RESUMEN
Obtaining comprehensive structural descriptions of macromolecules within their natural cellular context holds immense potential for understanding fundamental biology and improving health. Here, we present the landscape of protein synthesis inside human cells in unprecedented detail obtained using an approach which combines automated cryo-focused ion beam (FIB) milling and in situ single-particle cryo-electron microscopy (cryo-EM). With this in situ cryo-EM approach we resolved a 2.19 Å consensus structure of the human 80S ribosome and unveiled its 21 distinct functional states, nearly all higher than 3 Å resolution. In contrast to in vitro studies, we identified protein factors, including SERBP1, EDF1 and NAC/3, not enriched on purified ribosomes. Most strikingly, we observed that SERBP1 binds to the ribosome in almost all translating and non-translating states to bridge the 60S and 40S ribosomal subunits. These newly observed binding sites suggest that SERBP1 may serve an important regulatory role in translation. We also uncovered a detailed interface between adjacent translating ribosomes which can form the helical polysome structure. Finally, we resolved high-resolution structures from cells treated with homoharringtonine and cycloheximide, and identified numerous polyamines bound to the ribosome, including a spermidine that interacts with cycloheximide bound at the E site of the ribosome, underscoring the importance of high-resolution in situ studies in the complex native environment. Collectively, our work represents a significant advancement in detailed structural studies within cellular contexts.
Asunto(s)
Fístula del Seno Cavernoso de la Carótida , Trastornos de Deglución , Ronquera , Humanos , Fístula del Seno Cavernoso de la Carótida/complicaciones , Fístula del Seno Cavernoso de la Carótida/diagnóstico por imagen , Ronquera/etiología , Trastornos de Deglución/etiología , Masculino , Femenino , Persona de Mediana EdadRESUMEN
RATIONALE: Lhermitte-Duclos disease (LDD), or dysplastic cerebellar gangliocytoma (DCG), is a rare tumor originating from the cerebellar cortex. LDD is a benign neuroglial tumor with uncertain prognosis. Over 200 cases have been reported in the literature mostly in the form of case reports. Thus, we present a spectacular case of LDD with excessive calcification in a female septuagenarian. PATIENT CONCERNS: A 72-year-old female presented with progressive dizziness for 8 months and suffered a head and sacrococcygeal region injury 20 days prior to her admission in our neurosurgery department. DIAGNOSIS: Computed tomography scan showed a right nonspecific cerebellar mass with striated calcification. Magnetic resonance imaging revealed a right "tiger-striped" alteration of the cerebellar cortex. H&E staining revealed a low grade glial neural tumor which was consistent with the diagnosis of LDD or DCG. INTERVENTION: The lesion was total resected. OUTCOMES: The patient recovered well and the cerebellar dysfunctional symptoms subsided 3 months after the operation and 2 years follow-up revealed no recurrence of the lesion and no neurological deficits. LESION: We postulate that the calcification of LDD is age-related and the pathogenesis of disease often observed in young adulthood.
Asunto(s)
Neoplasias Encefálicas , Calcinosis , Glioma , Síndrome de Hamartoma Múltiple , Femenino , Humanos , Adulto Joven , Adulto , Anciano , Síndrome de Hamartoma Múltiple/complicaciones , Síndrome de Hamartoma Múltiple/diagnóstico , Síndrome de Hamartoma Múltiple/cirugía , Calcinosis/diagnóstico por imagen , Calcinosis/cirugía , Calcificación Fisiológica , CerebeloRESUMEN
Ivermectin (IVM), a semi-synthetic macrolide parasiticide, has demonstrated considerable effectiveness in combating internal and external parasites, particularly nematodes and arthropods. Its remarkable ability to control parasites has earned it significant recognition, culminating in Satoshi Omura and William C. Campbell's receipt of the 2015 Nobel Prize in Physiology or Medicine for their contributions to the development of IVM. In recent years, investigations have revealed that IVM possesses antitumor properties. It can suppress the growth of various cancer cells, including glioma, through a multitude of mechanisms such as selective targeting of tumor-specific proteins, inducing programmed cell death, and modulation of tumor-related signaling pathways. Hence, IVM holds tremendous potential as a novel anticancer drug. This review seeks to provide an overview of the underlying mechanisms that enable IVM's capacity to suppress glioma. Furthermore, it aims to elucidate the challenges and prospects associated with utilizing IVM as a new anticancer agent.
