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Most chemotherapeutic drugs are potent and have a very narrow range of dose safety and efficacy, most of which can cause many side effects. Chemotherapy-induced peripheral neuropathy (CIPN) is the most common and serious side effect of chemotherapy for cancer treatment. However, its mechanism of action is yet to be fully elucidated. In the present study, we found that the treatment of the chemotherapy drug elemene induced hyperalgesia accompanied by anxiety-like emotions in mice based on several pain behavioral assays, such as mechanical allodynia and thermal hyperalgesia tests. Second, immunostaining for c-fos (a marker of activated neurons) further showed that elemene treatment activated several brain regions, including the lateral septum (LS), cingulate cortex (ACC), paraventricular nucleus of the thalamus (PVT), and dorsomedial hypothalamic nucleus (DMH), most notably in the GABAergic neurons of the lateral septum (LS). Finally, we found that both chemogenetic inhibition and apoptosis of LS neurons significantly reduced pain- and anxiety-like behaviors in mice treated with elemene. Taken together, these findings suggest that LS is involved in the regulation of elemene-induced chemotherapy pain and anxiety-like behaviors, providing a new target for the treatment of chemotherapy pain induced by elemene.
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Dor , Doenças do Sistema Nervoso Periférico , Sesquiterpenos , Camundongos , Animais , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Neurônios GABAérgicos , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Ansiedade/induzido quimicamenteRESUMO
PURPOSE: To evaluate the association between facet joints cross-sectional area asymmetry (FCAA) and cervical intervertebral disc herniation (CDH). METHODS: Overall, we retrospectively recruited 390 consecutive patients with CDH who underwent surgical treatment at our institution and 50 normal participants. Clinical variables and radiological findings related to CDH were collected. RESULTS: Patients with CDH were more likely to have a higher absolute value of the facet asymmetry factor (FAF) (p < .001), in which the FAF value of the left group was significantly higher than the other groups (p < .001) and the right group was lower than the central group (p < .001). 9.62% (C3/4), 12.19% (C4/5), 8.70% (C5/6), and 8.14% (C6/7) were determined as cutoff values for each variable that maximized sensitivity and specificity. Furthermore, multivariate analysis showed that cross-sectional area asymmetry of the facet joint (FCAA) was an independent risk factor for the occurrence of CDH. Also, the Chi-square test showed a significant difference in the distribution of the degeneration classification of the disc between the facet-degenerated group and the nondegenerated group at C5/6 (p = 0.026) and C6/7 (p = 0.005) in the facet asymmetry (FA) group. CONCLUSIONS: FCAA is evaluated as an independent risk factor for CDH and associated with the orientation of disc herniation. And facet joint orientation may also play a role in cervical spine degeneration rather than facet joint tropism.
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Vértebras Cervicais , Deslocamento do Disco Intervertebral , Articulação Zigapofisária , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Articulação Zigapofisária/diagnóstico por imagem , Articulação Zigapofisária/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Adulto , Estudos Retrospectivos , IdosoRESUMO
OBJECTIVE: Patients with preoperative deep vein thrombosis (DVT) exhibit a notable incidence of postoperative deep vein thrombosis progression (DVTp), which bears a potential for silent, severe consequences. Consequently, the development of a predictive model for the risk of postoperative DVTp among spinal trauma patients is important. METHODS: Data of 161 spinal traumatic patients with preoperative DVT, who underwent spine surgery after admission, were collected from our hospital between January 2016 and December 2022. The least absolute shrinkage and selection operator (LASSO) combined with multivariable logistic regression analysis was applied