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Sarcopenia is known as age-related muscle atrophy, which influences over a quarter of the elderly population worldwide. It is characterized by a progressive decline in muscle mass, strength, and performance. To date, clinical treatments in sarcopenia are limited to rehabilitative interventions and dietary supplements. Tetrahedral framework nucleic acids (tFNAs) represent a novel kind of DNA-based nanomaterial with superior antiapoptosis capacity in cells, tissues, organs, and systems. In our study, the therapeutic effect of tFNAs treatment on sarcopenia was evaluated both in vivo and in vitro. Results from muscular biophysiological characteristics demonstrated significant improvement in muscle function and endurance in the aged mouse model, and histologic examinations also showed beneficial morphological changes in muscle fibers. In vitro, DEX-induced sarcopenic myotube atrophy was also ameliorated through the inhibition of mitochondria-mediated cell apoptosis. Collectively, tFNAs treatment might serve as an alternative option to deal with sarcopenia in the near future.
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Ácidos Nucleicos , Sarcopenia , Humanos , Idoso , Camundongos , Animais , Sarcopenia/tratamento farmacológico , Sarcopenia/patologia , Ácidos Nucleicos/uso terapêutico , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/patologia , Apoptose , Mitocôndrias/patologiaRESUMO
Osteoarthritis (OA) is one of the main causes of disabilities among older people. To date, multiple disease-related molecular networks in OA have been identified, including abnormal mechanical loadings and local inflammation. These pathways have not, however, properly elucidated the mechanism of OA progression. Recently, sufficient evidence has suggested that rhythmic disturbances in the central nervous system (CNS) and local joint tissues affect the homeostasis of joint and can escalate pathological changes of OA. This is accompanied with an exacerbation of joint symptoms that interfere with the rhythm of CNS in reverse. Eventually, these processes aggravate OA progression. At present, the crosstalk between joint tissues and biological rhythm remains poorly understood. As such, the mechanisms of rhythm changes in joint tissues are worth study; in particular, research on the effect of rhythmic genes on metabolism and inflammation would facilitate the understanding of the natural rhythms of joint tissues and the OA pathology resulting from rhythm disturbance. Video Abstract.
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Cartilagem Articular , Osteoartrite , Idoso , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Humanos , Inflamação/metabolismo , Osteoartrite/metabolismoRESUMO
The pathophysiology behind the instigation and progression of scoliosis in Chiari malformation type I (CMI) patients has not been elucidated yet. This study aims to explore the initiating and progressive factors for scoliosis secondary to CMI. Pediatric patients with CMI were retrospectively reviewed for radiological characteristics of tonsillar herniation, craniocervical anomaly, syrinx morphology, and scoliosis. Subgroup analyses of the presence of syrinx, scoliosis, and curve progression were also performed. A total of 437 CMI patients were included in the study; 62% of the subjects had syrinx, and 25% had scoliosis. In the subgroup analysis of 272 CMI patients with syrinx, 78 of them (29%) had scoliosis, and multiple logistic regression analysis showed that tonsillar herniation ≥ 10 mm (OR 2.13; P = 0.033) and a clivus canal angle ≤ 130° (OR 1.98; P = 0.025) were independent risk factors for scoliosis. In the subgroup analysis of 165 CMI patients without syrinx, 31 of them (19%) had scoliosis, and multiple logistic regression analysis showed that a clivus canal angle ≤ 130° (OR 3.02; P = 0.029) was an independent risk factor for scoliosis. In the subgroup analysis of curve progression for 97 CMI patients with scoliosis, multiple logistic regression analysis showed that anomalies of the craniocervical junction and syrinx were not risk factors for curve progression. Many complex factors including craniocervical angulation, tonsillar herniation, and syrinx might participate in the instigation of scoliosis for CMI patients, and the relationship between craniocervical angulation and scoliosis deserves further study.
