vertical femoral neck fractures. METHODS: A total of 62 eligible patients with an average age of 56.2 years (range, 19-45 years; 40 male and 22 female) with Pauwels' type III femoral neck fractures were recruited in our study from January 2016 to December 2017. Among the patients, 30 underwent TCLS fixation (TCLS group), and the others were treated with OCS fixation (OCS group). The baseline data, perioperative outcomes (operative time, intra-operative blood loss, reduction quality, and hospital time), postoperative outcomes evaluated by a variety of scales including visual analogue scale (VAS) score, EuroQol five dimensions questionnaire (EQ-5D) and Harris hip scores (HHS), and complications (nonunion, femoral head necrosis, femoral neck shortening, and failure of fixation) of the two groups were recorded to compare at 12-month follow-up. RESULTS: The mean follow-up time of included patients was 13.4 ± 1.6 months in the TCLS group and 13.7 ± 0.9 months in the OCS group. There was no statistically significant difference in the baseline data as well as perioperative outcomes, including operative time, intra-operative blood loss, the hemoglobin difference before and after treatment, quality of reduction, and hospital time between two groups. Likewise, the VAS score, the EQ-5D score, and complications rates including nonunion and femoral head necrosis had no distinct difference in two groups. However, HHS in the TCLS group were superior to those in the OCS group at 12-month follow-up, and the femoral neck shortening rate was prominently reduced in the TCLS group when compared with the OCS group. CONCLUSIONS: Treating vertical femoral neck fractures with the TCLS technique could significantly improve hip functional recovery and reduce the postoperative femoral neck shortening rate. The present study provides novel insight for the treatment of vertical femoral neck fractures.
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Parafusos Ósseos , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas/instrumentação , Adulto , Perda Sanguínea Cirúrgica , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Medição da Dor , Inquéritos e Questionários , Adulto JovemRESUMO
PURPOSE: For the parallel external fixator, there are some defects, such as uneven distraction rate, unbearable pain and uncontrollable movement trajectory in practical clinical applications. In order to solve the problems, a new deformity correction algorithm, which is used to calculate the elongation of the six struts, is developed. Meanwhile, the corresponding computer software for getting the electronic prescription is developed. METHODS: First, the trajectory of the moving bone is planned by Cartesian coordinate path control. Next, the prescription is obtained from the trajectory by the inverse pose solution algorithm. Finally, the genetic algorithm is utilized to optimize the achieved prescription. From the year of 2015 to 2018, twenty-three patients with complicated tibia deformity are treated by using parallel external fixator and the developed computer software. All patients have standing, patella-forward, full-length post-operative AP and lateral radiographs of the lower limbs with the complete proximal ring for getting the deformity parameters and frame parameters. These parameters are input into the computer software to calculate a daily prescription schedule for strut adjustment. Radiographs are taken regularly to determine the effects of recovery during the correction process. RESULTS: The mean time of follow-up is 18 months (range 11-40 months). All patients reach the requirements for deformity correction, and their symptoms and appearance are improved significantly. No cases of wound infections or complications occur, and no severe pain came as well during the correction process. CONCLUSIONS: By using the computer-aided parallel external fixator for the correction of lower limb deformities, satisfactory outcomes can be achieved. Hence, this method greatly improved the treatment of these patients in a clinical application.
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Algoritmos , Prescrição Eletrônica/normas , Fixadores Externos , Fêmur/cirurgia , Desigualdade de Membros Inferiores/cirurgia , Procedimentos Ortopédicos/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Fêmur/anormalidades , Fêmur/diagnóstico por imagem , Seguimentos , Humanos , Desigualdade de Membros Inferiores/diagnóstico , Masculino , Pessoa de Meia-Idade , Radiografia , Software , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Human sacum is regulatory adaptor protein involved in cellular signaling network of colorectal cancer. Molecular evidences suggest that the protein is integrated into oncogenic signaling network by binding to SH3-containing proteins through its proline-rich motifs. In this study, we have performed a transcriptome-wide analysis and identification of sacum-binding partners in the genome profile of human colorectal cancer. The sacum-binding potency of SH3-containing proteins found in colorectal cancer was investigated by using bioinformatics modeling and intermolecular binding analysis. With the protocol we were able to predict those high-affinity domain binders of the proline-rich peptides of human sacum in a high-throughput manner, and to analyze sequence-specific interaction in the domain-peptide recognition at molecular level. Consequently, a number of putative domain binders with both high affinity and specificity were identified, from which the Src SH3 domain was selected as a case study and tested for its binding activity towards the sacum peptides. We also designed two peptide variants that may have potent capability to competitively disrupt sacum interaction with its partners.
