Modulation of temporal and occipital cortex by acupuncture in non-menstrual MWoA patients: a rest BOLD fMRI study.

OBJECTIVE: To investigate the changes in amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) values before and after acupuncture in young women with non-menstrual migraine without aura (MWoA) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI). METHODS: Patients with non-menstrual MWoA (Group 1, n = 50) and healthy controls (Group 2, n = 50) were recruited. fMRI was performed in Group 1 at 2 time points: before acupuncture (time point 1, TP1); and after the end of all acupuncture sessions (time point 2, TP2), and performed in Group 2 as a one-time scan. Patients in Group 1 were assessed with the Migraine Disability Assessment Questionnaire (MIDAS) and the Short-Form McGill Pain Questionnaire (SF-MPQ) at TP1 and TP2 after fMRI was performed. The ALFF and DC values were compared within Group 1 at two time points and between Group 1 and Group2. The correlation between ALFF and DC values with the statistical differences and the clinical scales scores were analyzed. RESULTS: Brain activities increased in the left fusiform gyrus and right angular gyrus, left middle occipital gyrus, and bilateral prefrontal cortex and decreased in left inferior parietal lobule in Group 1, which had different ALFF values compared with Group 2 at TP1. The bilateral fusiform gyrus, bilateral inferior temporal gyrus and right middle temporal gyrus increased and right angular gyrus, right superior marginal gyrus, right inferior parietal lobule, right middle occipital gyrus, right superior frontal gyrus, right middle frontal gyrus, right anterior central gyrus, and right supplementary motor area decreased in activity in Group 1 had different DC values compared with Group 2 at TP1. ALFF and DC values of right inferior temporal gyrus, right fusiform gyrus and right middle temporal gyrus were decreased in Group1 at TP1 compared with TP2. ALFF values in the left middle occipital area were positively correlated with the pain degree at TP1 in Group1 (correlation coefficient r, r = 0.827, r = 0.343; P < 0.01, P = 0.015). The DC values of the right inferior temporal area were positively correlated with the pain degree at TP1 in Group 1 (r = 0.371; P = 0.008). CONCLUSION: Spontaneous brain activity and network changes in young women with non-menstrual MwoA were altered by acupuncture. The right temporal area may be an important target for acupuncture modulated brain function in young women with non-menstrual MwoA.

The anti-hepatocellular carcinoma effects of polysaccharides from Ganoderma lucidum by regulating macrophage polarization via the MAPK/NF-κB signaling pathway.

The response of macrophages to environmental signals demonstrates its heterogeneity and plasticity. After different forms of polarized activation, macrophages reach the M1 or M2 activation state according to their respective environment. Ganoderma lucidum polysaccharide (GLPS) is a major bioactive component of Ganoderma lucidum, a well-known medicinal mushroom. Although the immunomodulatory and anti-tumor effects of GLPS have been proven, GLPS's effect on inhibiting hepatocellular carcinoma (HCC) by regulating macrophage polarization is little known. Our data showed that GLPS notably inhibited the growth of a Hepa1-6 allograft. The expression of M1 marker CD86 was higher in the tumor tissue of the GLPS treatment group than in the control group in vivo. In vitro, the phagocytic activity and NO production of macrophages were increased by GLPS treatment. Moreover, it was discovered that GLPS was able to increase the expression of the M1 phenotype marker CD86, iNOS, and pro-inflammatory cytokines comprising IL-12a, IL-23a, IL-27 and TNF-α, but inhibited macrophage polarization towards the M2 phenotype by decreasing the expression of CD206, Arg-1, and inflammation-related cytokines comprising IL-6 and IL-10. The data suggest that GLPS may regulate macrophage polarization. Mechanistically, GLPS increased the phosphorylation of MEK and ERK. In addition, the phosphorylation of IκBα and P65 was increased by GLPS treatment. These data showed that GLPS can regulate the MAPK/NF-κB signaling pathway responsible for M1 polarization. In a nutshell, our research puts forward a new application of GLPS in anti-HCC treatment by regulating macrophage polarization through activating MAPK/NF-κB signaling.

The Changes of Brain Function After Spinal Manipulation Therapy in Patients with Chronic Low Back Pain: A Rest BOLD fMRI Study.

