Function of AXL and molecular mechanisms in regulation of nasopharyngeal carcinoma / 中南大学学报(医学版)

OBJECTIVES@#Nasopharyngeal carcinoma (NPC) is a highly invasive epithelial malignant tumor with unique geographical and ethnic distribution characteristics. NPC is mostly found in south China and Southeast Asia, and its treatment mainly depends on radiotherapy and chemotherapy. However, NPC is usually found in the late stage, and local recurrence and distant metastasis are common, leading to poor prognosis. The receptor tyrosine kinase AXL is up-regulated in various tumors and it is involved in tumor proliferation, migration, invasion, and other processes, which are associated with poor prognosis of tumors. This study aims to detect the expression of AXL in NPC cell lines and tissues, and to investigate its biological function of AXL and the underlying molecular mechanisms in regulation of NPC.@*METHODS@#The expression levels of AXL in normal nasopharyngeal epithelial tissues and NPC tissues were analyzed by GSE68799, GSE12452, and GSE53819 data sets based on Gene Expression Omnibus (GEO) database. The Cancer Genome Atlas (TCGA) database was used to analyze the relationship between AXL and prognosis of head and neck squamous cell carcinoma (HNSC). The indicators of prognosis included overall survival (OS), disease-free interval (DFI), disease-specific survival (DSS), and progression-free interval (PFI). Western blotting assay was used to detect the AXL protein expression levels in normal nasopharyngeal epithelial cell line and NPC cell lines. Immunohistochemical method was used to detect AXL expression levels in normal nasopharyngeal epithelial tissues and NPC tissues. Cell lines with stable AXL knockdown were established by infecting 5-8F and Fadu cells with lentivirus interference vector, and cell lines with stable AXL overexpression were established by infecting C666-1 and HK-1 cells with lentivirus expression vector. Real-time PCR and Western blotting were used to detect the efficiency of knockdown and overexpression in stable cell lines. The effects of AXL knockdown or overexpression on proliferation, migration, and invasion of NPC cells were detected by CCK-8, plate colony formation, and Transwell assays, and the effect of AXL knockdown on tumor growth in nude mice was detected by subcutaneous tumor formation assay. The sequence of AXL upstream 2.0 kb promoter region was obtained by UCSC online database. The PROMO online database was used to predict AXL transcription factors with 0% fault tolerance, and the JASPAR online database was used to predict the binding sites of ETS1 to AXL. Real-time PCR and Western blotting were used to detect the effect of ETS1 on AXL protein and mRNA expression. The AXL upstream 2.0 kb promoter region was divided into 8 fragments, each of which was 250 bp in length. Primers were designed for 8 fragments. The binding of ETS1 to AXL promoter region was detected by chromatin immuno-precipitation (ChIP) assay to determine the direct regulatory relationship between ETS1 and AXL. Rescue assay was used to determine whether ETS1 affected the proliferation, migration, and invasion of NPC cells through AXL.@*RESULTS@#Bioinformatics analysis showed that AXL was highly expressed in NPC tissues (P<0.05), and AXL expression was positively correlated with OS, DFI, DSS, and PFI in HNSC patients. Western blotting and immunohistochemical results showed that AXL was highly expressed in NPC cell lines and tissues compared with the normal nasopharyngeal epithelial cell line and tissues. Real-time PCR and Western blotting results showed that knockdown and overexpression efficiency in the stable cell lines met the requirements of subsequent experiments. The results of CCK-8, plate colony formation, Transwell assays and subcutaneous tumor formation in nude mice showed that down-regulation of AXL significantly inhibited the proliferation, migration, invasion of NPC cells and tumor growth (all P<0.05), and the up-regulation of AXL significantly promoted the proliferation, migration, and invasion of NPC cells (all P<0.05).As predicted by PROMO and JASPAR online databases, ETS1 was a transcription factor of AXL and had multiple binding sites in the AXL promoter region. Real-time PCR and Western blotting results showed that knockdown or overexpression of ETS1 down-regulated or up-regulated AXL protein and mRNA expression levels. ChIP assay result showed that ETS1 bound to AXL promoter region and directly regulate AXL expression. Rescue assay showed that AXL rescued the effects of ETS1 on proliferation, migration and invasion of NPC cells (P<0.05).@*CONCLUSIONS@#AXL is highly expressed in NPC cell lines and tissues, which can promote the malignant progression of NPC, and its expression is regulated by transcription factor ETS1.