Asunto(s)
Antineoplásicos , Glioma , Humanos , Ivermectina/farmacología , Ivermectina/uso terapéutico , Ivermectina/historia , Glioma/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Premio Nobel , ApoptosisRESUMEN
BACKGROUND: The prognosis of diffuse midline glioma (DMG) patients with H3K27M (H3K27M-DMG) alterations is poor; however, a model that encourages accurate prediction of prognosis for such lesions on an individual basis remains elusive. We aimed to construct an H3K27M-DMG survival model based on DeepSurv to predict patient prognosis. METHODS: Patients recruited from a single center were used for model training, and patients recruited from another center were used for external validation. Univariate and multivariate Cox regression analyses were used to select features. Four machine learning models were constructed, and the consistency index (C-index) and integrated Brier score (IBS) were calculated. We used the receiver operating characteristic curve (ROC) and area under the receiver operating characteristic (AUC) curve to assess the accuracy of predicting 6-month, 12-month, 18-month and 24-month survival rates. A heatmap of feature importance was used to explain the results of the four models. RESULTS: We recruited 113 patients in the training set and 23 patients in the test set. We included tumor size, tumor location, Karnofsky Performance Scale (KPS) score, enhancement, radiotherapy, and chemotherapy for model training. The accuracy of DeepSurv prediction is highest among the four models, with C-indexes of 0.862 and 0.811 in the training and external test sets, respectively. The DeepSurv model had the highest AUC values at 6 months, 12 months, 18 months and 24 months, which were 0.970 (0.919-1), 0.950 (0.877-1), 0.939 (0.845-1), and 0.875 (0.690-1), respectively. We designed an interactive interface to more intuitively display the survival probability prediction results provided by the DeepSurv model. CONCLUSION: The DeepSurv model outperforms traditional machine learning models in terms of prediction accuracy and robustness, and it can also provide personalized treatment recommendations for patients. The DeepSurv model may provide decision-making assistance for patients in formulating treatment plans in the future.
RESUMEN
Objective: Blood-blister aneurysms (BBAs) of the internal carotid artery (ICA) are challenging lesions with high morbidity and mortality rates. Although research on BBAs is well documented in different populations, the study of BBAs in the Tibetan population is extremely rare. This study aimed to evaluate the characteristics of BBAs and analyze the treatment modalities and long-term outcomes in the Tibetan population in comparison with the Han population. Methods: The characteristics of patients with BBAs of the ICA from January 2009 to January 2021 at our institution were reviewed. The features of aneurysms, treatment modalities, complications, and follow-up outcomes were retrospectively analyzed. Results: A total of 130 patients (41 Tibetan and 89 Han patients) with BBAs of the ICA who underwent treatment were enrolled. Compared with the Han group, the Tibetan group significantly demonstrated a high ratio of BBAs among ICAs (8.6%, 41/477 vs. 1.6%, 89/5563; p<0.05), a high ratio of vasospasm (34.1%, 14/41 vs. 6.7%, 6/89; p=0.001), a high risk of ischemic events (43.9%, 18/41 vs. 22.5%, 20/89; p<0.05), and a low ratio of good outcomes (modified Rankin Scale, 0-2) at the 1-year follow-up (51.2%, 21/41 vs. 74.2%, 66/89; p<0.05). The multivariate regression model showed that ischemic events significantly contributed to the prediction of outcomes at 1 year. Further analysis revealed that microsurgery and vasospasm were associated with ischemic events. Conclusion: In comparison with Han patients, the Tibetan population had a high ratio of BBA occurrence, a high incidence of ischemic events, and a high ratio of poor outcomes. The endovascular approach showed more benefits in BBA patients.