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Malformação de Arnold-Chiari , Escoliose , Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/epidemiologia , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Fatores de Risco , Escoliose/diagnóstico por imagem , Escoliose/epidemiologiaRESUMO
OBJECTIVES: Ipriflavone (IP) is one of the over-the-counter drugs and found in foods, which is available for prevention of osteoporosis (OP) since 1989 in over 22 countries. Although some clinical trials have suggested that IP is appropriate for treatment of OP, there continues to be controversy regarding the efficacy and safety due to some contradictory reports. With the wide usage of IP for osteoporotic women, there is a critical need for evaluation of the evidence for IP in clinical practice. METHODS AND MATERIALS: We searched randomized control trials (RCTs) in PubMed, CENTRAL and CNKI which used the regimen of IP in postmenopausal women with osteopenia or OP. The efficacy referred to the absolute change and relative change in bone mineral density (BMD) and bone turnover markers. The safety profiles were associated with adverse events and the number of subject withdrawals due to adverse reactions. RESULTS: Eleven RCTs (n = 1605) met the eligibility criteria were included. The increase of the BMD in lumbar spine of the IP group is greater than that of the placebo group (random effect model: SMD = 0.36; 95%CI= (0.09, 0.62)). For safety profile, most frequent reactions are gastrointestinal symptoms, but withdrawals due to adverse reactions are similar in both the IP group and placebo control at the same time intervals. CONCLUSIONS: IP significantly increases BMD and has inhibitory effect on bone resorption markers in postmenopausal women with osteopenia or OP. Gastrointestinal symptoms may occur, but adverse drug withdrawal events were not statistically increased when compared with placebo group.
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Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/tratamento farmacológico , Remodelação Óssea/efeitos dos fármacos , Isoflavonas/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Conservadores da Densidade Óssea/efeitos adversos , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/fisiopatologia , Feminino , Humanos , Isoflavonas/efeitos adversos , Osteoporose Pós-Menopausa/diagnóstico , Osteoporose Pós-Menopausa/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
The natural liver extracellular matrix (ECM) achieved by decellularization holds great potential in the fields of tissue engineering and regenerative medicine. Additionally, the use of crosslinking agents on the ECM to stabilize its ultrastructure and enhance scaffold durability is gaining interest in tissue engineering. The objective of this study was to compare the scaffold properties of porcine liver ECM crosslinked with different agents (glutaraldehyde, genipin, and quercetin) to find the best strategy for producing a decellularized matrix with optimal and stable characteristics for transplantation and regeneration. The properties examined include mechanical properties, material stability, immunogenicity, and angiogenic capacity. Scaffolds were implanted into the greater omentum of rats, and their abilities to induce immune cell subpopulation invasion and neovascularization were evaluated. The results show that genipin crosslinking of decellularized liver matrices increased the mechanical and proangiogenic properties and reduced the inflammatory response in vivo.
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Matriz Extracelular/efeitos dos fármacos , Iridoides/farmacologia , Fígado/efeitos dos fármacos , Transplante Heterólogo , Animais , Glutaral/farmacologia , Fígado/cirurgia , Masculino , Ratos , Suínos , Engenharia Tecidual , Alicerces Teciduais/efeitos adversosRESUMO
BACKGROUND: Muscle imbalance has long been recognized as one of the possible pathogeneses for adolescent idiopathic scoliosis (AIS). PIEZO2, the susceptibility gene of AIS, has been identified to play an important role in neuromuscular activities. OBJECTIVE: This study aims to compare the mRNA expression of PIEZO2 between concave and convex paraspinal muscles of AIS patients and to identify the relationship between the ratio of PIEZO2 expression and curve magnitude. METHODS: Twenty female AIS patients (right thoracic curve) who underwent spinal correction surgery were divided into moderate (n= 12) and severe (⩾ 70 degrees) curve groups (n= 8). The morphology of the paraspinal muscles was assessed with spinal MRI. Multifidus specimens were collected during surgical operations from the concave and convex sides of the apical region, and mRNA expression of the PIEZO2 gene was compared between sides. The localization of PIEZO2 protein expression was confirmed with the markers PAX7 and PAX3, and the percentage of PIEZO2+ cells was also investigated. RESULTS: In the moderate curve group, fatty infiltration in the deep paraspinal muscle was significantly higher on the concave side than on the convex side. There were no differences in deep muscle area, superficial muscle area, or fatty infiltration of superficial paraspinal muscle. The mRNA expression of PIEZO2 was significantly increased on the concave side, and the asymmetric expression predominantly occurred in moderate curves rather than severe ones. PIEZO2 was expressed on satellite cells instead of fibers of the muscle spindle. The percent of PIEZO2+PAX7+ cells in myofibers was significantly higher on the concave side in the moderate curve group, but not in the severe curve group. CONCLUSIONS: Asymmetric morphological changes occur in the deep paraspinal muscles of AIS. The PIEZO2 is asymmetrically expressed in the multifidus muscle and is preferentially expressed in satellite cells.
