Online dynamic nomogram for predicting pain recurrence after microvascular decompression in trigeminal neuralgia.

Trigeminal neuralgia (TN) is one of the most common causes of facial pain. Microvascular decompression (MVD) is the first-choice surgical treatment. The present study aimed to develop a novel practical assessment system based on preoperative clinical and imaging factors for clinicians to predict the likelihood of pain recurrence following MVD in TN. A total of 56 patients with primary unilateral TN who underwent MVD were retrospectively analyzed. Patients were followed up to observe pain recurrence 1 year after MVD. An online dynamic nomogram was constructed for predicting the probability of pain recurrence after MVD in patients with TN based on multivariate logistic model. The concordance index (C-index) and receiver operating characteristic (ROC) were used to measure model discrimination. Bootstrap resampling was used for internal validation of the model and calibration curve was constructed. Decision curve analysis (DCA) was used to assess clinical applicability. Factors such as numeric rating scale (to score pain degree of patients with TN), response to neuroanalgesic drugs and neurovascular contact on magnetic resonance imaging were independent risk factors affecting the pain recurrence rate (all P<0.05). C-index was 0.973 (95%CI, 0.938-1.000) and the area under the ROC was 0.973 (95%CI, 0.938-1.000). Calibration curve with a 1,000 bootstrap resampling showed a good fit between dynamic nomogram prediction and actual observations. The DCA showed that at a threshold probability between 0 and 100%, this model can achieve a greater net benefit than if all patients had surgery or none had surgery. In conclusion, this online dynamic nomogram reliably predicted risk of pain recurrence in patients with TN following MVD.

Experimental study on tilting deformation and a new method for landslide prediction with retaining-wall locked segment.

The destruction of the locked-segment type landslide is often accompanied by the destruction of the locked segment with cumulative effects. Investigating the failure mode and instability mechanism of locked-segment type landslides is crucial. The study uses physical models to examine the evolution of locked-segment type landslides with retaining-walls. It utilizes a variety of instruments (tilt sensors, micro earth pressure sensors, pore water pressure sensors, strain gauges, and others) to conduct physical model tests of locked-segment type landslide with retaining-wall and to reveal the tilting deformation and evolution mechanism of retaining-wall locked landslide under the condition of rainfall. The results showed that the regularity of tilting rate, tilting acceleration, strain, and stress change in the retaining-wall locked segment is consistent with the landslide evolution process, indicating that tilting deformation can be used as the criterion of landslide instability and that the locked segment plays a vital role in controlling the landslide stability. The tertiary creep stages of tilting deformation are divided into initial, medium, and high tertiary creep stages using an improved angle tangent method. This establishes the failure criterion for locked-segment type landslides with tilting angles of 0.34°, 1.89°, and 4.38°. In addition, the tilting deformation curve of a locked-segment type landslide with a retaining-wall is utilized to predict the landslide instability by the reciprocal velocity method.

Secondary cerebellopontine angle oligodendroglioma after cranial irradiation: a case report and literature review.

PURPOSE/AIM: Cerebellopontine angle (CPA) oligodendrogliomas are very rare, and only three preoperative cases have been confirmed. Secondary CPA oligodendrogliomas after radiation therapy are exceptionally rare, and no other cases have been reported. CASE REPORT: We present a case of a 25-year-old male with CPA oligodendroglioma who experienced hearing loss in right ear with walking instability for more than 2 months. The patient underwent craniotomy in our hospital because of grade II astrocytoma of the right temporal lobe 10 years ago. Postoperative radiotherapy lasted for 30 days, and six rounds of chemotherapy were performed. Magnetic resonance imaging (MRI) of the head revealed a cystic lesion located in the right CPA. The patient underwent surgery without obvious complications, and the tumor was subtotally removed. Histopathological examination revealed a diagnosis of oligodendroglioma, World Health Organization (WHO) grade II. The patient was discharged on the tenth postoperative day with a good recovery. Two weeks after discharge, chemotherapy with temozolomide and radiotherapy were performed. The patient remained well at 8 months follow-up. CONCLUSIONS: To the best of our knowledge, no other cases of secondary CPA oligodendroglioma after cranial irradiation have been reported in the literature. Compared with general oligodendroglioma, the tumor has no typical calcification and is more aggressive. The cranial nerves in the CPA area are closely adhered, and the blood supply is abnormally rich. It is difficult to completely remove the tumor. Postoperative radiotherapy and chemotherapy should be carried out as soon as possible.