RESUMEN
BACKGROUND: H3K27M mutation status significantly affects the prognosis of patients with diffuse midline gliomas (DMGs), but this tumor presents a high risk of pathological acquisition. We aimed to construct a fully automated model for predicting the H3K27M alteration status of DMGs based on deep learning using whole-brain MRI. METHODS: DMG patients from West China Hospital of Sichuan University (WCHSU; n = 200) and Chengdu Shangjin Nanfu Hospital (CSNH; n = 35) who met the inclusion and exclusion criteria from February 2016 to April 2022 were enrolled as the training and external test sets, respectively. To adapt the model to the human head MRI scene, we use normal human head MR images to pretrain the model. The classification and tumor segmentation tasks are naturally related, so we conducted cotraining for the two tasks to enable information interaction between them and improve the accuracy of the classification task. RESULTS: The average classification accuracies of our model on the training and external test sets was 90.5% and 85.1%, respectively. Ablation experiments showed that pretraining and cotraining could improve the prediction accuracy and generalization performance of the model. In the training and external test sets, the average areas under the receiver operating characteristic curve (AUROCs) were 94.18% and 87.64%, and the average areas under the precision-recall curve (AUPRC) were 93.26% and 85.4%. CONCLUSIONS: The developed model achieved excellent performance in predicting the H3K27M alteration status in DMGs, and its good reproducibility and generalization were verified in the external dataset.
Asunto(s)
Aprendizaje Profundo , Glioma , Humanos , Reproducibilidad de los Resultados , Imagen por Resonancia Magnética , Encéfalo , Glioma/diagnóstico por imagen , Glioma/genéticaRESUMEN
H3 K27M-mutant diffuse midline glioma (H3 K27M-mt DMG) is a rare, highly invasive tumor with a poor prognosis. The prognostic factors of H3 K27M-mt DMG have not been fully identified, and there is no clinical prediction model for it. This study aimed to develop and validate a prognostic model for predicting the probability of survival in patients with H3 K27M-mt DMG. Patients diagnosed with H3 K27M-mt DMG in the West China Hospital from January 2016 to August 2021 were included. Cox proportional hazard regression was used for survival assessment, with adjustment for known prognostic factors. The final model was established using the patient data of our center as the training cohort and data from other centers for external independent verification. One hundred and five patients were ultimately included in the training cohort, and 43 cases from another institution were used as the validation cohort. The factors influencing survival probability in the prediction model included age, preoperative KPS score, radiotherapy and Ki-67 expression level. The adjusted consistency indices of the Cox regression model in internal bootstrap validation at 6, 12, and 18 months were 0.776, 0.766, and 0.764, respectively. The calibration chart showed high consistency between the predicted and observed results. The discrimination in external verification was 0.785, and the calibration curve showed good calibration ability. We identified the risk factors that affect the prognosis of H3 K27M-mt DMG patients and then established and validated a diagnostic model for predicting the survival probability of these patients.
Asunto(s)
Astrocitoma , Neoplasias Encefálicas , Glioma , Humanos , Pronóstico , Neoplasias Encefálicas/patología , Glioma/diagnóstico , Glioma/genética , Glioma/patología , Histonas/genética , Nomogramas , MutaciónRESUMEN
In this case report, we present an extremely rare and previously unreported case of skull osteoma relapse without any attachment to the skull after hydroxyapatite cement (HAC) cranioplasty. The 49-year-old male patient was admitted with recurrence of the left frontal skull lesion; he underwent craniectomy and HAC cranioplasty for a left frontal osteoma 14 years before. Intraoperative findings disclosed multiple irregular lesions located on the HAC flap without any attachment to the bony structure and the roots of the lesions originating from the outer layer of the dura through several reserved holes. Pathological diagnosis was osteoma. The purpose of this report is to document this rare occurrence and provide the most probable pathogenesis for this rare event.