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Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais/genética , Transcriptoma , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Colorretais/metabolismo , Humanos , Ligação de Hidrogênio , Modelos Moleculares , Peptídeos/química , Peptídeos/metabolismo , Ligação Proteica , Transdução de Sinais , Relação Estrutura-Atividade , Domínios de Homologia de srcRESUMO
OBJECTIVE: This meta-analysis aimed to evaluate the safety and efficacy of aminocaproic acid in total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: The electronic databases include PubMed, Medline, Embase, Web of Science and the Cochrane Library from inception to January, 2018. Two reviewers abstracted total blood loss, hemoglobin drop, transfusion requirements, and postoperative complications. Data were using fixed-effects or random-effects models with weighted mean differences and risk difference for continuous and dichotomous variables, respectively. STATA 14.0 was used to perform the meta-analysis. RESULTS: Six studies encompassing 756 participants were retrieved for this meta-analysis. Our study indicated that intravenous aminocaproic acid was associated with a significantly reduction in total blood loss, hemoglobin drop and need for transfusion. Additionally, no increased risk of thromboembolic events were identified. CONCLUSION: Based on the present meta-analysis, intravenous aminocaproic acid is effective and safe in total knee and hip arthroplasty without increasing the incidence of thromboembolic events. Further studies should focus on the comparison of aminocaproic acid and TXA in arthroplasties.
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Ácido Aminocaproico/uso terapêutico , Antifibrinolíticos/uso terapêutico , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Administração Intravenosa , Ácido Aminocaproico/efeitos adversos , Antifibrinolíticos/efeitos adversos , Transfusão de Sangue/estatística & dados numéricos , Feminino , Hemoglobinas/análise , Humanos , Masculino , Resultado do TratamentoRESUMO
Human sacum is regulatory adaptor protein involved in cellular signaling network of colorectal cancer. Molecular evidence suggests that the protein is integrated into oncogenic signaling network by binding to SH3-containing proteins through its proline-rich motifs. In this study, we have performed a transcriptome-wide analysis and identification of sacum-binding partners in the genome profile of human colorectal cancer. The sacum-binding potency of SH3-containing proteins found in colorectal cancer was investigated by using bioinformatics modeling and intermolecular binding analysis. With the protocol we were able to predict those high-affinity domain binders of the proline-rich peptides of human sacum in a high-throughput manner, and to analyze sequence-specific interaction in the domain-peptide recognition at molecular level. Consequently, a number of putative domain binders with both high affinity and specificity were identified, from which the Src SH3 domain was selected as a case study and tested for its binding activity towards the sacum peptides. We also designed two peptide variants that may have potent capability to competitively disrupt sacum interaction with its partners.
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The purpose of this article is to evaluate the efficacy and feasibility of preoperative surgery with 3D printing-assisted internal fixation of complicated acetabular fractures. A retrospective case review was performed for the above surgical procedure. A 23-year-old man was confirmed by radiological examination to have fractures of multiple ribs, with hemopneumothorax and communicated fractures of the left acetabulum. According to the Letounel and Judet classification, T-shaped fracture involving posterior wall was diagnosed. A 3D printing pelvic model was established using CT digital imaging and communications in medicine (DICOM) data preoperatively, with which surgical procedures were simulated in preoperative surgery to confirm the sequence of the reduction and fixation as well as the position and length of the implants. Open reduction with internal fixation (ORIF) of the acetabular fracture using modified ilioinguinal and Kocher-Langenbeck approaches was performed 25 days after injury. Plates that had been pre-bent in the preoperative surgery were positioned and screws were tightened in the directions determined in the preoperative planning following satisfactory reduction. The duration of the operation was 170 min and blood loss was 900 mL. Postoperative X-rays showed that anatomical reduction of the acetabulum was achieved and the hip joint was congruous. The position and length of the implants were not different when compared with those in preoperative surgery on 3D printing models. We believe that preoperative surgery using 3D printing models is beneficial for confirming the reduction and fixation sequence, determining the reduction quality, shortening the operative time, minimizing preoperative difficulties, and predicting the prognosis for complicated fractures of acetabulam.