Influence of preventive use of vasopressin tannate on diabetes insipidus and serum sodium at the early postoperation of craniopharyngioma / 中南大学学报(医学版)

To explore the influence of preventive use of vasopressin tannate on diabetes insipidus and serum sodium at the early postoperation of craniopharyngioma.
 Methods: The data of 83 patients, who underwent unilateral sub-frontal approach resection of craniopharyngioma between 2010 and 2014 by the same senior neurosurgeon, were retrospectively analyzed. The patients were divided into a vasopressin tannate group (used group) and a control group. The diabetes insipidus and serum sodium changes were compared between the two groups.
 Results: Compared with the control group, the incidence of diabetes insipidus decreased at the early postoperation in the vasopressin tannate group (P<0.05). There was high incidence of diabetes insipidus in patients with pituitary stalk excision and tumor close adhesion to the third ventricle floor at the early postoperation (P<0.05). Under such conditions, the incidence of diabetes insipidus in the vasopressin tannate group was decreased compared with the control group (P<0.05). Postoperative hypernatremia occurred in 37 patients (44.6%), and hyponatremia occurred in 60 patients (72.3%), the average time of the occurrence of hpernatremia and hyponatremia was 1.4 and 3.7 days after surgery. Postoperative high serum sodium and low serum sodium appeared alternately in 19 patients (22.9%). There was significant difference in the serum sodium distribution in the first day after surgery in both groups (P<0.05), and the percent of hpernatremia in the vasopressin tannate group was significantly less than that in the control group (P<0.05).
 Conclusion: Preventive use of vasopressin tannate can effectively reduce diabetes insipidus and hypernatremia incidence at the early postoperative stage after microsurgery for craniopharyngioma.

Simulation of acoustic response of microvessel containing microbubble in ultrasound field based on finite element analysis and lumped parameter model / 中国组织工程研究

BACKGROUND:Exploration on nonlinear acoustic response of the contrast agent microbubble contained in microvessel under ultrasound excitation is of great significance to maximizing ultrasonic energy deposition, promoting the development of quantitative imaging algorithm, revealing the damage mechanism or evaluating the targeted therapy, and overcoming the limitations of the traditional methods that are mainly used in large-size vessels, and measuring microvessel elasticity. OBJECTIVE:To build a microvessel containing an ultrasound microbubble, revealing the internal mechanism among ultrasound, microbubble, blood flow and microvessel. METHODS:Based on the finite element analysis and the lumped parameter model, three-dimensional microvessel containing microbubble model was built and simulated on Comsol Multiphysics 4.4 platform. RESULTS AND CONCLUSION:Microbubble exhibited slower radial motion compared with axial motion due to vascular wal limitation, but maximum displacement and stress were found near the microbubble center because of the oscil ation coupling of the microbubble with the vascular wal . Under the same ultrasound pressure, the excitation frequency increased, accompanied by decreased and stabilized microvessl constriction and dilation;under the same frequency, with the enhancement of ultrasound pressure, the local microbubble oscil ation lasted longer. With the increase of Young’s modulus of the microvessel wal , the frequency of microbubble oscil ation was reduced, while the amplitude increased. Al these findings indicate that the frequency of microbubble oscil ation increased with the reduction of microvessel size, while its amplitude decreased. The frequency of microbubble oscil ation increased with the enhancement of ultrasound excitation, while the amplitude decreased. On the contrary, ultrasound pressure affected the dynamic characteristics of microbubble and microvessel. In particular, it was the first to demonstrate that the elasticity of microvessel has approximate linear positive correlation with the amplitude of microbubble oscil ation, which reveals the relationship between microvessel elasticity and microbubble response so as to provide theoretical basis for indirect measurement of microvessel elasticity.

Clinical features of 417 patients with chronic subdural hematoma / 中南大学学报(医学版)

OBJECTIVE@#To discuss the clinical features of chronic subdural hematoma (CSDH) in different age groups.@*METHOD@#A total of 417 patients with CSDH were divided into 3 groups: 0 to 39, 40 to 59 and elder than 60 years. We analyzed the clinical features in different groups, including sex, trauma history, potential hemorrhage factors, trauma to symptoms interval, encephalatrophy, onset symptom and hematoma volume.@*RESULTS@#The incidence of trauma, potential hemorrhage factors, encephalatrophy, consciousness disorders and paralysis increased with age, while the incidence of intracranial hypertension symptoms and seizures decreased with age (P<0.001). The trauma to symptom interval in the group elder than 60 was longer than in other groups (P<0.05) and the hematoma volume increased with age(P<0.05).@*CONCLUSION@#The clinical features of CSDH including onset symptoms, trauma history, potential hemorrhage factors, encephalatrophy, trauma to symptoms interval and hematoma volume vary in different age groups.