to select variables for the development of the predictive logistic regression models. One logistic regression model was formulated simply with the Caprini risk score (Model A), while the other model incorporated not only the previously screened variables but also the age variable (Model B). The model's capability was evaluated using sensitivity, specificity, positive predictive value, negative predictive value, accuracy, F1 score, and receiver operating characteristic (ROC) curve. Nomograms simplified and visually presented Model B for the clinicians and patients to understand the predictive model. The decision curve was used to analyze the clinical value of Model B. RESULTS: A total of 161 DVT patients were enrolled in this study. Postoperative DVTp occurred in 48 spinal trauma patients, accounting for 29.81% of the total patient enrolled. Model A inadequately predicted postoperative DVTp in spinal trauma patients, with ROC AUC values of 0.595 for the training dataset and 0.593 for the test dataset. Through the application of LASSO regression and multivariable logistic regression, a screening process was conducted for seven risk factors: D-dimer, blood platelet, hyperlipidemia, blood group, preoperative anticoagulant, spinal cord injury, lower extremity varicosities. Model B demonstrated superior and consistent predictive performance, with ROC AUC values of 0.809 for the training dataset and 0.773 for the test dataset. According to the calibration curves and decision curve analysis, Model B could accurately predict the probability of postoperative DVTp after spine surgery. The nomograms enhanced the interpretability of Model B in charts and graphs. CONCLUSIONS: In summary, we established a logistic regression model for the accurate predicting of postoperative deep vein thrombosis progression in spinal trauma patients, utilizing D-dimer, blood platelet, hyperlipidemia, blood group, preoperative anticoagulant, spinal cord injury, lower extremity varicosities, and age as predictive factors. The proposed model outperformed a logistic regression model based simply on CRS. The proposed model has the potential to aid frontline clinicians and patients in identifying and intervening in postoperative DVTp among traumatic patients undergoing spinal surgery.
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Antígenos de Grupos Sanguíneos , Hiperlipidemias , Traumatismos da Medula Espinal , Trombose Venosa , Humanos , Fatores de Risco , Trombose Venosa/diagnóstico , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Anticoagulantes , Traumatismos da Medula Espinal/complicações , Hiperlipidemias/complicações , Estudos RetrospectivosRESUMO
BACKGROUND: Pressure ulcers (PUs) is ischemic necrosis caused by long-term local tissue pressure, directly affecting postoperative functional recovery. There is evidence that inflammation has an adverse impact on the development of PUs and contributes to unfavorable outcomes, suggesting that blocking the inflammatory response may be a promising therapeutic strategy for PUs. Tryptanthrin (Tryp), a natural product isolated from indigenous plants, has an anti-inflammatory biological function. However, the efficacy of Tryp in PUs remains unclear. METHODS: Efficacy of Tryp suppressed inflammation was assessed using magnets-induced PUs model in mice. Hematoxylin-Eosin staining, masson staining and immunohistochemistry were used to evaluate the histologic changes after the formation of PUs. The expression of inflammatory cytokines was detected by qRT-PCR. And we detected the expression of protein by Western blotting. RESULTS: Tryp could promote wound healing, such as epidermal thickening, revascularization, and nerve regeneration. Then the treatment of Tryp was able to promote fibroblast migration and collagen deposition. Moreover, Tryp attenuated inflammation through inducing macrophage polarization to M2 phenotype by suppressing the activation of cGAS-STING pathway. CONCLUSION: Tryp could reduce the release of inflammatory cytokines, and induce RAW 264.7 polarization to M2 phenotype by targeting cGAS/STING/TBK1 pathways. In summary, Tryp may be a novel medicine for the treatment of PUs in the future.
