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Abstract Background This study aims to investigate a novel instrument OM-100 with low-frequency magnetic fields (LFMFs) for its potential applicability in the treatment of liver cancer. Methods Liver cancer cell lines (HepG2 and Huh7) and normal liver cell line THLE-2 were exposed to OM-100 at LFMFs of 0, 10, 25, 50, and 100 kHz for 2 h in the morning, noon, and evening, respectively. The effects of LFMF on cell viability, apoptosis, migration, and invasion capabilities were examined. Additionally, impacts of LFMF on ROS production was assessed. In vivo studies were conducted to examine the safety profile of OM-100 and its effects on tumor growth. Results In vitro, OM-100 reduced the viability of liver cancer cells, increased cell apoptosis, and inhibited cell migration and invasion abilities in a frequency-dependent manner (P

Abstract Objective This study aims to explore the effect of Internet + E-Coach chronic disease system intervention on fasting blood glucose (FPG), 2-hour postprandial blood glucose(2hPG), fasting serum insulin (FINS), triglyceride (TG), alanine transaminase (ALT) and quality of life in patients with chronic diabetic retinopathy. Methods 208 patients with chronic diabetic retinopathy who were treated in the hospital from March 2021 to March 2023 are chosen and separated into two groups by random number Table 104 patients in the control group received routine continuous intervention, and the research group received Internet + E-Coach chronic disease system intervention. The cognition of disease related knowledge, blood related indicators inflammatory factor levels and improvement of life quality between the two groups before intervention, 6 and 12 months after intervention were compared. Results Before the intervention, the comparison between the two groups in disease related knowledge scores, blood glucose, blood lipid, liver function indicators, inflammatory factor, and low vision quality of life scale (CLVQOL) scores was with P > 0.05. After 6 and 12 months of intervention, the research group had significantly higher scores for basic blood glucose intervention, healthy diet, reasonable exercise, and correct medication use compared to the control group (P

Abstract Glioblastoma (GBM) is associated with a median survival rate of less than 15 months, necessitating innovative treatment approaches. This study investigates the safety and efficacy of the low-frequency magnetic field (LFMF) OM-100 instrument in GBM therapy. In vitro experiments utilized normal astrocyte and GBM cell lines, determining that OM-100 at 100 kHz for 72 h selectively targeted GBM cells without harming normal cells. Subsequent analyses revealed OM-100’s impact on cell viability, apoptosis, migration, invasion, reactive oxide species levels, and PD-L1 expression. In vivo studies on mice with U87-induced GBM demonstrated OM-100's synergy with anti-PD-1 therapy, leading to significant tumor volume reduction and increased apoptosis. Notably, OM-100 exhibited safety in healthy mice. Overall, OM-100 could enhance anti-PD-1 immunotherapy effectiveness probably by directly inhibiting tumor proliferation and migration as well as promoting PD-L1 expression, offering a promising therapeutic strategy for GBM treatment.

BackgroundPrevious studies have evaluated the safety and efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) for the treatment of Parkinson’s disease (PD). However, the mechanism underlying the effect of taVNS on PD remains to be elucidated. This study aimed to investigate the immediate effects of taVNS in PD patients.MethodsThis crossover self-controlled study included 50 PD patients. Each patient underwent three sessions of resting-state functional magnetic resonance imaging (rs-fMRI) under three conditions: real taVNS, sham taVNS, and no taVNS intervention. We analyzed whole-brain amplitude of low-frequency fluctuations (ALFF) from preprocessed fMRI data across different intervention conditions. ALFF values in altered brain regions were correlated with clinical symptoms in PD patients.ResultsForty-seven participants completed the study and were included in the final analysis. Real taVNS was associated with a widespread decrease in ALFF in the right hemisphere, including the superior parietal lobule, precentral gyrus, postcentral gyrus, middle occipital gyrus, and cuneus (voxel p

Abstract Background Paranasal sinus angiosarcoma is an uncommon malignancy, with only a few reported cases worldwide. Although it exhibits multiple symptoms, facial paralysis has not been previously documented as a noticeable presentation. Case Presentation In this case, we report a 40-year-old male who presented with facial numbness and pain for one month, weakness of his facial muscles for 15 days, and recurrent right epistaxis for 1 year. He had a history of nasal inflammatory polyps with chronic sinusitis. Computed tomography and magnetic resonance imaging showed space-occupying lesions in the right nasal cavity and maxillary sinus, with bone destruction occurring in the sinus wall and turbinate. This patient then underwent endoscopic surgery. According to the histopathological and immunohistochemical results, he was eventually diagnosed with paranasal sinus angiosarcoma in April 2021. To date, this patient has not initiated any radiotherapy or chemotherapy and has survived with lymphatic metastasis for at least 3 years. Conclusions This manuscript suggests that paranasal sinus angiosarcoma can present with facial paralysis. Moreover, pathological and immunohistochemical tests are still vital for diagnosing paranasal sinus angiosarcoma and differential diagnosis. Additionally, regular follow-up is crucial for patients with paranasal sinus angiosarcoma, enabling monitoring of recurrence, metastasis, and recovery while contributing valuable clinical data to understanding this rare disease and associated research endeavours.

