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OBJECTIVES: As 2 novel peripheral nerve blocks, the erector spinae plane block (ESPB) and thoracolumbar interfascial plane (TLIP) block can relieve postoperative pain in spinal surgery. This systematic review and meta-analysis aimed to determine the efficacy and safety of ESPB versus TLIP block in patients undergoing spine surgery. METHODS: An extensive search of English online databases, including PubMed, Web of Sciences, Embase, Medline, and Cochrane Central Register of Controlled Trials, and Chinese online databases like Wanfang Data, CNKI, and CQVIP until March 31, 2023, with no language restrictions, was performed. This systematic review and meta-analysis are based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and have been registered on PROSPERO (International Prospective Register of Systematic Reviews) with registered ID: CRD42023420987. RESULTS: Five studies involving 457 patients were eligible for inclusion in this study. Compared with TLIP block, ESPB had lower postoperative opioid consumption at postoperative 48 hours (standard mean difference =-1.31, 95% CI:-2.54 to -0.08, P =0.04, I2 =80%) and postoperative pain score at postoperative 24 hours (standard mean difference =-0.72, 95% CI=-1.43 to -0.02, P =0.04, I2 =95%) in patients undergoing spine surgery. Complications associated with ESPB and TLIP block were not reported in the included studies. DISCUSSION: ESPB and TLIP block are 2 novel and effective block methods. Patients receiving ESPB had lower postoperative opioid consumption and postoperative pain scores compared with patients receiving TLIP block; there was no statistically significant difference's between the 2 groups in intraoperative opioid consumption, adverse events, and rescue analgesia.
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Bloqueio Nervoso , Humanos , Analgésicos Opioides , Dor Pós-Operatória/tratamento farmacológicoRESUMO
BACKGROUND: Intervertebral disc degeneration (IDD) is a main contributor to low back pain. Oxidative stress, which is highly associated with the progression of IDD, increases senescence of nucleus pulposus-derived mesenchymal stem cells (NPMSCs) and weakens the differentiation ability of NPMSCs in degenerated intervertebral discs (IVDs). Quercetin (Que) has been demonstrated to reduce oxidative stress in diverse degenerative diseases. AIM: To investigate the role of Que in oxidative stress-induced NPMSC damage and to elucidate the underlying mechanism. METHODS: In vitro, NPMSCs were isolated from rat tails. Senescence-associated ß-galactosidase (SA-ß-Gal) staining, cell cycle, reactive oxygen species (ROS), real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, and western blot analyses were used to evaluated the protective effects of Que. Meanwhile the relationship between miR-34a-5p and Sirtuins 1 (SIRT1) was evaluated by dual-luciferase reporter assay. To explore whether Que modulates tert-butyl hydroperoxide (TBHP)-induced senescence of NPMSCs via the miR-34a-5p/SIRT1 pathway, we used adenovirus vectors to overexpress and downregulate the expression of miR-34a-5p and used SIRT1 siRNA to knockdown SIRT1 expression. In vivo, a puncture-induced rat IDD model was constructed, and X rays and histological analysis were used to assess whether Que could alleviate IDD in vivo. RESULTS: We found that TBHP can cause NPMSCs senescence changes, such as reduced cell proliferation ability, increased SA-ß-Gal activity, cell cycle arrest, the accumulation of ROS, and increased expression of senescence-related proteins. While abovementioned senescence indicators were significantly alleviated by Que treatment. Que decreased the expression levels of senescence-related proteins (p16, p21, and p53) and senescence-associated secreted phenotype (SASP), including IL-1ß, IL-6, and MMP-13, and it increased the expression of SIRT1. In addition, the protective effects of Que on cell senescence were partially reversed by miR-34a-5p overexpression and SIRT1 knockdown. In vivo, X-ray, and histological analyses indicated that Que alleviated IDD in a puncture-induced rat model. CONCLUSION: In summary, the present study provides evidence that Que reduces oxidative stress-induced senescence of NPMSCs via the miR-34a/SIRT1 signaling pathway, suggesting that Que may be a potential agent for the treatment of IDD.
