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1.
Cell Death Dis ; 11(2): 103, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029706

RESUMO

N6 methyladenosine (m6A) is one of the most prevalent epitranscriptomic modifications of mRNAs, and plays a critical role in various bioprocesses. Bone-derived mesenchymal stem cells (BMSCs) can attenuate apoptosis of nucleus pulposus cells (NPCs) under compression; however, the underlying mechanisms are poorly understood. This study showed that the level of m6A mRNA modifications was decreased, and the autophagic flux was increased in NPCs under compression when they were cocultured with BMSCs. We report that under coculture conditions, RNA demethylase ALKBH5-mediated FIP200 mRNA demethylation enhanced autophagic flux and attenuated the apoptosis of NPCs under compression. Specific silencing of ALKBH5 results in impaired autophagic flux and a higher proportion of apoptotic NPCs under compression, even when cocultured with BMSCs. Mechanistically, we further identify that the m6A "reader" YTHDF2 is likely to be involved in the regulation of autophagy, and lower m6A levels in the coding region of FIP200 lead to a reduction in YTHDF2-mediated mRNA degradation of FIP200, a core molecular component of the ULK1 complex that participates in the initiating process of autophagy. Taken together, our study reveals the roles of ALKBH5-mediated FIP200 mRNA demethylation in enhancing autophagy and reducing apoptosis in NPCs when cocultured with BMSCs.

2.
Comput Methods Programs Biomed ; 189: 105352, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31991316

RESUMO

BACKGROUND AND OBJECTIVE: To compare the biomechanical changes of adjacent segment degeneration (ASD) after one- or two-level anterior cervical discectomy and fusion (ACDF) versus cervical disc arthroplasty (CDA). METHODS: A three-dimensional finite element (FE) model of intact C2-C7 segments was constructed and validated. In the one-level surgery model, the cage with plate implant or Prestige LP cervical disc prosthesis were integrated at C5-C6 segment into the FE model; while in the two-level surgery model, the prostheses were integrated at both C4-C5 and C5-C6 segments into the FE model. A pure moment of 1.0 Nm combined with a follower load of 73.6 N were imposed on C2 to investigate the flexion-extension, lateral bending, and axial rotation of different segments in the FE model. The segmental range of motion (ROM) and intradiscal pressure of the surgery models were investigated and compared with the intact model. RESULTS: In the one-level model of ACDF, the ROM at C5-C6 was decreased, the ROM and intradiscal pressure at C4-C5 and C6-C7 segments were increased. In the two-level model of ACDF, the ROM at C4-C5 and C5-C6 were decreased, the ROM and intradiscal pressure at C3-C4 and C6-C7 were increased. However, in both one- and two-level models of CDA, the ROM of surgery segments were preserved, avoiding the increase of the ROM and intradiscal pressure at the adjacent segments. CONCLUSIONS: Abnormal ROM and intradiscal pressure at the adjacent segments may contribute to the higher risk of ASD after ACDF compared with CDA.

3.
World Neurosurg ; 133: e84-e88, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31470152

RESUMO

BACKGROUND: Spinopelvic sagittal parameters have a significant influence on adjacent segment degeneration (ASD) after fusion surgery. The association between ASD and sagittal balance is not well understood. The purpose of this study was to investigate the biomechanical influence of various sacral slope (SS) degrees on adjacent segments after transforaminal lumbar interbody fusion (TLIF) at the L4-L5 level. METHODS: We conducted a finite element model of the L1-S1 based on computed tomography scan images. The L1-S1 model with L4-L5 TLIF was modified with various SS degrees (33°, 38°, 43°, and 48°) to investigate the biomechanical influence of SS on adjacent segments. The range of motion (ROM) and intradiscal pressure (IDP) of the adjacent segments (L3-L4 and L5-S1) were compared among models using various SS angles. RESULTS: When the SS angle increased, the ROM and IDP in L5-S1 decreased gradually after TLIF at the L4-L5 level in all motion patterns. Nevertheless, the ROM and IDP in L3-L4 were not significantly different among various SS angles. CONCLUSIONS: Decreased SS after lumbar fusion surgery may pose a higher risk of ASD. Therefore, restoring appropriate SS should be considered during decision-making prior to fusion surgery to reduce the risk of degenerative changes.


