Clinical Outcomes of Anterior Cervical Decompression and Fusion Therapy for Patients With Hirayama Disease.

OBJECTIVES: To investigate the clinical outcomes of anterior cervical decompression and fusion (ACDF) surgery for the treatment of Hirayama disease (HD). METHODS: In this study, 15 patients with HD who underwent ACDF operation between March 2022 and March 2023 with complete data were retrospectively analyzed. Following the diagnosis, conservative treatment was ineffective, and thus, disease progression severely affected the quality of life (QOL) of patients. ACDF was performed in the China-Japan Friendship Hospital, and patients were regularly followed up postoperatively. The cervical range of motion (ROM), the anteroposterior and transverse diameter of the spinal cord, and their ratio was measured before and after the operation. The neurologic function of patients before and after the last follow-up was evaluated using the selected brief-Michigan Hand Questionnaire (sb-MHQ), whilst the overall therapeutic effect after the operation was evaluated using Odom's criteria. RESULTS: All patients were followed up for an average of 12 ± 4.5 (6-18) months. Dynamic X-ray displayed that the ROM of cervical vertebrae decreased from 72.73 ± 12.72° (53-97°) to 33.53° ± 10.34° (15-54°) (P < 0.001). Moreover, flexion cervical magnetic resonance imaging (MRI) performed after the operation revealed that spinal cord compression was markedly relieved, and the ratio of the anteroposterior diameter of the spinal cord to the transverse diameter increased from 0.27 ± 0.09 to 0.43 ± 0.03 (P < 0.001). At the last follow-up visit, finger extension tremor symptoms were alleviated, although they did not completely disappear. Contrastingly, muscle atrophy showed no significant improvement. Finally, the sb-MHQ score significantly increased from 17.33±1.76 preoperatively to 24.80±1.78 at the last follow-up (P<0.001). CONCLUSIONS: Our results collectively highlighted the efficacy of ACDF for the treatment of HD. This procedure can limit excessive cervical flexion and repeated compression of the spinal cord during cervical movement and considerably improve upper limb functions.

[Rapid determination of five halobenzoquinones in aquatic products by QuEChERS-ultra performance liquid chromatography-tandem mass spectrometry].

Halobenzoquinones (HBQs), which are emerging chlorinated disinfection byproducts (DBPs), have attracted increasing attention because they are frequently detected in treated tap water, entrainment water, etc. These compounds are mainly generated during the water treatment process using chlorine, chloramine, and chlorine dioxide as disinfectants, and display more toxic effects than regulated DBPs, such as trihalomethane and haloacetic acid. HBQs have been recognized as potential bladder carcinogens and are harmful to the nervous system. Additionally, they can exert genotoxic effects and cause oxidative damage to DNA and proteins. The risk of HBQs in aquatic products is expected to rise because the disinfection of public facilities has significantly increased in recent years. Therefore, developing a sensitive and accurate analytical method to detect HBQs in aquatic products is of great importance. Several analytical methods, including gas chromatography, gas chromatography-mass spectrometry, electrochemical methods, liquid chromatography, and liquid chromatography-tandem mass spectrometry, can be used to identify and quantify HBQs in water. However, to the best of our knowledge, no reports on the determination of HBQ levels in aquatic products are yet available. Further, pretreatment is essential for HBQ determination because of the complex matrix effects of aquatic products. Herein, a sensitive and accurate method based on the QuEChERS technique coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of five HBQs in aquatic products. For the QuEChERS procedure, the pretreatment conditions, such as the extraction solvent and adsorbent species, were systematically optimized. The sample was extracted with 10 mL of 10% methanol acetonitrile solution (containing 0.1% formic acid), dehydrated, and centrifuged with sodium chloride and anhydrous magnesium sulfate. The supernatant was purified using a QuEChERS packing material consisting of 50 mg N-propylethylenediamine (PSA), 30 mg of graphitized carbon black (GCB), and 30 mg of neutral alumina (Al2O3), dried with nitrogen, and concentrated. The five HBQs were separated on a Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm) using 0.25% acetonitrile formate solution and 0.25% formic acid aqueous solution as the mobile phase under a gradient elution program and then detected using UPLC-MS/MS with negative electrospray ionization (ESI-) under multiple reaction monitoring (MRM) mode. Quantitative analysis was performed using a matrix-matched external standard method. The five HBQs achieved rapid separation within 6 min, indicating that the proposed method has a much shorter separation time compared with previous studies. The matrix effect was evaluated by establishing a matrix-matched calibration curve. The results showed that 2,5-dichloro-1,4-benzoquinone (2,5-DCBQ) presented a matrix-enhancing effect, whereas the other HBQs displayed matrix-inhibiting effects. In particular, tetrachlorobenzoquinone (TCBQ) exhibited strong inhibitory effects. Under the optimized experimental conditions, the five HBQs demonstrated good linear relationships in the range of 1.0-50.0 µg/L, with correlation coefficients (r)≥0.9992. The detection limits of the method were 0.15-0.8 µg/kg, and the recoveries of the target compounds were 85.9%-116.5%. The relative standard deviations were 1.4%-8.2%, which indicates good reproducibility. The proposed method was successfully applied to actual sample detection, and 2,6-dichloro-3-methyl-1,4-benzoquinone (2,6-DCMBQ) was detected in grass carp. The proposed method is convenient, sensitive, accurate, and suitable for the simultaneous determination of five HBQs in aquatic products. Moreover, the developed method provides a reliable reference for the routine monitoring of trace HBQs in food samples.