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Úlcera por Pressão , Quinazolinas , Camundongos , Animais , Inflamação/tratamento farmacológico , Inflamação/patologia , Cicatrização , Citocinas/metabolismo , Macrófagos/metabolismo , Nucleotidiltransferases/metabolismo , SupuraçãoRESUMO
Percutaneous endoscopic lumbar discectomy (PELD) is one of the main means of minimally invasive spinal surgery, and is an effective means of treating lumbar disc herniation, but its early recurrence is still difficult to predict. With the development of machine learning technology, the auxiliary model based on the prediction of early recurrent lumbar disc herniation (rLDH) and the identification of causative risk factors have become urgent problems in current research. However, the screening ability of current models for key factors affecting the prediction of rLDH, as well as their predictive ability, needs to be improved. Therefore, this paper presents a classification model that utilizes wrapper feature selection, developed through the integration of an enhanced bat algorithm (BDGBA) and support vector machine (SVM). Among them, BDGBA increases the population diversity and improves the population quality by introducing directional mutation strategy and guidance-based strategy, which in turn allows the model to secure better subsets of features. Furthermore, SVM serves as the classifier for the wrapper feature selection method, with its classification prediction results acting as a fitness function for the feature subset. In the proposed prediction method, BDGBA is used as an optimizer for feature subset filtering and as an objective function for feature subset evaluation based on the classification results of the support vector machine, which improves the interpretability and prediction accuracy of the model. In order to verify the performance of the proposed method, this paper proves the performance of the model through global optimization experiments and prediction experiments on real data sets. The accuracy of the proposed rLDH prediction model is 93.49% and sensitivity is 88.33%. The experimental results show that Level of herniated disk, Modic change, Disk height, Disk length, and Disk width are the key factors for predicting rLDH, and the proposed method is an effective auxiliary diagnosis method.
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Discotomia Percutânea , Deslocamento do Disco Intervertebral , Humanos , Discotomia Percutânea/métodos , Deslocamento do Disco Intervertebral/genética , Deslocamento do Disco Intervertebral/cirurgia , Máquina de Vetores de Suporte , Vértebras Lombares/cirurgia , Recidiva , Resultado do Tratamento , Estudos RetrospectivosRESUMO
Glioblastoma (GBM) is one of the most common intracranial primary malignancies with the highest mortality rate, and there is a lack of effective treatments. In this study, we examined the anti-GBM activity of Tenacissoside H (TH), an active component isolated from the traditional Chinese medicine Marsdenia tenacissima (Roxb.) Wight & Arn (MT), and investigated the potential mechanism. Firstly, we found that TH decreased the viability of GBM cells by inducing cell cycle arrest and apoptosis, and inhibited the migration of GBM cells. Furthermore, combined with the Gene Expression Omnibus database (GEO) and network pharmacology as well as molecular docking, TH was shown to inhibit GBM progression by directly regulating the PI3K/Akt/mTOR pathway, which was further validated in vitro. In addition, the selective PI3K agonist 740 y-p partially restored the inhibitory effects of TH on GBM cells. Finally, TH inhibited GBM progression in an orthotopic transplantation model by inactivating the PI3K/Akt/mTOR pathway in vivo. Conclusively, our results suggest that TH represses GBM progression by inhibiting the PI3K/Akt/mTOR signaling pathway in vitro and in vivo, and provides new insight for the treatment of GBM patients.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Neoplasias Encefálicas/genética , Proliferação de CélulasRESUMO
Glioblastoma (GBM) is the most aggressive and lethal type of tumor in the central nervous system, characterized by a high incidence and poor prognosis. Thiotert, as a novel dual targeting agent, has potential inhibitory effects on various tumors. Here, we found that Thiotert effectively inhibited the proliferation of GBM cells by inducing G2/M cell cycle arrest and suppressed the migratory ability in vitro. Furthermore, Thiotert disrupted the thioredoxin (Trx) system while causing cellular DNA damage, which in turn caused endoplasmic reticulum (ER) stress-dependent autophagy. Knockdown of ER stress-related protein ATF4 in U251 cells inhibited ER stress-dependent autophagy caused by Thiotert to some extent. Orthotopic transplantation experiments further showed that Thiotert had the same anti-GBM activity and mechanism as in vitro. Conclusively, these results suggest that Thiotert induces ER stress-dependent autophagy in GBM cells by disrupting redox homeostasis and causing DNA damage, which provides new insight for the treatment of GBM.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/metabolismo , Linhagem Celular Tumoral , Estresse do Retículo Endoplasmático , Autofagia , Pontos de Checagem da Fase G2 do Ciclo Celular , Neoplasias Encefálicas/genética , ApoptoseRESUMO
ABSTRACT: The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury. Regulation of shifting microglia polarization from M1 (neurotoxic and proinflammatory type) to M2 (neuroprotective and anti-inflammatory type) after spinal cord injury appears to be crucial. Tryptanthrin possesses an anti-inflammatory biological function. However, its roles and the underlying molecular mechanisms in spinal cord injury remain unknown. In this study, we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro. Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway. Additionally, we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury, inhibited neuronal loss, and promoted tissue repair and functional recovery in a mouse model of spinal cord injury. Finally, using a conditional co-culture system, we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis. Taken together, these results suggest that by targeting the cGAS/STING/NF-κB axis, tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.
