Severe hypoxemia after radiofrequency ablation for atrial fibrillation in palliatively repaired tetralogy of Fallot: A case report.

BACKGROUND: Patients with tetralogy of Fallot (TOF) often have arrhythmias, commonly being atrial fibrillation (AF). Radiofrequency ablation is an effective treatment for AF and does not usually cause severe postoperative hypoxemia, but the risk of complications may increase in patients with conditions such as TOF. CASE SUMMARY: We report a young male patient with a history of TOF repair who developed severe hypoxemia after radiofrequency ablation for AF and was ultimately confirmed to have a new right-to-left shunt. The patient subsequently underwent atrial septal occlusion and eventually recovered. CONCLUSION: Radiofrequency ablation may cause iatrogenic atrial septal injury; thus possible complications should be predicted in order to ensure successful treatment and patient safety.

Head-nodding: a driving force for the circulation of cerebrospinal fluid.

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.

Identification and Functional Prediction of Long Non-Coding RNAs in Dilated Cardiomyopathy by Bioinformatics Analysis.

Dilated cardiomyopathy (DCM) is a relatively common cause of heart failure and the leading cause of heart transplantation. Aberrant changes in long non-coding RNAs (lncRNAs) are involved in DCM disorder; however, the detailed mechanisms underlying DCM initiation and progression require further investigation, and new molecular targets are needed. Here, we obtained lncRNA-expression profiles associated with DCM and non-failing hearts through microarray probe-sequence re-annotation. Weighted gene co-expression network analysis revealed a module highly associated with DCM status. Then eight hub lncRNAs in this module (FGD5-AS1, AC009113.1, WDFY3-AS2, NIFK-AS1, ZNF571-AS1, MIR100HG, AC079089.1, and EIF3J-AS1) were identified. All hub lncRNAs except ZNF571-AS1 were predicted as localizing to the cytoplasm. As a possible mechanism of DCM pathogenesis, we predicted that these hub lncRNAs might exert functions by acting as competing endogenous RNAs (ceRNAs). Furthermore, we found that the above results can be essentially reproduced in an independent external dataset. We observed the localization of hub lncRNAs by RNA-FISH in human aortic smooth muscle cells and confirmed the upregulation of the hub lncRNAs in DCM patients through quantitative RT-PCR. In conclusion, these findings identified eight candidate lncRNAs associated with DCM disease and revealed their potential involvement in DCM partly through ceRNA crosstalk. Our results facilitate the discovery of therapeutic targets and enhance the understanding of DCM pathogenesis.

The morphology, biomechanics, and physiological function of the suboccipital myodural connections.

The myodural bridge (MDB) connects the suboccipital musculature to the spinal dura mater (SDM) as it passed through the posterior atlanto-occipital and the atlanto-axial interspaces. Although the actual function of the MDB is not understood at this time, it has recently been proposed that head movement may assist in powering the movement of cerebrospinal fluid (CSF) via muscular tension transmitted to the SDM via the MDB. But there is little information about it. The present study utilized dogs as the experimental model to explore the MDB's effects on the CSF pressure (CSFP) during stimulated contractions of the suboccipital muscles as well as during manipulated movements of the atlanto-occiptal and atlanto-axial joints. The morphology of MDB was investigated by gross anatomic dissection and by histological observation utilizing both light microscopy and scanning electron microscopy. Additionally biomechanical tensile strength tests were conducted. Functionally, the CSFP was analyzed during passive head movements and electrical stimulation of the suboccipital muscles, respectively. The MDB was observed passing through both the dorsal atlanto-occipital and the atlanto-axial interspaces of the canine and consisted of collagenous fibers. The tensile strength of the collagenous fibers passing through the dorsal atlanto-occipital and atlanto-axial interspaces were 0.16 ± 0.04 MPa and 0.82 ± 0.57 MPa, respectively. Passive head movement, including lateral flexion, rotation, as well as flexion-extension, all significantly increased CSFP. Furthermore, the CSFP was significantly raised from 12.41 ± 4.58 to 13.45 ± 5.16 mmHg when the obliques capitis inferior (OCI) muscles of the examined specimens were electrically stimulated. This stimulatory effect was completely eliminated by severing the myodural bridge attachments to the OCI muscle. Head movements appeared to be an important factor affecting CSF pressure, with the MDB of the suboccipital muscles playing a key role this process. The present study provides direct evidence to support the hypothesis that the MDB may be a previously unappreciated significant power source (pump) for CSF circulation.