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Background: The mechanisms underlying M2 macrophage polarization induced by nucleus pulposus (NP) cells are unclear. The effects that M2-polarized macrophages have on NP cells are also controversial. Methods: Transcriptome sequencing was performed to detect the gene change profiles between NP cells from ruptured intervertebral disc (IVD) and normal IVD. The main difference on biological activities between the two cell groups were analyzed by GO analysis and KEGG analysis. Virus transduction, flow cytometry, immunofluorescence, RT-PCR, western blot, CCK-8, TUNEL staining, and AO/EB staining were performed to explore the interactions between NP cells and RAW264.7 macrophages. Statistics were performed using SPSS26. Results: 801 upregulated and 276 downregulated genes were identified in NP cells from ruptured IVD in mouse models. According to GO and KEGG analysis, we found that the differentially expressed genes (DEG) were dominantly enriched in inflammatory response, extracellular matrix degradation, blood vessel morphogenesis, immune effector process, ossification, chemokine signaling pathway, macrophage activation, etc. CX3CL1 was one of the top 20% DEG, and we confirmed that both NP tissue and cells expressed remarkably higher level of CX3CL1 in mouse models (p < 0.001∗). Besides, we further revealed that both the recombinant CX3CL1 and NP cells remarkably induced M2 polarization of RAW264.7 (p < 0.001∗), respectively, while this effect was significantly reversed by si-CX3CL1 or JMS-17-2 (p < 0.001∗). Furthermore, we found that M2 macrophages significantly decreased the apoptosis rate (p < 0.001∗) and the catabolic gene levels (p < 0.001∗) of NP cells, while increased the viability, proliferation as well as the anabolic gene levels of NP cells (p < 0.01∗). Conclusions: Via regulating CX3CL1/CX3CR1 pathway, NP cells can induce the M2 macrophage polarization. M2 polarized macrophages can further promote NP cell viability, proliferation, and anabolism, while inhibit NP cell apoptosis and catabolism.
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The oral absorption of exenatide, a type 2 diabetes medication, can be increased by employing lipid nanocapsules (LNC). To increase mucus permeability and exenatide intestinal absorption, reverse micelle lipid nanocapsules (RM-LNC) were prepared and their surface was modified with DSPE-PEG-FA. The RM-LNC with surface modification of DSPE-PEG-FA (FA-RM-LNC) were able to target enterocytes and reduce mucus aggregation in the intestine. Furthermore, in vitro absorption at different intestinal sites and flip-flop intestinal loop experiments revealed that LNCs with surface modification significantly increased their absorption efficiency in the small intestine. FA-RM-LNC delivers more drugs into Caco-2 cells via caveolin-, macrophagocytosis-, and lipid raft-mediated endocytosis. Additionally, the enhanced transport capacity of FA-RM-LNC was observed in a study of monolayer transport in Caco-2 cells. The oral administration of exenatide FA-RM-LNC resulted in a prolonged duration of hypoglycemia in diabetic mice and a relative bioavailability (BR) of up to 7.5% in rats. In conclusion, FA-RM-LNC can target enterocytes and has promising potential as a nanocarrier for the oral delivery of peptides.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Nanocápsulas , Sistemas de Liberação de Fármacos por Nanopartículas , Animais , Humanos , Camundongos , Ratos , Células CACO-2 , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Exenatida , Ácido Fólico , Intestinos , Lipídeos , Micelas , PeptídeosRESUMO
The development of oral drug delivery systems is challenging, and issues related to the mucus layer and low intestinal epithelial permeability have not yet been surmounted. The purpose of this study was to develop a promising formulation that is more adapted to in vivo absorption and to facilitate the administration of oral liraglutide. Cationic liposomes (CLs) linked to AT-1002 were prepared using a double-emulsion method, and BSA was adsorbed on the surface of the AT-CLs, resulting in protein corona cationic liposomes with AT-1002 (Pc-AT-CLs). The preparation method was determined by investigating various process parameters. The particle size, potential, and encapsulation efficiency (EE%) of the Pc-AT-CLs were 202.9 ± 12.4 nm, 1.76 ± 4.87 mV, and 84.63 ± 5.05%, respectively. The transmission electron microscopy (TEM) imaging revealed a nearly spherical structure of the Pc-AT-CLs, with a recognizable coating. The circular dichroism experiments confirmed that the complex preparation process did not affect the secondary structure of liraglutide. With the addition of BSA and AT-1002, the mucosal accumulation of the Pc-AT-CLs was nearly two times lower than that of the AT-CLs, and the degree of enteric metaplasia was 1.35 times higher than that of the PcCLs. The duration of the intestinal absorption of the Pc-AT-CLs was longer, offering remarkable biological safety.
