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1.
Front Oncol ; 14: 1367603, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38803532

RESUMO

Objectives: The safety and feasibility of repeat biopsy after systemic treatment for non-small cell lung cancer have received extensive attention in recent years. The purpose of this research was to compare complication rates between initial biopsy and rebiopsy in non-small cell lung cancer patients with progressive disease and to assess complication risk factors and clinical results after rebiopsy. Methods: The study included 113 patients initially diagnosed with non-small cell lung cancer who underwent lung biopsy at initial biopsy and rebiopsy after progression while on epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and/or chemotherapy from January 2018 to December 2021. We compared the incidence of complications between the initial biopsy and rebiopsy and analyzed the predictors factors that influenced complications in patients who underwent rebiopsy. Results: The successful rate of rebiopsy was 88.5% (100/113). With the exception of two cases where lung adenocarcinoma changed into small cell lung cancer with gefitinib treatment, 98 individuals retained their initial pathological type. The secondary EGFR T790M mutation accounts for 55.6% of acquired resistance. The total number of patients with complications in initial biopsy was 25 (22.1%) and 37 (32.7%) in the rebiopsy. The incidence of pulmonary hemorrhage increased from 7.1% at the initial biopsy to 10.6% at rebiopsy, while the incidence of pneumothorax increased from 14.2% to 20.4%. Compared with the initial biopsy, the incidence of overall complications, parenchymal hemorrhage, and pneumothorax increased by 10.6%, 3.5%, and 6.2%, respectively. In all four evaluations (pneumorrhagia, pneumothorax, pleural reaction, and overall complication), there were no significant differences between the rebiopsy and initial biopsy (all p > 0.05). The multivariate logistic regression analysis suggested that male sex (odds ratio [OR] = 5.064, p = 0.001), tumor size ≤ 2 cm (OR = 3.367, p = 0.013), EGFR-TKIs with chemotherapy (OR = 3.633, p =0.023), and transfissural approach (OR = 7.583, p = 0.026) were independent risk factors for overall complication after rebiopsy. Conclusion: Compared with the initial biopsy, the complication rates displayed a slight, but not significant, elevation in rebiopsy. Male sex, tumor size ≤ 2 cm, transfissural approach, and EGFR-TKIs combined with chemotherapy were independent risk factors for rebiopsy complications.

2.
Sci Rep ; 14(1): 582, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182634

RESUMO

Vertically dynamic model of a large-diameter pile in frozen soil is established, in which the frozen soil is described to a saturated frozen porous media, and the large diameter end-bearing pile is simplified to a one-dimensional rod considering the influence of the transverse inertia effect. Analytical solutions of the longitudinal coupling vibration between the end-bearing pile and the frozen soil are obtained using Helmholtz decomposition and variable separation methods in the frequency domain. By comparing the dynamic responses of the longitudinal vibration of the large diameter end-bearing pile with the traditionally one-dimensional pile, as well as the impedance factor of the frozen soil layer induced by the pile vibration, these demonstrate the influence of the transverse inertia effect on the high frequency vibration of large diameter pile is significant, and the influence on the pile with a smaller slenderness ratio is larger. The temperature and the Poisson's ratio also have significant effects on the vertical vibration of large diameter piles in frozen soil, which cannot be ignored in the analysis.

3.
Thorac Cancer ; 15(5): 361-368, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38155425

RESUMO

BACKGROUND: This study aimed to investigate the value of nonenhanced computed tomography (CT)-based radiomics in determining disease progression in breast cancer patients with bone marrow metastases and to develop a model for assessing treatment efficacy. METHODS: A total of 134 breast cancer patients with bone metastases were enrolled from three hospitals. Nonenhanced CT was performed after two cycles of drug treatment. The images were categorized into an invalid and a valid group according to disease progression status. The largest osteolytic lesions' maximum cross-sections in the CT images were selected as regions of interest (ROIs) for feature extraction. Variance threshold, SelectKBest, and least absolute shrinkage and selection operator (LASSO) were used to reduce feature dimensionality. K-nearest neighbor algorithm (KNN), support vector machine (SVM), extreme gradient boosting (XGBoost), random forest (RF), logistic regression (LR), and decision tree (DT) algorithms were trained to establish radiomics models. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic performance of the models. RESULTS: The KNN classifier demonstrated the best performance compared to the random grouping method. In the validation group, the area under the ROC curve (AUC) was 0.810. In the cross-validation method, the RF classifier showed the best performance with an AUC of 0.84. CONCLUSION: Nonenhanced CT-based radiomics provides a promising method for evaluating the efficacy of systemic drug therapy in breast cancer patients with osteolytic bone metastases.


