Prognostic nomogram for microvascular decompression-treated trigeminal neuralgia.

This study aimed to establish an effective prognostic nomogram for microvascular decompression (MVD)-treated trigeminal neuralgia (TN). The nomogram was based on a retrospective cohort study of 1054 patients with TN. During the period 2005-2014, 845 patients at our department treated TN with MVD and served as a development cohort. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. The model was externally validated by 209 TN patients during 2014-2016. Multivariate cox analysis suggested that the patient's age, atypical pain, vascular type, number of offending vessels, and second MVD were significant factors influencing the prognosis of MVD-treated TN. The C index of nomogram in the development cohort was 0.767 (95% CI, 0.739-0.794), and 0.749 (95% CI, 0.688-0.810) in the validation cohort. We developed and validated a nomogram to predict 3-year overall remission rate after MVD treatment of TN. The nomogram can be used in clinical trials to determine the likelihood of pain recurrence in TN patients treated with MVD for 3 years to aid in the comprehensive treatment of TN.

Prognosis Comparison of Different Branches of Trigeminal Neuralgia.

OBJECTIVE: We explored the remission rate of different branches of the trigeminal nerve after microvascular decompression. METHODS: A retrospective analysis of trigeminal neuralgia patients treated with microvascular decompression in our department from January 2014 to January 2015 was conducted to investigate the prognosis and factors affecting prognosis. RESULTS: One-hundred and fifty-five patients with trigeminal neuralgia including 2 patients with V1 division had a remission rate of 100% at 1 day, 3 months, 1 year, and 3 years after surgery; 93.5%, 93.5%, 90.3%, and 67.7% of patients with V1-2 division. The patients with V1-3 division had rates of 91.7%, 87.5%, 75.0%, and 66.7%; V2 division rates were 88.4%, 81.4%, 76.7%, and 69.8%; V2-3 division rates were 90.2%, 90.2%, 87.8%, and 75.6%; and V3 division were 100%, 100%, 92.9%, and 92.9%. CONCLUSIONS: Postoperative remission rate of non-V2-related branches (V1, V3) are higher than V2-related branches (V2, V1-2, V1-3, V2-3).

Surgical effect and electrophysiological study of patients with hemifacial spasm treated with botulinum toxin or acupuncture before microvascular decompression.

OBJECTIVE: We investigated patients with hemifacial spasm (HFS) who received a botulinum toxin (BT) injection or acupuncture before receiving microvascular decompression (MVD) to determine whether it affects the success rate of surgery. Abnormal Muscle Response (AMR) and Compound Motor Action Potential (CMAP) are commonly used as electrophysiological monitoring methods in surgery, and we will compare the differences between these patients in this regard. PATIENTS AND METHODS: A total of 539 patients with HFS underwent MVD treatment in our department between January 2014 and June 2017. Among them, 83 patients had received BT injection before surgery and were recorded as BT group. Eighty-three patients underwent acupuncture before surgery and were recorded as acupuncture group. Five patients received both BT injection and acupuncture before surgery and were recorded as mixed group. A total of 368 patients who had not received any treatment before surgery were recorded as simple MVD group. We calculated the immediate and long-term remission rates after surgery. AMR and CMAP monitoring were routinely performed during surgery. RESULTS: Immediate remission rate after surgery was 96.4% (80/83) in BT group, 100% (83/83) in acupuncture group, 100% (5/5) in mixed group, and 95.1% (350/368) in simple MVD group, and the immediate remission rate of BT group is significantly higher than that of simple MVD group (p = 0.04). Long-term remission rate: the remission rates of the four groups were 94.0% (78/83), 97.6% (81/83), 100.0% (5/5) and 92.7%(341/368), respectively, and there is no statistical difference between them (p > 0.05). The amplitude of one branch or several branches of CMAP on the affected side was lower than the healthy side in BT or acupuncture treatment patients. CONCLUSIONS: A preoperative BT injection or acupuncture treatment do not reduce the postoperative remission rate of HFS patients treated with MVD, and the amplitude of CMAP on the affected side was lower than the healthy side.

The Risk Factors for Facial Numbness After Microvascular Decompression in Patients With Trigeminal Neuralgia.