Risk Prediction in Patients With Heart Failure With Preserved Ejection Fraction Using Gene Expression Data and Machine Learning.

Heart failure with preserved ejection fraction (HFpEF) has become a major health issue because of its high mortality, high heterogeneity, and poor prognosis. Using genomic data to classify patients into different risk groups is a promising method to facilitate the identification of high-risk groups for further precision treatment. Here, we applied six machine learning models, namely kernel partial least squares with the genetic algorithm (GA-KPLS), the least absolute shrinkage and selection operator (LASSO), random forest, ridge regression, support vector machine, and the conventional logistic regression model, to predict HFpEF risk and to identify subgroups at high risk of death based on gene expression data. The model performance was evaluated using various criteria. Our analysis was focused on 149 HFpEF patients from the Framingham Heart Study cohort who were classified into good-outcome and poor-outcome groups based on their 3-year survival outcome. The results showed that the GA-KPLS model exhibited the best performance in predicting patient risk. We further identified 116 differentially expressed genes (DEGs) between the two groups, thus providing novel therapeutic targets for HFpEF. Additionally, the DEGs were enriched in Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways related to HFpEF. The GA-KPLS-based HFpEF model is a powerful method for risk stratification of 3-year mortality in HFpEF patients.

Extensive craniospinal disseminated metastasis after the resection of intradural extramedullary ependymoma in the craniocervical junction: a case report and literature review.

PURPOSE/AIM: Intradural extramedullary (IDEM) ependymomas are very rare, and IDEM ependymomas with craniospinal disseminated metastasis are exceptionally rare; only 2 preoperative cases have been confirmed, and postoperative cases have not been reported. CASE REPORT: We present a case of a 21-year-old female with an IDEM ependymoma of the craniocervical junction who experienced head and neck pain for more than 1 month. Magnetic resonance imaging (MRI) of the cervical spine revealed a large IDEM cystic lesion located in the medulla oblongata and the upper cervical spinal cord. The patient underwent surgery without complications, and the tumor was completely removed. Histopathological examination revealed a diagnosis of aplastic ependymoma, World Health Organization (WHO) grade III. The patient failed to follow-up with radiotherapy for one month after discharge. Nearly three months after surgery, craniospinal disseminated metastasis was found in the patient; subsequently, chemoradiotherapy was administered to prolong the survival time of the patient. Unfortunately, the patient underwent radiotherapy and chemotherapy for only 7 days; then, the patient gave up treatment and died 5 months later. CONCLUSIONS: To the best of our knowledge, no other cases of craniocervical junction anaplastic ependymomas with craniospinal disseminated metastasis have been reported in the literature. Total resection does not completely prevent recurrence and metastasis, and MRI of the entire neuraxis and timely postoperative craniospinal radiotherapy are necessary for the treatment of this disease.

TGF-ß-mediated repression of MST1 by DNMT1 promotes glioma malignancy.

Human gliomas are related to high rates of morbidity and mortality. TGF-ß promotes the growth of glioma cells, and correlate with the degree of malignancy of human gliomas. However, the molecular mechanisms involved in the malignant function of TGF-ß are not fully elucidated. Here, we showed that TGF-ß induced the downregulation of MST1 expression in U87 and U251 glioma cells. Treatment of glioma cells with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-AzadC) prevented the loss of MST1 expression. Addition of 5-AzadC also reduced the TGF-ß-stimulated proliferation, migration and invasiveness of glioma cells. Furthermore, Knockdown of DNMT1 upregulated MST1 expression in gliomas cells. In addition, the inhibition of DNMT1 blocked TGF-ß-induced proliferation, migration and invasiveness in glioma cells. These results suggest that TGF-ß promotes glioma malignancy through DNMT1-mediated loss of MST1 expression.