Pacemaker and Atrioventricular Junction Ablation in Patients With Atrial Fibrillation-A Systematic Review of Systematic Review and Meta-Analysis.

BACKGROUND: Cardiac resynchronization therapy (CRT) could be considered for heart failure (HF) patients with atrial fibrillation (AF) unless a potent ventricular capture strategy is conducted. However, the benefit of a pacemaker (PM; as part of CRT) in patients with AF and whether atrioventricular junction (or nodal) ablation (AVAB) can improve the prognosis of these patients compared with those treated medically to support ventricular capture are unclear. METHODS AND RESULTS: Systematic reviews and meta-analyses investigating the roles of PMs and AVAB in patients with AF were obtained in a search of the PubMed, Embase, and Medline databases and then analyzed with respect to the following outcomes: mortality, left ventricular ejection fraction, and clinical findings including the New York Heart Association class, 6-min walk distance (6MWD), quality of life as assessed in a specific questionnaire, and response to CRT. The quality of the included reviews was assessed using the Assessing the Methodological Quality of Systematic Reviews 2 tool, which includes 16 items. This study was finally based on 13 systematic reviews or meta-analyses. The results showed that patients with AF have higher all-cause mortality rates compared with patients with sinus rhythm and that AVAB can reduce all-cause mortality in patients with AF. Although the functional improvement was better in sinus rhythm than in patients with AF, in the latter, AVAB increased the 6MWD and reduced the CRT nonresponse rate in patients with AF. CONCLUSION: Atrial fibrillation is associated with a higher all-cause mortality rate in patients with CRT implantation. AVAB, by increasing the 6MWD and survival, can improve the prognosis of these patients.

Clinical efficacy of computed tomography-guided iodine-125 seed implantation therapy for patients with metastatic epidural spinal cord compression: A retrospective study.

BACKGROUND: This study evaluated the clinical efficacy of computed tomography (CT)-guided radioactive iodine-125 (125 I) seed implantation in patients with metastatic epidural spinal cord compression (MESCC). MATERIALS AND METHODS: A cohort of 22 patients with MESCC were retrospectively enrolled. All patients underwent CT-guided 125 I seed implantation therapy via standard procedures. Clinical indexes, including the University of Texas MD Anderson Cancer Center (MDA) criteria for tumor responses, numerical rating scale (NRS) for the degree of pain, Karnofsky Performance Status (KPS) for quality of life, American Spinal Injury Association (ASIA) impairment scale, grade of ESCC, and radiation dose, were evaluated and recorded pre- and post-operation. A follow-up evaluation was performed at least 3 months after the operation. Finally, pre- and post-operative differences in these clinical indexes were compared. Overall survival was recorded. RESULTS: Operations were successfully performed on all patients. A median of 48 (range, 7-103) seeds were implanted in lesions, and the postoperative target verified dose D90 was 11,072.4 ± 1773.5 cGy. Patients were followed for a median of 6 months (range, 3-38 months). The median survival time was 10 months; the response rate was 18/22 (82%); the local control rates at 3, 6, and 12 months were 91.3%, 81.9%, and 81.9%, respectively; and the survival rates were 80%, 50.0%, and 21.9% at 6, 12, and 18 months, respectively. The ESCC grade was significantly lower (P < 0.05). Based on the ASIA impairment scale, the nerve functional reservation, recovery, and decline rates were 63.7% (14/22), 27.3% (6/22), and 9% (2/22), respectively. The NRS and KPS were both significantly improved in the 3rd month of follow-up (P < 0.05). CONCLUSION: CT-guided 125 I seed implantation represents an effective and safe palliative care for patients with MESCC, which can effectively relieve pain and spinal cord compression and improve nerve function and quality of life.

Correlations between quantitative parameters of contrast-enhanced ultrasound and vasculogenic mimicry in murine tumor model: a novel noninvasive technique for assessment?

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 <  0.0001), whereas EV density positively correlated to IMAX (r = 0.4519, P = 0.0034). The vascular diameter of VM was substantially larger than that of EV (43.81 ± 5.88 µm vs 11.21 ± 4.13 µm). CONCLUSION: Three quantitative parameters related to VM were obtained and the relationships between CEUS and VM were established. CEUS might thus provide a novel noninvasive method to assess VM in vivo.

Existence and features of the myodural bridge in Gallus domesticus: indication of its important physiological function.

