Cancer screening in hospitalized ischemic stroke patients: a multicenter study focused on multiparametric analysis to improve management of occult cancers.

Background/aims: The reciprocal promotion of cancer and stroke occurs due to changes in shared risk factors, such as metabolic pathways and molecular targets, creating a "vicious cycle." Cancer plays a direct or indirect role in the pathogenesis of ischemic stroke (IS), along with the reactive medical approach used in the treatment and clinical management of IS patients, resulting in clinical challenges associated with occult cancer in these patients. The lack of reliable and simple tools hinders the effectiveness of the predictive, preventive, and personalized medicine (PPPM/3PM) approach. Therefore, we conducted a multicenter study that focused on multiparametric analysis to facilitate early diagnosis of occult cancer and personalized treatment for stroke associated with cancer. Methods: Admission routine clinical examination indicators of IS patients were retrospectively collated from the electronic medical records. The training dataset comprised 136 IS patients with concurrent cancer, matched at a 1:1 ratio with a control group. The risk of occult cancer in IS patients was assessed through logistic regression and five alternative machine-learning models. Subsequently, select the model with the highest predictive efficacy to create a nomogram, which is a quantitative tool for predicting diagnosis in clinical practice. Internal validation employed a ten-fold cross-validation, while external validation involved 239 IS patients from six centers. Validation encompassed receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and comparison with models from prior research. Results: The ultimate prediction model was based on logistic regression and incorporated the following variables: regions of ischemic lesions, multiple vascular territories, hypertension, D-dimer, fibrinogen (FIB), and hemoglobin (Hb). The area under the ROC curve (AUC) for the nomogram was 0.871 in the training dataset and 0.834 in the external test dataset. Both calibration curves and DCA underscored the nomogram's strong performance. Conclusions: The nomogram enables early occult cancer diagnosis in hospitalized IS patients and helps to accurately identify the cause of IS, while the promotion of IS stratification makes personalized treatment feasible. The online nomogram based on routine clinical examination indicators of IS patients offered a cost-effective platform for secondary care in the framework of PPPM. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00354-8.

Clinicopathological features of kidney injury in patients receiving immune checkpoint inhibitors (ICPi) combined with anti-vascular endothelial growth factor (anti-VEGF) therapy.

BACKGROUND: Immune checkpoint inhibitor (ICPi) combined with anti-vascular endothelial growth factor (VEGF) therapy has increasingly become a promising strategy in various malignancies. However, the combination might be associated with increased risk of nephrotoxicity. METHODS: We retrospectively recruited patients who suffered kidney injury and received renal biopsy after anti-VEGF/ICPi mono- or combination therapy and divided them into three groups: anti-VEGF monotherapy, ICPi monotherapy and combination therapy. Clinical and histopathological features of three groups were analysed. All patients were followed-up for 3 months after biopsy, with or without glucocorticoid treatment, and renal outcome were compared. RESULTS: A total of 46 patients were enrolled. Eighteen patients received anti-VEGF monotherapy, 12 received ICPi monotherapy and 16 received combined treatment of anti-VEGF and ICPi. Proteinuria level of anti-VEGF group, ICPi group and combination group were 4.07±3.17 g/day, 0.60±0.61 g/day and 2.05±2.50 g/day, respectively (p=0.002). The peak serum creatinine level of combination group (1.75±0.77 mg/dL) was also in between ICPi group (2.79±0.90 mg/dL) and anti-VEGF group (1.34±0.60 mg/dL) (p<0.001). Multiple histopathological patterns involving glomerulus, tubulointerstitium and vessel existed in the majority of cases in combination group (68.8%). Renal complete and partial recovery rate of combination therapy were also in between monotherapy (57.1% vs 40.0% in anti-VEGF group, 100.0% in ICPi group, respectively). CONCLUSIONS: Kidney injury in patients treated with combination therapy of ICPi and anti-VEGF shows hybrid pathological patterns and intermediate clinical features compared with monotherapy. Cohorts with larger sample and better design, as well as basic research, are needed to elucidate the mechanism of 'protection' effect of combination anti-cancer therapy to renal function.

Development and validation of a nomogram model for central venous access device-related thrombosis in hospitalized children.