OBJECTIVE: To investigate the changes of regional homogeneity (Reho) values before and after spinal manipulative therapy (SMT) in patients with chronic low back pain (CLBP) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI). METHODS: Patients with CLBP (Group 1, n = 20) and healthy control subjects (Group 2, n = 20) were recruited. The fMRI was performed three times in Group 1 before SMT (time point 1, TP1), after the first SMT (time point 2, TP2), after the sixth SMT (time point 3, TP3), and for one time in Group 2, which received no intervention. The clinical scales were finished in Group 1 every time before fMRI was performed. The Reho values were compared among Group 1 at different time points, and between Group 1 and Group 2. The correlation between Reho values with the statistical differences and the clinical scale scores were calculated. RESULTS: The bilateral precuneus and right mid-frontal gyrus in Group 1 had different Reho values compared with Group 2 at TP1. The Reho values were increased in the left precuneus and decreased in the left superior frontal gyrus in Group 1 at TP2 compared with TP1. The Reho values were increased in the left postcentral gyrus and decreased in the left posterior cingulate cortex and the superior frontal gyrus in Group 1 at TP3 compared with TP1. The ReHo values of the left precuneus in Group 1 at TP1 were negatively correlated with the pain degree at TP1 and TP2 (r = -0.549, -0.453; p = 0.012, 0.045). The Reho values of the middle temporal gyrus in Group 1 at TP3 were negatively correlated with the changes of clinical scale scores between TP3 and TP1 (r = 0.454, 0.559; p = 0.044, 0.01). CONCLUSION: Patients with CLBP showed abnormal brain function activity, which was altered after SMT. The Reho values of the left precuneus could predict the immediate analgesic effect of SMT.

The Instant and Sustained Effect of Electroacupuncture in Postgraduate Students with Depression: An fMRI Study.

OBJECTION: This study was a primary study to evaluate the instant and sustained effect of electroacupuncture (EA) at GV20 (Baihui) in postgraduate students with mild depression by using a special flexible head coil. METHODS: A total of 20 postgraduate students with mild depression underwent EA stimulation at GV20 and 3 phases of resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Phase I: Preparation (before needle insertion); Phase II: during EA; Phase III: 15 minutes after needle removal. The Rs-fMRI data were processed using DPABI and SPSS 25. RESULTS: 1) ReHo values showed significantly differences in the right posterior cingulate cortex, right calcarine gyrus, right angular gyrus, right precuneus, right cuneus, and bilateral postcentral gyri among Phase I, Phase II and Phase III; 2) Relative to the Phase I, increased brain activity in the Phase II was observed in the bilateral postcentral gyri, right calcarine gyrus, right cuneus. Compared with the Phase II, decreased brain activity in the Phase III was observed in the right precuneus, right posterior cingulate cortex, right angular gyrus. Relative to the Phase I, Significantly increased brain activity in the Phase III was observed in the right calcarine gyrus, right cuneus, and bilateral postcentral gyri. While decreased ReHo values were found in the right posterior cingulate cortex, right angular gyrus, right precuneus; and 3) Correlation analysis showed that the ReHo values of multiple brain regions in Phase I and Phase III were significantly correlated with the VAS and HRSD-17 scores. CONCLUSION: This study focuses on the instant and sustained effect in postgraduate students with depression. Our study showed that instant effect produced by EA stimulation at GV20 firstly induced changes in somatosensory and visual area, and then, sustained effect (Phase III) have a higher intensity and more extensive than instant effects. Meanwhile, we provide a visualization way to study the instant effects of head acupoints by using a flexible head coil.

Distribution of pericellular matrix molecules in the temporomandibular joint and their chondroprotective effects against inflammation.

The objectives of this study were to (1) determine the distribution and synthesis of pericellular matrix (PCM) molecules (collagen VI, collagen IV and laminin) in rat temporomandibular joint (TMJ) and (2) investigate the effects of PCM molecules on chondrocytes against inflammation in osteoarthritis. Four zones (fibrous, proliferating, mature and hypertrophic) of condylar cartilage and three bands (anterior, intermediate and posterior) of disc were analysed by immunohistochemistry for the presence of PCM molecules in rat TMJs. Isolated chondrocytes were pre-treated with PCM molecules before being subjected to interleukin (IL)-1ß treatment to stimulate inflammation. The responses of the chondrocytes were analysed using gene expression, nitric oxide release and matrix metalloproteinase (MMP)-13 production measures. Histomorphometric analyses revealed that the highest areal deposition of collagen VI (67.4%), collagen IV (45.7%) and laminin (52.4%) was in the proliferating zone of TMJ condylar cartilage. No significant difference in the distribution of PCM molecules was noted among the three bands of the TMJ disc. All three PCM molecules were expressed intracellularly by chondrocytes cultured in the monolayer. Among the PCM molecules, pre-treatment with collagen VI enhanced cellular proliferation, ameliorated IL-1ß-induced MMP-3, MMP-9, MMP-13 and inducible nitric oxide synthase gene expression, and attenuated the downregulation of cartilage matrix genes, including collagen I, aggrecan and cartilage oligomeric matrix protein (COMP). Concurrently, collagen VI pretreatment inhibited nitric oxide and MMP-13 production. Our study demonstrates for the first time the distribution and role of PCM molecules, particularly collagen VI, in the protection of chondrocytes against inflammation.