Assuntos
Neoplasias Ósseas , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Radiômica , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Tomografia Computadorizada por Raios X , Progressão da Doença , Estudos Retrospectivos
4.
Materials (Basel) ; 16(21)2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37959611

RESUMO

It is necessary to prepare marine UHPC with synthetic fibers instead of steel fibers, owing to the corrosion risk of steel fibers in marine environments. Currently, the performance of UHPC prepared with different types of fibers has not been comparatively investigated. This work prepared UHPC with steel fiber, polyoxymethylene (POM) fiber, polypropylene (PP) fiber, and polyvinyl alcohol (PVA) fiber. The effects of different fibers on the mechanical properties, impact, and abrasion resistance of UHPC were studied and compared. The results showed that increasing POM fiber can increase the mechanical strength, flexural toughness, impact, and abrasion resistance of UHPC. When its content reaches 2%, the adsorbed-in-fracture energy and abrasion strength of UHPC are 2670 J and 105 h/(kg/m2), respectively. At the same fiber content, POM fiber-reinforced UHPC shows better mechanical strength, toughness, and impact- and abrasion-resistance than the polypropylene (PP)- and polyvinyl alcohol (PVA)-fiber-reinforced UHPCs. Microstructure investigation found that PP fiber has the weakest binding with UHPC paste, which would directly pull out of the matrix under external tensile loading. This weak connection limits the strengthening and toughening effect on the UHPC. PVA fiber has an excellent interfacial connection with the UHPC paste. However, the low tensile strength of PVA fiber limits the strength and toughness of UHPC. POM fiber has a high tensile strength and can absorb tensile loading through debonding, fracture, and tearing. The fracture interface of POM fiber is large, indicating its significant role in strengthening and toughening the UHPC.

5.
Nat Commun ; 14(1): 7722, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38001092

RESUMO

Mutations in mitochondrial DNA (mtDNA) play critical roles in many human diseases. In vivo visualization of cells bearing mtDNA mutations is important for resolving the complexity of these diseases, which remains challenging. Here we develop an integrated nano Cas12a sensor (InCasor) and show its utility for efficient imaging of mtDNA mutations in live cells and tumor-bearing mouse models. We co-deliver Cas12a/crRNA, fluorophore-quencher reporters and Mg2+ into mitochondria. This process enables the activation of Cas12a's trans-cleavage by targeting mtDNA, which efficiently cleave reporters to generate fluorescent signals for robustly sensing and reporting single-nucleotide variations (SNVs) in cells. Since engineered crRNA significantly increase Cas12a's sensitivity to mismatches in mtDNA, we can identify tumor tissue and metastases by visualizing cells with mutant mtDNAs in vivo using InCasor. This CRISPR imaging nanoprobe holds potential for applications in mtDNA mutation-related basic research, diagnostics and gene therapies.


Assuntos
Sistemas CRISPR-Cas , Neoplasias , Humanos , Animais , Camundongos , Sistemas CRISPR-Cas/genética , Mutação , DNA Mitocondrial/genética , Mitocôndrias/genética , Neoplasias/genética
6.
J Neuroimmune Pharmacol ; 18(3): 476-494, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37658943