This study aimed to develop and validate a nomogram model of central venous access device-related thrombosis (CRT) for hospitalized children. A total of 503 consecutive cases from a hospital in Changsha City, Hunan Province were stochastically classified into the training set and internal validation set at a ratio of 7:3, and 85 consecutive cases in two hospitals in Urumqi City, Xinjiang Uygur Autonomous Region were collected as an external validation set. Univariate analysis and multivariate analysis on CRT-related risk factors of hospitalized children were conducted, a logistic regression model was employed to establish the nomogram, and the discrimination, calibration, and decision curve analysis was performed to assess the proposed nomogram model. The nomogram model involved seven independent risk factors, including blind catheterization, abnormal liver function, central line-associated bloodstream infection, infection, number of catheter lines, leukemia, and bed rest > 72 h. The discrimination results showed that the area under the receiver operating characteristic curve of the training set, internal validation set, and external validation set was 0.74, 0.71, and 0.76 respectively, and the accuracy rates of the proposed nomogram model were 79%, 72%, and 71% in the training set, internal validation set, and external validation set. The calibration results also showed that the calibration curve had great fitness for each dataset. More importantly, the decision curve suggested that the proposed nomogram model had a prominent clinical significance. CONCLUSION: The nomogram model can be used as a risk assessment tool to reduce the missed diagnosis rate and the incidence of CRT in hospitalized children. WHAT IS KNOWN: • Central venous access device-related thrombosis is generally asymptomatic for hospitalized children, causing the missed diagnosis of central venous access device-related thrombosis easily. • No risk prediction nomogram model for central venous access device-related thrombosis in hospitalized children has been established. WHAT IS NEW: • A visual and personalized nomogram model was built by seven accessible variables (blind catheterization, abnormal liver function, central line-associated bloodstream infection, infection, number of catheter lines, leukemia, and bed rest > 72 h). • The model can effectively predict the risk of central venous access device-related thrombosis for hospitalized children.

Ononin ameliorates inflammation and cartilage degradation in rat chondrocytes with IL-1ß-induced osteoarthritis by downregulating the MAPK and NF-κB pathways.

BACKGROUND: Osteoarthritis (OA) treatment aims to improve inflammation and delay cartilage degeneration. However, there is no effective strategy presently available. Ononin, a representative isoflavone glycoside component extracted from natural Chinese herbs, exerts anti-inflammatory and proliferative effects. However, the therapeutic effect of ononin on chondrocyte inflammation remains unclear. METHODS: In this study, we explored the therapeutic effect and potential mechanism of ononin in OA by establishing an interleukin-1 beta (IL-1ß)-induced chondrocyte inflammation model. RESULTS: Our results verified that ononin alleviated the IL-1ß-induced decrease in chondrocyte viability, attenuated the overexpression of the inflammatory factors tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6), and simultaneously inhibited the expression of cartilage extracellular matrix (ECM)-degrading enzymes such as matrix metalloproteinase-13 (MMP-13). Furthermore, the decomposition of Collagen II protein could be alleviated in the OA model by ononin. Finally, ononin improved chondrocyte inflammation by downregulating the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signalling pathways. CONCLUSION: Our findings suggested that ononin could inhibit the IL-1ß-induced proinflammatory response and ECM degradation in chondrocytes by interfering with the abnormal activation of the MAPK and NF-κB pathways, indicating its protective effect against OA.

Fraxetin Inhibits the Proliferation and Metastasis of Glioma Cells by Inactivating JAK2/STAT3 Signaling.

Glioma is the most common brain tumor and is characterized by high mortality rates, high recurrence rates, and short survival time. Migration and invasion are the basic features of gliomas. Thus, inhibition of migration and invasion may be beneficial for the treatment of patients with glioma. Due to its antitumor activity and chemical reactivity, fraxetin has attracted extensive interest and has been proven to be an effective antitumor agent in various cancer types. However, currently, the potential effects of fraxetin on glioma have not been investigated. Here, we demonstrate that fraxetin can inhibit the proliferation, invasion, and migration of glioma and induce apoptosis of glioma cells in vitro and in vivo. Therefore, these findings establish fraxetin as a drug candidate for glioma treatment. Furthermore, fraxetin was able to effectively inhibit the JAK2/STAT3 signaling in glioma. In summary, our results show that fraxetin inhibits proliferation, invasion, and migration of glioma by inhibiting JAK2/STAT3 signaling and inducing apoptosis of glioma cells. The present study provides a solid basis for the development of new glioma therapies.

Machine learning may predict individual hand motor activation from resting-state fMRI in patients with brain tumors in perirolandic cortex.