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OBJECTIVE: Surgical site infection (SSI), a common serious complication within 1 month after transforaminal lumbar interbody fusion (TLIF), usually leads to poor prognosis and even death. The objective of this study is to investigate the factors related to SSI within 1 month after TLIF. We have developed a dynamic nomogram to change treatment or prevent infection based on accurate predictions. MATERIALS AND METHODS: We retrospectively analyzed 383 patients who received TLIF at our institution from January 1, 2019, to June 30, 2022. The outcome variable in the current study was the occurrence of SSI within 1 month after surgery. Univariate logistic regression analysis was first performed to assess risk factors for SSI within 1 month after surgery, followed by inclusion of significant variables at P < 0.05 in multivariate logistic regression analysis. The independent risk variables were subsequently utilized to build a nomogram model. The consistency index (C-index), calibration curve and receiver operating characteristic curve were used to evaluate the performance of the model. And the decision curve analysis (DCA) was used to analyze the clinical value of the nomogram. RESULTS: The multivariate logistic regression models further screened for three independent influences on the occurrence of SSI after TLIF, including lumbar paraspinal (multifidus and erector spinae) muscles (LPM) fat infiltration, diabetes and surgery duration. Based on the three independent factors, a nomogram prediction model was built. The area under the curve for the nomogram including these predictors was 0.929 in both the training and validation samples. Both the training and validation samples had high levels of agreement on the calibration curves, and the nomograms C-index was 0.929 and 0.955, respectively. DCA showed that if the threshold probability was less than 0.74, it was beneficial to use this nomograph to predict the risk of SSI after TLIF. In addition, the nomogram was converted to a web-based calculator that provides a graphical representation of the probability of SSI occurring within 1 month after TLIF. CONCLUSION: A nomogram including LPM fat infiltration, surgery duration and diabetes is a promising model for predicting the risk of SSI within 1 month after TLIF. This nomogram assists clinicians in stratifying patients, hence boosting decision-making based on evidence and personalizing the best appropriate treatment.
