Identification of clinically relevant subsets CD39+PD-1+CD8+ T cells and CD39+ regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF.

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy with limited treatment options and a dismal prognosis. The tumor immune microenvironment (TIME) is crucial for iCCA progression, yet its comprehensive characterization remains incomplete. This study utilized mass cytometry by time of flight (CyTOF) to comprehensively analyze immune cell populations in fresh iCCA tumor samples and adjacent peritumor liver tissues. Notably, NK cell percentages significantly decreased in iCCA lesions compared to peritumor liver tissues. Conversely, an enrichment of immunosuppressive CD39+Foxp3+CD4+ regulatory T cells (CD39+T-regs) and exhausted-like CD8+T cells (with pronounced CD39 and PD-1 expression) within TIME was identified and confirmed by multiplex immunofluorescence staining in an independent patient cohort (n = 140). Crucially, tumor-infiltrating CD39+T-regs and CD39+PD-1+CD8+T cells emerged as independent prognostic indicators associated with an unfavorable prognosis in iCCA. These findings unveil the intricate immune landscape within iCCA, offering valuable insights for disease management and novel cancer immunotherapies.

Gas7 attenuates hepatocellular carcinoma progression and chemoresistance through the PI3K/Akt signaling pathway.

Growth arrest-specific gene 7 (Gas7) was involved in various cellular functions, although its specific roles and molecular mechanisms in hepatocellular carcinoma (HCC) remained unclear. So the current study was to investigate the role of Gas7 in HCC. Our findings revealed that Gas7 was downregulated in various HCC cell lines and low Gas7 expression was associated with decreased overall survival in patients with HCC. Additionally, our functional assays showed that Gas7 inhibited cell proliferation and migration, induced cell cycle arrest, apoptosis, and autophagy, and enhanced oxaliplatin sensitivity by inhibiting the PI3K/Akt signaling pathway. We also observed that transcription factorSp1 was responsible for inhibiting Gas7. These findings provide insights into the role and elucidated a potential mechanism of Gas7 in HCC progression and metastasis. It was also observed that the Sp1/Gas7/PI3K/Akt axis was critical for malignant phenotype and oxaliplatin sensitivity in HCC. Therefore, Gas7 can be considered as a prognostic predictor and therapeutic target for HCC.

Reexamining the Causes and Effects of Cholesterol Deposition in the Brains of Patients with Alzheimer's Disease.

Alzheimer's disease (AD) is a degenerative disease of the central nervous system. Numerous studies have shown that imbalances in cholesterol homeostasis in the brains of AD patients precede the onset of clinical symptoms. In addition, cholesterol deposition has been observed in the brains of AD patients even though peripheral cholesterol does not enter the brain through the blood‒brain barrier (BBB). Studies have demonstrated that cholesterol metabolism in the brain is associated with many pathological conditions, such as amyloid beta (Aß) production, Tau protein phosphorylation, oxidative stress, and inflammation. In 2022, some scholars put forward a new hypothesis of AD: the disease involves lipid invasion and its exacerbation of the abnormal metabolism of cholesterol in the brain. In this review, by discussing the latest research progress, the causes and effects of cholesterol retention in the brains of AD patients are analyzed and discussed. Additionally, the possible mechanism through which AD may be improved by targeting cholesterol is described. Finally, we propose that improving the impairments in cholesterol removal observed in the brains of AD patients, instead of further reducing the already impaired cholesterol synthesis in the brain, may be the key to preventing cholesterol deposition and improving the corresponding pathological symptoms.

PVR-A Prognostic Biomarker Correlated with Immune Cell Infiltration in Hepatocellular Carcinoma.