OBJECTIVE: The study aimed to evaluate the predictive validity of the neural network (NN) method for presurgical mapping of motor areas using resting-state functional MRI (rs-fMRI) data of patients with brain tumor located in the perirolandic cortex (PRC). METHODS: A total of 109 patients with brain tumors occupying PRC underwent rs-fMRI and hand movement task-based fMRI (tb-fMRI) scans. Using a NN model trained on fMRI data of 47 healthy controls, individual task activation maps were predicted from their rs-fMRI data. NN-predicted maps were compared with task activation and independent component analysis (ICA)-derived maps. Spatial Pearson's correlation coefficients (CC) matrices and Dice coefficients (DC) between task activation and predicted activation using NN (DCNN_Act) and ICA (DCICA_Act) were calculated and compared using non-parametric tests. The effects of tumor types and head motion on predicted maps were demonstrated. RESULTS: The CC matrix of NN-predicted maps showed higher diagonal values compared with ICA-derived maps (p < 0.001). DCNN_Act were higher than DCICA_Act (p < 0.001) for patients with or without motor deficits. Lower DCs were found in subjects with head motion greater than one voxel. DCs were higher on the nontumor side than on the tumor side (p < 0.001), especially in the glioma group compared with meningioma and metastatic groups. CONCLUSIONS: This study indicated that the NN approach could predict individual motor activation using rs-fMRI data and could have promising clinical applications in brain tumor patients with anatomical and functional reorganizations. KEY POINTS: • The neural network machine learning approach successfully predicted hand motor activation in patients with a tumor in the perirolandic cortex, despite space-occupying effects and possible functional reorganization. • Compared to the conventional independent component analysis, the neural network approach utilizing resting-state fMRI data yielded a higher correlation to the active task hand activation data. • The Dice coefficient of machine learning-predicted activation vs. task fMRI activation was different between tumor and nontumor side, also between tumor types, which might indicate different effects of possible neurovascular uncoupling on resting-state and task fMRI.

LncRNA MIAT downregulates IL-1ß, TNF-ɑ to suppress macrophage inflammation but is suppressed by ATP-induced NLRP3 inflammasome activation.

Cardiovascular disease (CVD) has been identified as the leading cause of premature deaths in rheumatoid arthritis (RA), accounting for about 40 to 50% of all deaths. Macrophage inflammation is regarded as a key point to link to the two diseases. Recently, long non-coding RNAs (lncRNAs) have acknowledged as a regulator of inflammation significantly. Here, we firstly found that lncRNA myocardial infarction associated transcript (lncRNA MIAT), a crucial lncRNA to regulate CVD, expressed increasingly in synovium and myocardial tissues of collagen-induced arthritis (CIA) mice. Besides, we also verified that the increased infiltration of macrophage occurred in those tissues of the CIA. In vitro, we found that macrophage inflammation induced by LPS could up-regulate lncRNA MIAT expression. LncRNA MIAT seemed to inhibit the expression of IL-1ß, TNF-ɑ and be suppressed by ATP-induced NLRP3 inflammasome activation pathway. Therefore, these data indicated an anti-inflammatory effect of lncRNA MIAT in macrophage and an original research direction for high cardiovascular risk in RA.

A Longitudinal, Prospective Study to Evaluate the Effects of Treatment on the Inhibitory Control Function After Transsphenoidal Surgery for Pituitary Adenomas.

OBJECTIVES: Injured cognitive abilities have been reported in patients with pituitary adenoma. However, to date, few researchers have directly investigated the electrophysiological study of inhibitory control function of pituitary patients both pre- and postsurgery. Thus, this study aimed to identify the factors affecting the inhibitory control function of pituitary patients. METHODS: Thirty presurgery pituitary patients were recruited and 26 patients of them completed the postsurgery follow-up. Thirty healthy people were recruited for control group. Visual Go/Nogo tasks were carried out by the patients and controls to assess the inhibitory control function before surgery and 6 months after the surgery, respectively. The function of inhibitory control was analyzed with the components of N2 and P3. RESULTS: Across 3 groups, Nogo stimuli evoked larger frontal-central N2nogo and P3nogo than Go stimuli did. Furthermore, N2d of presurgery patients (-1.14 µV) and postsurgery patients(-0.61 µV) were significantly decreased compared with that of control group (-3.09 µV), F(2, 83) = 13.92, P < .01, whereas no difference was detected between pre- and postsurgery groups. There was no remarkable difference in the amplitude of P3d among the 3 groups, F(2, 83) = 0.19, P > .05. With regard to the amplitude of P3 for Go condition, The P3 amplitude of healthy group (4.38 µV) was larger than both pre- and postsurgery (1.00 µV and 3.01 µV). With regard to the amplitude of P3 for Nogo condition, The P3 amplitude of healthy group (5.25 µV) was larger than both pre- and postsurgery groups (2.35 µV and 4.18 µV). CONCLUSIONS: These results indicated that presurgery patients showed the dysfunction of inhibition, due to the nerve tissue damage or brain structure alteration caused by the presurgery physical pressure from tumor and abnormal hormone levels. Postsurgery patients showed a tendency toward recovery, but there was no obvious improvement in the inhibitory control function after successful treatments.