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Fusão Vertebral , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Estudos Retrospectivos , Nomogramas , Vértebras Lombares/cirurgia , Fusão Vertebral/efeitos adversosRESUMO
OBJECTIVE: Cervical traumatic spinal cord injury (CTSCI) is a seriously disabling disease that severely affects the physical and mental health of patients and imposes a huge economic burden on patients and their families. Accurate identification of the prognosis of CTSCI patients helps clinicians to design individualized treatment plans for patients. For this purpose, a dynamic nomogram was developed to predict the recovery of CTSCI patients after 6 months. METHODS: We retrospectively included 475 patients with CTSCI in our institution between March 2013 and January 2022. The outcome variable of the current study was a satisfactory recovery of patients with CTSCI at 6 months. Univariate analyses and univariate logistic regression analyses were used to assess the factors affecting the prognosis of patients with CTSCI. Subsequently, variables (P < 0.05) were included in the multivariate logistic regression analysis to evaluate these factors further. Eventually, a nomogram model was constructed according to these independent risk factors. The concordance index (C-index) and the calibration curve were utilized to assess the model's predictive ability. The discriminating capacity of the prediction model was measured by the receiver operating characteristic (ROC) area under the curve (AUC). One hundred nine patients were randomly selected from 475 patients to serve as the center's internal validation test cohort. RESULTS: The multivariate logistic regression model further screened out six independent factors that impact the recovery of patients with CTSCI. Including admission to the American Spinal Injury Association Impairment Scale (AIS) grade, the length of high signal in the spinal cord, maximum spinal cord compression (MSCC), spinal segment fractured, admission time, and hormonal therapy within 8 h after injury. A nomogram prediction model was developed based on the six independent factors above. In the training cohort, the AUC of the nomogram that included these predictors was 0.879, while in the test cohort, it was 0.824. The nomogram C-index incorporating these predictors was 0.872 in the training cohort and 0.813 in the test cohort, while the calibration curves for both cohorts also indicated good consistency. Furthermore, this nomogram was converted into a Web-based calculator, which provided individual probabilities of recovery to be generated for individuals with CTSCI after 6 months and displayed in a graphical format. CONCLUSION: The nomogram, including ASIA grade, the length of high signal in the spinal cord, MSCC, spinal segment fractured, admission time, and hormonal therapy within 8 h after injury, is a promising model to predict the probability of content recovery in patients with CTSCI. This nomogram assists clinicians in stratifying patients with CTSCI, enhancing evidence-based decision-making, and individualizing the most appropriate treatment.
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Lesões dos Tecidos Moles , Compressão da Medula Espinal , Traumatismos da Medula Espinal , Traumatismos da Coluna Vertebral , Humanos , Nomogramas , Estudos Retrospectivos , PrognósticoRESUMO
AIMS: TANK-binding kinase 1 (TBK1) is involved in regulating the pathological process of a variety of inflammatory diseases in the central nervous system. However, its role and underlying molecular mechanisms in spinal cord injury (SCI) remain largely unknown. METHODS: We employed the TBK1 inhibitor amlexanox (ALX) to address this question. An in vivo clip-compressive SCI model and in vitro lipopolysaccharide (LPS)-induced astrocyte inflammation model were established to examine the effects of TBK1 inhibition on the expression of proinflammatory cytokines. RESULTS: In this study, we found that TBK1 and TBK1-medicated innate immune pathways, such as TBK1/IRF3 and noncanonical NF-κB signaling, were activated in astrocytes and neurons after SCI. Furthermore, inhibition of TBK1 by ALX alleviated neuroinflammation response, reduced the loss of motor neurons, and improved the functional recovery after SCI. Mechanistically, inhibition of TBK1 activity promoted the activation of the noncanonical NF-κB signaling pathway and inhibited p-IRF3 activity in LPS-induced astrocytes, and the TBK1 activity was required for astrocytic activation through yes-associated protein (YAP) signaling after SCI and in LPS-induced astrocytes inflammation model. CONCLUSION: TBK1-medicated innate immune pathway in astrocytes through YAP signaling plays an important role in the pathogenesis of SCI and inhibition of TBK1 may be a potential therapeutic drug for SCI.