BackgroundPrevious studies have shown a significant response to acute transcutaneous vagus nerve stimulation (taVNS) in regions of the vagus nerve pathway, including the nucleus tractus solitarius (NTS), raphe nucleus (RN) and locus coeruleus (LC) in both healthy human participants and migraine patients. This study aims to investigate the modulation effect of repeated taVNS on these brainstem regions by applying seed-based resting-state functional connectivity (rsFC) analysis.Methods70 patients with migraine were recruited and randomized to receive real or sham taVNS treatments for 4 weeks. fMRI data were collected from each participant before and after 4 weeks of treatment. The rsFC analyses were performed using NTS, RN and LC as the seeds.Results59 patients (real group: n = 33; sham group: n = 29) completed two fMRI scan sessions. Compared to sham taVNS, real taVNS was associated with a significant reduction in the number of migraine attack days (p = 0.024) and headache pain intensity (p = 0.008). The rsFC analysis showed repeated taVNS modulated the functional connectivity between the brain stem regions of the vagus nerve pathway and brain regions associated with the limbic system (bilateral hippocampus), pain processing and modulation (bilateral postcentral gyrus, thalamus, and mPFC), and basal ganglia (putamen/caudate). In addition, the rsFC change between the RN and putamen was significantly associated with the reduction in the number of migraine days.ConclusionOur findings suggest that taVNS can significantly modulate the vagus nerve central pathway, which may contribute to the potential treatment effects of taVNS for migraine.Clinical Trial Registration: http://www.chictr.org.cn/hvshowproject.aspx?id=11101, identifier ChiCTR-INR-17010559.

Abstract Background A growing body of evidence suggests that transcutaneous auricular vagus nerve stimulation (taVNS) may relieve symptoms of migraineurs. Frequency is one of the key stimulation parameters. The aim of this study is to investigate the modulation effect of taVNS frequency on the descending pain modulation system (DPMS) in patients with migraine. Methods Twenty-four episodic migraineurs without aura (21 females) were recruited for the single-blind, crossover, functional magnetic resonance imaging (fMRI) study. Each participant attended two separate fMRI scan sessions, one for 1 Hz and another for 20 Hz taVNS, in a random order. Seed-based functional connectivity analysis was applied using the ventrolateral periaqueductal gray (PAG) as the region of interest. Results Compared with the pre-taVNS resting state, continuous 1 Hz taVNS (during) produced a significant increase in functional connectivity between the PAG and the bilateral middle cingulate cortex (MCC), right precuneus, left middle frontal gyrus (MFG), and left cuneus. Compared with 20 Hz taVNS, 1 Hz taVNS produced greater PAG connectivity increases with the MCC, right precuneus/posterior cingulate cortex, left insula, and anterior cingulate cortex (ACC). A significant negative correlation was observed between the number of migraine attacks in the previous 4 weeks and the PAG-MCC functional connectivity in the pre-taVNS resting-state before 1 Hz taVNS. Conclusions Our findings suggest that taVNS with different frequencies may produce different modulation effects on the descending pain modulation system, demonstrating the important role of stimulation frequency in taVNS treatment.

PurposeMany high-risk osteopenia and osteoporosis patients remain undiagnosed. We proposed to construct a convolutional neural network model for screening primary osteopenia and osteoporosis based on the lumbar radiographs, and to compare the diagnostic performance of the CNN model adding the clinical covariates with the image model alone.MethodsA total of 6,908 participants were collected for analysis, including postmenopausal women and men aged 50–95 years, who performed conventional lumbar x-ray examinations and dual-energy x-ray absorptiometry (DXA) examinations within 3 months. All participants were divided into a training set, a validation set, test set 1, and test set 2 at a ratio of 8:1:1:1. The bone mineral density (BMD) values derived from DXA were applied as the reference standard. A three-class CNN model was developed to classify the patients into normal BMD, osteopenia, and osteoporosis. Moreover, we developed the models integrating the images with clinical covariates (age, gender, and BMI), and explored whether adding clinical data improves diagnostic performance over the image mode alone. The receiver operating characteristic curve analysis was performed for assessing the model performance.ResultsAs for classifying osteoporosis, the model based on the anteroposterior+lateral channel performed best, with the area under the curve (AUC) range from 0.909 to 0.937 in three test cohorts. The models with images alone achieved moderate sensitivity in classifying osteopenia, in which the highest AUC achieved 0.785. The performance of models integrating images with clinical data shows a slight improvement over models with anteroposterior or lateral images input alone for diagnosing osteoporosis, in which the AUC increased about 2%–4%. Regarding categorizing osteopenia and the normal BMD, the proposed models integrating images with clinical data also outperformed the models with images solely.ConclusionThe deep learning-based approach could screen osteoporosis and osteopenia based on lumbar radiographs.