The myodural bridge (MDB) is a dense connective tissue that connects muscles with the cervical spinal dura mater via the posterior atlanto-occipital and atlato-axial interspaces. To date, the physiological function of the MDB has not been fully elucidated. Recent studies have identified the presence of the MDB in mammals, but very little information is available on the existence of the MDB in avifauna. We selected Gallus domesticus to explore the existence and the fiber property of the MDB in avifauna. We found that in this species, fibers originating from the ventral aspect of the rectus capitis dorsal minor are fused with the dorsal atlanto-occipital membrane and that numerous trabeculae connect the dorsal atlanto-occipital membrane with the cervical spinal dura mater. Furthermore, the occipital venous sinus is located between the trabeculae. The MDB is mainly composed of collagen type I fibers. Our results show that the MDB is present in G. domesticus and lead us to infer that the MDB is a highly conservative evolutionary structure which may play essential physiological roles.

Guiding the "misguided" - functional conditioning of dendritic cells for the DC-based immunotherapy against tumours.

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.

[Screening and characterization of peptides specifically binding to the schistosomulum tegument of Schistosoma japonicum].

OBJECTIVE: To screen and analyze the peptides in 12 phage-display peptide library specifically binding to the schistosomulum tegument of Schistosoma japonicum. METHODS: A 12 phage-display peptide library was screened with the S. japonicum schistosomula as the target cells for biopanning by degrees, positive clones picked randomly were deduced by DNA sequencing. According the sequence seeing result, immunohistochemical staining was performed to determine the specificity of the phages to the tegument. To test their targeting efficacy, the interested phage clones were infused back to the mice infected with S. japonicum, mice were sacrificed 2.5 hours later, and the phage distribution in the liver and the tegument of schistosomula was appraised, respectively. RESULTS: After 3 rounds of biopanning, the phage recovery rate increased from 0.77 x 10(-8) to 0.75 x 10(-5), indicating that the phage library was successfully enriched in the tegument of schistosomula. Seventy-five percent (15/20) of the analyzed sequences were identical with a sequence of QHPRIRKOOOOO. The immunohistochemical stainings showed this sequence specifically binding to the tegument. In vivo titering displayed that this sequence selectively targeted the tegument. CONCLUSION: The peptide of QHPRIRKOOOOO specifically binds to the schistosomulum tegument.

Increased expression of cyclooxygenase-2 and increased infiltration of regulatory T cells in tumors of patients with hepatocellular carcinoma.

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-beta1 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-beta1 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.

Correlation between expression of cyclooxygenase-2 and the presence of CD4+ infiltrating T-lymphocyte in human primary hepatocellular carcinoma.

BACKGROUND/AIMS: Recent studies have found that Cyclooxygenase-2(Cox-2) is frequently inappropriately expressed in primary hepatocellular carcinoma (HCC), suggesting that abnormal Cox-2 expression plays an important role in hepatocarcinogenesis. But it remains controversial in these reports. Moreover, there are only a few studies on the correlation between Cox-2 and infiltrating immunocytes in the tumor-microenvironment. CD4+ tumor-infiltrating lymphocytes (TIL) and infiltrating immunocytes around the tumor are closely correlated to the development of the tumor, but so far no reports are available showing the relationship among Cox-2, CD4+ TIL of tumor and CD4+ infiltrating T-lymphocytes of adjoining non-tumorous (ANT) tissues in tumor-microenvironment. This study is designed to appropriately select and collect patients' specimens to better reflect Cox-2 expression in human HCC, and also to stress the correlation among Cox-2, CD4+ TIL and CD4+ infiltrating T-lymphocytes in the tumor-microenvironment. METHODOLOGY: Tumor tissue, and its matched ANT tissue removed less than 1 cm from the solid tumor border, were obtained from 25 HCC patients all of whom came from Hunan province, China, and were infected with hepatitis B virus (HBV). Normal liver tissues of 10 hemangiomas were collected as controls. Both Cox-2 expression and the number of CD4+ TIL and CD4+ infiltrating T-lymphocyte were detected by immunohistochemistry, and data were analyzed closely with patients' clinical figures so as to investigate the correlation between the 3 elements. RESULTS: In 25 HCC patients, remarkably higher Cox-2 expression in both tumor and ANT tissues was observed compared with normal liver tissues (p < 0.001). The percentage of Cox-2 positive cells was, remarkably, higher in ANT tissues than in tumors (p < 0.001). Similarly the distribution of CD4+ T cells was significantly higher in ANT tissue than in tumor tissue (p < 0.0001), and also significantly higher in tumor tissue than in normal tissue (p < 0.0001). Importantly, in the group of patients with Cox-2-expressing tumors, the number of CD4+ infiltrating T-lymphocyte in ANT tissues was 79.4(+)9.92/hpf, which is obviously lower (p = 0.019) than that of the group with non-Cox-2-expressing tumors with the number of CD4+ infiltrating T-lymphocyte in ANT tissues at 118.13(+)12.47/hpf. Cox-2 expression of tumors showed a significant negative correlation with number of CD4+ infiltrating T cells of ANT tissues (r = 0.499, p = 0.024). The number of CD4+ TILs are lower in Cox-2-expressing tumors than in non-Cox-2-expressing tumors, but there was not statistical significance (p = 0.057). CONCLUSIONS: Taken together we suggest in the tumor-microenvironment of HCC the expression of Cox-2 may inhibit the number CD4+ infiltrating T-lymphocyte in ANT tissues. As a result, Cox-2 overexpression may contribute to both suppression of local immune responses and enhancement of metastatic potential in human HCC.