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NF-kappa B , Proteínas Serina-Treonina Quinases , Traumatismos da Medula Espinal , Proteínas de Sinalização YAP , Astrócitos/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , NF-kappa B/metabolismo , Transdução de Sinais , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Animais , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
OBJECTIVE: This study aimed to construct and verify a useful nomogram that predicts the risk of preoperative deep vein thrombosis (DVT) progression after elective spine surgery. METHODS: Data of patients were collected from 366 patients with preoperative DVT who underwent elective spine surgery at our hospital between July 2017 and May 2022. The least absolute shrinkage and selection operator method combined with multivariable logistic regression analysis were applied to select features for the preoperative DVT progression risk model. The model's capability was evaluated using the concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve. The decision curve and bootstrapping were used to analyze the clinical value of the nomogram. RESULT: A total of 366 DVT patients were enrolled in this study. Preoperative DVT progression after elective spine surgery was 24.04% (88 cases). Among these patients, 86 patients had thrombosis extending into a proximal vein or appearing in a different branch of the vein, either ipsilateral or contralateral, and two had a symptomatic pulmonary embolism. D-dimer, lower extremity varicosities, hyperlipidemia, lower limb paralysis, and operation time were among the predictors in the nomogram. Furthermore, the C-index of the prediction nomogram was 0.805 (95ï¼ CI: 0.754-0.856), with an interval bootstrapping validation of 0.786 and an area under the ROC curve value of 0.800. According to the calibration curves and decision curve analysis, the nomogram could accurately predict the probability of preoperative DVT progression after elective spine surgery. CONCLUSION: The advantages of the nomogram included the unique discrimination capability, clinical utility, and predictive accuracy, which was beneficial for clinicians to distinguish high-risk groups of DVT progression after elective spine surgery and formulate relevant prevention measures.
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Nomogramas , Trombose Venosa , Humanos , Coluna Vertebral/cirurgia , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Trombose Venosa/diagnóstico , Fatores de Risco , Estudos RetrospectivosRESUMO
Glioblastoma (GBM) is the most malignant glioma in brain tumors with low survival and high recurrence rate. Irigenin, as an isoflavone compound extracted from Shegan, has shown many pharmacological functions such as antioxidant, anti-inflammatory and anti-tumor. However, the effects of irigenin on GBM cells and the related molecular mechanisms remain unexplored. In this study, we found that irigenin inhibited the proliferation of GBM cells in a dose-dependent manner by several assays in vitro. Subsequently, we found that irigenin arrested cell cycle at G2/M phase and induced apoptosis of GBM cells in vitro. In addition, irigenin inhibited the migration of GBM cells. Mechanically, we found that irigenin treatment decreased the expression of YAP (yes-associated protein), suppressed ß-catenin signaling. Furthermore, overexpression of YAP partially restored the anti-tumor effects of irigenin on GBM cells in vitro. Finally, we found that irigenin inhibited the growth of tumor in GBM xenograft mice model through inactivation of YAP. Taken together, these results suggest that irigenin exerts its anticancer effects on GBM via inhibiting YAP/ß-catenin signaling, which may provide a new strategy for the treatment of GBM.
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OBJECTIVE: To develop and validate a nomogram useful in predicting recurrent lumbar disk herniation (rLDH) within 6 months after percutaneous endoscopic lumbar discectomy (PELD). METHODS: Information on patients' lumbar disk herniation (LDH) between January 2018 and May 2019 in addition to 26 other features was collected from the authors' hospital. The least absolute shrinkage and selection operator (LASSO) method was used to select the most important risk factors. Moreover, a nomogram was used to build a prediction model using the risk factors selected from LASSO regression. The concordance index (C-index), the receiver operating characteristic (ROC) curve, and calibration curve were used to assess the performance of the model. Finally, clinical usefulness of the nomogram was analyzed using the decision curve and bootstrapping used for internal validation. RESULTS: Totally, 352 LDH patients were included into this study. Thirty-two patients had recurrence within 6 months while 320 showed no recurrence. Four potential factors, the course of disease, Pfirrmann grade, Modic change, and migration grade, were selected according to the LASSO regression model. Additionally, the C-index of the prediction nomogram was 0.813 (95% CI, 0.726-0.900) and the area under receiver operating characteristic curve (AUC) value was 0.798 while the interval bootstrapping validation C-index was 0.743. Hence, the nomogram might be a good predictive model. CONCLUSION: Each variable, the course of disease, Pfirrmann grade, Modic change, and migration grade in the nomogram had a quantitatively corresponding risk score, which can be used in predicting the overall recurrence rate of rLDH within 6 months.