RESUMO

Transplantation of curcumin-activated olfactory ensheathing cells (aOECs) improved functional recovery in spinal cord injury (SCI) rats. Nevertheless, little is known considering the underlying mechanisms. At the present study, we investigated the promotion of regeneration and functional recovery after transplantation of aOECs into rats with SCI and the possible underlying molecular mechanisms. Primary OECs were prepared from the olfactory bulb of rats, followed by treatment with 1µM CCM at 7-10 days of culture, resulting in cell activation. Concomitantly, rat SCI model was developed to evaluate the effects of transplantation of aOECs in vivo. Subsequently, microglia were isolated, stimulated with 100 ng/mL lipopolysaccharide (LPS) for 24 h to polarize to M1 phenotype and treated by aOECs conditional medium (aOECs-CM) and OECs conditional medium (OECs-CM), respectively. Changes in the expression of pro-inflammatory and anti-inflammatory phenotypic markers expression were detected using western blotting and immunofluorescence staining, respectively. Finally, a series of molecular biological experiments including knock-down of triggering receptor expressed on myeloid cells 2 (TREM2) and analysis of the level of apolipoprotein E (APOE) expression were performed to investigate the underlying mechanism of involvement of CCM-activated OECs in modulating microglia polarization, leading to neural regeneration and function recovery. CCM-activated OECs effectively attenuated deleterious inflammation by regulating microglia polarization from the pro-inflammatory (M1) to anti-inflammatory (M2) phenotype in SCI rats and facilitated functional recovery after SCI. In addition, microglial polarization to M2 elicited by aOECs-CM in LPS-induced microglia was effectively reversed when TREM2 expression was downregulated. More importantly, the in vitro findings indicated that aOECs-CM potentiating LPS-induced microglial polarization to M2 was partially mediated by the TREM2/nuclear factor kappa beta (NF-κB) signaling pathway. Besides, the expression of APOE significantly increased in CCM-treated OECs. CCM-activated OECs could alleviate inflammation after SCI by switching microglial polarization from M1 to M2, which was likely mediated by the APOE/TREM2/NF-κB pathway, and thus ameliorated neurological function. Therefore, the present finding is of paramount significance to enrich the understanding of underlying molecular mechanism of aOECs-based therapy and provide a novel therapeutic approach for treatment of SCI.


Assuntos
Microglia , Mucosa Olfatória , Traumatismos da Medula Espinal , Animais , Ratos , Anti-Inflamatórios/farmacologia , Apolipoproteínas E/metabolismo , Apolipoproteínas E/farmacologia , Apolipoproteínas E/uso terapêutico , Curcumina/metabolismo , Curcumina/farmacologia , Curcumina/uso terapêutico , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Microglia/metabolismo , NF-kappa B/metabolismo , Recuperação de Função Fisiológica , Transdução de Sinais , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Mucosa Olfatória/metabolismo , Mucosa Olfatória/transplante
7.
Front Immunol ; 14: 1134521, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37520528

RESUMO

Background: Neutrophil extracellular traps (NETs) have been shown to play a pivotal role in promoting metastasis and immune escape in hepatocellular carcinoma (HCC). Therefore, noninvasive tests to detect the formation of NETs in tumors can have significant implications for the treatment and prognoses of patients. Here, we sought to develop and validate a computed tomography (CT)-based radiomics model to predict the gene expression profiles that regulate the formation of NETs in HCC. Methods: This study included 1133 HCC patients from five retrospective cohorts. Based on the mRNA expression levels of 69 biomarkers correlated with NET formation, a 6-gene score (NETs score, NETS) was constructed in cohort 1 from TCIA database (n=52) and validated in cohort 2 (n=232) from ICGC database and cohort 3 (n=365) from TCGA database. And then based on the radiomics features of CT images, a radiomics signature (RNETS) was developed in cohort 1 to predict NETS status (high- or low-NETS). We further employed two cohorts from Nanfang Hospital (Guangzhou, China) to evaluate the predictive power of RNETS in predicting prognosis in cohort 4 (n=347) and the responses to PD-1 inhibitor of HCC patients in cohort 5 (n=137). Results: For NETS, in cohort 1, the area under the curve (AUC) values predicting 1, 2, and 3-year overall survival (OS) were 0.836, 0.879, and 0.902, respectively. The low-NETS was associated with better survival and higher levels of immune cell infiltration. The RNETS yielded an AUC value of 0.853 in distinguishing between high-NETS or low-NETS and patients with low-RNETS were associated with significantly longer survival time in cohort 1 (P<0.001). Notably, the RNETS was competent in predicting disease-free survival (DFS) and OS in cohort 4 (P<0.001). In cohort 5, the RNETS was found to be an independent risk factor for progression-free survival (PFS) (P<0.001). In addition, the objective response rate of HCC patients treated with PD-1 inhibitor was significantly higher in the low-RNETS group (27.8%) than in the high-RNETS group (10.8%). Conclusions: This study revealed that RNETS as a radiomics biomarker could effectively predict prognosis and immunotherapy response in HCC patients.