RESUMEN
Diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) are the most lethal brain tumors that primarily occur in pediatric and adult patients, respectively. Both tumors exhibit significant heterogeneity, shaped by distinct genetic/epigenetic drivers, transcriptional programs including RNA splicing, and microenvironmental cues in glioma niches. However, the spatial organization of cellular states and niche-specific regulatory programs remain to be investigated. Here, we perform a spatial profiling of DMG and GBM combining short- and long-read spatial transcriptomics, and single-cell transcriptomic datasets. We identify clinically relevant transcriptional programs, RNA isoform diversity, and multi-cellular ecosystems across different glioma niches. We find that while the tumor core enriches for oligodendrocyte precursor-like cells, radial glial stem-like (RG-like) cells are enriched in the neuron-rich invasive niche in both DMG and GBM. Further, we identify niche-specific regulatory programs for RG-like cells, and functionally confirm that FAM20C mediates invasive growth of RG-like cells in a neuron-rich microenvironment in a human neural stem cell derived orthotopic DMG model. Together, our results provide a blueprint for understanding the spatial architecture and niche-specific vulnerabilities of DMG and GBM.
Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Adulto , Humanos , Niño , Transcriptoma/genética , Ecosistema , Células Ependimogliales , Glioma/genética , Glioma/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Glioblastoma/genética , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: The pineal tumor was once considered as a restricted area for surgery. Such cases are rare, with many different opinions on surgical treatment. This study aimed to review our experience of tumor treatment in the pineal region and explore the optimal treatment strategy. METHODS: The clinical data of 72 patients with pineal tumors from January 1997 to May 2015 (18 years) were retrospectively analyzed. Preoperative preparation, pathology type, tumor resection rate, surgical approach, and follow-up outcomes were used as the indicators to evaluate the treatment efficacy. RESULTS: The Krause approach was used in 46 cases, the Poppen approach in 10 cases, and the transcallosal-lateral ventricle-choroid fissure approach in 16 cases. The postoperative pathological results were as follows: 24 cases of germinoma, 11 of teratoma, 15 of glioma, 6 of meningioma, 11 of Pineocytoma, 2 of cholesteatoma, 2 of cavernous hemangioma, and 1 of choriocarcinoma. Further, the study included 64 cases of total surgical resections, 8 of subtotal resections, and 2 deaths. The follow-up period was from 7 months to 10 years. Further, 51 (70.8%) patients were followed up. The multivariate regression model showed that the surgical method and the pathological type contributed significantly to predicting outcomes. CONCLUSIONS: The type of pathology, extent of excision, and surgical approach had a significant impact on the prognosis of patients. The transcallosal-lateral ventricle-choroid fissure approach for large and medium-sized pineal tumors near the posterior part of the third ventricle had good efficacy.
Asunto(s)
Neoplasias Encefálicas , Neoplasias Meníngeas , Glándula Pineal , Pinealoma , Humanos , Pinealoma/cirugía , Pinealoma/patología , Estudios Retrospectivos , Glándula Pineal/cirugía , Glándula Pineal/patología , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Neoplasias Meníngeas/patologíaRESUMEN
BACKGROUND: The current molecular classifications cannot completely explain the polarized malignant biological behavior of low-grade gliomas (LGGs), especially for tumor recurrence. Therefore, we tried to identify suspicious hub genes related to tumor recurrence in LGGs. METHODS: In this study, we constructed a gene-miRNA-lncRNA co-expression network for LGGs by a weighted gene co-expression network analysis (WGCNA). GDCRNATools and the WGCNA R package were mainly used in data analysis. RESULTS: Sequencing data from 502 LGG patients were analyzed in this study. Compared with recurrent glioma tissues, we identified 774 differentially expressed (DE) mRNAs, 49 DE miRNAs, and 129 DE lncRNAs in primary LGGs and ultimately determined that the expression of MKLN1 was related to tumor recurrence in LGG. CONCLUSION: This study identified the potential biomarkers for the pathogenesis and recurrence of LGGs and proposed that MKLN1 could be a potential therapeutic target.