The poliovirus receptor (PVR) is a member of the immunoglobulin superfamily (Ig SF) and is essential for the promotion of cancer cell proliferation and invasion. However, the correlation between PVR expression and prognosis as well as immune infiltration in hepatocellular carcinoma (HCC) remains unclear. The expression level of PVR was quantified using the Tumor and Tumor Immunity Evaluation Resource (TIMER) and Sangerbox. The Gene Expression Omnibus (GEO) database was used to validate the PVR expression. The receiver operating characteristic (ROC) curve was used to evaluate the feasibility of using PVR as a differentiating factor according to the area under curve (AUC) score. A PVR binding protein network was built using the STRING tool. An enrichment analysis using the R package clusterProfiler was used to explore the potential function of PVR. Immune infiltration analysis was calculated with ESTIMATE algorithms. We also assessed the correlation between PVR expression and immune infiltration by the single-sample Gene Set Enrichment Analysis (ssGSEA) method from the R package GSVA and TIMER database. The results showed that PVR was commonly overexpressed in multiple types of tumors including HCC. The data of GSE64041 confirmed the same result. The ROC curve suggested that PVR could be a potential diagnostic biomarker. Additionally, high mRNA expression of PVR in HCC was significantly correlated with poor overall survival (OS) and relapse free survival (RFS). Results also indicated correlations between PVR mRNA expression with the level of infiltration immune cells including B cells, CD8+ T cells, cytotoxic cells, DCs, CD56dim NK cells, pDCs, and Th2 cells. Furthermore, the PVR level was significantly correlated with immune markers for immunosuppressive cells in HCC. In conclusion, PVR might be an important regulator of tumor immune cell infiltration and a valuable prognostic biomarker in HCC. However, additional work is needed to fully elucidate the underlying mechanisms.

Altered spontaneous brain activity patterns in patients with hyperthyroidism exophthalmos using amplitude of low-frequency fluctuation: a resting-state fMRI study.

AIM: To assess changed spontaneous brain activity in hyperthyroid exophthalmos (HE) patients by the amplitude of the low-frequency fluctuation (ALFF) method, and to analyze the correlation between brain activity and ALFF values in these patients. METHODS: Totally 18 HE and 18 hyperthyroid non-exophthalmos (HNE) patients were enrolled. The participants were tested by resting-state functional magnetic resonance imaging, and receiver operating characteristic (ROC) curves were generated to classify the ALFF values of the study population. Pearson's correlation analysis was utilized to evaluate the relationship between the ALFF values obtained from different brain areas and clinical manifestations. RESULTS: Contrary to HNE patients, we observed lower ALFF values in the left calcarine fissure and surrounding cortex (LCFSC) in HE patients. In the ROC curve analysis of the LCFSC, the area under the curve reflected a high degree of accuracy. In addition, there was positive correlation between mean ALFF values of the LCFSC and the best-corrected visual acuity of the affected eyes. CONCLUSION: The study displays abnormal brain activity in LCFSC in patients with HE, which might suggest pathological mechanism of visual impairment of HE patients.

Carbohydrate antigen 125, carbohydrate antigen 15-3 and low-density lipoprotein as risk factors for intraocular metastases in postmenopausal breast cancer.

ABSTRACT: The prognosis of patients with postmenopausal breast cancer (PBC) could be improved by the early detection of intraocular metastases (IOMs). However, serum biomarkers for IOMs in PBC remain elusive. In the current study, we investigated patients with PBC, and compared serum parameters in an IOM and a non-IOM group, and then differentiated the risk factors related to IOMs. A comparison between an IOM and a non-IOM (NIOM) group was performed using Student t-test and a Chi-Squared test. After constructing a Poisson regression model to identify risk factors, we plotted receiver operating characteristic curves to evaluate the predictive value of significant risk factors in detecting IOMs. The incidence of IOMs in PBC was 1.16%. The histopathology results were not significantly different between the 2 groups. The levels of serum carbohydrate antigen 125 (CA-125), carbohydrate antigen 15-3 (CA15-3) and alkaline phosphatase were significantly elevated in IOMs compared with NIOMs (P = .082, P < .001, and P < .001, respectively). Compared with NIOMs, age, carbohydrate antigen 19 to 9, hemoglobin, calcium, total cholesterol, low-density lipoprotein (LDL) and apolipoprotein A1 were remarkably lower in IOMs (P = .038, P < .001, P < .001, P = .032, P = .041, P < .001, and P = .001, respectively). Poisson regression suggested that CA-125, CA15-3 and LDL were contributing to IOMs in PBC as risk factors (OR = 1.003, 95% CI: 1.001-1.005; OR = 1.025, 95% CI: 1.019-1.033; OR = 0.238, 95% CI: 0.112-0.505, respectively). A receiver operating characteristic curve revealed that the cut-off values for CA-125, CA15-3 and LDL were 16.78 0 U/mL, 63.175 U/mL, and 2.415 mmol/L, respectively. The combination of CA-125 and CA15-3 showed significant diagnostic value (area under the curve [AUC] = 0.982, P < .001). Our investigation suggests that CA-125, CA15-3 and LDL remarkably predict IOMs in PBC as risk factors, and the combination of CA-125 and CA15-3 shows considerable diagnostic value.