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Cifose , Escoliose , Humanos , Adolescente , Feminino , Escoliose/genética , Músculos Paraespinais/metabolismo , Coluna Vertebral , RNA Mensageiro/metabolismo , Canais Iônicos/genética , Canais Iônicos/metabolismoRESUMO
BACKGROUND CONTEXT: Cage subsidence is a common complication after lumbar interbody fusion surgery, with low bone mineral density (BMD) being a significant risk factor. ໿Endplate bone quality (EBQ) obtained from clinical MRI scans has been deemed reliable in determining regional BMD. However, the association between EBQ score and cage subsidence following oblique lumbar interbody fusion (OLIF) has not been clearly established. PURPOSE: This study aims to assess the relationship between EBQ score and cage subsidence in patients who underwent single-level OLIF. STUDY DESIGN/SETTING: A retrospective study. PATIENT SAMPLE: The study included adults with degenerative spinal conditions who underwent single-level OLIF at our institution. OUTCOME MEASURES: Cage subsidence, disc height, EBQ score, fusion rate. METHODS: This retrospective study analyzed data from patients who underwent single-level OLIF surgery at our institution between October 2017 and August 2022. Postoperative CT scans were used to measure cage subsidence, while the EBQ score was calculated using preoperative non-contrast T1-weighted MRI. To determine the predictive ability of the EBQ score, receiver operating characteristic (ROC) curve analysis was conducted. Additionally, univariable and multivariable logistic regression analyses were performed. RESULTS: In this study, a total of 88 patients were included and followed up for an average of 15.8 months. It was observed that 32.9% (n=29/88) of the patients experienced cage subsidence. The post-surgery disc height was significantly higher in patients who experienced subsidence compared to those who did not. The mean EBQ scores for patients with non-subsidence and subsidence were 2.31±0.6 and 3.48±1.2, respectively, and this difference was statistically significant. The ROC curve analysis showed that the AUC for the EBQ score was 0.811 (95% CI: 0.717-0.905). The most suitable threshold for the EBQ score was determined to be 2.318 (sensitivity: 93.1%, specificity: 55.9%). Additionally, the multivariate logistic regression analysis revealed a significant association between a higher EBQ score and an increased risk of subsidence (odds ratio [OR]=6.204, 95% CI=2.520-15.272, p<.001). CONCLUSIONS: Our findings indicate that higher preoperative EBQ scores are significantly linked to cage subsidence following single-level OLIF. Preoperative measurement of MRI can serve as a valuable tool in predicting cage subsidence.
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With the increase in human lifespan and the aggravation of global aging, the incidence of osteoarthritis (OA) is increasing annually. To better manage and control the progression of OA, prompt diagnosis and treatment for early-stage OA are important. However, a sensitive diagnostic modality and therapy for early OA have not been well developed. The exosome is a class of extracellular vesicles containing bioactive substances, that can be delivered directly from original cells to neighboring cells to modulate cellular activities through intercellular communication. In recent years, exosomes have been considered important in the early diagnosis and treatment of OA. Synovial fluid exosome and its encapsulated substances, e.g., microRNA, lncRNA, and proteins, can not only distinguish OA stages but also prevent the progression of OA by directly targeting cartilage or indirectly modulating the immune microenvironment in the joints. In this mini-review, we include recent studies on the diagnostic and therapeutic modalities of exosomes and hope to provide a new direction for the early diagnosis and treatment of OA disease in the future.