Rapid determination of 14 odorous compounds in drinking water using gas chromatography-mass spectrometry coupled with headspace solid-phase microextraction pretreatment.

A sensitive and effective method was developed for the simultaneous determination of 14 odorous compounds in drinking water using gas chromatography-mass spectrometry (GC-MS) coupled with headspace solid phase microextraction (HS-SPME) pretreatment. The influencing factors including SPME fiber, ionic strength, temperature and time on the pretreatment procedure were evaluated systematically. Under the optimized conditions, 10 mL of the samples added with 1.0 g sodium chloride was extracted by CAR/PDMS fiber at 60 °C for 30 min and then desorbed at 280 °C for 3 min. The analytes achieved good linearity as the mass concentrations were in the range of 0.0020-10.0 µg L-1 with correlation coefficients higher than 0.9990. The limits of detection (LODs) ranging between 0.2 and 50 ng L-1 were lower than the olfactory threshold of these studied compounds. Satisfactory recoveries were obtained ranging from 84.8% to 110.6%, and good reproducibility indicated by relative standard deviation (RSD) in the range of 0.50-9.5% was obtained as well. The proposed method was convenient, sensitive and accurate, which was suitable for the routine monitoring 14 odorous compounds in water.

Analysis of power spectrum and phase lag index changes following deep brain stimulation of the anterior nucleus of the thalamus in patients with drug-resistant epilepsy: A retrospective study.

OBJECTIVES: The mechanisms underlying the anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) for the treatment of drug-resistant epilepsy (DRE) have not been fully explored. The present study aimed to measure the changes in whole-brain activity generated by ANT DBS using interictal electroencephalography (EEG). MATERIALS AND METHODS: Interictal EEG signals were retrospectively collected in 20 DRE patients who underwent ANT DBS surgery. Patients were classified as responders or non-responders depending on their response to ANT DBS treatment. The power spectrum (PS) and Phase Lag Index (PLI) were determined and data analyzed using a paired sample t-test to evaluate activity differences between pre-and-post-treatment on different frequency categories. Student's t-test, Mann-Whitney test (non-parametric test) and Fisher exact test were used to compare groups in terms of clinical variables and EEG metrics. P values < 0.05 were considered statistically significant, and FDR-corrected values were used for multiple testing. RESULTS: PS analysis revealed that whole-brain spectral power had a significant decrease in the beta (p = 0.005) and gamma (p = 0.037) bands following ANT DBS treatment in responders. The analysis of scalp topographic images of all patients showed that ANT DBS decreases PS in the beta band at the F3, F7 and Cz electrode sites. The findings indicated a decrease in PS in the gamma band at the Fp2, F3, Cz, T3, T5 and Oz electrode sites. After ANT DBS treatment, PLI analysis showed a significant decrease in PLI between Fp1 and T3 in the gamma band in responders. CONCLUSION: The findings showed that ANT DBS induces a decrease in power in the left frontal lobe, left temporal lobe and midline areas in the beta and gamma bands. Lower whole-brain power in the beta and gamma bands can be used as biomarkers for a favorable therapeutic response to ANT DBS, and decreased synchronization between the left frontal pole and temporal lobe in the gamma band can also be used as a biomarker for effective clinical stimulation to guide postoperative programming.

Vagus nerve stimulation for drug-resistant epilepsy induced by tuberous sclerosis complex.

