Hongzeng Li

Identification of microRNA-205 as a potential prognostic indicator for human glioma

Altered microRNA-205 (miR-205) expression has been found in glioma tissue samples and cell lines; however, the clinical significance of this is unclear. The aim of this study was to confirm the miR-205 expression pattern in human glioma and to investigate its clinical relevance. Quantitative reverse-transcription polymerase chain reaction assays showed that miR-205 expression was significantly lower in glioma tissues than in non-neoplastic brain tissues (P<0.001). Statistical analysis revealed a significant correlation between low miR-205 expression and both high grade glioma (World Health Organization [WHO] criteria, P=0.008) and a low Karnofsky performance status score (P=0.02). Survival analysis demonstrated that the cumulative 5-year overall survival rate of patients with glioma in the high miR-205 expression group was significantly higher than that in the low miR-205 expression group (P<0.001). Multivariate Cox regression analysis further indicated that miR-205 expression (P=0.01) and WHO grade (P=0.01) were independent prognostic indicators of the overall survival of patients with glioma. Moreover, subgroup analyses revealed that the cumulative 5-year overall survival rate of patients with high grade (III-IV) glioma was significantly worse for the low miR-205 expression group than for the high miR-205 expression group (P<0.001), but no significant difference was found for patients with low grade (I-II) glioma (P=0.09). In conclusion, down-regulation of miR-205 was associated with glioma progression. Our data are the first to suggest that miR-205 holds potential as a prognostic factor for glioma, especially for patients with advanced disease.

Thymic TFH cells involved in the pathogenesis of myasthenia gravis with thymoma

Follicular helper CD4+ T (TFH) cells are the specialized providers of B cell help in germinal centers (GCs). Formation of GCs in thymi is the primary thymi characteristic in MG patients. TFH cells are involved in the pathogenic process of many autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis and autoimmune thyroid disease. The role thymic TFH cells played in MG with thymoma has not been elucidated. Here, we analyzed surface markers CXCR5, Bcl-6, ICOS and IL-21 on TFH cells in thymus derived from thymoma patients with ocular MG (OMG), generalized MG (GMG) or without MG using immunohistochemical staining, immunofluorescence, western blotting, and real-time PCR analysis. We show that clinical severity of MG is correlated with higher mRNA expression of the four markers. Indeed, results show higher expression of all four markers in thymoma with GMG patients compared with both OMG and non-MG patients. We found no significant difference in the expression of CXCR5, Bcl-6 and ICOS in OMG compared with non-MG patients. Regression analysis shows a positive correlation between thymic CXCR5, BCL-6, ICOS and IL-21 levels and quantitative MG score (QMGS) in GMG patients. In addition, we found no significant correlation between TFH cell expression and QMGS in OMG patients. Our findings show that higher expression of TFH cells in the thymoma is related to the clinical severity of MG and suggests a role in the pathogenesis of MG. However, the real source of these TFH cells is still uncertain and needs further study.

Severe sleep-disordered breathing in a patient with Brown–Vialetto–Van Laere syndrome: Polysomnographic findings

Brown-Vialetto-Van Laere (BVVL) syndrome is a rare disorder with clinical features that include progressive bilateral sensorineural deafness and a variety of cranial nerve impairments. Respiratory compromise has been observed in most familial and sporadic cases; however, few studies have been published regarding sleep-disordered breathing in this syndrome. We report the unique case of a 16-year-old girl with the clinical features of BVVL syndrome who presented with bilateral sensorineural hearing loss and then progressively developed paralysis of the 7th and 9th-12th cranial nerves. More importantly, she presented with the unusual feature of severe sleep-disordered breathing. A polysomnographic study showed evidence of dominant central sleep apnea, and the majority of apneic episodes more likely occurred in stage 2 during NREM sleep. The central sleep apnea was associated with rapid respiratory deterioration and death. This report raises the fact that a patient with BVVL syndrome may present with severe sleep-disordered breathing as a life-threatening condition, which emphasizes the need for greater attention to the early detection of potential sleep-disordered breathing in these afflicted with the BVVL syndrome for optimal clinical management.