Early prediction of functional outcome using dynamic contrast enhanced magnetic resonance imaging in experimental stroke.

BACKGROUND AND PURPOSE: Early prediction of functional outcome in cerebral ischemia stroke using MRI remains a challenge. The aim of this study was to evaluate the predictive value of dynamic contrast-enhanced (DCE) MRI in terms of functional outcome of ischemia stroke. METHODS: Right middle cerebral artery occlusion (MCAO) was performed in male SD rats (n=50), followed by withdrawal of the occluding filament after 3 (n = 10), 4 (n = 10), 5 (n = 10), 6 (n = 10) or 7 (n = 10) h to establish ischemia and reperfusion stroke. DCE and conventional MRI were performed in each animal 60 ± 15 min before and after reperfusion. The outcome was assessed by the modified Neurological Severity Scores (mNSS) (before reperfusion and at 72 h after reperfusion) and the infarct volume. Comparisons of functional prognosis and DCE parameters (K(trans), Ve and Kep) were performed using binary logistic regression and operating characteristic (ROC) analysis. RESULTS: DCE parameters results indicated that blood brain barrier (BBB) permeability increased with prolonged reperfusion timing. Using binary logistic regression analysis on stroke characteristics (reperfusion timing, infarct volume) and BBB permeability parameters (drK(trans)subcortex, drK(trans)cortex, drVesubcortex, drVecortex, drKepsubcortex and drKepcortex) as covariates , the results demonstrated that reperfusion timing, infarct volume, drK(trans)subcortex and drKepsubcortex were independent factors that were associated with prognosis (OR=0.01, OR=0.23, OR=245.23, OR=1.29). ROC analysis indicated that a drK(trans)subcortex threshold of 0.88 with a sensitivity of 95.7% and a specificity of 85.2% and a drKepsubcortex threshold of -0.25 with a sensitivity of 69.6% and a specificity of 70.4% for differentiation between favourable and unfavourable prognosis. CONCLUSIONS: Quantitative DCE-MRI can be used to predict the functional outcomes of cerebral ischemia injury.

Detecting isocitrate dehydrogenase gene mutations in oligodendroglial tumors using diffusion tensor imaging metrics and their correlations with proliferation and microvascular density.

PURPOSE: Isocitrate dehydrogenase (IDH) mutations are frequently present in oligodendroglial tumors (OTs) and have prognostic value. We assessed whether diffusion tensor imaging (DTI) metrics could aid the noninvasive detection of IDH mutations and their correlations with tumor proliferation and microvascular density (MVD) in OTs. MATERIALS AND METHODS: Ninety patients with OTs who underwent conventional magnetic resonance imaging (MRI) and DTI were retrospectively reviewed (3T). IDH mutations were determined by immunohistochemical staining or direct sequencing. MVD and cell proliferation were evaluated by immunohistochemical staining with anti-CD31 and Ki-67, respectively. The Mann-Whitney U-test was applied to each of the imaging parameters. Spearman correlation analysis and receiver operating characteristic curve analysis were performed. RESULTS: The maximal fractional anisotropy (FA), ratio of maximal FA (rmFA), minimal ADC, and ratio of minimal (rmADC) values were demonstrated to be significantly different between the OTs with IDH1/2 mutations and those without mutations (P < 0.05). The areas under the curve (AUCs) for the maximal FA, rmFA, minimal ADC, and rmADC were 0.79, 0.82, 0.77, and 0.80, respectively. A combination rmFA and rmADC for the diagnosis of IDH1/2 mutations led to sensitivity, specificity, and AUC of 91.5%, 76.5%, and 0.86, respectively. The Ki-67 and MVD levels in the IDH-mutated samples were lower than those in the IDH wildtype cases (P < 0.05). CONCLUSION: DTI metrics may provide a noninvasive method for assessing the IDH statuses of OTs. Significantly higher minimal ADC and lower maximal FA in OTs with IDH mutations may suggest that IDH mutations lead to proliferation inhibition and an angiogenesis decrease.

Prediction of Reperfusion-Associated Hemorrhagic Transformation Using Dynamic Contrast-Enhanced Imaging in a Rat Stroke Model.