Risk Factors for Central Venous Access Device-Related Thrombosis in Hospitalized Children: A Systematic Review and Meta-Analysis.

OBJECTIVE: To identify the potential associations of patient-, treatment-, and central venous access device (CVAD)-related factors with the CVAD-related thrombosis (CRT) risk in hospitalized children. METHODS: A systematic search of PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, Wanfang, and VIP database was conducted. RevMan 5.3 and Stata 12.0 statistical software were employed for data analysis. RESULTS: In terms of patient-related factors, the patient history of thrombosis (odds ratio [OR] = 3.88, 95% confidence interval [CI]: 2.57-5.85), gastrointestinal/liver disease (OR = 1.85, 95% CI: 0.99-3.46), hematologic disease (OR = 1.45, 95% CI: 1.06-1.99), and cancer (OR = 1.58, 95% CI: 1.01-2.48) were correlated with an increased risk of CRT. In terms of treatment-related factors, parenteral nutrition (PN)/total PN (OR = 1.70, 95% CI: 1.21-2.39), hemodialysis (OR = 2.17, 95% CI: 1.34-3.51), extracorporeal membrane oxygenation (OR = 1.51, 95% CI: 1.31-1.71), and cardiac catheterization (OR = 3.92, 95% CI: 1.06-14.44) were associated with an increased CRT risk, while antibiotics (OR = 0.46, 95% CI: 0.32-0.68) was associated with a reduced CRT risk. In terms of the CVAD-related factors, CRT risk was more significantly increased by peripherally inserted central catheter than tunneled lines (OR = 1.81, 95% CI: 1.15-2.85) or totally implantable venous access port (OR = 2.81, 95% CI: 1.41-5.60). And subclavian vein catheterization significantly contributed to a lower CRT risk than femoral vein catheterization (OR = 0.36, 95% CI: 0.14-0.88). Besides, multiple catheter lines (OR = 4.06, 95% CI: 3.01-5.47), multiple catheter lumens (OR = 3.71, 95% CI: 1.99-6.92), central line-associated bloodstream infection (OR = 2.66, 95% CI: 1.15-6.16), and catheter malfunction (OR = 1.65, 95% CI: 1.07-2.54) were associated with an increased CRT risk. CONCLUSION: The exact identification of the effect of risk factors can boost the development of risk assessment tools with stratifying risks.

A Case Report of Sporadic Adult Neuronal Intranuclear Inclusion Disease (NIID) With Stroke-Like Onset.

Background: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. The clinical manifestations of NIID are complex and easily misdiagnosed. Based on the current knowledge of this disease, it is usually chronic, with almost no acute cases. Stroke-like disease is an extremely rare type of NIID. Case Presentation: A 61-year-old woman was admitted to our hospital with sudden left limb weakness. Diffusion magnetic resonance imaging (MRI) demonstrated high signal intensity in the skin-medullary junction area. Tissue pathology showed eosinophilic inclusions in the nuclei of the sweat gland cells and fat cells of the skin. Subsequent genetic analysis of the fragile X chromosome mental retardation gene 1 (FMR1) gene showed that the CGG repeat number was in the normal range, excluding fragile X-related tremor/ataxia syndrome (FXTAS). After 3 weeks of hospitalization, the patient's condition improved, and the left limb muscle strength recovered. Her symptoms were almost completely diminished after 3 months. Conclusion: This case demonstrates the strong clinical heterogeneity of NIID. NIID can manifest as acute hemiplegia and a stroke-like attack. This case study provides new information for the diagnosis of NIID and the classification of the clinical characteristics.