Different molecular expression in thymoma with ocular or generalized myasthenia gravis

BACKGROUND Increasing evidence supports a link between expressions of CD4, CD25, Foxp3, and CXCL13 in thymic hyperplasia with myasthenia gravis (MG) patients. Herein, we investigated the expressions of these molecules in thymoma patients with ocular MG (OMG) or generalized MG (GMG). METHODS A total of 58 thymoma patients with MG (23 GMG and 35 OMG) and 73 thymoma patients without MG were analyzed using immunohistochemistry for CD4, CD25, Foxp3 and CXCL13. RESULTS OMG was more frequent than GMG in late-onset thymoma males (P=0.037), but no difference was observed in females (P=0.128). There was no significant difference of Foxp3 expression among all types of thymoma from patients with OMG and Non-MG. Compared to patients with OMG, a decreased Foxp3 expression was seen in types AB, B1 and B2 thymoma with GMG, with the decrease in the former two types reaching significance (P=0.001, 0.043, respectively). However, a significantly increased expression of CXCL13 was observed in types B1 and B2 thymoma patients with GMG (P=0.027, 0.048, respectively, compared to those with OMG). Furthermore, the CXCL13 expression in type AB thymoma patients with GMG was higher than those with Non-MG (P=0.003).There were no differences among expressions of CD4, CD25, Foxp3, and CXCL13 in type A and B3 thymoma patients, regardless of with OMG, GMG or Non-MG. CONCLUSION Differential expressions of Foxp3 and CXCL13 in various types of thymoma patients with OMG or GMG might suggest the differential immunological processes underlying the two subtype of MG.

Expression of Immune Molecules CD25 and CXCL13 Correlated with Clinical Severity of Myasthenia Gravis

Differential expressions of immune molecules have been shown in the thymi with pathological results, including myasthenia gravis (MG). CD25 is an activation marker expressed on T cells. CXCL13 mediates the homing and motility of B cells in secondary lymphoid tissues. Herein, we investigated the expressions of CD25 and CXCL13 in the thymi of thymic hyperplasia patients with MG or with non-MG. A total of 34 thymic hyperplasia patients with MG (20 generalized MG (GMG) and 14 ocular MG (OMG) and six thymic hyperplasia patients without MG were enrolled and analyzed using immunohistochemical staining and real-time polymerase chain reaction for CD25 and CXCL13. Our study demonstrated a higher expression of both CD25 and CXCL13 in hyperplastic thymi with OMG or GMG compared to those with non-MG. According to the immunohistochemical results, we observed that CD25 expression was significantly lower in atrophic thymi and non-MG hyperplastic thymi, compared with that in infant thymi (P = 0.002 and 0.005, respectively). In contrast to CD25 expression, we did not observe differential expression of CXCL13 among three control groups. And a similar CD25 mRNA expression was found in real-time polymerase chain reaction (PCR) results. We observed that both hyperplastic thymi with OMG or GMG expressed significantly higher levels of CD25 than those with non-MG (P = 0.007 and 0.001, respectively). And an increase of CD25 expression was observed in hyperplastic thymi with GMG compared to those with OMG (P = 0.030). Similarly, CXCL13 expression was significantly higher in hyperplastic thymi with GMG or with OMG than those with non-MG (P = 0.001 and 0.050, respectively). No significant CXCL13 expression difference was found between hyperplastic thymi with GMG and those with OMG (P > 0.05). The real-time PCR results showed a similar tendency of CD25 mRNA expression among the thymi of non-MG, OMG, and GMG patients, but the difference did not reach significance (P > 0.05). An obvious increased expression of CXCL13 was found in hyperplastic thymi with GMG patients, compared to those with non-MG and OMG patients (P = 0.003 and 0.071, respectively). There was no difference found between hyperplastic thymi with non-MG and with OMG. Regression analysis showed a positive correlation between thymic CD25 level and MG symptom severity (F = 28.240; P = 0.000, r = 0.523). Similarly, a positive correlation was found between thymic CXCL13 expression and MG disease severity (F = 36.093; P = 0.000, r = 0.671). Taken together, our findings suggest CD25 and CXCL13 participate in the pathogenesis of MG and may influence the clinical symptoms of MG.

Severe bilateral pyramidal tract involvement in a patient with Parry-Romberg syndrome.