OBJECTIVE: This study investigated the dynamic and long-term efficacy of vagus nerve stimulation (VNS) in patients with drug-resistant epilepsy (DRE) induced by tuberous sclerosis complex (TSC). In addition, the impact of VNS on cognition and emotion after a one-year follow-up was evaluated. METHODS: A total of 17 patients diagnosed with DRE induced by TSC were retrospectively recruited between 2008 and 2019. Dynamic changes in seizure frequency were observed in the responders (≥50% reduction of seizure frequency at last follow-up) and non-responders. Clinical characteristics and seizure outcomes were comprehensively analyzed to determine factors associated with seizure outcomes. The Wechsler intelligence scale was applied in a subgroup of six pediatric patients, whereas the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were assessed in a subgroup of nine patients to determine the impact of VNS therapy on cognitive performance and emotional state. RESULTS: The follow-up duration for the 17 patients who underwent VNS treatment ranged from 0.5 to 10 years (mean ±â€¯SD: 4.1 ±â€¯3.2 years). Monthly seizures decreased significantly from three months to four years post-treatment (p < 0.05). At the last follow-up, 70.6% of the patients achieved at least a 50% reduction in seizure frequency, and three patients were completely seizure free. Comparatively, non-responder patients experienced deterioration of seizure frequency after the first year. Notably, after one-year follow-up the mean standard score of full-scale intelligence quotient increased from 67.33 to 69.5 (p = 0.078) while the mean, standard score of SDS decreased from 49.22 to 45.67 (p = 0.003) compared to preoperative neuropsychological evaluation results. CONCLUSION: VNS is a safe and effective treatment for patients with DRE caused by TSC. Although early outcomes were encouraging, a follow-up of at least one-year was required to predict long-term outcomes in patients receiving VNS treatment. Moreover, VNS may improve depressive mood in patients with DRE caused by TSC. Further investigations are needed to validate the present results.

Molecular Characterization of AEBP1 at Transcriptional Level in Glioma.

BACKGROUND: Glioma is the most common malignant tumor of the brain in adult patients. The standardized treatment protocol is based on surgical therapy, supplemented with radiotherapy and chemotherapy. However, the prognosis is still unsatisfied. Chemoresistance is one of the most important reason for the poor prognosis of glioma patients. It has confirmed that glioma stem cell (GSC) is one of the reasons for chemoresistance. METHODS: In this study, three datasets (GSE23806, COSMIC, and TCGA) were used to perform the analysis to search for the key genes related to GSC, temozolomide (TMZ) resistance, and prognosis. The key gene for further research was selected by reviewing the previous studies. The selected gene investigated the relation between expression levels and clinical characteristics in both TCGA and CGGA dataset. The bioinformatics analysis was performed by Gene Ontology (GO) analysis. The survival analysis was performed by Kaplan-Meier survival analysis. RESULTS: AE binding protein 1 (AEBP1) was selected for further analysis. AEBP1 was overexpressed in GSCs and TMZ resistance cells. In both TCGA and CGGA dataset, the results showed that the expression level of AEBP1 was increased in glioblastoma (GBM) samples, IDH wild-type samples, and MGMT promoter unmethylated samples. Meanwhile, AEBP1 expression was positively related to several GSC markers. GO analysis showed that AEBP1 was related to immune response, cell adhesion, apoptotic process, inflammatory response, positive regulation of cell proliferation, angiogenesis, response to drug, and response to hypoxia. The survival analysis showed that the overexpressed level of AEBP1 was correlated with short survival time in both glioma and GBM patients. CONCLUSION: In summary, AEBP1 was related with GSC-induced TMZ resistance. Our study showed that AEBP1 might be an oncogene and a new effective therapeutic target for the treatment of glioma.

A concordance study determining language dominance between navigated transcranial magnetic stimulation and the Wada test in patients with drug-resistant epilepsy.

OBJECTIVE: It remains unclear whether transcranial magnetic stimulation (TMS) can replace the Wada test to determine language hemisphere dominance (HD). Using the Wada test as the gold standard, this study aimed to investigate the accuracy of navigated TMS (nTMS) in determining language HD. METHODS: This study enrolled nine right-handed patients with drug-resistant epilepsy. We hypothesized that application of nTMS to language-related areas of the language-dominant hemisphere would induce positive manifestation of language dysfunction (LD). To test our hypothesis, the patients were instructed to perform a visual object-naming task while nTMS was applied to the anterior (e.g., Broca's area) and posterior (e.g., Wernicke's area) regions, which are closely related to language processing. The Wada test result was used as the gold standard, and the diagnostic value of nTMS was assessed using the Kappa consistency test. RESULTS: The nTMS-induced LD positive rate for the bilateral anterior language areas (85.7%) was higher than that for the posterior language areas (57.1%). There was high consistency between nTMS stimulation of the left anterior and posterior language areas and the Wada test results for determining language HD. In contrast, the consistency of stimulation of the right anterior and posterior transfer sites was moderate (Kappa value = 0.545, P = 0.171) and low, respectively. For the latter, no statistical calculation was performed because stimulation of the right posterior speech area was negative in all patients compared with the Wada test results. CONCLUSIONS: Our findings revealed that using nTMS to stimulate language-related left anterior and posterior areas could predict language HD with high accuracy. When the stimulation performance of these areas is positive, nTMS and the Wada test are equally accurate. Observing only negative performance may indicate that language HD has been transferred to the right side.