Assuntos
Carcinoma Hepatocelular , Armadilhas Extracelulares , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Imunoterapia
8.
Hepatol Int ; 17(4): 1016-1027, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36821045

RESUMO

OBJECTIVES: In this multicenter study, we sought to develop and validate a preoperative model for predicting early recurrence (ER) risk after curative resection of intrahepatic cholangiocarcinoma (ICC) through artificial intelligence (AI)-based CT radiomics approach. MATERIALS AND METHODS: A total of 311 patients (Derivation: 160; Internal and two external validations: 36, 74 and 61) from 8 medical centers who underwent curative resection were collected retrospectively. In derivation cohort, radiomics and clinical-radiomics models for ER prediction were constructed by LightGBM (a machine learning algorithm). A clinical model was also developed for comparison. Model performance was validated in internal and two external cohorts by ROC. In addition, we investigated the interpretability of the LightGBM model. RESULTS: The combined clinical-radiomics model that included 15 radiomic features and 3 clinical features (CA19-9 > 1000 U/ml, vascular invasion and tumor margin), resulting in the area under the curves (AUCs) of 0.974 (95% CI 0.946-1.000) in the derivation cohort, and 0.871-0.882 (95% CI 0.672-0.962) in the internal and external validation cohorts, respectively, which are higher than the AJCC 8th TNM staging system (AUCs: 0.686-0.717, p all < 0.05). Especially, the sensitivity of this machine learning model could reach 94.6% on average for all the cohorts. CONCLUSIONS: This AI-driven combined radiomics model may provide as a useful tool to preoperatively predict ER and improve therapeutic management of ICC patients.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Inteligência Artificial , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia
9.
bioRxiv ; 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38234727

RESUMO

Hepatitis B virus (HBV) infection is largely noncytopathic and requires the establishment of covalently closed circular DNA (cccDNA), which is considered stable in the nuclei of infected cells. Although challenging, approaches to directly target cccDNA molecules or kill infected cells are recommended to eliminate cccDNA. Herein, cccDNA levels were investigated in HBV-infected chimeric mice with humanized livers. HBV-infected cells support robust replication, progressively retain viral products, and head for cytopathic destruction and cccDNA loss. It is difficult for infected cells to retain cccDNA and remain noncytopathic. Replication-driven cccDNA loss is observed at both phases of spread of and persistent infection. The cccDNA replenishment is required to compensate for cccDNA loss. Blocking cccDNA replenishment pathways reduces cccDNA levels by >100-fold. These results prove an unconventional cccDNA elimination strategy that does not directly target cccDNA but aims to transform spontaneous cccDNA loss into progressive cccDNA elimination by blocking cccDNA replenishment.

10.
Front Endocrinol (Lausanne) ; 13: 1081185, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36568075

RESUMO

Low back pain (LBP) is one of the most common musculoskeletal symptoms and severely affects patient quality of life. The majority of people may suffer from LBP during their life-span, which leading to huge economic burdens to family and society. According to the series of the previous studies, intervertebral disc degeneration (IDD) is considered as the major contributor resulting in LBP. Furthermore, non-coding RNAs (ncRNAs), mainly including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), can regulate diverse cellular processes, which have been found to play pivotal roles in the development of IDD. However, the potential mechanisms of action for ncRNAs in the processes of IDD are still completely unrevealed. Therefore, it is challenging to consider ncRNAs to be used as the potential therapeutic targets for IDD. In this paper, we reviewed the current research progress and findings on ncRNAs in IDD: i). ncRNAs mainly participate in the process of IDD through regulating apoptosis of nucleus pulposus (NP) cells, metabolism of extracellular matrix (ECM) and inflammatory response; ii). the roles of miRNAs/lncRNAs/circRNAs are cross-talk in IDD development, which is similar to the network and can modulate each other; iii). ncRNAs have been attempted to combat the degenerative processes and may be promising as an efficient bio-therapeutic strategy in the future. Hence, this review systematically summarizes the principal pathomechanisms of IDD and shed light on the therapeutic potentials of ncRNAs in IDD.