Hormone levels are related to functional compensation in prolactinomas: A resting-state fMRI study.

Prolactinomas are tumors of the pituitary gland, which overproduces prolactin leading to dramatic fluctuations of endogenous hormone levels throughout the body. While it is not fully understood how endogenous hormone disorders affect a patient's brain, it is well known that fluctuating hormone levels can have negative neuropsychological effects. Using resting-state functional magnetic resonance imaging (rs-fMRI), we investigated whole-brain functional connectivity (FC) and its relationship with hormone levels in prolactinomas. By performing seed-based FC analyses, we compared FC metrics between 33 prolactinoma patients and 31 healthy controls matched for age, sex, and hand dominance. We then carried out a partial correlation analysis to examine the relationship between FC metrics and hormone levels. Compared to healthy controls, prolactinoma patients showed significantly increased thalamocortical and cerebellar-cerebral FC. Endogenous hormone levels were also positively correlated with increased FC metrics, and these hormone-FC relationships exhibited sex differences in prolactinoma patients. Our study is the first to reveal altered FC patterns in prolactinomas and to quantify the hormone-FC relationships. These results indicate the importance of endogenous hormones on functional compensation of the brain in patients with prolactinomas.

Spectrum of SLC20A2, PDGFRB, PDGFB, and XPR1 mutations in a large cohort of patients with primary familial brain calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder with four causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1) that have been identified. Here, we aim to describe the mutational spectrum of four causative genes in a series of 226 unrelated Chinese PFBC patients. Mutations in four causative genes were detected in 16.8% (38/226) of PFBC patients. SLC20A2 mutations accounted for 14.2% (32/226) of all patients. Mutations in the other three genes were relatively rare, accounting for 0.9% (2/226) of all patients, respectively. Clinically, 44.8% of genetically confirmed patients (probands and relatives) were considered symptomatic. The most frequent symptoms were chronic headache, followed by movement disorders and vertigo. Moreover, the total calcification score was significantly higher in the symptomatic group compared to the asymptomatic group. Functionally, we observed impaired phosphate transport induced by seven novel missense mutations in SLC20A2 and two novel mutations in XPR1. The mutation p.D164Y in XPR1 might result in low protein expression through an enhanced proteasome pathway. In conclusion, our study further confirms that mutations in SLC20A2 are the major cause of PFBC and provides additional evidence for the crucial roles of phosphate transport impairment in the pathogenies of PFBC.

Polyunsaturated fatty acids and inflammatory markers in major depressive episodes during pregnancy.

INTRODUCTION: Prenatal depression (PND) is a common psychiatric disorder in pregnant women and leads to psychosocial dysfunction, high suicidal rate, and adverse childcare. Patients with PND have omega-3 polyunsaturated fatty acid (omega-3 or n-3 PUFAs) deficits, which might link to chronic low-grade inflammatory process and the pathophysiological mechanisms of depression. In this case-control study, we examined the levels of PUFAs and inflammatory cytokines in PND. METHOD: Blood samples were obtained and analyzed from 16 healthy controls and 17 depressed cases (PND group) diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Independent sample t-test and correlation analysis were performed with Statistical Package for the Social Sciences (SPSS) logistics correlation analysis. RESULTS: PND group had significantly lower levels of total n-3 (p=0.026), docosahexaenoic acid (DHA) (p=0.020) and eicosapentaenoic (EPA) (p=0.019) but a higher omega-6 (n-6)/n-3 PUFAs ratio (p=0.007) and tumor necrosis factor alpha (TNF-α) (p=0.016) level. Moreover, the duration of current PND episodes were also significantly correlated with DHA, EPA, n-3 PUFAs, n-6/n-3 ratio and TNF-α. In terms of PUFAs and cytokine levels, only DHA was inversely correlated with TNF-α. CONCLUSION: PND is significantly associated with lower DHA, EPA, and total n-3 PUFAs levels and an increased n-6/n-3 PUFAs ratio, while the duration of PND is associated with lower levels of n-3 PUFAs, including DHA and EPA. The correlation of PUFAs levels with depression and TNF-α level grant further investigation into the inflammatory process underlying PND, mediated by PUFAs.

Cognitive Function and Serum Hormone Levels Are Associated with Gray Matter Volume Decline in Female Patients with Prolactinomas.