Effect of PCSK9 on Vascular Smooth Muscle Cell Functions: A New Player in Atherosclerosis.

Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is a secretory serine protease that plays multiple biological functions in the regulation of physiological and pathological processes. PCSK9 inhibitors decrease the circulating LDL-cholesterol level with well-known preventive and therapeutic effects on atherosclerosis (AS). Still, increasing evidence shows that the direct impact of PCSK9 on the vascular wall also plays an important role in atherosclerotic progression. Compared with other vascular cells, a large proportion of PCSK9 is originated from vascular smooth muscle cells (VSMC). Therefore, defining the effect of VSMC-derived PCSK9 on response changes, such as phenotypic switch, apoptosis, autophagy, inflammation, foam cell formation, and calcification of VSMC, helps us better understand the "pleiotropic" effects of VSMC on the atherosclerotic process. In addition, our understanding of the mechanisms of PCSK9 controlling VSMC functions in vivo is far from enough. This review aims to holistically evaluate and analyze the current state of our knowledge regarding PCSK9 actions affecting VSMC functions and its mechanism in atherosclerotic lesion development. A mechanistic understanding of PCSK9 effects on VSMC will further underpin the success of a new therapeutic strategy targeting AS.

Design of a High-Efficiency and -Gain Antenna Using Novel Low-Loss, Temperature-Stable Li2Ti1-x(Cu1/3Nb2/3)xO3 Microwave Dielectric Ceramics.

Microwave dielectric ceramics are vital for filters, dielectric resonators, and dielectric antennas in the 5G era. It was found that the (Cu1/3Nb2/3)4+ substitution can effectively adjust the TCF (temperature coefficient of resonant frequency) of Li2TiO3 and simultaneously increase its Q × f (Q and f denote the quality factor and the resonant frequency, respectively) value. Notably, excellent microwave dielectric properties (εr (permittivity) ≈ 18.3, Q × f ≈ 77,840 GHz, and TCF ≈ +9.8 ppm/°C) were achieved in the Li2Ti0.8(Cu1/3Nb2/3)0.2O3 (LTCN0.2) ceramic sintered at 1140 °C. Additionally, the sintering temperature of LTCN0.2 was reduced to 860 °C by the addition of 3 wt % H3BO3, exhibiting superior microwave dielectric properties (εr ≈ 21.0, Q × f ≈ 51,940 GHz, and TCF ≈ 1.4 ppm/°C) and being chemically compatible with silver. Moreover, LTCN0.2 + 3 wt % H3BO3 ceramics were designed as a patch antenna and a dielectric resonator antenna, both of which showed high simulated radiation efficiencies (88.4 and 93%) and gains (4.1 and 4.03 dBi) at the center frequencies (2.49 and 10.19 GHz). The LTCN0.2 + 3 wt % H3BO3 materials have promising future application for either 5G mobile communication devices and/or in low-temperature co-fired ceramic technology owing to their high Q, low sintering temperature, small density, and good temperature stability.

The abnormal fractional amplitude of low-frequency fluctuation changes in patients with diabetic optic neuropathy: a steady-state fMRI study.