Assuntos
Degeneração do Disco Intervertebral , MicroRNAs , RNA Longo não Codificante , Humanos , Degeneração do Disco Intervertebral/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Circular/genética , Qualidade de Vida , MicroRNAs/genética , MicroRNAs/metabolismo
11.
J Clin Med ; 11(24)2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36556095

RESUMO

Objective: To investigate the independent influencing factors of bone cement displacement following percutaneous vertebral augmentation (PVA) in patients with stage I and stage II Kümmell's disease. Methods: We retrospectively reviewed the records of 824 patients with stage Ⅰ and stage Ⅱ Kümmell's disease treated with percutaneous vertebroplasty (PVP) or percutaneous vertebroplasty (PKP) from January 2016 to June 2022. Patients were divided into the postoperative bone cement displacement group (n = 150) and the bone cement non-displacement group (n = 674) according to the radiographic inspection results. The following data were collected: age, gender, body mass index (BMI), underlying disease, bone mineral density (BMD), involved vertebral segment, Kümmell's disease staging, anterior height, local Cobb angle, the integrity of anterior vertebral cortex, the integrity of endplate in surgical vertebrae, surgical method, surgical approach, the volume of cement, distribution of cement, the viscosity of cement, cement leakage, and postoperative anti-osteoporosis treatment. Binary logistic regression analysis was performed to determine the independent influencing factors of bone cement displacement. The discrimination ability was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC). Results: The results of logistic regression analysis revealed that thoracolumbar junction (odds ratio (OR) = 3.23, 95% confidence interval (CI) 2.12−4.50, p = 0.011), Kümmell's disease staging (OR = 2.23, 95% CI 1.81−3.41, p < 0.001), anterior cortex defect (OR = 5.34, 95% CI 3.53−7.21, p < 0.001), vertebral endplates defect (OR = 0.54, 95% CI 0.35−0.71, p < 0.001), cement distribution (OR = 2.86, 95% CI 2.03−3.52, p = 0.002), cement leakage (OR = 4.59, 95% CI 3.85−5.72, p < 0.001), restoration of local Cobb angle (OR = 3.17, 95% CI 2.40−5.73, p = 0.024), and postoperative anti-osteoporosis treatment (OR = 0.48, 95% CI 0.18−0.72, p = 0.025) were independently associated with the bone cement displacement. The results of the ROC curve analysis showed that the AUC was 0.816 (95% CI 0.747−0.885), the sensitivity was 0.717, and the specificity was 0.793. Conclusion: Thoracolumbar fracture, stage Ⅱ Kümmell's disease, anterior cortex defect, uneven cement distribution, cement leakage, and high restoration of the local Cobb angle were risk factors for cement displacement after PVA in Kümmell's disease, while vertebral endplates defect and postoperative anti-osteoporosis treatment are protective factors.

13.
Front Endocrinol (Lausanne) ; 13: 994307, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36213280

RESUMO

Background context: Low back pain, affecting nearly 40% of adults, mainly results from intervertebral disc degeneration (IVDD), while the pathogenesis of IVDD is still not fully elucidated. Recently, some researches have revealed that necroptosis, a programmed necrosis, participated in the progression of IVDD, nevertheless, the underlying mechanism remains unclear. Purpose: To study the mechanism of necroptosis of Nucleus Pulposus (NP) cells in IVDD, focusing on the role of MyD88 signaling. Study design: The expression and co-localization of necroptotic indicators and MyD88 were examined in vivo, and MyD88 inhibitor was applied to determine the role of MyD88 signaling in necroptosis of NP cells in vitro. Methods: Human disc specimens were collected from patients receiving diskectomy for lumbar disc herniation (LDH) or traumatic lumbar fractures after MRI scanning. According to the Pfirrmann grades, they were divided into normal (Grades 1, 2) and degenerated groups (4, 5). Tissue slides were prepared for immunofluorescence to assess the co-localization of necroptotic indicators (RIP3, MLKL, p-MLKL) and MyD88 histologically. The combination of TNFα, LPS and Z-VAD-FMK was applied to induce necroptosis of NP cells. Level of ATP, reactive oxygen species (ROS), live-cell staining and electron microscope study were employed to study the role of MyD88 signaling in necroptosis of NP cells. Results: In vivo, the increased expression and co-localization of necroptotic indicators (RIP3, MLKL, p-MLKL) and MyD88 were found in NP cells of degenerated disc, while very l low fluorescence intensity in tissue of traumatic lumbar fractures. In vitro, the MyD88 inhibitor effectively rescued the necroptosis of NP cells, accompanied by increased viability, ATP level, and decreased ROS level. The effect of MyD88 inhibition on necroptosis of NP cells was further confirmed by ultrastructure of mitochondria shown by Transmission Electron Microscope (TEM). Conclusion: Our results indicated that the involvement of MyD88 signaling in the necroptosis of NP cells in IVDD, which will replenish the pathogenesis of IVDD and provide a novel potential therapeutic target for IVDD.