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BACKGROUND: Chronic neck pain is a common musculoskeletal disorder. Previous studies have found that chronic neck pain is associated with changes in neck muscle morphology and fat infiltration (FI). This systematic review summarizes and analyzes all studies on neck muscle morphology in patients with chronic nonspecific neck pain (CNNP). The main objective of this study was to review and analyze measurements of neck muscles in all patients with CNNP, including morphologic changes in the multifidus muscle (MF), longus colli muscle (LC), and semis-spinalis capitis muscle (SCa) in patients with CNNP compared with controls. METHODS: This was a systematic review with meta-analysis A comprehensive search of online databases, including PubMed, Web of Sciences, Embase, and Medline was conducted to identify relevant studies reporting changes in neck muscle morphology in patients with chronic neck pain versus healthy controls. Search scope was from inception to June 30, 2022, with no language restrictions. Two reviewers participated in the screening process independently. Due to the lack of relevant data from other studies, only studies that reported morphologic changes of MF, LC, and SCa in patients with CNNP, including muscle cross-sectional area (CSA), lateral diameter (LD), and anteroposterior diameter (APD), were selected. A modified Newcastle-Ottawa scale was used to assess study quality and risk of bias. A total of 11 studies were included based on inclusion and exclusion criteria, of which 8 were included in the meta-analysis. RESULTS: The results showed that the CSA of LC was slightly smaller in patients with CNNP (mean difference-0.23, 95% confidence interval -0.37 to -0.08), and the multiplied linear dimensions (multiplied linear dimensions: lateral diameter × anteroposterior diameter) of SCa was slightly smaller (mean difference -0.19, 95% confidence interval -0.34 to -0.03). There was no difference in MF muscle size between Patients with CNNP and healthy controls. CONCLUSIONS: LC and SCa sizes were slightly smaller in patients with CNNP; there was no difference in MF muscle size between the 2 groups. In addition, no conclusions could be drawn in fat infiltration due to insufficient evidence. In summary, CNNP has influence on neck muscle morphology but the evidence is limited.
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Dor Crônica , Cervicalgia , Humanos , Vértebras Cervicais/diagnóstico por imagem , Músculos do Pescoço , PescoçoRESUMO
BACKGROUND: Posterior internal fixation (PIF) is commonly used in the treatment of thoracolumbar fracture (TLF), but there is still no standard for the number of fixed segments. The objective of this meta-analysis was to evaluate the efficacy and safety of short segment (SS), intermediate segment (IS) and long segment (LS) in the fixation of TLF. METHODS: Two authors independently searched through PubMed, Embase, Cochrane Library and Web of Science for studies of thoracolumbar fracture treated by posterior internal fixation, which were published until the end of April 2021. The Aggregate Data Drug Information System (ADDIS) software was used for data evaluation according to the Markov chain Monte Carlo (MCMC) method based on the Bayesian theorem. RESULTS: Nineteen trials evaluating a total of 970 patients were enrolled in these studies, of which 340 in the SS group, 429 in the IS group and 201 in the LS group. For anterior vertebral height ratio (AVHR), IS had the highest AVHR, LS had the second highest AVHR. IS also ranked first in reducing visual analogue scale (VAS), SS ranked second. For sagittal Cobb's angle (SCA), LS had the lowest SCA and IS had the second lowest SCA. In terms of adverse events, IS had the lowest implant failure rate and LS had the second lowest implant failure rate. CONCLUSIONS: IS may be the most desirable treatment option for TLF in reducing SCA, implant failure rate, VAS, and improving AVHR. However, more randomized controlled trials are needed to verify these results.