BACKGROUND AND OBJECTIVE: Cognitive impairments have been reported in patients with hyperprolactinemia; however, there is a lack of knowledge of brain structure alterations relevant to hyperprolactinemia in prolactinomas. Thus, we aimed to identify changes in brain structure in prolactinomas and to determine whether these changes are related to cognitive performance and clinical characteristics. METHODS: Participants were 32 female patients with prolactinomas and 26 healthy controls (HC) matched for age, sex, education, and handedness. All participants underwent magnetic resonance imaging brain scans, neuropsychological assessments, and clinical evaluations. Voxel-based morphometry analysis was used to identify changes in gray matter volume (GMV). Partial correlation analysis and multiple linear regression were performed to determine the relationship between GMV, cognition, and clinical characteristics. RESULTS: Compared to HC, patients with prolactinomas demonstrated a decrease in GMV in the left hippocampus, left orbitofrontal cortex, right middle frontal cortex (MFC), and right inferior frontal cortex (IFC). In addition, patients performed worse than controls on tests for verbal memory and executive function, and this was significantly related to the GMV of the left hippocampus and right MFC, respectively. Moreover, in the patients, we found a negative relationship between serum prolactin levels and the GMV of the left hippocampus and right IFC, whereas a positive relationship was found between the GMV of the left hippocampus and serum levels of estradiol and luteinizing hormone. CONCLUSION: In patients with prolactinomas, specific brain structure abnormalities have been identified and are associated with cognitive impairments and dysfunctional hormones. This study enhances our understanding of brain structure changes that may occur with prolactinomas and provides novel and fundamental evidence for previous behavioral findings relevant to hyperprolactinemia.

Impact of capillary invasion on the prognosis of gastric adenocarcinoma patients: A retrospective cohort study.

Capillary invasion (CI) has been found to play an important role in metastasis and recurrence of gastric adenocarcinoma (GAC). However, the prognostic significance of CI is still controversial. From January 2005 to December 2011, 1398 patients with GAC who underwent gastrectomy were retrospectively enrolled and divided into CI (+) and CI (-) groups. Clinicopathological features and survival outcomes were compared between these groups. In our study, 227 (16.2%) patients were CI (+). Patients with CI (+) had significantly more advanced tumors and worse prognosis than those with CI (-) (p < 0.001). CI was demonstrated as an independent prognostic factor (p = 0.023) in patients with GAC. When stratified by TNM stage, the prognosis of CI (+) group in stage III was remarkably worse than CI (-) group (p = 0.006), while the differences were not significant in stage I-II and stage IV (both p > 0.05). The nomograms indicated that CI was part of the individual prognostic prediction system. The predictive accuracy of CI and other characteristics was better than TNM alone (p < 0.001). Our finding suggested that CI was an independent prognostic factor in patients with GAC, and the nomogram based on CI and other clinicopathological factors was a valuable and accurate tool in individual prognostic prediction.

Assessing Region of Interest Schemes for the Corticospinal Tract in Patients With Brain Tumors.

Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) techniques are widely used for identifying the corticospinal tract (CST) white matter pathways as part of presurgical planning. However, mass effects in patients with brain tumors tend to cause anatomical distortions and compensatory functional reorganization of the cortex, which may lead to inaccurate mapping of white matter tracts. To overcome these problems, we compared different region-of-interest (ROI) selection schemes to track CST fibers in patients with brain tumors. Our study investigated the CSTs of 16 patients with intracranial tumors. The patients were classified into 3 subgroups according to the spatial relationships of the lesion and the primary motor cortex (PMC)/internal capsule. Specifically, we investigated the key factors that cause distorted tractography in patients with tumors. We compared 3 CST tractography methods that used different ROI selection schemes. The results indicate that CST fiber tracking methods based only on anatomical ROIs could possibly lead to distortions near the PMC region and may be unable to effectively localize the PMC. In contrast, the dual ROI method, which uses ROIs that have been selected from both blood oxygen level-dependent functional MRI (BOLD-fMRI) activation and anatomical landmarks, enabled the tracking of fibers to the motor cortex. The results demonstrate that the dual ROI method can localize the entire CST fiber pathway and can accurately describe the spatial relationships of CST fibers relative to the tumor. These results illustrate the reliability of using fMRI-guided DTT in patients with tumors. The combination of fMRI and anatomical information enhances the identification of tracts of interest in brains with anatomical deformations, which provides neurosurgeons with a more accurate approach for visualizing and localizing white matter fiber tracts in patients with brain tumors. This approach enhances surgical performance and perserves brain function.