The prevention cerebrospinal fluid leakage during operating anterior skull base meningioma involving paranasal sinuses / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To introduce a kind of method for skull base reconstruction after resecting anterior skull base tumors involving paranasal sinuses.@*METHOD@#A retrospective analysis was carried out on 13 patients who underwent anterior skull base reconstruction. Pericranial flap were detached with integrity from the frontal bone during craniotomy, after the tumor had been resected partitionedly, the cribriform plate of ethmoid bone which was involved by tumor was resected. Using the fat tissue to fill the skull-base defects and sutured the pedicled pericranial flap with surrounding normal dura mater. Then reinforced at the junction of pericranial flap and dura mater with biogel.@*RESULT@#The pathogenic diagnosis of all cases were meningioma. I grade resection was acquired in 12 cases and II grade in 1 case according to Simpson grading standard of meningioma resection. The postoperative complications were 3 cases aseptic meningitis, 3 cases frontal syndrome. No CSF leakage, intracranial infection, nor death occurred. An average of 3. 4-year follow-up was achieved in all the cases from 9 months to 8 years, no tumor relapse.@*CONCLUSION@#CSF leakage can be effectively prevented by filling the skull-base defects with the fat tissue, suturing the pedicled pericranial flap with surrounding normal dura mater, and reinforcing at the junction of pericranial flap and dura mater with biogel.

The comprehension of preservation for petrosal vein in 147 operative cases with acoustic neuroma / 中华显微外科杂志

Objective To discuss the preservation and clinical significance of petrosal vein in microsurgical operation of acoustic neuroma. Methods 147 patients with acoustic neuroma were operated, with internal decompression of the tumor firstly then dissected the tumor with surrounding structures, the petrosal vein were protected well in 143 cases and failed to protect in 4 cases. Results No hemorrhagic infarction in cerebellar was observed in 143 cases with intact petrosal vein. One case occurred with extensive cerebellar edema, which has gait disturbance after 18 months follow-up. The other three cases occurred with vein infarction and hemorrhagic edema after petrosal vein damage. One was dead and the other two were recovered well after decompression of posterior cranial fossa. One has no significant neurological deficit after 33 months follow-up, while the other has difficulty in line walking after 12 months follow-up. Conclusion Petrosal vein should be well protected in the operation of acoustic neuroma, the decompression of posterior cranial fossa should be considered if petrosal vein failed to protect.

Clinical characteristics and operative effect of hippocampus lesions / 中南大学学报(医学版)

OBJECTIVE@#To study the clinical characteristics and operative effect of hippocampus lesions.@*METHODS@#We retrospectively analyzed the clinical characteristics and operative outcome of 44 patients with hippocampus lesions between August 2005 and April 2010.@*RESULTS@#Seizure attack was the initial symptom among 40 of the 44 patients. Pathological examinations revealed 18 gliomas, 9 cavernous malformations, 12 hippocampus sclerosis, 2 focal cortical dysplasia, 1 atypical hyperplasia, 1 injury glial scar, and 1 encephalomalacia. Thirteen patients received anterior medial temporal lobectomy and the other 31 received lesionectomy or selective amygdalohippocampectomy via transsylvian approach. An average of 15.7 month follow-up was accomplished in 37 patients. Postoperative epileptic outcomes were evaluated according to Engel classification: Grade I 73.0%(27/37), Grade II 13.5%(5/37), Grade III 10.8%(4/37) and Grade IV 2.7%(1/37). No perioperative death occurred. One patient experienced hemiplegia but recovered 8 months after the operation. Noticeable postoperative visual field deficit was left in 2 patients. Two patients with glioma died of remote tumor recurrence during follow-up.@*CONCLUSION@#Seizure attack is a major complaint of hippocampus lesions. Satisfactory seizure and tumor control may be achieved through anterior medial temporal lobectomy or selective amygdalohippocampectomy with lesionectomy.