A novel DNA damage response signature of IDH-mutant grade II and grade III astrocytoma at transcriptional level.

PURPOSE: The WHO classification for IDH-mutant grade II and grade III astrocytoma may not be as prognostically meaningful as expected. We aimed to develop a novel classification system based on the DNA damage response signature. METHODS: We developed the gene signature of DNA damage response with 115 samples from The Cancer Genome Atlas (TCGA) database. The dataset from Chinese Glioma Genome Atlas (CGGA) database with 41 samples was used as the validation set. Lasso Cox regression model was applied for selection of the best signature. Gene set enrichment analysis (GSEA) and gene ontology (GO) analysis were implemented to reveal its biological phenotype. RESULTS: A two-gene DNA damage response signature (RAD18, MSH2) was developed using the lasso Cox regression model based on the TCGA dataset. Its prognostic efficiency was validated in the CGGA cohort. The result of Cox regression analysis showed that the signature has a better predictive accuracy than the WHO grade. The risk score was an independent prognostic factor for the overall survival of the IDH-mutant grade II and grade III astrocytoma. GSEA and GO analysis confirmed enhanced processes related to DNA damage response in high-risk group. CONCLUSION: We developed a two-gene signature which can effectively predict the prognosis of patients with IDH-mutant grade II and grade III astrocytoma. It suggests a novel classification of astrocytoma with better prognostic accuracy based on the expression of DNA damage response genes.

High expression of VAT1 is a prognostic biomarker and predicts malignancy in glioblastoma.

Vesicle amine transport protein 1 (VAT1) has been reported as a pathogenic factor in a variety of tumors. VAT1 has been revealed to be upregulated in glioblastoma (GBM) and promotes cell migration. However, the possible mechanism of VAT1 in promoting malignant development in GBM is unclear. The present study applied transcriptome data and functional experiments to explore the exact role of VAT1. Kaplan­Meier survival analysis, univariate and multivariate Cox analyses were used to perform survival analysis. Furthermore, Gene Ontology analysis was used to analyze the biological implication of VAT1 expression. The in vitro experiment was performed to verify the hypothesis. The expression of VAT1 was detected in gliomas and control tissues. A functional experiment was performed and the sensitivity to TMZ was assessed after knocking down the expression of VAT1. In total, 120 patients with GBM were enrolled in the present study. The results of multivariate analysis revealed that VAT1 was an independent prognostic factor for survival. Patients with high VAT1 expression levels had shorter overall survival (P=0.009) and progression­free survival (P=0.055) than those with low expression levels. Gene Ontology analysis revealed that the genes which were positively associated with VAT1 were functionally involved in proteolysis, oxidation­reduction processes and immune response. The results of functional experiments demonstrated that VAT1 exhibited high expression levels in GBM, which could be inhibited by microRNA­218. Upon VAT1 knockdown, cell proliferation and migration were markedly suppressed, while the sensitivity toward temozolomide chemotherapy was enhanced. Thus, VAT1 expression was revealed to be a prognostic factor for GBM. High expression of VAT1 may promote cell proliferation, migration and temozolomide chemotherapy­resistance, which may be a potential therapeutic target for GBM.

Survivin is a prognostic indicator in glioblastoma and may be a target of microRNA-218.

Accumulating evidence has revealed that survivin expression is associated with a malignant phenotype and poor prognosis in glioma. Survivin is also a potential target of microRNA (miRNA/miR)-218. The aim of the present study was to investigate the expression and function of survivin in glioblastoma, and to examine the association between survivin and miR-218. For that purpose, survivin mRNA levels were analyzed in 144 frozen samples of glioblastoma using whole-genome RNA sequencing. In vitro cell proliferation, migration, invasion and apoptosis assays were performed, and survivin expression was detected by western blotting. The results revealed that the mRNA expression levels of survivin were negatively and significantly associated with overall survival in glioblastoma. Further in vitro analyses suggested that miR-218 may inhibit the expression of survivin. Expression of miR-218 in the LN229 cell line was significantly lower than that in the immortalized human gliocyte HEB cell line. miR-218 markedly inhibited tumor cell proliferation, migration and invasion capacities, and decreased apoptosis. miR-218 also inhibited the expression of survivin. These results indicated that survivin may be a target of miR-218 and could serve as a predictive biomarker.