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Fraturas Ósseas , Parafusos Pediculares , Fraturas da Coluna Vertebral , Teorema de Bayes , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/etiologia , Humanos , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Metanálise em Rede , Estudos Retrospectivos , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia , Resultado do TratamentoRESUMO
Oral drug delivery to treat diabetes is being increasingly researched. The mucus and the epithelial cell layers hinder drug delivery. We designed a self-ablating nanoparticle to achieve smart oral delivery to overcome the gastrointestinal barrier. We used the zwitterionic dilauroyl phosphatidylcholine, which exhibits a high affinity toward Oligopeptide transporter 1, to modify poly(lactic-co-glycolic acid) nanoparticles and load hemagglutinin-2 peptide to facilitate its escape from lysosomes. Nanoparticles exhibit a core-shell structure, the lipid layer is degraded by the lysosomes when the nanoparticles are captured by lysosomes, then the inner core of the nanoparticles gets exposed. The results revealed that the self-ablating nanoparticles exhibited higher encapsulation ability than the self-assembled nanoparticles (77% vs 64%) and with better stability. Quantitative cellular uptake, cellular uptake mechanisms, and trans-monolayer cellular were studied, and the results revealed that the cellular uptake achieved using the self-ablating nanoparticles was higher than self-assembling nanoparticles, and the number of uptake pathways via which the self-ablating nanoparticles functioned were higher than the self-assembling nanoparticles. Intestinal mucus permeation, in vivo intestinal circulation, was studied, and the results revealed that the small self-assembling nanoparticles exhibit a good extent of intestinal uptake in the presence of mucus. In vitro flip-flop, intestinal circulation revealed that the uptake of the self-ablating nanoparticles was 1.20 times higher than the self-assembled nanoparticles. Pharmacokinetic study and the pharmacodynamic study showed that the bioavailability and hypoglycemic effect of self-ablating nanoparticles were better than self-assembled nanoparticles.
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Hipoglicemiantes/farmacologia , Liraglutida/farmacologia , Sistemas de Liberação de Fármacos por Nanopartículas/química , Animais , Transporte Biológico , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Absorção Intestinal/efeitos dos fármacos , Absorção Intestinal/fisiologia , Lipídeos/química , Liraglutida/administração & dosagem , Liraglutida/farmacocinética , Muco/efeitos dos fármacos , Tamanho da Partícula , Fosfatidilcolinas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Propriedades de SuperfícieRESUMO
OBJECTIVE: The ideal management of thoracolumbar burst fracture (TLBF) remains controversial. We conducted this study to compare the effectiveness and safety of trans-Kambin triangle versus transpedicular bone grafting combined with posterior internal fixation (PIF) for TLBF. METHODS: Fifty-four patients were retrospectively analyzed and divided into 2 groups: the observation group (PIF combined with bone grafting via the Kambin triangle, n = 28) and the control group (PIF combined with bone grafting via transpedicular, n = 26). The anterior vertebral height ratio, sagittal Cobb angle, visual analog scale score, Oswestry Disability Index, bone healing rate, and neurologic complications were measured. RESULTS: All patients were followed up regularly for a mean period of 17.94 months (12 - 24 months). The anterior vertebral height ratio in the observation group was higher than that in the control group (93.93 ± 2.92 vs. 89.90 ± 5.54%, P = 0.006), and the loss of correction was lower (1.59 ± 1.20 vs. 3.00 ± 1.98%, P = 0.008). The observation group had lower sagittal Cobb angle at final follow-up (8.68 ± 3.75 vs. 11.33 ± 4.77 degrees, P = 0.046) and less correction loss (1.96 ± 1.32 ± 1.15 vs. 3.90 ± 2.39 degrees, P = 0.002). The visual analog scale score and Oswestry Disability Index in the observation group were lower (0.61 ± 0.43 vs. 0.92 ± 0.38, P = 0.016; 15.86 ± 4.11 vs. 19.18 ± 4.04, P = 0.010), while the fracture healing rate showed no significant difference (P > 0.05). No internal fixation failure or neurologic complications occurred in both groups during the follow-up. CONCLUSIONS: Bone grafting via the Kambin triangle combined with PIF is a safe and effective technology for thoracolumbar burst fracture.