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Discotomia Percutânea/métodos , Endoscopia/métodos , Deslocamento do Disco Intervertebral/cirurgia , Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Nomogramas , Adulto , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Risco , Fatores de Risco , Fatores de TempoRESUMO
Glioblastoma multiforme (GBM) is one of the deadliest cancers in brain. There have been few treatment advances for GBM despite increasing scientific understanding of this disease. ß-hexosaminidase (Hex) is an important enzyme system in human body, encoded by two genes, HEXA and HEXB, are closely related to central nervous system (CNS) diseases such as Sandhoff disease (SD) and Tay-Sachs disease (TSD). However, the expression pattern and function of HEXA and HEXB in GBM remains unclear. Here, we found that both the mRNA and protein expression levels of HEXA and HEXB were significantly upregulated in GBM patient samples. The results from single-cell RNA-sequencing (scRNA-seq) database and double immunostaining showed that HEXA and HEXB were specifically expressed in microglia in GBM patient samples. Furthermore, our in vitro experiments revealed that conditioned media from HEXA and HEXB knockdown-microglia cells could inhibit the proliferation and migration of GBM cells. Finally, according to survival analysis based on online database, higher expression of HEXA and HEXB was associated with poor prognosis in GBM patients. In conclusion, these results suggest that microglial HEXA and HEXB play fundamental role in GBM progression, and they will be potential biomarkers for GBM.
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OBJECTIVE: To modify the conventional methods of grooving and direction during the single-door cervical laminoplasty (SDCL) in the subaxial cervical spine. METHODS: The distance between the left and the right lamina-lateral mass junction at the upper, middle, and lower levels of each segment (DLL-U, DLL-M, DLL-L), angle between the posterior edge of the vertebral body and the lamina (AVL) and thickness of lamina (TL) were measured in the transverse plane. The parameters of preoperative computed tomography scans of 200 patients who had undergone SDCL were measured. The patients were divided into male and female groups and developmental canal stenosis (DCS) and non-DCS (NDCS) groups. RESULTS: DLL-M gradually increased from the cranial to the caudal except for C7, and DLL-L > DLL-M > DLL-U in each vertebra. AVL increased from C3 to C7, TL decreased from C3 to C5 and increased from C5 to C7, with both parameters showing no significant differences between the left and right sides. AVL of the DCS group was less than that of the NDCS group (P < 0.01). CONCLUSIONS: In the SDCL, the ideal surgical trough should be several discontinuous lines sloping from top to bottom, rather than a straight line. The abduction angle during drilling should gradually increase from C3 to C7 in the SDCL averaging 40 degrees. This method mentioned above improves the efficiency of the operation with less blood loss as an extended cut into the lateral mass is avoided.
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Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Laminoplastia/métodos , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Axonal degeneration is a common pathological feature in many acute and chronic neurological diseases such as spinal cord injury (SCI). SARM1 (sterile alpha and TIR motif-containing 1), the fifth TLR (Toll-like receptor) adaptor, has diverse functions in the immune and nervous systems, and recently has been identified as a key mediator of Wallerian degeneration (WD). However, the detailed functions of SARM1 after SCI still remain unclear. Methods: Modified Allen's method was used to establish a contusion model of SCI in mice. Furthermore, to address the function of SARM1 after SCI, conditional knockout (CKO) mice in the central nervous system (CNS), SARM1Nestin-CKO mice, and SARM1GFAP-CKO mice were successfully generated by Nestin-Cre and GFAP-Cre transgenic mice crossed with SARM1flox/flox mice, respectively. Immunostaining, Hematoxylin-Eosin (HE) staining, Nissl staining and behavioral test assays such as footprint and Basso Mouse Scale (BMS) scoring were used to examine the roles of SARM1 pathway in SCI based on these conditional knockout mice. Drugs such as FK866, an inhibitor of SARM1, and apoptozole, an inhibitor of heat shock protein 70 (HSP70), were used to further explore the molecular mechanism of SARM1 in neural regeneration after SCI. Results: We found that SARM1 was upregulated in neurons and astrocytes at early stage after SCI. SARM1Nestin-CKO and SARM1GFAP-CKO mice displayed normal development of the spinal cords and motor function. Interestingly, conditional deletion of SARM1 in neurons and astrocytes promoted the functional recovery of behavior performance after SCI. Mechanistically, conditional deletion of SARM1 in neurons and astrocytes promoted neuronal regeneration at intermediate phase after SCI, and reduced neuroinflammation at SCI early phase through downregulation of NF-κB signaling after SCI, which may be due to upregulation of HSP70. Finally, FK866, an inhibitor of SARM1, reduced the neuroinflammation and promoted the neuronal regeneration after SCI. Conclusion: Our results indicate that SARM1-mediated prodegenerative pathway and neuroinflammation promotes the pathological progress of SCI and anti-SARM1 therapeutics are viable and promising approaches for preserving neuronal function after SCI.