Assuntos
Degeneração do Disco Intervertebral , Núcleo Pulposo , Proteínas Adaptadoras de Transdução de Sinal/farmacologia , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/farmacologia , Adulto , Humanos , Lipopolissacarídeos , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/farmacologia , Necroptose , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
14.
Front Surg ; 9: 994536, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36299569

RESUMO

Background: Traumatic spinal cord injuries (TSCIs) are worldwide public health problems that are difficult to cure and impose a substantial economic burden on society. There has been a lack of extensive multicenter review of TSCI epidemiology in northwest China during the Corona Virus Disease 2019 (COVID-19) pandemic. Method: A multicenter retrospective study of 14 selected hospitals in two provinces in northwest China was conducted on patients admitted for TSCI between 2017 and 2020. Variables assessed included patient demographics, etiology, segmental distribution, treatment, waiting time for treatment, and outcomes. Results: The number of patients with TSCI showed an increasing trend from 2017 to 2019, while there were 12.8% fewer patients in 2020 than in 2019. The male-to-female ratio was 3.67:1, and the mean age was 48 ± 14.9 years. The primary cause of TSCI was high falls (38.8%), slip falls/low falls (27.7%), traffic accidents (23.9%), sports (2.6%), and other factors (7.0%). The segmental distribution showed a bimodal pattern, peak segments were C6 and L1 vertebra, L1 (14.7%), T12 (8.2%), and C6 (8.2%) were the most frequently injured segments. In terms of severity, incomplete injury (72.8%) occurred more often than complete injury (27.2%). The American Spinal Injury Association impairment scale of most patients did not convert before and after treatment in the operational group (71.6%) or the conservative group (80.6%). A total of 975 patients (37.2%) from urban and 1,646 patients (62.8%) from rural areas were included; almost all urban residents could rush to get treatment after being injured immediately (<1 h), whereas most rural patients get the treatment needed 4-7 h after injury. The rough annual incidence from 2017 to 2020 is 112.4, 143.4, 152.2, and 132.6 per million people, calculated by the coverage rate of the population of the sampling hospital. Conclusion: The incidence of TSCI in northwest China is high and on the rise. However, due to pandemic policy reasons, the incidence of urban residents decreased in 2020. The promotion of online work may be an effective primary prevention measure for traumatic diseases. Also, because of the further distance from the good conditional hospital, rural patients need to spend more time there, and the timely treatment of patients from remote areas should be paid attention to.

15.
Neurochem Res ; 47(12): 3733-3744, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36103106

RESUMO

Spinal cord injury (SCI) usually results in loss or reduction in motor and sensory functions. Despite extensive research, no available therapy can restore the lost functions after SCI. Reactive astrocytes play a pivotal role in SCI. Rho kinase inhibitors have also been shown to promote functional recovery of SCI. However, the role of Rho kinase inhibitors in reactive astrocytic phenotype switch within SCI remains largely unexplored. In this study, astrocytes were treated with proinflammatory cytokines and/or the Rho kinase inhibitor Y27632. Concomitantly the phenotype and morphology of astrocytes were examined. Meanwhile, the SCI model of SD rats was established, and nerve functions were evaluated following treatment with Y27632. Subsequently, the number of A1 astrocytes in the injured area was observed and analyzed. Eventually, the expression levels of nuclear factor kappa B (NF-κB), C3, and S100A10 were measured. The present study showed that the Rho kinase inhibitor Y27632 improved functional recovery of SCI and elevated the proliferation and migration abilities of the astrocytes. In addition, Y27632 treatment initiated the switch of astrocytes morphology from a flattened shape to a process-bearing shape and transformed the reactive astrocytes A1 phenotype to an A2 phenotype. More importantly, further investigation suggested that Y27632 was actively involved in promoting the functional recovery of SCI in rats by inhabiting the ROCK/NF-κB/C3 signaling pathway. Together, Rho kinase inhibitor Y27632 effectively promotes the functional recovery of SCI by shifting astrocyte phenotype and morphology. Furthermore, the pro-regeneration event is strongly associated with the ROCK/NF-κB/C3 signal pathway.