Parry-Romberg syndrome (PRS) is a rare clinical entity of unknown etiology, generally characterized by a slow and progressive atrophy that affects 1 side of the face. A variety of neurologic abnormalities have been shown to coexist with PRS. However, few studies regarding pyramidal tract involvement in this disorder have been reported. We report a unique case, in which the patient presented with bilateral pyramidal tract insult and an unusual sequence of disease onset and progression. This case suggests a rarer variant of PRS, and the neurologic findings indicate that the underlying essential neural degeneration may contribute to the processing of pyramidal tract insult or this syndrome.

T Follicular Helper-Like Cells Are Involved in the Pathogenesis of Experimental Autoimmune Encephalomyelitis

Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) have been proved to be T cell-mediated autoimmune diseases. Recent researches indicate that humoral immunity is also involved in the pathogenesis of these disorders. T follicular helper (Tfh) cells are critical for B cell differentiation and antibody production. However, the role of Tfh cells in MS and EAE remains unclear. Here, we found elevated frequencies of CD4+CXCR5+PD-1+ Tfh-like cells in both MS patients and EAE. In EAE mice, Tfh-like cells, together with B cells, were found in the ectopic lymphoid structures in spinal cords. Moreover, Tfh-like cells promoted the antibody production via IL-21/IL-21R and CD40 ligand/CD40 interaction and the synergy effect of STAT3 and non-canonical NF-κB signaling pathway inside B cells. Moreover, adoptive transfer of Tfh-like cells could increase the severity and delay the remission of EAE. In conclusion, our data indicate that Tfh-like cells contribute to the pathogenesis of EAE.

Current overview of myasthenia gravis and experience in China

Myasthenia gravis (MG) is an acquired autoimmune disease affecting synaptic transmission via the neuromuscular junction mainly due to the presence of auto-antibodies targeting acetylcholine receptors. Ocular or generalized MG is clinically diagnosed when the extra-ocular muscles or other muscle groups beyond the extra-ocular muscles are involved. MG occurs in both sexes at any ages from all races but shows a wide variability in incidence and prevalence. Differences in clinical phenotypes of MG patients between West and East countries have been observed. Herein, we review the current concept on epidemiology, classification, and generalized progression in MG, mainly focusing on the differential features from mainland China.

Delayed parkinsonism with a selective symmetric basal ganglia lesion after manual strangulation

A 21-year-old woman, who experienced manual strangulation, developed delayed parkinsonism associated with a selective symmetric basal ganglia lesion. The patient had recovered completely one year after early combination therapy. This case emphasizes the need for greater attention in detecting early brain injuries in those afflicted with strangulation so as to provide optimal management.

Role of perforin secretion from CD8+ T-cells in neuronal cytotoxicity in multiple sclerosis

Abstract Objectives: Multiple sclerosis (MS) is the most prevalent autoimmune disease of the central nervous system, and is characterized by inflammation and myelin damage. The immune system initiates the autoimmune response, although the mechanisms of neuronal damage have not been elucidated. The purpose of the present study was to investigate autoreactive CD4+ and CD8+ T lymphocytes, in conjunction with other inflammatory cells and cytokines in active MS lesions. Methods: EAE animal models was established by plantar injections of MBP (200 μg per rat). Purified CD4+ or CD8+ T-cells were isolated from heparinized peripheral blood (EAE animals and control animals) via negative selection. To examine effects of presence of autoreactive CD4+ and CD8+ T lymphocytes, we carried out ELISA, Western blot analysis and TUNEL. In addition, we examined the direct effects of various factors on neuronal cell death using MTT assay. Results: The data revealed that CD8+ T-cells were more toxic to neurons compared to CD4+ T-cells, in both the MBP and EAE conditions. Bax was greater increased when neurons were co-cultured with CD8+ T-cells in the MBP group. There is a significant increase in IL-17 secretion by CD4+ T-cells in both the MBP group and EAE group. Neuronal viability were affected by Perforin (1.5 μg/mL). Conclusion: The present study extends previous research by demonstrating the role of CD8+ T-cells in MS and supports perforin secretion by CD8+ T-cells as a potential therapeutic factor. Furthermore, we determined that CD4+ T-cells can enhance CD8+ T-cell neuronal cytotoxicity via induction of intense inflammation.