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The myodural bridge (MDB) is a dense connective tissue bridge connecting the suboccipital muscles to the spinal dura mater, and it has been proven to be a normal common existing structure in humans and mammals. Some scholars believe that the suboccipital muscles can serve as a dynamic cerebrospinal fluid (CSF) pump via the MDB, and they found head rotations promote the CSF flow in human body, which provided evidence for this hypothesis. Head movement is a complex motion, but the effects of other forms of head movement on CSF circulation are less known. The present study explored the effects of head-nodding on CSF circulation. The CSF flow of 60 healthy volunteers was analyzed via cine phase-contrast magnetic resonance imaging at the level of the occipitocervical junction before and after one-minute-head-nodding period. Furthermore, the CSF pressures of 100 volunteers were measured via lumbar puncture before and after 5 times head-nodding during their anesthetizing for surgical preparation. As a result, it was found that the maximum and average CSF flow rates at the level of the upper border of atlas during ventricular diastole were significantly decreased from 1.965 ± 0.531 to 1.839 ± 0.460 ml/s and from 0.702 ± 0.253 to 0.606 ± 0.228 ml/s respectively. In the meantime, the changes in the ratio of cranial and caudal orientation of the net flow volume were found differed significantly after the one-minute-head-nodding period (p = 0.017). And on the other hand, the CSF pressures at the L3–L4 level were markedly increased 116.03 ± 26.13 to 124.64 ± 26.18 mmH2O. In conclusion, the head-nodding has obvious effects on CSF circulation and head movement is one of the important drivers of cerebrospinal fluid circulation. We propose that the suboccipital muscles, participating in various head movements, might pull the dura sac via the myodural bridge, and thus, head movement provides power for the CSF circulation.

Objective Vasculogenic mimicry (VM) is a novel mechanism of tumor blood supply distinct from endothelial vessel (EV). VM is associated with malignancy, invasion, metastasis, and poor prognosis. Hitherto a noninvasive method for the assessment of VM in vivo has been lacking. Methods Contrast-enhanced ultrasound (CEUS) was performed to evaluate the quantitative parameters of tumors in mice. CD31 immunohistochemistry-Periodic Acid-Schiff double staining was conducted to identify the VM or EV in tumor tissues. Correlations between perfusion parameters and VM density was analyzed by Pearson correlation test. Results By the 15th day after tumor inoculation, the EV and VM density was 31.15 ± 7.14 and 14.11 ± 2.99 per 200× field. The maximal intensity (IMAX) was 301.19 ± 191.56%, and the rise time (RT), time to peak (TTP) and mean transit time (mTT) were 17.38 ± 7.82 s, 20.27 ± 9.61 s and 58.09 ± 26.44 s, respectively. VM density positively correlated to RT (r = 0.3598, P = 0.0226), TTP (r = 0.3733, P = 0.0177) and mTT(r = 0.6483, P

Background: Studies on Cox-2 and Foxp3+ regulatory T cells (Treg) in hepatocellular carcinoma (HCC) showed that Treg suppress local immune response in a Cox-2-dependent fashion. Aims: To investigate Cox-2 expression, Foxp3+ Treg infiltration and CD4+ T cell frequency in HCC tumors. Methods: Tumors and the corresponding nontumor hepatitis B virus-related liver tissues from 40 HCC patients with hepatitis B virus infection, plus 10 liver samples from patients with hemangioma as controls, were assessed for Cox-2 expression, Foxp3+ Treg and total CD4+ T cell numbers using immunohistochemistry. Serum TGF-β1 was assessed by ELISA. Results: Reduced Cox-2 expression, increased Treg and increased CD4+ T cells were shown in tumor as compared with nontumor tissues. Moreover, of 40 tumor tissues, 23 that expressed Cox-2 showed increased Foxp3+ Treg and reduced CD4+ T cells compared with the remaining 17 that did not express Cox-2. Correlation analyses showed that within tumors Treg infiltration correlated positively with Cox-2 expression, and that Treg infiltration or Cox-2 expression correlated negatively with CD4+ T cells. Additionally, serum TGF-β1 was higher in HCC patients than in controls. Conclusion: Within tumors, Cox-2 expression, Treg infiltration and CD4+ T cell frequency were increased, and the Cox-2 expression correlated positively with Treg infiltration and negatively with CD4+ T cell frequency.

The concept of DC-based tumour vaccine has been tested both clinically and experimentally for the past two decades. Even though only limited success has been achieved to date, DC vaccination remains a promising immunological approach against tumours and deserves further exploration. It aims to elicit and establish specific immunity to destroy tumours. By such an approach, DC are used not only as a vector to deliver tumour antigens, but also as a “natural adjuvant” to boost vaccine efficacy. Tumours are however of mutated “self”, to which the host immune system is essentially tolerated in the absence of external perturbation otherwise. Such a live cell-based approach is unfortunately extremely sensitive to, hence its efficacy inevitably limited by, the tumour microenvironment. Certain immunosuppressive mechanisms triggered by the tumour cells are therefore major obstacles against successful DC vaccination. Attempts have since been made in order to overcome these hurdles. This brief review summarises some of the earlier and current findings, and compares the effectiveness of various approaches used in these studies. It focuses particularly on strategies aimed at enhancing DC immunogenicity, through molecular modifications and functional conditioning of the cell vectors, targeting both the positive and negative regulators of DC functions. By dissecting the roles of DC in immunity versus tolerance induction, and the very mechanisms underlying autoimmunity, we examine further and try to explain how the suppressed or “misguided” immunity may be alternatively switched-on and more effectively redirected for cancer therapy.

The dendritic cell (DC)-based tumor immunotherapy has been a new promise of cure for cancer patients, but animal studies and clinical trials have thus far only shown limited success, especially in treating established tumors. Certain immunosuppressive mechanisms triggered by tumor cells or the derivatives are believed to be a major obstacle. We studied the role of DC-derived IL-10 and its negative impact on vaccine efficacy in mouse models. Liver tumor cells were injected via the portal vein, giving rise to disseminated intrahepatic tumors, or s.c. to form solid but extrahepatic tumors. Bone marrow-derived DCs were generated from normal or IL-10-deficient mice and used as the vector to deliver tumor Ags. We demonstrate here that DCs devoid of IL-10, a potent immunosuppressive cytokine, are superior over conventional DCs in triggering antitumor immunity. The IL-10−/−DCs were highly immunogenic, expressed enhanced levels of surface MHC class II molecules, and secreted increased amounts of Th1-related cytokines. By inducing tumor-specific killing and through the establishment of immunological memory, the vaccines delivered by IL-10−/−DCs could evoke strong therapeutic and protective immunity against hepatocellular carcinoma in the mouse models. These findings will have great clinical impact once being translated into the treatment of malignant, and potentially infectious, diseases in humans.