Assuntos
Astrócitos , Inibidores de Proteínas Quinases , Traumatismos da Medula Espinal , Animais , Ratos , Astrócitos/metabolismo , NF-kappa B/metabolismo , Fenótipo , Inibidores de Proteínas Quinases/farmacologia , Ratos Sprague-Dawley , Quinases Associadas a rho/antagonistas & inibidores , Quinases Associadas a rho/metabolismo , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo
16.
Mol Neurobiol ; 59(10): 6447-6459, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35962300

RESUMO

Neural regeneration has troubled investigators worldwide in the past decades. Currently, cell transplantation emerged as a breakthrough targeted therapy for spinal cord injury (SCI) in the neurotrauma field, which provides a promising strategy in neural regeneration. Olfactory ensheathing cells (OECs), a specialized type of glial cells, is considered as the excellent candidate due to its unique variable and intrinsic regeneration-supportive properties. In fact, OECs could support olfactory receptor neuron turnover and axonal extension, which is essential to maintain the function of olfactory nervous system. Hitherto, an increasing number of literatures demonstrate that transplantation of OECs exerts vital roles in neural regeneration and functional recovery after neural injury, including central and peripheral nervous system. It is common knowledge that the deteriorating microenvironment (ischemia, hypoxia, scar, acute and chronic inflammation, etc.) resulting from injured nervous system is adverse for neural regeneration. Interestingly, recent studies indicated that OECs could promote neural repair through improvement of the disastrous microenvironments, especially to the overwhelmed inflammatory responses. Although OECs possess unusual advantages over other cells for neural repair, particularly in SCI, the mechanisms of OEC-mediated neural repair are still controversial with regard to anti-inflammation. Therefore, it is significant to summarize the anti-inflammation property of OECs, which is helpful to understand the biological characteristics of OECs and drive future studies. Here, we mainly focus on the anti-inflammatory role of OECs to make systematic review and discuss OEC-based therapy for CNS injury.


Assuntos
Bulbo Olfatório , Traumatismos da Medula Espinal , Anti-Inflamatórios/metabolismo , Transplante de Células/métodos , Humanos , Regeneração Nervosa/fisiologia , Neuroglia/metabolismo , Bulbo Olfatório/metabolismo , Medula Espinal
17.
Am J Transl Res ; 14(2): 1114-1122, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35273715

RESUMO

Osteochondroma is a common benign bone tumor that is rarely seen in the spine, especially in the atlas. Although most solitary atlas osteochondromas have no symptoms, some exostosis may cause severe clinical symptoms that need treatment within the spine. Here, we report a 21-year-old male who presented with apsychia as well as numbness in his right upper and lower limbs for 2 months. The patient reported a history of neck trauma 10 years ago. He received a posterior laminectomy without reconstruction later, and the symptoms improved immediately. During a 32 month follow-up, there was no recurrence of the osteochondroma. Novel techniques for the treatment of this case were applied: simulated surgical resection using 3-Matic 9.0 software, 3D printed model, 3D Digital Image Microscopy, and piezoelectric surgery. These novel techniques provided significant benefits to the patients, the surgeon, and medical education.

18.
Cell Biosci ; 12(1): 23, 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35246244

RESUMO

OBJECTIVE: The aim of this study was to investigate the pro-angiogenic potential of olfactory ensheathing cells (OECs) activated by curcumin (CCM) and lipopolysaccharide (LPS) and the possible underlying mechanisms. METHODS: Vascular endothelial cells or tissues were cultured and treated with conditioned medium (CM) extracted from activated OECs activated through the addition of LPS and CCM or unactivated controls. Concomitantly, the pro-angiogenic potential of OECs was assessed in vitro by aortic ring sprouting assay, endothelial wound healing assay, CCK-8 assay, and tube formation assay. Subsequently, the OECs were co-cultured with endothelial cells to evaluate their promoting effect on endothelial cell proliferation and migration following a mechanical scratch. Moreover, the spinal cord injury (SCI) model in rats was established, and the number of endothelial cells and vascular structure in the injured area after SCI was observed with OEC transplantation. Finally, the underlying mechanism was investigated by western blot analysis of phosphorylated kinase expression with or without the MK-2206 (Akt-inhibitor). RESULT: The present results showed that the activated OECs can effectively promote vascular endothelial cells' proliferation, migration, and vessel-like structure formation. Strikingly, several pro-angiogenic growth factors such as VEGF-A and PDGF-AA, which facilitate vessel formation, were found to be significantly elevated in CM. In addition, the PI3K/Akt signaling pathway was found to be involved in pro-angiogenic events caused by activated OEC CM, displaying higher phosphorylation levels in cells. In contrast, the delivery of MK2206 can effectively abrogate all the positive effects. CONCLUSIONS: OECs activated by LPS and CCM have a pro-angiogenic effect and can effectively promote angiogenesis and improve the microenvironment at the injury site when transplanted in the injured spinal cord. This potentiated ability of OECs to provide pro-angiogenic effects is likely mediated through the PI3K/Akt pathway.