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BACKGROUND CONTEXT: Oblique lumbar interbody fusion (OLIF) has been proven to be effective in treating degenerative lumbar spinal stenosis (DLSS). Whether OLIF is suitable for treating patients with DLSS with osteoporosis (OP) is still controversial. Bone cement augmentation is widely used to enhance the internal fixation strength of osteoporotic spines. However, the effectiveness of OLIF combined with bone cement stress end plate augmentation (SEA) and anterolateral screw fixation (AF) for DLSS with OP have not confirmed yet. PURPOSE: To evaluate the clinical, radiological, and functional outcomes of OLIF-AF versus OLIF-AF-SEA in the treatment of DLSS with OP. STUDY DESIGN: Retrospective case-control study. PATIENT SAMPLE: A total of 60 patients with OP managed for DLSS at L4-L5. OUTCOME MEASURES: Visual analog scale (VAS) score of the lower back and leg, Oswestry Disability Index (ODI), disk height (DH), lumbar lordosis (LL), segmental lordosis (SL), cage subsidence and fusion rate. METHODS: The study was performed as a retrospective matched-pair caseâcontrolled study. Patients with OP managed for DLSS at L4-L5 between October 2017 and June 2020 and completed at least 2 years of follow-up were included, which were 30 patients treated by OLIF-AF and 30 patients undergoing OLIF-AF-SEA. The demographics and radiographic data, fusion status and functional outcomes were therefore compared to evaluate the efficacy of the two approaches. RESULTS: Pain and disability improved similarly in both groups at the 24-month follow-up. However, the SEA group had lower pain and functional disability at 3 months postoperatively (p<.05). The mean postoperative disc height decrease (â³DH) was significantly lower in the SEA group than in the control group (1.17±0.81 mm vs 2.89±2.03 mm; p<.001). There was no significant difference in lumbar lordosis (LL) or segmental lordosis (SL) between the groups preoperatively and 1 day postoperatively. However, a statistically significant difference was observed in SL and LL between the groups at 24 months postoperatively (p<.05). CS was observed in 4 cases (13.33%) in the SEA group and 17 cases (56.67%) in the control group (p<.001). A nonsignificant difference was observed in the fusion rate between the SEA and control groups (p=.347) at 24 months postoperatively. CONCLUSIONS: This study revealed that OLIF-AF-SEA was safe and effective in the treatment of DLSS with OP. Compared with OLIF-AF, OLIF-AF-SEA results in a minor postoperative disc height decrease, a lower rate of CS, better sagittal balance, and no adverse effect on interbody fusion.
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Lordose , Fusão Vertebral , Estenose Espinal , Humanos , Estudos de Casos e Controles , Estudos Retrospectivos , Lordose/etiologia , Estenose Espinal/complicações , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Cimentos Ósseos , Resultado do Tratamento , Parafusos Ósseos , Dor/etiologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Fusão Vertebral/efeitos adversosRESUMO
OBJECTIVE: Paravertebral muscle asymmetry may be involved in the pathogenesis of adolescent idiopathic scoliosis (AIS), and the Tent5a protein was recently identified as a novel active noncanonical poly(A) polymerase. We, therefore, explored the function of the AIS susceptibility gene Tent5a in myoblasts. MATERIALS AND METHODS: RNA-seq of AIS paravertebral muscle was performed, and the molecular differences in paravertebral muscle were investigated. Twenty-four AIS susceptibility genes were screened, and differential expression of Tent5a in paravertebral muscles was confirmed with qPCR and Western blot. After the knockdown of Tent5a, the functional effects of Tent5a on C2C12 cell proliferation, migration, and apoptosis were detected by Cell Counting Kit-8 assay, wound-healing assay, and TUNEL assay, respectively. Myogenic differentiation markers were tested with immunofluorescence and qPCR in vitro, and muscle fiber formation was compared in vivo. RESULTS: The AIS susceptibility gene Tent5a was differentially expressed in AIS paravertebral muscles. Tent5a knockdown inhibited the proliferation and migration of C2C12 cells and inhibited the maturation of type I muscle fibers in vitro and in vivo. Mechanistically, the expression of myogenin was decreased along with the suppression of Tent5a. CONCLUSIONS: Tent5a plays an important role in the proliferation and migration of myoblasts, and it regulates muscle fiber maturation by maintaining the stability of myogenin. Tent5a may be involved in the pathogenesis of AIS by regulating the formation of muscle fiber type I.