OBJECT: Microvascular decompression (MVD) is the most popular surgical procedure for treating Trigeminal neuralgia (TN). In this article, the authors conducted a large case series in which patients underwent MVD for TN, and focus on surgical outcomes, intraoperative findings, complications and risk factors. METHODS: From January 2017 to June 2017, a total of 84 patients with TN were treated with MVD in our department. The authors retrospectively analyzed the surgical outcomes and postoperative complications of these patients. Risk factors were analyzed by binary logistic regression analysis. RESULTS: Of the 84 patients, 69 had complete postoperative symptom relief (BNI I-II). A total of 28 patients developed postoperative facial numbness (BNI III-IV) and 1 patient died intraoperatively. With binary logistic regression analysis, significant risk factors for postoperative Facial numbness (FN) were longer operation time (odds ratio [OR] 1.153, P <0.05) and longer hospital stay (OR 1.371, P <0.05). The patients' age, the length of the disease, the gender, and the side of the disease did not affect the occurrence of postoperative FN. CONCLUSIONS: The study found that patients with TN treated with MVD had a good response rate after surgery. The incidence of FN after surgery is not low, and longer duration of surgery and longer hospital stay are risk factors for FN. In the case of ensuring the success rate of surgery, reducing unnecessary operations, reducing the operation time, will help to reduce the occurrence of FN.

Evidence for the association of chromatin and microRNA regulation in the human genome.

Both microRNAs (miRNAs) and chromatin regulation play important roles in cellular processes and they function at different regulatory levels of transcription. Although efforts have been devoted to the investigation of miRNA and chromatin regulation, there's still no comprehensive work to illustrate their relationships due tothe lack of whole-genome wide datasets in different human cellular contexts. Based on the recently published large-scale epigenetic data, we examined the association between miRNA and epigenetic machinery. Our work confirmed a general relationship between miRNA biogenesis and chromatin features around pre-miRNA genomic regions. Obvious enrichments of DNA methylation and several histone modifications were observed within the pre-miRNA genomic region, which werecorrelated with miRNA expression levels. Furthermore, chromatin features at genepromoter regionsweretightly associated with miRNA regulation. Interestingly, we found that genes with their promoter regions located in the active chromatin state regions tend to have a higher probability to be targeted by miRNAs. This worksuggests that miRNAs and chromatin features are often highly coordinated, which provides a guide to deeply understand the complexity of gene regulation.

Knockdown of HDAC1 expression suppresses invasion and induces apoptosis in glioma cells.

Glioma is the most common malignant tumor of the central nervous system, with a low survival rate of five years worldwide. Although high expression and prognostic value of histone deacetylase 1 (HDAC1) have been recently reported in various types of human tumors, the molecular mechanism underlying the biological function of HDAC1 in glioma is still unclear. We found that HDAC1 was elevated in glioma tissues and cell lines. HDAC1 expression was closely related with pathological grade and overall survival of patients with gliomas. Downregulation of HDAC1 inhibited cell proliferation, prevented invasion of glioma cell lines, and induced cell apoptosis. The expression of apoptosis and metastasis related molecules were detected by RT-PCR and Western blot, respectively, in U251 and T98G cells with HDAC1 knockdown. We found that HDAC1 knockdown upregulated expression of BIM, BAX, cleaved CASPASE3 and E-CADHERIN, and decreased expression of TWIST1, SNAIL and MMP9 in U251 and T98G cells with HDAC1 knockdown. In vivo data showed that knockdown of HDAC1 inhibited tumor growth in nude mice. In summary, HDAC1 may therefore be considered an unfavorable progression indicator for glioma patients, and may also serve as a potential therapeutic target.

Overexpression of TREM2 enhances glioma cell proliferation and invasion: a therapeutic target in human glioma.