19.
Spinal Cord ; 60(4): 332-338, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34628476

RESUMO

STUDY DESIGN: Experimental animal study. OBJECTIVES: To assess the feasibility of a custom-designed parallel-moving (PM) clip, compared with a single-axle-lever (SAL) clip, for the development of a compressional spinal cord injury (SCI) model in rats. SETTING: Hospital laboratory in China. METHODS: We used a PM clip and a SAL clip with same compression rate, to develop a SCI model in rats, and set a sham group as a blank control. Within 3 weeks, each group of rats was evaluated for behavioral (Basso-Beattie-Bresnahan locomotor rating score, BBB), and electrophysiological changes (somatosensory evoked potential), and historical staining to observe the differences between the three groups. In particular, the mechanical results of the PM group were calculated. RESULTS: The BBB scores for the SAL and PM groups were significantly lower than those for the sham group (P < 0.05), no significant difference between the two methods (P > 0.05), but the values corresponding to the PM group had smaller standard deviations. The interpeak-latency (IPL) was significantly prolonged (P < 0.0001) and the peak-peak amplitude (PPA) was significantly reduced (P < 0.01) in SAL and PM groups than those in the sham group, but there was no statistical difference in both IPL and PPA between the two SCI groups (P > 0.05). Histological staining showed obvious pathological changes in two SCI groups, and the shape of the lesion zone in the PM group was more symmetrical than that in the SAL groups. CONCLUSIONS: The use of a compressional SCI model in rats with the PM clip we designed is an appropriate method to quantify the injury. The degree of the injury caused by this clip is more stable and uniform than those with classical methods.


Assuntos
Compressão da Medula Espinal , Traumatismos da Medula Espinal , Animais , Modelos Animais de Doenças , Potenciais Somatossensoriais Evocados , Humanos , Ratos , Ratos Sprague-Dawley , Medula Espinal/patologia , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/patologia , Traumatismos da Medula Espinal/patologia , Instrumentos Cirúrgicos
20.
J Pain Res ; 14: 3815-3826, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34934355

RESUMO

OBJECTIVE: The purpose of this study was to introduce and evaluate the early clinical outcomes of the full-endoscopic posterior lumbar interbody fusion (Endo-PLIF) technique with epidural anesthesia (EA) for single-segment lumbar degenerative diseases. METHODS: In this retrospective case series study, we explored the feasibility and effectiveness of the Endo-PLIF with EA for single-segment lumbar degenerative diseases. Between March 2018 and January 2019, a series of 24 patients with single-segment lumbar degenerative diseases underwent Endo-PLIF surgery and were followed up for a minimum of 12 months (15.21±2.27 months). Clinical outcomes including visual analog scale (VAS) scores for back and leg pain, Oswestry Disability Index (ODI) scores, and the Short Form-36 health survey questionnaire (SF-36) were evaluated preoperatively, and postoperatively at 3 days and at 3, 6, and 12-months. RESULTS: All patients underwent successful single-segment Endo-PLIF surgery. The mean operation time was 209.17±39.49 min, and average amount of bleeding was 43.33±14.87 mL. The VAS for lower extremity pain and back pain significantly improved at 3 days, and at 3, 6, 12 months compared with preoperative, respectively. The ODI scores decreased from 42.04±3.96 to 12.75±2.71 (P<0.001) at preoperative and 12 months postoperatively, respectively. The SF-36 Physical Component Scores (PCS) improved from 34.96±4.63 preoperatively to 52.08±6.05 (P<0.001) at 12 months postoperatively. Additionally, the SF-36 Mental Component Scores (MCS) improved from 39.38±5.70 at preoperative to 53.13±5.97 (P<0.001) at 12 months postoperatively. Two patients experienced dysesthesia, and one patient had a wound infection. CONCLUSION: Endo-PLIF with EA is a feasible and valuable technique for the treatment of single-segment lumbar degenerative diseases in selected patients.

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