Asunto(s)
Neoplasias Encefálicas , Glioma , MicroARNs , Humanos , Neoplasias Encefálicas/patología , Recurrencia Local de Neoplasia/genética , Glioma/patología , MicroARNs/genética , Redes Reguladoras de GenesRESUMEN
BACKGROUND: Coronavirus disease-2019 (COVID-19) led to a global pandemic in March 2020 that has involved tens of millions of people. To date, prophylactic vaccines have been found to be the most effective method to contain the pandemic. Bullous pemphigoid (BP) is an autoimmune skin disease that mainly affects older individuals. CASE REPORTS: The authors report 2 confirmed cases of BP in patients with history of cerebral infarction who received the inactivated severe acute respiratory syndrome coronavirus 2 vaccine. A 67-year-old woman was hospitalized for a generalized rash that appeared 7 days after the first dose of inactivated COVID-19 vaccine. The rash was aggravated after the second dose. The second patient was a 66-year-old woman who was hospitalized for a generalized rash that appeared 10 days after the first dose of inactivated COVID-19 vaccine. There were no abnormalities in the baseline blood tests. Laboratory and histologic examinations confirmed the diagnosis of BP. The patients were treated with systemic glucocorticoids, antibiotics, topical corticosteroids, and emollients, which resulted in a significant reduction in pruritus and regression of lesions after 2 weeks. CONCLUSION: Two patients with a genetic background of HLA-DQB1*0302 had BP after vaccination in China. However, there is not enough evidence to indicate a requirement for genetic screening before receiving inactivated severe acute respiratory syndrome coronavirus 2 vaccines.
Asunto(s)
COVID-19 , Penfigoide Ampolloso , Femenino , Humanos , Anciano , SARS-CoV-2 , Vacunas de Productos Inactivados/uso terapéutico , Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , Pandemias/prevención & control , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/etiologíaRESUMEN
PURPOSE: We aimed to explore the influence of preoperative gamma knife treatment on the clinical effect of microsurgical resection of vestibular schwannoma. METHODS: The data of patients who underwent vestibular schwannoma resection in our hospital between November 2010 and December 2019 were retrospectively collected. According to the data collected retrospectively and the inclusion and exclusion criteria, we selected these patients and divided them into Group A (with preoperative gamma knife treatment) and Group B (without preoperative gamma knife treatment). The pre/postoperative clinical manifestations, neurological function grade, postoperative complications, tumor recurrence and increase were collected and compared between the two groups. RESULTS: There were 40 and 823 patients enrolled in Groups A and B, respectively. There were no significant differences in the general condition, tumor size and side, or neurological performance of the patients in those two groups before the operation. At the last follow-up, the number of patients with poor facial nerve function was 15 (39.5%) in Group A and 170 (20.7%) in Group B (P = 0.021 < 0.05). In Group A and Group B, disequilibrium occurred in 14 (36.8%) patients and 124 (15.1%) patients, respectively, after the operation (P = 0.012 < 0.05). Seven (17.5%) patients had pneumonia in Group A, and 21 (2.6%) patients had pneumonia in Group B (P = 0.04 < 0.05) after the operation. CONCLUSION: When a patient with vestibular schwannoma undergoes microsurgical surgery, the preoperative history with gamma knife treatment may make recovery from postoperative facial paralysis difficult for the patients, making them more prone to suffer from postoperative disequilibrium and postoperative pneumonia.
Asunto(s)
Neuroma Acústico , Radiocirugia , Humanos , Neuroma Acústico/patología , Estudios Retrospectivos , Resultado del Tratamiento , Recurrencia Local de Neoplasia/cirugía , Radiocirugia/efectos adversos , Nervio Facial/patologíaRESUMEN
Ventriculoperitoneal (VP) shunt disconnection, a VP shunt complication, can be caused by several factors. We report the case of a young man who suffered VP shunt disconnection, and whose entire distal catheter migrated into the abdominal cavity due to a seizure. To our knowledge, risk factors for seizures related to shunt disconnection have not been previously evaluated. We report this rare case to highlight the fact that seizures are not negligible in increasing the probability of disconnection and migration of the entire distal catheter into the abdominal cavity, and the standardized treatment of traumatic seizures is extremely important.