BackgroundMigraine is a common disorder, affecting many patients. However, for one thing, lacking objective biomarkers, misdiagnosis, and missed diagnosis happen occasionally. For another, though transcutaneous vagus nerve stimulation (tVNS) could alleviate migraine symptoms, the individual difference of tVNS efficacy in migraineurs hamper the clinical application of tVNS. Therefore, it is necessary to identify biomarkers to discriminate migraineurs as well as select patients suitable for tVNS treatment.MethodsA total of 70 patients diagnosed with migraine without aura (MWoA) and 70 matched healthy controls were recruited to complete fMRI scanning. In study 1, the fractional amplitude of low-frequency fluctuation (fALFF) of each voxel was calculated, and the differences between healthy controls and MWoA were compared. Meaningful voxels were extracted as features for discriminating model construction by a support vector machine. The performance of the discriminating model was assessed by accuracy, sensitivity, and specificity. In addition, a mask of these significant brain regions was generated for further analysis. Then, in study 2, 33 of the 70 patients with MWoA in study 1 receiving real tVNS were included to construct the predicting model in the generated mask. Discriminative features of the discriminating model in study 1 were used to predict the reduction of attack frequency after a 4-week tVNS treatment by support vector regression. A correlation coefficient between predicted value and actual value of the reduction of migraine attack frequency was conducted in 33 patients to assess the performance of predicting model after tVNS treatment. We vislized the distribution of the predictive voxels as well as investigated the association between fALFF change (post-per treatment) of predict weight brain regions and clinical outcomes (frequency of migraine attack) in the real group.ResultsA biomarker containing 3,650 features was identified with an accuracy of 79.3%, sensitivity of 78.6%, and specificity of 80.0% (p < 0.002). The discriminative features were found in the trigeminal cervical complex/rostral ventromedial medulla (TCC/RVM), thalamus, medial prefrontal cortex (mPFC), and temporal gyrus. Then, 70 of 3,650 discriminative features were identified to predict the reduction of attack frequency after tVNS treatment with a correlation coefficient of 0.36 (p = 0.03). The 70 predictive features were involved in TCC/RVM, mPFC, temporal gyrus, middle cingulate cortex (MCC), and insula. The reduction of migraine attack frequency had a positive correlation with right TCC/RVM (r = 0.433, p = 0.021), left MCC (r = 0.451, p = 0.016), and bilateral mPFC (r = 0.416, p = 0.028), and negative with left insula (r = −0.473, p = 0.011) and right superior temporal gyrus/middle temporal gyrus (r = −0.684, p < 0.001), respectively.ConclusionsBy machine learning, the study proposed two potential biomarkers that could discriminate patients with MWoA and predict the efficacy of tVNS in reducing migraine attack frequency. The pivotal features were mainly located in the TCC/RVM, thalamus, mPFC, and temporal gyrus.

Abstract Background Glioma is a common brain malignancy with high mortality. The competing endogenous RNA (ceRNA) networks may play key roles in cancer progression. This study was conducted to probe the role of long noncoding RNA (lncRNA) NCK1-AS1 in glioma progression and the involved mechanisms. Methods Microarray analyses were performed to explore the lncRNAs/miRNAs/genes with differential expression in glioma. NCK1-AS1 levels in glioma tissues and normal brain tissues, and in glioma cell lines and normal human glial cells were identified. The interactions among NCK1-AS1, miR-138-2-3p and TRIM24 were validated through luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Gain- and loss-of functions of NCK1-AS1, miR-138-2-3p and TRIM24 were performed to identify their roles in the behaviors of glioma cells. The activity of the Wnt/β-catenin pathway was measured. In vivo experiments were performed as well. Results High expression of NCK1-AS1 was found in glioma tissues and cells, especially in U251 cells. Online predictions and the integrated experiments identified that NCK1-AS1 elevated the TRIM24 expression through sponging miR-138-2-3p, and further activated the Wnt/β-catenin pathway. Artificial silencing of NCK1-AS1 or up-regulation of miR-138-2-3p led to inhibited proliferation, invasion and migration but promoted cell apoptosis of U251 cells, while up-regulation of TRIM24 reversed these changes, and it activated the Wnt/β-catenin pathway. The in vitro results were reproduced in in vivo experiments. Conclusions Our study suggested that NCK1-AS1 might elevate TRIM24 expression and further activate the Wnt/β-catenin pathway via acting as a ceRNA for miR-138-2-3p. Silencing of NCK1-AS1 might inhibit the progression of glioma.