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Transplante Ósseo/tendências , Fixação Interna de Fraturas/tendências , Vértebras Lombares/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/cirurgia , Adulto , Transplante Ósseo/métodos , Terapia Combinada/métodos , Terapia Combinada/tendências , Feminino , Seguimentos , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/lesões , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the efficacy and safety of tranexamic acid (TXA) for single-segment thoracolumbar burst fracture without neurologic injury underwent pedicle screw fixation via Wiltse approach. PATIENTS AND METHODS: We identified 264 patients with single-segment thoracolumbar burst fracture without neurologic injury underwent pedicle screw fixation via Wiltse approach (January 2016-June 2019) at a single center. The cohort was separated into three groups. Group A received 20 mg/kg TXA at 5 min before skin incision and 16 h after first dose; Group B received 20 mg/kg TXA at 5 min before skin incision; Group C received NS at each same time point. The outcomes were evaluated by hidden blood loss (HBL), total blood loss (TBL), intraoperative blood loss (IBL), transfusion rate, maximum hemoglobin (Hb) drop, prethrombotic state molecular markers, liver and renal function, coagulation function, inflammatory factor and adverse events. RESULTS: The HBL, TBL and maximum Hb drop were significantly lower in Group A than those of Group B and Group C, while the difference between Group B and Group C was statistically significant. The IBL was significantly lower in Group A and Group B than that of Group C. However, there was no significantly difference among the three groups in live and renal function, coagulation function, prethrombotic state molecular markers, transfusion rate and complications during the perioperative period. There was significantly lower level of interleukin-6 (IL-6) in Group A than Group C at the day after surgery, and lower level of C-reactive protein (CRP) at the third day after surgery. CONCLUSIONS: Intravenous TXA used in the treatment of thoracolumbar burst fracture underwent pedicle screw fixation via Wiltse approach is effective and safe in decreasing perioperative blood loss. The two-dose TXA regimen can further reduce blood loss and alleviate post-operative inflammation response, without affecting prethrombotic state molecular marks and without increasing the risk of complications.
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Antifibrinolíticos/uso terapêutico , Perda Sanguínea Cirúrgica/prevenção & controle , Fixação Interna de Fraturas/métodos , Procedimentos Neurocirúrgicos/métodos , Fraturas da Coluna Vertebral/cirurgia , Ácido Tranexâmico/uso terapêutico , Administração Intravenosa , Adulto , Antifibrinolíticos/efeitos adversos , Transfusão de Sangue , Proteína C-Reativa/análise , Estudos de Coortes , Feminino , Hemoglobinas/análise , Humanos , Interleucina-6/sangue , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Parafusos Pediculares , Estudos Retrospectivos , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia , Ácido Tranexâmico/efeitos adversosRESUMO
Physical education professionals aim to develop quality programmes for physical education. This study aimed to develop and validate a scale using professionals' perceptions of Quality Physical Education QPE in Asia using twenty-four items regarding QPE quality issues. The items covered status and roles, development of educational elements and supportive features in physical education. A sample of N = 799 sport and physical education professionals from eleven Asian cities participated in this questionnaire survey. Twenty-four items relating to QPE were examined via exploratory factor analysis (EFA) using maximum likelihood extraction and direct oblimin rotation methods. Nevertheless, only 20 items were extracted following the EFA examination. Items 1, 9, 14 and 18 were excluded because of low factor loadings. The remaining items were clustered into four subscales: Development and Supportive Elements for Quality Physical Education in Schools (DSFQPE; α = .918), Core Values of Quality Physical Education (CVPE; α = .908), Curriculum Arrangement of Physical Activities (CAPA; α = .884) and Provision and Norms in Physical Education (PNPE; α = .865). The Cronbach's alpha coefficient (α = .875) indicated excellent internal consistency for the overall measure. Furthermore, the 4 retained factors from the EFA were assessed via robust confirmatory factor analysis (CFA). The 4-factor model demonstrated a good fit with the data (CMIN/DF = 3.450, CFI = .928, TLI = .916, PCFI = .801, RMSEA = .078). The study identified a 4-factor structure with internal consistency and acceptable interfactor correlations. The structure seemed to be applicable, including the twenty items identified as useful and necessary tools for the framework of analysis in the investigation of diverse settings for the study of quality physical education.