Shp2 regulates chlorogenic acid-induced proliferation and adipogenic differentiation of bone marrow-derived mesenchymal stem cells in adipogenesis.

Chlorogenic acid (CGA) exhibits various biological properties, including the inhibition of oxidation, obesity, apoptosis and tumorigenesis. CGA is also able to promote cell survival and proliferation. The aim of the present study was to determine the effects and underlying molecular mechanisms of CGA on the adipogenesis of bone marrow­derived mesenchymal stem cells (BMSCs). Treatment with CGA had a marginal effect on cell proliferation, by promoting the expression levels of phosphorylated Akt and cyclin D1. Furthermore, treatment with CGA also upregulated the phosphorylation of extracellular signal­regulated kinase (Erk) and inhibited the adipocyte differentiation of BMSCs by inhibiting the expression of peroxisome proliferator­activated receptor (PPAR)γ and CCAAT/enhancer binding protein (C/EBP)α. However, knockdown of the expression of Shp2 attenuated CGA­induced proliferation and inhibited the phosphorylation of Akt and expression of cyclin D1. Furthermore, CGA treatment upregulated Erk phosphorylation and decreased the expression levels of PPARγ and CEBPα, which was inhibited by treatment with the Shp2 PTPase activity inhibitor, NSC­87877. The results of the present study suggested that CGA­induced Akt and Erk pathways regulate proliferation and differentiation and that Shp2 is important in the proliferation and differentiation of BMSCs.

Log-Gabor energy based multimodal medical image fusion in NSCT domain.

Multimodal medical image fusion is a powerful tool in clinical applications such as noninvasive diagnosis, image-guided radiotherapy, and treatment planning. In this paper, a novel nonsubsampled Contourlet transform (NSCT) based method for multimodal medical image fusion is presented, which is approximately shift invariant and can effectively suppress the pseudo-Gibbs phenomena. The source medical images are initially transformed by NSCT followed by fusing low- and high-frequency components. The phase congruency that can provide a contrast and brightness-invariant representation is applied to fuse low-frequency coefficients, whereas the Log-Gabor energy that can efficiently determine the frequency coefficients from the clear and detail parts is employed to fuse the high-frequency coefficients. The proposed fusion method has been compared with the discrete wavelet transform (DWT), the fast discrete curvelet transform (FDCT), and the dual tree complex wavelet transform (DTCWT) based image fusion methods and other NSCT-based methods. Visually and quantitatively experimental results indicate that the proposed fusion method can obtain more effective and accurate fusion results of multimodal medical images than other algorithms. Further, the applicability of the proposed method has been testified by carrying out a clinical example on a woman affected with recurrent tumor images.

Motor network plasticity and low-frequency oscillations abnormalities in patients with brain gliomas: a functional MRI study.

Brain plasticity is often associated with the process of slow-growing tumor formation, which remodels neural organization and optimizes brain network function. In this study, we aimed to investigate whether motor function plasticity would display deficits in patients with slow-growing brain tumors located in or near motor areas, but who were without motor neurological deficits. We used resting-state functional magnetic resonance imaging to probe motor networks in 15 patients with histopathologically confirmed brain gliomas and 15 age-matched healthy controls. All subjects performed a motor task to help identify individual motor activity in the bilateral primary motor cortex (PMC) and supplementary motor area (SMA). Frequency-based analysis at three different frequencies was then used to investigate possible alterations in the power spectral density (PSD) of low-frequency oscillations. For each group, the average PSD was determined for each brain region and a nonparametric test was performed to determine the difference in power between the two groups. Significantly reduced inter-hemispheric functional connectivity between the left and right PMC was observed in patients compared with controls (P<0.05). We also found significantly decreased PSD in patients compared to that in controls, in all three frequency bands (low: 0.01-0.02 Hz; middle: 0.02-0.06 Hz; and high: 0.06-0.1 Hz), at three key motor regions. These findings suggest that in asymptomatic patients with brain tumors located in eloquent regions, inter-hemispheric connection may be more vulnerable. A comparison of the two approaches indicated that power spectral analysis is more sensitive than functional connectivity analysis for identifying the neurological abnormalities underlying motor function plasticity induced by slow-growing tumors.