The spontaneous changes in brain activity in patients with diabetic optic neuropathy using steady-state fMRI. The fractional amplitude of the low-frequency fluctuation method was applied to evaluate neural activity changes. The Hospital Anxiety and Depression Scale was used to assess the anxiety and depression status of participants. The independent sample t-test and chi-squared test were applied to analyze the demographics of diabetic optic neuropathy patients and healthy controls. Receiver operating characteristic curves were applied to analyze the variation in mean fractional amplitude of low-frequency fluctuation values between diabetic optic neuropathy patients and healthy controls. Pearson's correlation analysis analyzed the relationships between the fractional amplitude of low-frequency fluctuation values of brain regions and clinical behaviors in the diabetic optic neuropathy group. The fractional amplitude of low-frequency fluctuation value of diabetic optic neuropathy patients was significantly higher than healthy controls in the right precentral gyrus. However, the fractional amplitude of low-frequency fluctuation values in the right anterior cingulate gyrus and left middle cingulate gyrus were markedly decreased in diabetic optic neuropathy patients. The area under the curve of receiver operating characteristics for each brain region showed high accuracy. Pearson's correlation analysis showed that fractional amplitude of low-frequency fluctuation values of the right anterior cingulate gyrus and left middle cingulate gyrus was negatively correlated with Hospital Anxiety and Depression Scale scores. The fractional amplitude of low-frequency fluctuation values of the left middle cingulate gyrus was negatively correlated with diabetic optic neuropathy disease duration. In conclusion, we found abnormal spontaneous brain activities in regions related to cognitive and emotional dysfunction, eye movement disorder, and vision loss in patients with diabetic optic neuropathy. These results may indicate the underlying neuropathological mechanisms of diabetic optic neuropathy and show that fractional amplitude of low-frequency fluctuation may be an effective method to distinguish patients with diabetic optic neuropathy from healthy individuals.

Synergistic anti-inflammatory effects of silibinin and thymol combination on LPS-induced RAW264.7 cells by inhibition of NF-κB and MAPK activation.

BACKGROUND: Combination drug therapy has become an effective strategy for inflammation control. The anti­inflammatory capacities of silibinin and thymol have each been investigated on its own, but little is known about the synergistic anti-inflammatory effects of these two compounds. PURPOSE: This study aims to investigate the synergistic anti-inflammatory effects of silibinin and thymol when administered in combination to lipopolysaccharide (LPS)-induced RAW264.7 cells. METHODS: RAW264.7 cells were pre-treated with silibinin and thymol individually or in combination for 2 h before LPS stimulation. Cell viability was detected by the MTT assay. Nitric oxide (NO) production was measured by Griess reagent. Reactive oxygen species (ROS) was evaluated by 2',7'-dichlorofluorescein-diacetate. ELISA was used to detect tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Western blot was performed to analyse the protein expression of LPS-induced RAW264.7 cells. RESULTS: We observed a synergistic anti-inflammatory effect of silibinin and thymol when administered in combination to LPS-induced RAW264.7 cells. Silibinin combined with thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) had more potent effects on the inhibition of NO, TNF-α, and IL-6 than those exerted by individual administration of these compounds in LPS-induced RAW264.7 cells. The combination of silibinin and thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) strongly inhibited ROS and cyclooxygenase-2 (COX-2). More importantly, the combination of silibinin and thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) was also successful in inhibiting nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) activities. Our results suggest that the synergistic anti-inflammatory effects of silibinin with thymol were associated with the inhibition of NF-κB and MAPK signalling pathways. CONCLUSION: The combination of silibinin and thymol (40 µM and 120 µM, respectively, with the molar ratio 1:3) could inhibit inflammation by suppressing NF-κB and MAPK signalling pathways in LPS-induced RAW264.7 cells.

Assessment of Serum Tumor Markers for Predicting Ocular Metastasis in Lung Adenocarcinoma: A Retrospective Study.

The purpose of this study was to detect clinical variations between lung adenocarcinoma patients with and without ocular metastasis (OM) to identify risk factors for OM and assess the diagnostic values. We included 1153 patients with lung adenocarcinoma in this study. Independent t-tests and chi-square tests were used to compare patients' clinical characteristics. Statistically significant parameters were analyzed by binary logistic regression to detect risk factors of OM. The results showed that the OM group had increased alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cytokeratin fragment 19 (CYFRA 21-1), carbohydrate antigen- (CA-) 125, CA-153, and total prostate-specific antigen (TPSA) compared with the NOM group. CYFRA21-1 is the most useful biomarker for detecting OM in this population.