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Educação Profissionalizante/normas , Educação Física e Treinamento/métodos , Professores Escolares/psicologia , Instituições Acadêmicas/normas , Análise Fatorial , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Vertebroplasty is the most widely used method for treating osteoporotic vertebral compression fractures (OVCF). During this procedure, bone cement is injected into the vertebral body. Fracture and additional fractures can occur adjacent to the treatment site. Thus, we studied factors causing such vertebral fractures after vertebroplasty and calculated the appropriate amount of bone cement to inject. METHODS: From September 2012 to March 2016, 187 patients with OVCF undergoing vertebroplasty were selected, and 112 patients with complete follow-up information were selected. Of these, 28 had adjacent vertebral fractures (refracture group) during the follow-up period, and 84 patients had no adjacent vertebral fractures (control group). Then, sex, age, body weight, bone mineral density (BMD), and bone cement injection (bone cement injection volume and bone fracture vertebral volume percent) were compared. RESULTS: All patients had significant pain relief within 24 h (preoperative and postoperative [24 h later] VAS scores were 7.4 ± 0.8 and 2.3 ± 0.5, respectively). The age and weight were not statistically significantly different (P > 0.05). BMD values were statistically significantly different between groups as was sex (P < 0.05). CONCLUSIONS: Bone cement injection volume, BMD values, and sex were statistically significantly related to adjacent vertebral fractures after vertebroplasty, and cement injection volumes exceeding 40.5% caused adjacent vertebral fractures.
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Cimentos Ósseos/efeitos adversos , Fraturas por Osteoporose/cirurgia , Complicações Pós-Operatórias/etiologia , Fraturas da Coluna Vertebral/cirurgia , Vertebroplastia/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Masculino , Fraturas por Osteoporose/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Fatores de Risco , Fatores Sexuais , Fraturas da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia , Resultado do Tratamento , Vertebroplastia/tendênciasRESUMO
BACKGROUND: Spinal cord and neuron injury result in loss of muscle function, sensation, or autonomic function in the body. Tet1 produces 5-hydroxymethylcytosin. The conversion was proposed as the initial step of deoxyribonucleic acid demethylation in mammals. However, effects of Tet1 expression and hydroxymethylation status on neuron injury remain unclear. Therefore the current study was designed to explore effects of Tet1 expression and hydroxymethylation status on cell survival and gene expression after neuron injury. METHODS: Mouse models of spinal cord injury and cell model of neuron injury were created. Animals were sacrificed, and injured spinal cord tissue was harvested. Neuron-like cells were cultured after scratch injury. Hydroxymethylated deoxyribonucleic acid concentration was detected, and Tet1 expression was examined by qPCR. Neuron-like cells were divided into 3 groups: control, injury, and azacytidine + injury (before injury, cells were pretreated with azacytidine) groups. Culture supernatant was collected, and lactate dehydrogenase concentration was detected. Meanwhile, injured neuron-like cells were divided into 3 groups: negative control, Tet1 overexpression, and Tet1 interference. Relative expression of Tet1, BDNF, NTF3, A20, FLIP, HSP70, HSP90, HSP27, and Bcl2 in neuron-like cells was detected by qPCR. In addition, neuron-like cells were divided into 7 groups. RESULTS: Tet1 expression and deoxyribonucleic acid hydroxymethylation increased initially and decreased thereafter after neuron injury in both animal and cell models. Percentages of dead cells increased significantly in neuron-like cells after injury. The percentages of dead cells markedly decreased in injured neuron-like cells that were pretreated with azacytidine. The percentages of dead cells increased markedly in the Tet1 interference group and decreased significantly in the Tet1 overexpression group. Expression of Tet1, BDNF, A20, FLIP, HSP70, HSP90, and Bcl2 decreased significantly after injury. Azacytidine pretreatment in injured neuron-like cells markedly increased expression of Tet1, BDNF, NTF3, A20, FLIP, HSP70, HSP90, HSP27, and Bcl2. Moreover, Tet1 interference significantly decreased the expression of Tet1, BDNF, A20, FLIP, HSP70, and HSP90 in neuron-like cells, whereas Tet1 overexpression markedly increased the expression of Tet1, BDNF, NTF3, A20, FLIP, HSP70, HSP90, HSP27, and Bcl2. BDNF interference significantly increased percentages of dead cells after injury. BDNF interference also markedly decreased the protection of azacytidine and Tet1 overexpression against cell death. CONCLUSIONS: Tet1 overexpression and demethylation caused by azacytidine protect neurons against cell death after injury by increasing expression of genes involved in cell survival.