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Proteínas do Domínio Armadillo/metabolismo , Proteínas do Citoesqueleto/metabolismo , Inflamação/metabolismo , NF-kappa B/metabolismo , Regeneração Nervosa/fisiologia , Neurônios/metabolismo , Transdução de Sinais/fisiologia , Traumatismos da Medula Espinal/metabolismo , Animais , Astrócitos/metabolismo , Axônios/metabolismo , Regulação para Baixo/fisiologia , Masculino , Camundongos , Camundongos Knockout , Recuperação de Função Fisiológica/fisiologia , Medula Espinal/metabolismo , Regulação para Cima/fisiologiaRESUMO
BACKGROUND: Kyphotic deformity occurrence after cervical laminoplasty is not rare. Several studies have emphasized the development of postoperative kyphotic deformity (PKD) will impair the functional outcome of cervical laminoplasty. We established and validated a nomogram prediction model for kyphotic deformity after laminoplasty in cervical spondylotic myelopathy patients (CSM) without preoperative kyphotic alignment. METHODS: Preoperative and 1-year postoperative data of 369 patients who underwent single-door cervical laminoplasty (SDCL) at the author's hospital between July 2010 and February 2018 were collected. Using the least absolute shrinkage and selection operator (LASSO) method, significant parameters were selected to develop a nomogram prediction model. The prognostic performance of the model was evaluated using concordance index (C-index) and calibration curve. The discriminatory ability of the prediction model was evaluated by the area under (receiver operating characteristic) curve (AUC). RESULTS: Of the 369 patients, 31 developed PKD in 1 year after the surgery. Using the LASSO regression, six significant variables composed the final model: age, C2-7 sagittal vertical axis, C7 slope, C2-7 angle, flexion range of motion and operation level were selected. The AUC of the nomogram was 0.771. The C-index for the prediction nomogram was 0.771 (95 % CI: 0.672-0.870). The calibration curve also indicated good consistency. CONCLUSION: A nomogram for predicting PKD after SDCL was established and validated. For patients evaluated by this model with predictive high risk of developing postoperative kyphosis, an alternative approach to the subaxial cervical spine such as anterior surgery should be considered.
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Vértebras Cervicais/diagnóstico por imagem , Cifose/diagnóstico por imagem , Laminoplastia/tendências , Nomogramas , Doenças da Medula Espinal/diagnóstico por imagem , Espondilose/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Vértebras Cervicais/cirurgia , Feminino , Seguimentos , Humanos , Cifose/etiologia , Laminoplastia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/tendências , Doenças da Medula Espinal/cirurgia , Espondilose/cirurgiaRESUMO
The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis. Microglia, as innate immune cells, play important roles in the maintenance of central nervous system homeostasis, injury response, and neurodegenerative diseases. Lactate has been considered a metabolic waste product, but recent studies are revealing ever more of the physiological functions of lactate. Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions, macrophage polarization, neuromodulation, and angiogenesis and has also been implicated in the development of various diseases. This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation, histone versus non-histone lactylation, and therapeutic approaches targeting lactate. Finally, we summarize the current research on microglia lactylation in central nervous system diseases. A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.