An ultra-broadband terahertz metamaterial coherent absorber using multilayer electric ring resonator structures based on anti-reflection coating.

We propose a method for achieving THz ultra-broadband coherent absorption using the anti-reflection theory of metamaterials. The metamaterial absorber consists of a periodic array of electric ring resonators with a multilayered structure which form the desired refractive index dispersion and provide continuous anti-reflection over a wide frequency range. The destructive interference mechanism and resonance absorption of the absorber are determined by simulation analysis and numerical simulation. Simulation results show that the absorption bandwidth is almost 8.02 THz (absorption rate >90%) over the entire terahertz band (0.1 THz-10 THz). This design provides an effective and viable method for constructing broadband absorbers for stealth technology and the construction of enhanced transmittance devices.

Diagnostic value of CA-153 and CYFRA 21-1 in predicting intraocular metastasis in patients with metastatic lung cancer.

Lung cancer is prone to metastasis to various organs. Although intraocular metastasis (IOM) occurs at a later stage than metastasis to other organs, it often adversely affects the quality of life and suggests a poor prognosis. In this study, we selected 1608 patients with lung cancer who had metastasis to at least one site and explored clinical differences between those with IOM and non-IOM (NIOM). An independent t test and chi-squared test were used to analyze the clinical features of the patients. The statistically significant parameters were analyzed by binary logistic regression to determine the risk factors for IOM. A receiver operating characteristic curve was constructed to assess their diagnostic value in IOM. The results showed that no significant differences were noted in age, gender, and pathological type between the IOM and NIOM groups. However, the IOM group had higher levels of alpha-fetoprotein, carcinoembryonic antigen, cancer antigen (CA)-125, CA-153, cytokeratin fragment 19 (CYFRA 21-1), and total prostate-specific antigen, compared with the NIOM group. Binary logistic regression indicated that CA-153 and CYFRA 21-1 were risk factors for IOM in patients with MLC (P < 0.05). Area under the curve of CA-153, CYFRA 21-1 and their combination were 0.791, 0.860, and 0.872 respectively. The cutoff values for CA-153 and CYFRA 21-1 were 22.2 U/mL and 6.785 ng/mL. In conclusion, both CA-153 and CYFRA 21-1 were independent risk factors for IOM in patients with metastatic lung cancer (MLC), whereas the combination of CA-153 and CYFRA 21-1 assessment yields the most value in the detection of IOM in patients with MLC.

The Cerebellum Posterior Lobe Associates with the Exophthalmos of Primary Hyperthyroidism: A Resting-State fMRI Study.

BACKGROUND: Exophthalmos occurs in patients with primary hyperthyroidism. There were few studies about the changes of brain functional networks of patients with exophthalmos of primary hyperthyroidism (EOPH). However, differences in spontaneous brain activity in patients with EOPH remain unclear. OBJECTIVE: This study explored alterations in the brain functional networks of patients with EOPH using a voxel-wise degree centrality (DC) method. METHODS: A total of 20 patients with EOPH (8 men and 12 women) were enrolled. In addition, 20 patients with primary hyperthyroidism without exophthalmos, matched in age, sex, and education status, were enrolled as a control group. The Hospital Anxiety and Depression Scale was used to assess the anxiety and depression status of participants. All participants were examined using resting-state functional MRI. Changes in spontaneous brain activity were investigated using the DC method. To distinguish between the DC values of the patients with EOPH and those of the control group, we analyzed the receiver operating characteristic (ROC) curve. The interrelationships between the DC values and clinical variables in the patients with EOPH were evaluated using Pearson's correlation coefficient. RESULTS: Patients with EOPH exhibited notably lower DC values in the cerebellum posterior lobe than the control group. In addition, there were negative correlations between the anxiety scores (AS) and the depression scores (DS) and DC values of the cerebellum posterior lobe. The ROC curve analysis of the cerebellum posterior lobe demonstrated that the area under the curve method had a high diagnostic accuracy. CONCLUSIONS: Our study was the first, to our knowledge, to explore changes in the brains of patients with EOPH using the DC method. The DC value was significantly different in the cerebellum posterior lobe in patients with EOPH, indicating that the cerebellum posterior lobe is associated with EOPH.