Gliomas are the most common and aggressive type of primary adult brain tumors. Although TREM2 mutation is reported to be related to Nasu-Hakola disease and Alzheimer's disease, little is known about the association between TREM2 and gliomas. Here, we reported that TREM2 was significantly overexpressed in glioma tissues compared with non-tumorous brain tissues. Furthermore, TREM2 expression was closely related to pathological grade and overall survival of patients with gliomas. Down-regulation of TREM2 in two glioma cell lines, U87 and U373, resulted in a significant reduction in cell proliferation, migration and invasion and a dramatic increase in S phase arrest and apoptosis. In vivo tumorigenesis experiment also revealed that depletion of TREM2 expression inhibited U87 cell proliferation. Moreover, based on gene set enrichment analysis (GSEA) with The Cancer Genome Atlas (TCGA) dataset, we found that TREM2 was positive related to Kyoto Encyclopedia of Genes and Genomes (KEGG) apoptosis, Cromer metastasis and KEGG chemokine pathways, which was further validated by western blot in TREM2 knockdown glioma cells and indicated a possible mechanism underlying its effects on glioma. In summary, our study suggests that TREM2 may work as an oncogene and a new effective therapeutic target for glioma treatment.

TMEM140 is associated with the prognosis of glioma by promoting cell viability and invasion.

BACKGROUND: Gliomas are the most common types of primary brain tumors in the adult central nervous system. TMEM140 is identified as an amplified gene in the human gastric cancer genome. However, the function of TMEM140 in gliomas has not been thoroughly elucidated. The aim of the current study was to determine the clinical significance of TMEM140 expression in patients with gliomas and its effect on tumor cell malignant phenotypes. METHODS: Immunohistochemical analysis and real-time reverse transcription PCR were performed to detect the expression levels of TMEM140 in 70 glioma brain tissue samples. Next, the correlation between the TMEM140 expression levels and the clinical characteristics and outcomes of glioma patients was statistically analyzed. TMEM140 expression was inhibited in two glioma cell lines (i.e., U87 and U373) using a knockdown method with small interfering RNA. Cell Counting Kit-8 and Transwell assays were used to investigate TMEM140 function during cell proliferation, invasion, and migration, respectively. Using flow cytometry and Western blot analysis, we subsequently determined the cell cycle and apoptosis profile of the TMEM140-silenced cells. RESULTS: TMEM140 protein expression was significantly higher in gliomas than in normal brain tissues (p < 0.0001). TMEM140 overexpression was strongly correlated with tumor size, histologic grade, and overall survival time (P < 0.05). TMEM140 decreased cell viability in vitro and dramatically decreased tumor volume in vivo. This phenomenon might be caused by G1 phase cell cycle arrest and cell apoptosis. TMEM140 silencing could suppress the viability, migration, and invasion of glioma cells. CONCLUSIONS: Our results suggest that TMEM140 expression is a prognostic factor that might play an important role in the viability, migration, and invasion of glioma cells. This study highlights the importance of TMEM140 as a novel prognostic marker and as an attractive therapeutic target for gliomas.

The IDO inhibitor coptisine ameliorates cognitive impairment in a mouse model of Alzheimer's disease.

Indoleamine 2,3-dioxygenase (IDO), the first and rate-limiting enzyme in the kynurenine pathway (KP) of tryptophan catabolism, was recently established as one of the potential players involved in the pathogenesis of Alzheimer's disease (AD). Coptisine is a main pharmacological active constituent of the traditional Chinese medicinal prescription Oren-gedoku-to (OGT) which has therapeutic potential for the treatment of AD. Our recent studies have demonstrated that OGT significantly inhibited recombinant human IDO activity, which shed light on the possible mechanism of OGT's action on AD. Here, we characterized the effects of coptisine in an AD mouse model on the basis of its IDO inhibitory ability. Coptisine was found to be an efficient uncompetitive IDO inhibitor with a Ki value of 5.8 µM and an IC50 value of 6.3 µM. In AßPP/PS1 transgenic mice, oral administration of coptisine inhibited IDO in the blood and decreased the activation of microglia and astrocytes, consequently prevented neuron loss, reduced amyloid plaque formation, and ameliorated impaired cognition. Neuronal pheochromocytoma (PC12) cells induced with amyloid-ß peptide 1-42 and interferon-γ showed reduction of cell viability and enhancement of IDO activity, while coptisine treatment increased cell viability based on its reversal effect on the enhanced activity of IDO. In conclusion, our present findings provide further evidence supporting the critical links between IDO, KP, and AD, and demonstrate coptisine, a novel IDO inhibitor, as a potential new class of drugs for AD treatment.