Molecular and clinical characterization of TMEM71 expression at the transcriptional level in glioma.

BACKGROUND: Glioma is the most common and aggressive type of primary brain tumor in adults. Although radiotherapy and chemotherapy are used in the treatment of glioma, survival remains unsatisfactory. Chemoresistance is one of the primary reasons for the poor prognosis of glioma. Several studies have demonstrated that glioma stem cells (GSC) may be one of the reasons for chemoresistance. In this article, we attempt to search for a new biomarker related to GSC and chemoresistance in glioma. METHODS: We used three datasets (GSE23806, COSMIC, and CGGA) to search for the genes related to GSC, temozolomide (TMZ) resistance, and overall survival. The selected gene was investigated with respect to the relationship between mRNA levels and clinical characteristics in the CGGA and TCGA dataset. Gene ontology (GO) analysis was used for bioinformatics analysis. Kaplan-Meier survival analysis and Cox regression analysis were used for survival analysis. RESULTS: The transmembrane protein 71 (TMEM71) gene was selected for further research. TMEM71 was highly expressed in GSCs and TMZ-resistant cells. The TMEM71 mRNA levels increased with increasing grades of glioma. In IDH-wild-type and MGMT-unmethylated samples, TMEM71 was overexpressed. The TMEM71 transcript levels were also increased significantly in mesenchymal subtype gliomas. GO analysis demonstrated that TMEM71 was related to the immune and inflammatory responses, cell proliferation, cell migration, chemotaxis, and the response to drugs. Specifically, PD-1, PD-L1, TIM-3, and B7-H3 were tightly associated with TMEM71 expression. This result indicates that TMEM71 may play an important role in the immune response. More importantly, high expression of TMEM71 was correlated with short survival time in both glioma and glioblastoma patients. CONCLUSION: In summary, TMEM71 expression was increased in GBM and associated with immune response. Our study suggests that TMEM71 may function as an oncogene and serve as a new effective therapeutic target for the treatment of glioma.

Behaviors of Glioblastoma Cells in in Vitro Microenvironments.

Glioblastoma (GBM) is the most malignant and highly aggressive brain tumor. In this study, four types of typical GBM cell lines (LN229, SNB19, U87, U251) were cultured in a microfabricated 3-D model to study their in vitro behaviors. The 3-D in vitro model provides hollow micro-chamber arrays containing a natural collagen interface and thus allows the GBM cells to grow in the 3-D chambers. The GBM cells in this model showed specific properties on the aspects of cell morphology, proliferation, migration, and invasion, some of which were rarely observed before. Furthermore, how the cells invaded into the surrounding ECM and the corresponding specific invasion patterns were observed in details, implying that the four types of cells have different features during their development in cancer. This complex in vitro model, if applied to patient derived cells, possesses the potential of becoming a clinically relevant predictive model.

Management of brain metastases: history and the present.

Brain metastases are significant causes of morbidity or mortality for patients with metastatic cancer. With the application of novel systematic therapy and improvement of overall survival, the prevalence of brain metastases is increasing. The paradigm of treatment for brain metastases evolved rapidly during the last 30 years due to the development of technology and emergence of novel therapy. Brain metastases used to be regarded as the terminal stage of cancer and left life expectancy to only 1 month. The application of whole brain radiotherapy for patients with brain metastases increased the life expectancy to 4-6 months in the 1980s. Following studies established surgical resection followed by the application of whole brain radiotherapy the standard treatment for patients with single metastasis and good systematic performance. With the development of stereotactic radiosurgery, stereotactic radiosurgery plus whole brain radiotherapy provides an alternative modality with superior neurocognitive protection at the cost of overall survival. In addition, stereotactic radiosurgery combined with whole brain radiotherapy may offer a promising modality for patients with numerous multiple brain metastases who are not eligible for surgical resection. With the advancing understanding of molecular pathway and biological behavior of oncogenesis and tumor metastasis, novel targeted therapy including tyrosine-kinase inhibitors and immunotherapy are applied to brain metastases. Clinical trials had revealed the efficacy of targeted therapy. Furthermore, the combination of targeted therapy and radiotherapy or chemotherapy is the highlight of current investigation. Advancement in this area may further change the treatment paradigm and offer better modality for patients who are not suitable for surgical resection or radiosurgery.