BACKGROUND AND PURPOSE: Reperfusion-associated hemorrhagic transformation (HT) is an important complication of recanalization therapy. A method to identify stroke victims that may undergo HT will improve the patient selection and safety of this treatment. In this study, we determined the relationship between timing of reperfusion and the frequency and severity of HT, and whether very early dynamic contrast-enhanced (DCE) imaging predicts the occurrence of reperfusion-associated HT in a model of experimental stroke. METHODS: Intraluminal suture occlusion of the middle cerebral artery was used to produce transient ischemia in male Sprague Dawley rats (n = 50). Reperfusion was performed by withdrawal of the occluding filament after 3 (n = 10), 4 (n = 10), 5 (n = 10), 6 (n = 10), or 7 (n = 10) hours. Magnetic resonance imaging studies were performed before reperfusion using DCE, susceptibility-weighted imaging, diffusion-weighted imaging, and T2- and T1-weighted imaging. Follow-up magnetic resonance imaging and histological studies were performed at 24 hours. RESULTS: Hemorrhagic transformation occurred by 24 hours after injury in 8 of 50 animals. The HT rate increased with prolonged ischemic duration. All animals exhibiting acute blood-brain barrier (BBB) perturbation subsequently developed HT by 24 hours. Statistically significant differences in the BBB permeability parameters (P < 0.05) between the HT group and non-HT group were detected by DCE imaging. There were also statistically significant differences (P < 0.05) between the HT area and adjacent HT area. Among the permeability parameters, subcortex rK was the most sensitive and specific predictor of HT. CONCLUSIONS: The results suggest that the use of quantitative BBB measurements may further improve early prediction and identification of HT. The DCE parameters were the sensitive early independent predictor of reperfusion-associated HT.

[Effect of spinal manipulation on brain functional activity in patients with lumbar disc herniation].

OBJECTIVE: To investigate the effects of spinal manipulation (SM) on brain functional activity in patients with lumbar disc herniation (LDH). METHODS: Eleven patients with LDH were recruited in the study. All patients received 6 times of lumbar SM treatment and then clinical efficacy was evaluated. All patients received brain functional magnetic resonance imaging (fMRI) scans before and after SM treatment. RESULTS: Three subjects dropped out and 8 subjects completed the study, among whom 4 cases were effective and 4 ineffective after SM treatment. The required pressure value producing the same level (VAS 50) pain was (7.43 ± 1.47) kg and (10.53 ± 0.55) kg before and after SM treatment in effective patients(P<0.05); however, there was no significant difference in ineffective patients (P>0.05). Compared to pre-treatment level, the brain functional activity in effective patients was mainly inhibited, the inhibited areas were located in the right side of prefrontal cortex and cerebellum; while the brain functional activity was generally enhanced in ineffective patients. CONCLUSION: SM can affect the brain functional activity of patients with LDH, the inhibited areas is mainly located in prefrontal cortex and cerebellum when SM treatment is effective.

Magnetic resonance imaging findings of intracranial papillary meningioma: a study on eight cases.

OBJECTIVES: To increase the awareness on intracranial papillary meningiomas (PMs) by presenting magnetic resonance imaging (MRI) findings on this disease. MATERIALS AND METHODS: The MRI findings and clinical presentations of nine discrete lesions in eight patients with pathologically documented PMs were retrospectively analyzed. RESULTS: Most tumors occurred in young adults. The tumors originated from the convexity meninges in five cases and from the parasagittal regions in four cases. The tumor shape was irregular in six cases, lobulated in two cases, and round in one case. By MRI, nine masses were primarily isointense (n=5) or mildly hypointense (n=4) to gray matter on T1-weighted images and inhomogeneous hyperintense (n=3) or isointense (n=6) to the cortex on T2-weighted and fluid-attenuated inversion recovery images. On diffusion-weighted imaging, the signal intensity of the tumor was increased in all lesions compared with the adjacent parenchyma. Tumor and brain interfaces were unclear in seven cases, cyst formation was observed in eight tumors, scattered hemorrhage was observed in three tumors, signal voids due to vessels were visible in four cases, and eight tumors had moderate or marked irregular peritumoral edema. Enhancement was homogeneous (n=2) or heterogeneous (n=7), an area of focal nodular enhancement was observed in three lesions, and the dural tail sign was visible in seven cases. CONCLUSION: Although PM is rare, it should be considered in the differential diagnosis when evaluating intracranial neoplasms. Younger patient age, as well as imaging features such as unclear tumor-brain interface, internal heterogeneity including cyst formation, irregular enhancement, signal voids of vessels, and marked peritumoral edema can help distinguish PM from typical benign meningiomas.