Assuntos
Vértebras Lombares/cirurgia , Sacro/diagnóstico por imagem , Fusão Vertebral/métodos , Antropometria , Fenômenos Biomecânicos , Análise de Elementos Finitos , Humanos , Disco Intervertebral/fisiopatologia , Vértebras Lombares/diagnóstico por imagem , Pressão , Amplitude de Movimento Articular , Sacro/patologia , Tomografia Computadorizada por Raios X
4.
J Cell Physiol ; 235(3): 2195-2208, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31478571

RESUMO

Intervertebral disc degeneration (IDD) is a complex and chronic disease that involves disc cell senescence, death, and extracellular matrix (ECM) degradation. HOTAIR, a long non-coding RNA (lncRNA) is reportedly associated with autophagy, whereas autophagy is shown to promote IDD. However, how it affects nucleus pulposus (NP) cells, the primary component of intervertebral discs is still unclear. We hypothesized that HOTAIR promotes NP cell apoptosis and senescence through upregulating autophagy. Thus, silencing HOTAIR should inhibit autophagy and exert a therapeutic effect on IDD. Our in vitro experiments in human NP cells revealed that HOTAIR expression positively correlated with IDD grade, and overexpression enhanced autophagy. Autophagy inhibition via 3-methyladenine reversed HOTAIR stimulatory effects on apoptosis, senescence, and ECM catabolism, while the AMP-activated protein kinase (AMPK) inhibitor Compound C suppressed HOTAIR-induced autophagy through regulating AMPK/mTOR/ULK1 pathways. Our in vivo experiment then illustrated that silencing HOTAIR ameliorates IDD in rats. Collectively, we demonstrated that HOTAIR stimulates autophagy to promote NP cell apoptosis, senescence, and ECM catabolism. Therefore, silencing HOTAIR has the potential to become a treatment option for IDD.

5.
J Int Med Res ; 47(6): 2746-2753, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31079513

RESUMO

OBJECTIVE: Spinal involvement of glomus tumors is extremely rare. We herein present a case of a spinal glomus tumor and reviewed the literature to identify the most effective surgical treatment of spinal glomus tumors. METHODS: A 48-year-old man presented with a huge paravertebral space-occupying lesion. In this report, we present the diagnostic process and surgical procedure in this case and review the literature of glomus tumors with spine involvement. RESULTS: We suspected a primary diagnosis of neurilemmoma based on the imaging results; however, the postoperative pathologic examination confirmed a glomus tumor. Considering the size of the tumor and involvement of surrounding areas, we performed complete tumor resection and unilateral fusion with pedicle screws at the T2 to T4 level. This unilateral approach with fixation was less invasive than the standard open posterior approaches that are used when one side of the spinal canal is intact without bony destruction. CONCLUSIONS: Surgical resection is a suitable treatment for most symptomatic glomus tumors. For most glomus tumors with spine involvement, total tumor resection with suitable internal fixation and fusion is recommended.


Assuntos
Tumor Glômico/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias Torácicas/cirurgia , Tumor Glômico/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Coluna Vertebral/patologia , Neoplasias Torácicas/patologia
6.
Indian J Orthop ; 53(2): 309-314, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30967702

RESUMO

Background: No standard preoperative preventive measure has been established to decrease the occurrence of C5 palsy after expansive open-door laminoplasty. The aim of this study is to establish a reliable measured parameter in predicting the risk of the postoperative C5 palsy. Materials and Methods: A total of 276 patients receiving posterior open-door laminoplasty for cervical spinal stenotic myelopathy were studied. The patients were divided into two groups according to the preoperative Pavlov ratio (Group A: Pavlov ratio <0.65 and Group B: Pavlov ratio ≥0.65). Correlations between the occurrence of postoperative C5 palsy and Pavlov ratio were analyzed, and Group A was further tested. The surgical procedures, clinical symptoms, and Pavlov ratio were described. Results: The patients with Pavlov ratio <0.65 had a higher risk of developing postoperative C5 palsy (P < 0.05, odds ratio [OR] = 2.91). No significant difference was found in gender, age, etiology, type of operation, and pre- and postoperative Japanese Orthopaedic Association scores between patients with and without postoperative C5 palsy. The cutoff (1.01) of receiver operating characteristic curve of the postoperative Pavlov ratio of the Group A was calculated. The postoperative Pavlov ratio ≥1.01 of the patients in Group A was a significant risk factor of the development of postoperative C5 palsy (P < 0.01, OR = 10.83). Conclusions: The preoperative Pavlov ratio <0.65 at the C5 level was more likely to develop the postoperative C5 palsy. When the preoperative Pavlov ratio is <0.65, the postoperative Pavlov ratio ≥1.01 at the C5 level is a reliable predictor for the development of postoperative C5 palsy. Pavlov ratio may be one of the reasons for postoperative C5 palsy.

7.
World Neurosurg ; 126: e819-e824, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30862579

RESUMO

OBJECTIVE: To analyze the biomechanical changes of lumbar adjacent segment by comparing the biomechanics after the surgery of transforaminal lumbar interbody fusion (TLIF) and oblique lumbar interbody fusion (OLIF). METHODS: The finite element model of the L1-S1 was reconstructed via computed tomography scan images. The models of TLIF and OLIF were constructed and analyzed. A 400-N vertical axial pre-load was imposed on the superior surface of L1 and a 10-N·m moment was applied on the L1 superior surface along the radial direction to simulate 4 different physiological motions: flexion, extension, bending, and torsion. The range of motion (ROM) and the intradiscal pressure (IDP) were evaluated and compared with investigate the biomechanical influences of TLIF and OLIF on the adjacent segments (L3-L4 and L5-S1). RESULTS: Compared with the normal model, TLIF and OLIF in all motion patterns increased the ROM and the IDP of adjacent segments. However, the ROM and the IDP between TLIF and OLIF had no significant difference. CONCLUSIONS: The biomechanical analysis showed that both TLIF and OLIF can increase ROM and IDP. It indicates that TLIF and OLIF probably increase the potential risk of adjacent segment degeneration similarly.