Background. A growing body of evidence suggests that both auricular acupuncture and transcutaneous auricular vagus nerve stimulation (taVNS) can induce antinociception and relieve symptoms of migraine. However, their instant effects and central treatment mechanism remain unclear. Many studies proved that the amygdalae play a vital role not only in emotion modulation but also in pain processing. In this study, we investigated the modulation effects of continuous taVNS at acupoints on the FC of the bilateral amygdalae in MwoA. Methods. Thirty episodic migraineurs were recruited for the single-blind, crossover functional magnetic resonance imaging (fMRI) study. Each participant attended two kinds of eight-minute stimulations, taVNS and sham-taVNS (staVNS), separated by seven days in random order. Finally, 27 of them were included in the analysis of seed-to-voxel FC with the left/right amygdala as seeds. Results. Compared with staVNS, the FC decreased during taVNS between the left amygdala and left middle frontal gyrus (MFG), left dorsolateral superior frontal gyrus, right supplementary motor area (SMA), bilateral paracentral lobules, bilateral postcingulum gyrus, and right frontal superior medial gyrus, so did the FC of the right amygdala and left MFG. A significant positive correlation was observed between the FC of the left amygdala and right SMA and the frequency/total time of migraine attacks during the preceding four weeks. Conclusion. Continuous taVNS at acupoints can modulate the FC between the bilateral amygdalae and pain-related brain regions in MwoA, involving the limbic system, default mode network, and pain matrix, with obvious differences between the left amygdala and the right amygdala. The taVNS may produce treatment effects by modulating the abnormal FC of the amygdala and pain networks, possibly having the same central mechanism as auricular acupuncture.

Background: Migraine is a common episodic neurological disorder. Literature has shown that transcutaneous auricular vagus nerve stimulation (taVNS) at 1 Hz can significantly relieve migraine symptoms. However, its underlying mechanism remains unclear. This study aims to investigate the neural pathways associated with taVNS treatment of migraine. Methods: Twenty-nine patients with migraine were recruited from outpatient neurology clinics. Each patient attended two magnetic resonance imaging/functional magnetic resonance imaging (MRI/fMRI) scan sessions separated by one week. Each session included a pre-stimulation resting state fMRI scan, fMRI scans during real or sham 1 Hz taVNS (with block design), and a post-stimulation resting state fMRI scan. Results: Twenty-six patients were included in the final analyses. Real taVNS evoked fMRI signal decreases in brain areas belonging to the default mode network (DMN) and brain stem areas including the locus coeruleus (LC), raphe nuclei, parabrachial nucleus, and solitary nucleus. Sham taVNS evoked fMRI signal decreases in brain areas belonging to the DMN. Compared to sham taVNS, real taVNS produced greater deactivation at the bilateral LC. Resting state functional connectivity (rsFC) analysis showed that after taVNS, LC rsFC with the right temporoparietal junction and left secondary somatosensory cortex (S2) significantly increased compared to sham taVNS. The increased rsFC of the left LC-left S2 was significantly negatively associated with the frequency of migraine attacks during the preceding month. Conclusion: Our results suggest that taVNS at 1 Hz can significantly modulate activity/connectivity of brain regions associated with the vagus nerve central pathway and pain modulation system, which may shed light on the neural mechanisms underlying taVNS treatment of migraine. Keywords: Transcutaneous auricular vagus nerve stimulation, Locus coeruleus, Resting state functional connectivity, Migraine

Background: Dysfunction of the thalamocortical connectivity network is thought to underlie the pathophysiology of the migraine. This current study aimed to explore the thalamocortical connectivity changes during 4 weeks of continuous transcutaneous vagus nerve stimulation (taVNS) treatment on migraine patients.Methods: 70 migraine patients were recruited and randomized in an equal ratio to receive real taVNS or sham taVNS treatments for 4 weeks. Resting-state functional MRI was collected before and after treatment. The thalamus was parceled into functional regions of interest (ROIs) on the basis of six priori-defined cortical ROIs covering the entire cortex. Seed-based functional connectivity analysis between each thalamic subregion and the whole brain was further compared across groups after treatment.Results: Of the 59 patients that finished the study, those in the taVNS group had significantly reduced number of migraine days, pain intensity and migraine attack times after 4 weeks of treatment compared with the sham taVNS. Functional connectivity analysis revealed that taVNS can increase the connectivity between the motor-related thalamus subregion and anterior cingulate cortex/medial prefrontal cortex, and decrease the connectivity between occipital cortex-related thalamus subregion and postcentral gyrus/precuneus.Conclusion: Our findings suggest that taVNS can relieve the symptoms of headache as well as modulate the thalamocortical circuits in migraine patients. The results provide insights into the neural mechanism of taVNS and reveal potential therapeutic targets for migraine patients. [ABSTRACT FROM AUTHOR]