RESUMEN
Numerous studies have elucidated the neuroprotective effect of 6-gingerol in central nervous system diseases. However, the potential role and mechanism of 6-gingerol on early brain injury (EBI) after subarachnoid hemorrhage (SAH) remains poorly understood. Here, we report that 6-gingerol exerts a neuroprotective effect on SAH-induced EBI through the GBP2/PI3K/AKT pathway. A SAH rat model was established by injecting femoral artery blood into the cisterna magna. 6-gingerol or vehicle was injected intraperitoneally 1 hour post-SAH induction. We found that the neurological function score and brain edema of SAH rats were significantly improved after 6-gingerol treatment, as well as neuronal apoptosis was attenuated in SAH rats by Nissl staining assay and TUNEL assay. To further explore potential molecular mechanisms associated with 6-gingerol, RNA sequencing was implemented to investigate the differences in transcriptomes between SAH rats with and without 6-gingerol treatment; and found that the expression of guanylate-binding protein 2 (GBP2) evidently was suppressed with 6-gingerol treatment compared to vehicle group. In addition, dual immunofluorescence was also employed to investigate changes in neurons, astrocytes, and microglia after 6-gingerol treatment. The results showed that GBP2 was expressed in neurons but not astrocytes or microglia. Western blotting analysis results demonstrated that the PI3K/AKT pathway was activated in the SAH rats treated with 6-gingerol. Furthermore, recombinant GBP2 protein and LY294002 (PI3K inhibitor) treatment reversed the effects of 6-gingerol treatment in SAH rats. These results indicate that 6-gingerol suppressed the expression of GBP2 to activate the PI3K/AKT pathway, improve neurologic outcomes, reduce brain edema and neuronal apoptosis. In summary, our findings suggest that 6-gingerol could attenuate EBI post-SAH in rats, and 6-gingerol may serve as a novel candidate neuroprotective drug for SAH-induced EBI.
RESUMEN
INTRODUCTION: Radiation induced gliomas often occurs after radiation therapy for other brain tumors. Medulloblastoma often occurs in children and its associated radiation-induced glioblastoma multiforme's (GBM) after radiotherapy often has a long latency period. Our case is very unique because the medulloblastoma was detected at an advance age and the latency period of radiation-induced GBM was relatively shorter. PATIENTS CONCERNS: A 64-year-old male was first admitted at our hospital in March 2018 with dizziness, vomiting, and blurred vision. DIAGNOSIS: Magnetic resonance imaging of brain revealed a lesion with local mixed density and mass enhancement in left cerebellar region. Histopathology established medulloblastoma (World Health Organization) grade 4 and a classic histological subtype after surgery. INTERVENTION: Surgical resection followed by radiation therapy were the initial therapeutic modalities. OUTCOMES: In April 2019, the patient was readmitted with dizziness and blurred vision. Magnetic resonance imaging showed the left cerebellar hemisphere bulky enhancement lesion. Again, a multimodal therapy comprising surgical resection, radiation therapy as well as chemotherapy was adapted after histopathology established GBM. LESION: Radiotherapy for medulloblastoma patients at advance ages is a critical predisposing factor for the development of radiation-induced GBM in a very short period of time. We suggest that, radiotherapy as adjuvant therapy for medulloblastoma patients at advance ages should be chosen with extreme caution.
Asunto(s)
Neoplasias Cerebelosas/terapia , Glioblastoma/etiología , Meduloblastoma/terapia , Neoplasias Inducidas por Radiación/etiología , Radioterapia Adyuvante/efectos adversos , Terapia Combinada , Humanos , Masculino , Persona de Mediana EdadRESUMEN
RATIONALE: Foramen magnum meningiomas are very rare lesions. They frequently originate from the arachnoid cells at the dura matter of the craniocervical junction. Foramen magnum meningiomas are challenging for neurosurgeons because of the complex anatomy of foramen magnum. We present a rare case of FMM with excessive calcification and without the dura tail sign which made the lesion mimic a teratoma. PATIENTS CONCERNS: A 63âyears old woman presented with progressive numbness and hyperesthesia of the shoulders and upper limbs for 2 and half years. She also experienced occasional headaches and dizziness with no nausea, vomiting or fever. DIAGNOSES: Computed tomography scan, and magnetic resonance imaging revealed a calcified mass at occipital cistern. The lesion did not show the usual "dura tail sign" which made it mimic a teratoma on magnetic resonance imaging. Histopathology established meningioma. INTERVENTION: The tumor was completely resected via suboccipital approach. OUTCOMES: Two years follow-up revealed no recurrence of the lesion and no neurological deficits. LESSONS: We advocate the use of electromyographic and auditory brainstem responses to monitor the inferior cranial nerves because the tumor often adheres to these nerves.