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Morte Celular/genética , Sobrevivência Celular/genética , Metilação de DNA , Proteínas de Ligação a DNA/genética , Neurônios/metabolismo , Proteínas Proto-Oncogênicas/genética , Traumatismos da Medula Espinal/genética , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Camundongos , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Traumatismos da Medula Espinal/metabolismoRESUMO
OBJECTIVE: We compared the mid-term efficacy and safety of anterior cervical discectomy and fusion (ACDF) using a Zero-Profile device for cervical degenerative disc disease (CDDD) with and without osteoporosis. METHODS: We performed a retrospective study of elderly patients with CDDD treated by single-level ACDF with a Zero-Profile device. The patients were divided into group A (osteoporosis) and group B (no osteoporosis) according to the bone mineral density. The clinical outcomes (Japanese Orthopaedic Association, neck disability index, visual analog scale, and short-form 36 scores), radiological outcomes (cervical lordosis and fusion rate), and complications were reviewed at each follow-up examination. RESULTS: All procedures were successfully performed in all patients. The Japanese Orthopaedic Association, neck disability index, visual analog scale, and short-form 36 scores and cervical lordosis were significantly improved postoperatively in both groups (P < 0.05). However, no significant difference was found between the 2 groups at each follow-up point (P > 0.05). No significant difference was found in the fusion rate at 3 months postoperatively (group A, 88.9%; group B, 90.0%), dysphagia rate at 1 month postoperatively (group A, 11.1%; group B, 15.0%), or cage subsidence rate at the final follow-up visit (group A, 11.1%; group B, 10.0%; P > 0.05). All patients achieved solid fusion, and no patient had dysphagia at the final follow-up examination. CONCLUSIONS: ACDF with the Zero-Profile device can be used as an effective and reliable treatment for single-level CDDD with osteoporosis.
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Spinal cord injury (SCI) is a serious neurological disease, often leading to segmental injury following severe limb dysfunction. Recent studies showed that epigenetic regulation is involved in the pathogenesis of SCI. In this study, we examined the change in 5-hydroxymethylcytosine (5hmC), a mechanism of demethylation, and its role in SCI in rats. We found that global 5hmC modification significantly increased in traumatic spinal cord tissues. Ten-eleven translocation (Tet) enzymes are the limiting-rate enzyme to catalyze the conversion of 5-methylcytosine to 5hmC. In our study, the data indicated that Tet2, but not Tet1 and Tet3, significantly increased in traumatic spinal cord tissues. Further, we treated rats with SC-1, a Tet2 expression inhibitor. SC-1 increased necrotic volume after SCI. To further demonstrate that the damage caused by SC-1 was related to DNA 5hmC, we examined the messenger RNA (mRNA) expression of many genes that related to cell death and cell survival. Our data showed that the 5hmC levels were related to the mRNA levels of these genes. In conclusion, targeting Tet2 to cause change in 5hmC levels in cell death-related genes may be new therapeutic strategy for the treatment of SCI.