Assuntos
Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Adulto , Fenômenos Biomecânicos/fisiologia , Parafusos Ósseos , Análise de Elementos Finitos , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Modelos Anatômicos , Amplitude de Movimento Articular/fisiologia , Tomografia Computadorizada por Raios X
8.
J Int Med Res ; 47(3): 1365-1372, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30761926

RESUMO

This report describes a case of idiopathic cervical spinal subdural haematoma (SSDH) in which the haematoma was spontaneously absorbed without any treatment. A 68-year-old male patient presented with persistent neck pain and no obvious cause. Magnetic resonance imaging (MRI) revealed a space-occupying lesion at the C4-T1 levels. The lesion was initially misdiagnosed as a tumour. An operation was arranged to remove the tumour, but a preoperative computed tomography scan showed no obvious abnormal soft tissue density in the cervical spinal canal. Repeat enhanced MRI showed degeneration of the cervical vertebrae, but no obvious abnormal soft tissue density and no obvious enhanced signals in the cervical spinal canal. Spontaneous resolution of an idiopathic cervical SSDH was considered. Idiopathic cervical SSDH without obvious neurological symptoms are difficult to diagnose, so suspected cases should be carefully monitored. If the neurological symptoms grow progressively more debilitating with time, emergency surgery might need to be considered. To avoid unnecessary surgery, conservative management should be an option for patients with minimal neurological deficits and re-examination with MRI could be the best way to observe the dynamic changes taking place in the idiopathic cervical SSDH.


Assuntos
Vértebras Cervicais/patologia , Vértebras Cervicais/cirurgia , Hematoma Subdural Espinal/patologia , Hematoma Subdural Espinal/cirurgia , Idoso , Humanos , Imagem por Ressonância Magnética , Masculino , Prognóstico , Tomografia Computadorizada por Raios X
9.
Medicine (Baltimore) ; 96(19): e6837, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28489769

RESUMO

RATIONALE: Psoas abscesses generally arise from a contiguous intra-abdominal or pelvic infectious process or hematogenous spreading of bacteria. The serum ß-human chorionic gonadotropin has been used to detect normal or ectopic pregnancy. It also can be utilized in following up carcinomas. PATIENT CONCERNS: Here, we reported a case of a 47-year-old woman who presented with a left psoas mass presumptively diagnosed as an abscess secondary to lumbar tuberculosis In addition, the patient had abnormal increase of ß-human chorionic gonadotropin. The computed tomography (CT) scan and magnetic resonance imaging (MRI) showed that the 5th lumbar vertebral infection or tuberculosis with left psoas abscess. CT-guided percutaneous biopsy, surgical exploration and biopsy, and F-FDG (fluorodeoxyglucose) positron emission tomography-CT (PET-CT) were used to make a definite diagnosis. The sigmoidoscopy and biopsy were used to further diagnose. DIAGNOSES: The biopsy of left psoas demonstrated metastatic or infiltrating poorly differentiated carcinoma with secretion of ß-human chorionic gonadotropin. The subsequent pathological examination of neoplasm showed the same pathologic morphology. INTERVENTIONS: Appropriate treatment of infected retroperitoneal mass, systematic chemotherapy and cancer biotherapy for metastatic poorly differentiated carcinoma were taken. OUTCOMES: Interventions provided little help until the patient died of secondary infection and multiple organ failure. LESSONS: This case represents an extremely unusual clinical presentation of metastatic poorly differentiated carcinoma with secretion of ß-human chorionic gonadotropin presenting as a psoas abscess. Physicians also need to sharpen their awareness of the potential malignant carcinomas mimicking psoas abscess.


Assuntos
Carcinoma/diagnóstico , Carcinoma/metabolismo , Gonadotropina Coriônica Humana Subunidade beta/metabolismo , Abscesso do Psoas/diagnóstico , Neoplasias Retroperitoneais/diagnóstico , Neoplasias Retroperitoneais/metabolismo , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Abscesso do Psoas/etiologia , Abscesso do Psoas/patologia , Neoplasias Retroperitoneais/tratamento farmacológico , Neoplasias Retroperitoneais/patologia , Espaço Retroperitoneal/diagnóstico por imagem , Espaço Retroperitoneal/patologia , Espaço Retroperitoneal/cirurgia
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