Osteosarcoma of the skull base: An analysis of 19 cases and literature review.

BACKGROUND: Osteosarcoma of the skull base is rarely observed; most published studies comprise case reports. The clinical features and optimal treatments have not been clearly established. The purpose of this article is to present 19 cases of skull base osteosarcoma and review the literature to analyse the clinical features and treatment of skull base osteosarcoma. METHODS: The clinical data of 19 patients with skull base osteosarcoma from January 2005 to December 2016 were retrospectively analysed; pertinent English literature from 1976 to 2016 was reviewed. RESULTS: Six female and 13 male patients were included. The ages ranged from 11 to 55years (mean 34years). Gross-total resection of the tumour was achieved in 13 cases, and nearly total resection was achieved in 6 cases. Five cases were treated with surgery alone, whereas 14 cases received comprehensive treatment. The follow-up period ranged from 3 to 132months (mean 33months) with 17 patients who underwent follow-up. The median survival durations of the patients who underwent surgery alone and who received comprehensive treatment were 18 and 50months, respectively. The literature results were similar to the current findings. Overall, the 5-year survival rates of the patients in our series and in the literature were 30.5% and 37.8%, respectively. CONCLUSIONS: Skull base osteosarcoma had a low complete resection rate, a high recurrence rate and a poor prognosis because of the complex anatomy and vital structures involved. Radical surgery with comprehensive treatment is most appropriate for this disease.

Glia-derived ATP inversely regulates excitability of pyramidal and CCK-positive neurons.

Astrocyte responds to neuronal activity with calcium waves and modulates synaptic transmission through the release of gliotransmitters. However, little is known about the direct effect of gliotransmitters on the excitability of neuronal networks beyond synapses. Here we show that selective stimulation of astrocytes expressing channelrhodopsin-2 in the CA1 area specifically increases the firing frequency of CCK-positive but not parvalbumin-positive interneurons and decreases the firing rate of pyramidal neurons, phenomena mimicked by exogenously applied ATP. Further evidences indicate that ATP-induced increase and decrease of excitability are caused, respectively, by P2Y1 receptor-mediated inhibition of a two-pore domain potassium channel and A1 receptor-mediated opening of a G-protein-coupled inwardly rectifying potassium channel. Moreover, the activation of ChR2-expressing astrocytes reduces the power of kainate-induced hippocampal ex vivo gamma oscillation. Thus, through distinct receptor subtypes coupled with different K+ channels, astrocyte-derived ATP differentially modulates the excitability of different types of neurons and efficiently controls the activity of neuronal network.

A novel size-based sorting mechanism of pinocytic luminal cargoes in microglia.

Microglia are the resident immune cells in the CNS and play diverse roles in the maintenance of CNS homeostasis. Recent studies have shown that microglia continually survey the CNS microenvironment and scavenge cell debris and aberrant proteins by phagocytosis and pinocytosis, and that reactive microglia are capable to present antigens to T cells and initiate immune responses. However, how microglia process the endocytosed contents and evoke an immune response remain unclear. Here we report that a size-dependent selective transport of small soluble contents from the pinosomal lumen into lysosomes is critical for the antigen processing in microglia. Using fluorescent probes and water-soluble magnetic nanobeads of defined sizes, we showed in cultured rodent microglia, and in a cell-free reconstructed system that pinocytosed proteins become degraded immediately following pinocytosis and the resulting peptides are selectively delivered to major histocompatibility complex class II (MHC-II) containing lysosomes, whereas undegraded proteins are retained in the pinosomal lumen. This early size-based sorting of pinosomal contents relied on the formation of transient tunnel between pinosomes and lysosomes in a Rab7- and dynamin II-dependent manner, which allowed the small contents to pass through but restricted large ones. Inhibition of the size-based sorting markedly reduced proliferation and cytokine release of cocultured CD4(+) T cells, indicating that the size-based sorting is required for efficient antigen presentation by microglial cells. Together, these findings reveal a novel early sorting mechanism for pinosomal luminal contents in microglial cells, which may explain how microglia efficiently process protein antigens and evoke an immune response.