[Effects of endurance exercise on synaptic plasticity in cerebral cortex of aged rats and related regulatory mechanism].

OBJECTIVE: To understand and analyze the rules of endurance exercise on the cerebral cortex adaptive mechanism in aged rats. METHODS: In this study, 3-month-old (n=20), 13-month-old (n=24) and 23-month-old (n=24) specific-pathogen free (SPF) male Sprague-Dawley Rat (SD) rats were divided into young (Y-SED), middle-aged (M-SED) and old-aged (O-SED) sedentary control group, and the corresponding Y-EX, M-EX and O-EX in the endurance exercise runner group. The 10-weeks of regular moderate-intensity aerobic exercise intervention were carried out in the endurance exercise runner group. The exercise mode is treadmill exercise (slope 0), and the exercise intensity gradually increases from 60%～65% of the maximum oxygen consumption (V·O2max) to 70%～75%, and the exercise time is 10 weeks. Hematoxylin and eosin (HE) staining was used to detect age-related morphological changes. The expressions of superoxide dismutase(SOD) and brain-derived neurotrophic factor (BDNF) and the expressions of synapsin 1 (SYN1) and Ca2+/calmodulin- dependent protein kinases IIα (CaMK IIα) / AMP-activated protein kinase α1(AMPKα1) / mammalian target of rapamycin (mTOR) pathway -related genes were detected. RESULTS: The cerebral cortex structure of the rats in each group showed age-related aging changes, the expression of SOD in the cortex showed a gradual decline, the expression of BDNF showed an age-increasing trend, and the expression levels of SYN1 and CaMK IIα were increased with age. The changes in AMPKα1 and SirT2 and IP3R, AKT1 and mTOR mRNA levels were increased slightly in middle-aged rats and decreased in aged rats. Compared with the rats in each sedentary control group, the nucleus of the cerebral cortex was tightly arranged and the number of nuclei observed under the microscope was increased significantly in each exercise group. Exercise promoted the expressions of SOD, BDNF and synaptophysin SYN1 in the cortex of rats, and the expression levels of SOD and BDNF in aged rats were up-regulated significantly (P＜ 0.01). The expression level of SYN1 in rats was up-regulated significantly (P＜0.05) in the young and aged rats. The expression of CaMK IIα in the cortex of middle-aged and aged rats was up-regulated (P＜0.01), while the expression level of CaMK IIα in young rats was down-regulated (P＜0.01). Exercise could up-regulate the expression level of AMPKα1 in the cortex of young rats (P＜ 0.05), but not in middle-aged and old-age rats. Exercise could up-regulate the expression of SirT2 in the cortex of rats in all age groups (P＜0.05). Exercise up-regulated the expression of phosphoinositide 3-kinase (IP3R)/ protein kinase B 1(AKT1) /mTOR in the cortex of rats, among which young IP3R was significantly up-regulated (P＜0.01) in the young group, mTOR was significantly up-regulated in young and middle-aged group (P＜0.01), and mTOR was also significantly up-regulated in the aged group (P＜0.05). CONCLUSION: Endurance exercise up-regulates BDNF expression, regulates CaMKIIα signaling, activates AMPK signaling pathway and IP3R / AKT1 / mTOR signaling pathway, and improves synaptic plasticity in the cortex.

Altered Regional Homogeneity in Patients With Corneal Ulcer: A Resting-State Functional MRI Study.