Assuntos
Metilação de DNA/genética , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Animais , Western Blotting , Dioxigenases/genética , Dioxigenases/metabolismo , Epigênese Genética/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RatosRESUMO
OBJECTIVE: Spinal cord injury (SCI) is a serious trauma without efficient treatment currently. Necroptosis can be blocked post injury by special inhibitors. This study is to investigate the effects, mechanism, and potential benefit of necrosulfonamide (NSA) for SCI therapy. METHODS: Pathologic condition was detected using hematoxylin-eosin staining on injured spinal cord and other major organs. Necroptosis-related factors-RIP1, RIP3, and MLKL-were detected using Western blot. Detections on mitochondrial functions such as adenosine triphosphate generation and activities of superoxide dismutase and caspase-3 were also performed. Finally, ethologic performance was detected using a 21-point open-field locomotion test. RESULTS: Reduced lesions and protected neurons were found in the injured spinal cord after treatment with NSA using hematoxylin-eosin staining for pathologic detection. No obvious toxicity on rat liver, kidney, heart, and spleen was detected. Rather than RIP1 and RIP3, MLKL was significantly inhibited by the NSA using Western blot detection. Adenosine triphosphate generation was obviously decreased post injury but slightly increased after the NSA treatment, especially 24 hours post injury. No significant changes were found on activities of superoxide dismutase and caspase-3 after the treatment of NSA. Ethologic performance was significantly improved using a 21-point, open-field locomotion test. CONCLUSIONS: Our research indicates NSA attenuates the spinal cord injury via necroptosis inhibition. It might be a potential and safe chemical benefit for SCI therapy. To our knowledge, this is the first study on the effects of NSA as treatment of traumatic SCI.
Assuntos
Acrilamidas/farmacologia , Acrilamidas/uso terapêutico , Apoptose/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Animais , Apoptose/fisiologia , Masculino , Necrose/tratamento farmacológico , Necrose/patologia , Ratos , Ratos Sprague-DawleyRESUMO
Results on the relationships between vitamin D receptor (VDR) gene polymorphisms and postmenopausal osteoporosis (PMOP) susceptibility and bone mineral density (BMD) are conflicting. The aim of the study is to identify more eligible studies that calculated pooled OR and WMD with 95% CI to assess their associations. Overall, there were significant correlations between VDR ApaI, VDR FokI and PMOP susceptibility. Subgroup analysis showed that VDR ApaI polymorphism significantly decreased the osteoporosis risk in Caucasian postmenopausal women. In Asian populations, VDR BsmI and VDR FokI were associated with an increased risk of PMOP. As to the associations between VDR polymorphisms and BMD, Caucasian PMOP women carrying the ApaI aa genotype were at risk of high BMD in femoral neck, and low femoral neck BMD was observed in Caucasian PMOP women with FokI Ff genotype. PMOP women with the Cdx2 GA genotype had a lower lumbar spine BMD in overall and Caucasian populations compared with PMOP women with GG genotype. Different VDR gene polymorphisms have different impacts on PMOP risk and BMD.
Assuntos
Predisposição Genética para Doença , Osteoporose Pós-Menopausa/genética , Polimorfismo de Fragmento de Restrição , Receptores de Calcitriol/genética , Povo Asiático , Densidade Óssea , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Desoxirribonucleases de Sítio Específico do Tipo II/química , Feminino , Expressão Gênica , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/etnologia , Osteoporose Pós-Menopausa/patologia , Pós-Menopausa/genética , Pós-Menopausa/metabolismo , Receptores de Calcitriol/metabolismo , População BrancaRESUMO
AIM: To compare the clinical outcome and complications between Zero-P implant and cage with anterior plate in patients undergoing anterior cervical discectomy and fusion (ACDF). MATERIAL AND METHODS: 50 patients underwent ACDF operation of which 23 patients had Zero-P implanted and 27 had cage and plate implanted. Preoperative and Post-operative clinical evaluation included Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI) score and Short form 36 (SF-36). Incidences of dysphagia-related symptoms were recorded. Plain radiographs were performed 2 days postoperatively and at follow-up to evaluate cervical prevertebral soft tissue, sagittal alignment, fusion rate and implant failure. RESULTS: In both groups, the JOA and SF-36 scores significantly increased, cervical sagittal alignment significantly corrected and the NDI score dropped compared to the preoperative at follow-up. All patients achieved solid fusion and no implant displacement was observed. The thickness of the prevertebral soft tissue at 2 days and 3 months postoperatively was lower in the Zero-P group. The incidence of dysphagia in the Zero-P group was significantly lower and the duration was much shorter. CONCLUSION: Zero-P used in ACDF could lead to similar clinical and radiographical outcomes compared with cage and plate, but with lower incidence and shorter duration of dysphagia.