A crucial role for dendritic cell (DC) IL-10 in inhibiting successful DC-based immunotherapy: superior antitumor immunity against hepatocellular carcinoma evoked by DC devoid of IL-10.

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.

[Boost effect of recombinant IL-4 on protection of Schistosoma japonicum cathepsin B DNA vaccine in mice against the parasite].

OBJECTIVE: To investigate the enhancement effect of IL-4 expression plasmid on cathepsin B DNA vaccine of Schistosoma japonicum (Sj) in mice. METHODS: The recombinant IL-4 plasmid constructed by cloning PCR amplified product of murine IL-4 gene into eukaryotic expression vector pcDNA3.1 was co-injected intramuscularly with Sj cathepsin B expression plasmid DNA to mice as the test group. The other three groups of mice were set up as control including IL-4 expression plasmid, Sj cathepsin B expression plasmid and two vacant vector plasmids. The expression of IL-4 and cathepsin B was visualized by immunohistochemistry. Challenge infection in mice was carried out 3 weeks after the last vaccination and immune protection was assessed by worm and egg reduction rates. RESULTS: The recombinant mIL-4 plasmid and cathepsin B DNA vaccine were expressed in muscular cells of the vaccinated mice. Immunization with cathepsin B DNA plus recombinant mIL-4 plasmid yielded a 43.2 % of worm reduction rate and a 76.6% of egg reduction rate, showing a significant difference (P<0.01, P<0.05) compared with that of cathepsin B DNA vaccine alone. CONCLUSION: As an adjuvant, IL-4 DNA can improve the protective effect of cathepsin B DNA vaccine in mice against S. japonicum infection.

[Cloning and characterization of new genes of Schistosoma japonicum].

OBJECTIVE: To clone and characterize new genes of Schistosoma japonicum, Sj, and to provide efficient vaccine candidates. METHODS: Sj adult cDNA library was screened with rabbit sera raised against male worm soluble antigen. The inserted cDNA fragments from the positively selected clones were amplified with PCR and further sequenced, as well as characterized through internet NCBI GenBank software. RESULTS: Eleven positive clones were obtained and two were verified by GenBank as new, including a novel gene designated as Sj-P8 (GenBank accession No. AF517843) and a new partial cDNA of Sj myosin (GenBank accession No. AY770506). The two new genes encoded a transmembrane protein of 75 amino acids and a myosin protein fragment of 212 amino acids respectively. CONCLUSION: The newly obtained genes may provide useful information for the research on Sj vaccine.

Molecular cloning, expression and vaccination of a novel gene Sj-MA of Schistosoma japonicum.

In order to obtain new gene and to develop the new vaccine candidate of immunoprotection against Schistosoma japonicum (Sj), Sj adult worm cDNA library was screened with anti-sera to soluble male adult worm antigen and resulted in the discovery of a novel gene designated as Sj-MA. Sequence analysis showed that Sj-MA as a complete cDNA contains one open reading frame. It was deduced to contain 249 amino acid residues and encode a 28.8 kD soluble protein with plenty of phosphorylation sites, supposing its action in signal transduction. Furthermore, Sj-MA cDNA was cloned into a prokaryotic expression vector pGEX-5X to construct the recombinant plasmid which was transformed and highly expressed in E. coli as a 54.8 kD glutathione-S-transferase (GST) fusion protein. The fusion protein rSj-MA/GST could be recognized with both anti-male adult worm sera and anti-GST sera in Western blotting. Mice vaccinated with the fusion protein revealed significant worm reduction rate of 34.29% (P<0.001), compared with the control groups. Taken together, the novel gene Sj-MA can be expressed in E. coli as a fusion protein that can elicit immunity against Schistosoma japonicum, suggesting its potential as a new vaccine candidate.