OBJECTIVE: To investigate the potential regional homogeneity (ReHo) brain activity changes in patients with corneal ulcer (CU) and their possible relationship with clinical symptoms. MATERIALS AND METHODS: Forty patients with CU (26 men and 14 women), and 40 healthy controls (HCs) (26 men and 14 women) closely matched in age, sex, and weight underwent resting-state functional MRI scans, respectively. The ReHo method was applied to evaluate synchronous neural activity changes. Receiver operating characteristic curve (ROC curve) was used to show high test-retest stability and high degree of sensitivity and specificity. We utilized the correlation analysis to calculate the relationship between the average ReHo signal values in different brain areas and the clinical symptoms in CU patients. RESULTS: Compared with the HCs, CU patients had significantly increased ReHo values in right cerebellum posterior lobe, left cerebellum posterior lobe, left inferior temporal gyrus, right lingual gyrus, left middle frontal gyrus, left angular gyrus, left cingulate gyrus, right angular gyrus and bilateral superior frontal gyrus, and decreased ReHo values in right anterior cingulate and left precentral gyrus. ROC curve analysis of each brain regions showed the accuracy of AUC was perfect except the right cerebellum posterior lobe. Nevertheless, there was no clear evidence of prominent relevance between the average ReHo values in brain areas and the clinical symptoms. CONCLUSION: Corneal ulcer caused dysfunctional adaption in different brain areas, which including relatively increased values and decreased values. This finding may help us take a further step in exploring the underlying pathologic mechanisms of CU.

Application of amplitude of low­frequency fluctuation to altered spontaneous neuronal activity in classical trigeminal neuralgia patients: A resting­state functional MRI study.

Recent studies have reported structural and functional abnormalities in multiple brain regions of classical trigeminal neuralgia (CTN) patients. Differences in spontaneous neuronal activity between CTN patients and healthy subjects, however, remain unknown. The aim of the present study was to investigate alterations in brain activity by application of amplitude of low frequency fluctuation (ALFF), thus analyzing the correlation between durations of spontaneous pain intensity and ALFF values in CTN patients. A total of 28 CTN patients (male, n=12; female, n=16) and 28 healthy controls (HCs; male, n=12; female, n=16) matched for age and sex were enrolled. All subjects underwent resting­state functional magnetic resonance imaging and changes in spontaneous brain activity were investigated using an ALFF method. Receiver operating characteristic (ROC) curve analysis was applied to differentiate ALFF values of CTN patients from HCs. Altered ALFF values and clinical manifestations were evaluated using Pearson's correlation analysis. ALFF values of the bilateral inferior cerebellum, bilateral fusiform gyrus, right precentral gyrus, left inferior temporal gyrus, right superior cerebellum, left inferior occipital gyrus and right superior occipital gyrus were significantly higher in CTN patients when compared to HCs. ROC curve analysis of each brain revealed a near­perfect AUC accuracy. Pearson's correlation analysis revealed the visual analog scale of the right eye to be positively correlated with both left inferior temporal and occipital gyral findings, while episode duration likewise was positively associated with left inferior temporal gyral findings. CTN patients exhibited abnormal spontaneous activity in multiple brain regions closely related to pain regulation and perception, while VAS and CTN episode duration were positively correlated with ALFF signal values in some brain regions. The present findings provide further insight into the pathological mechanisms underlying CTN.

Altered spontaneous brain activity patterns in patients with corneal ulcer using amplitude of low-frequency fluctuation: An fMRI study.

The aim of the present study was to investigate the altered spontaneous brain activity in patients with corneal ulcer (CU) through the amplitude of low-frequency fluctuation (ALFF) technique and the association with their visual performance. A total of 40 patients with CU and 40 healthy controls (HCs) matched for sex, age and educational level were enrolled. Resting-state functional magnetic resonance imaging (rs-fMRI) was performed to examine the probands. Spontaneous cerebral activity variations were investigated using the ALFF technique. The average ALFF values of the CU patients and the HCs were classified by utilizing receiver operating characteristic (ROC) curves. Contrary to HCs, the CU patients had significantly lower ALFF values in the left cerebellar anterior lobe, right middle frontal gyrus and left middle frontal gyrus, but higher ALFF values in the right cerebellar inferior lobe, left cerebellar inferior lobe, left inferior temporal gyrus, right fusiform gyrus, left superior frontal gyrus, right angular gyrus and bilateral superior frontal gyrus. ROC curve analysis of each brain region indicated that the accuracy of ALFF value specificity between the CU and HCs of the area under the curve was perfect. In conclusion, abnormal spontaneous activities were detected in numerous brain regions of CU patients, which may provide useful information for understanding the dysfunction of CU. These activity changes in brain regions may be used as effective clinical indicators for CU.