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Fibras Musculares Esqueléticas/metabolismo , Mioblastos/citologia , Miogenina/metabolismo , Polinucleotídeo Adenililtransferase/metabolismo , Adolescente , Diferenciação Celular/genética , Criança , Feminino , Expressão Gênica/fisiologia , Humanos , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/metabolismo , Miogenina/genética , RNA Mensageiro/metabolismo , Escoliose/genéticaRESUMO
BACKGROUND: Postoperative chylothorax is usually regarded as a complication associated with cardiothoracic surgery; however, it is one of the rare complications in orthopedic surgery. This case report describes a female patient who developed chylothorax after a successful L4-S1 transforaminal lumbar interbody fusion surgery. The etiology, diagnosis, and treatment were analyzed and discussed. CASE SUMMARY: A 50-year-old woman was admitted with repeated back and leg pain. She was diagnosed with L4 degenerative spondylolisthesis, L4/L5 and L5/S1 intervertebral disc herniation and L5 instability, and underwent successful posterior L4-S1 instrumentation and fusion surgery. Unfortunately, thoracic effusion was identified 2 d after operation. The thoracic effusion was finally confirmed to be chylous based on twice positive chyle qualitative tests. The patient was discharged after 12-d persisting drainage, 3-d total parenteral nutrition and fasting, and other supportive treatments. No recurring symptoms were observed within 12 mo follow-up. CONCLUSION: Differential diagnosis is crucial for unusual thoracic effusion. Comprehensive diagnosis and treatment of chylothorax are necessary. Thorough intraoperative protection to relieve high thoracic pressure caused by the prone position is important.
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BACKGROUND: The scoring of Ki-67 is highly relevant for the diagnosis, classification, prognosis, and treatment in breast invasive ductal carcinoma (IDC). Traditional scoring method of Ki-67 staining followed by manual counting, is time-consumption and inter-/intra observer variability, which may limit its clinical value. Although more and more algorithms and individual platforms have been developed for the assessment of Ki-67 stained images to improve its accuracy level, most of them lack of accurate registration of immunohistochemical (IHC) images and their matched hematoxylin-eosin (HE) images, or did not accurately labelled each positive and negative cell with Ki-67 staining based on whole tissue sections (WTS). In view of this, we introduce an accurate image registration method and an automatic identification and counting software of Ki-67 based on WTS by deep learning. METHODS: We marked 1017 breast IDC whole slide imaging (WSI), established a research workflow based on the (i) identification of IDC area, (ii) registration of HE and IHC slides from the same anatomical region, and (iii) counting of positive Ki-67 staining. RESULTS: The accuracy, sensitivity, and specificity levels of identifying breast IDC regions were 89.44, 85.05, and 95.23%, respectively, and the contiguous HE and Ki-67 stained slides perfectly registered. We counted and labelled each cell of 10 Ki-67 slides as standard for testing on WTS, the accuracy by automatic calculation of Ki-67 positive rate in attained IDC was 90.2%. In the human-machine competition of Ki-67 scoring, the average time of 1 slide was 2.3 min with 1 GPU by using this software, and the accuracy was 99.4%, which was over 90% of the results provided by participating doctors. CONCLUSIONS: Our study demonstrates the enormous potential of automated quantitative analysis of Ki-67 staining and HE images recognition and registration based on WTS, and the automated scoring of Ki67 can thus successfully address issues of consistency, reproducibility and accuracy. We will provide those labelled images as an open-free platform for researchers to assess the performance of computer algorithms for automated Ki-67 scoring on IHC stained slides.