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1.
World Neurosurg ; 189: e841-e856, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38986944

ABSTRACT

OBJECTIVE: We designed this study to introduce the surgical strategy cerebrospinal fluid (CSF) decompression in treatment of Chiari malformation type I and compared CSF decompression with other surgical strategies to provide a solid basis for patient counseling. METHODS: The study enrolled 528 consecutive patients with CMI who underwent surgical interventions from 2012 to 2022. The surgical strategy for these patients was bony and dural decompression, anatomical reduction of herniated tonsils, or CSF decompression. Short-term results were determined after 3 months; long-term outcomes were evaluated at last follow-up (at least 18 months). RESULTS: CSF decompression was independently associated with better long- or short-term primary outcomes than anatomical reduction of herniated tonsils or bony and dural decompression (P < 0.001). Compared with short-term, the long-term outcomes were better in patients who underwent CSF decompression (P = 0.035), but were worse in patients with bony and dural decompression (P = 0.03). Specific surgical techniques cannot affect the long- and short-term outcomes of patients with Chiari malformation type I. CSF decompression provided better long-term syringomyelia improvement than short-term (181/218, 83% vs. 169/218, 77.5%; P < 0.001). CONCLUSIONS: CSF decompression, but not a specific surgical technique or operative method, was associated with favorable neurological outcomes in ADULT patients with Chiari malformation type I. The surgical technique and operative method should be selected according to the characteristics of each patient and the intraoperative condition to normalize CSF circulation at the craniovertebral junction area. The intraoperative target, smooth CSF flow out from the fourth ventricle and in to the bilateral Luschka foramina, could be observed.


Subject(s)
Arnold-Chiari Malformation , Decompression, Surgical , Humans , Arnold-Chiari Malformation/surgery , Arnold-Chiari Malformation/diagnostic imaging , Female , Male , Adult , Decompression, Surgical/methods , Treatment Outcome , Middle Aged , Young Adult , Adolescent , Syringomyelia/surgery , Syringomyelia/diagnostic imaging , Aged , Neurosurgical Procedures/methods , Retrospective Studies , Dura Mater/surgery
2.
Acta Neurochir (Wien) ; 165(10): 3051-3063, 2023 10.
Article in English | MEDLINE | ID: mdl-37221435

ABSTRACT

BACKGROUND: Basilar invagination (BI) is a common disease in the craniocervical junction (CVJ) area. Posterior fossa decompression with/without fixation is a controversial surgical strategy for BI type B. This study aimed to evaluate the efficacy of simple posterior fossa decompression in treating BI type B. METHODS: This study retrospectively enrolled BI type B patients who underwent simple posterior fossa decompression at Huashan Hospital, Fudan University between 2014.12 and 2021.12. Patient data and images were recorded pre- and postoperatively (at the last follow-up) to evaluate the surgical outcomes and craniocervical stability. RESULTS: A total of 18 BI type B patients (13 females), with a mean age of 44.2±7.9 years (range 37-62 years), were enrolled. The mean follow-up period was 47.7±20.6 months (range 10-81 months). All patients received simple posterior fossa decompression without any fixation. At the last follow-up, compared with preoperation, the JOA scores were significantly higher (14.2±1.5 vs. 9.9±2.0, p = 0.001); the CCA was improved (128.7±9.6° vs. 121.5±8.1° p = 0.001), and the DOCL was reduced (7.9±1.5 mm vs. 9.9±2.5 mm, p = 0.001). However, the follow-up and preoperative ADI, BAI, PR, and D/L ratio were similar. No patients had an unstable condition between the C1-2 facet joints that was observed in the follow-up CT and dynamic X-ray. CONCLUSIONS: In BI type B patients, simple posterior fossa decompression could improve neurological function and will not induce CVJ instability in BI type B patients. Simple posterior fossa decompression could be a satisfactory surgical strategy for BI type B patients, but preoperative CVJ stability assessment is crucial.


Subject(s)
Atlanto-Axial Joint , Joint Dislocations , Neck Injuries , Spinal Fusion , Female , Humans , Adult , Middle Aged , Retrospective Studies , Decompression, Surgical , Atlanto-Axial Joint/diagnostic imaging , Atlanto-Axial Joint/surgery , Joint Dislocations/surgery , Neck Injuries/surgery , Treatment Outcome
3.
Medicine (Baltimore) ; 102(4): e32699, 2023 Jan 27.
Article in English | MEDLINE | ID: mdl-36705347

ABSTRACT

INTRODUCTION: While China continues to optimize the tiered medical care system, the status quo of patients preferring higher-tier hospitals has not improved. Herein, we aimed to analyze the factors influencing patients' healthcare choices in China and to provide an evidentiary basis for optimizing the tiered healthcare system. PATIENT CONCERNS: Most patients are concerned that primary care services will not provide appropriate treatment or health advice. Also, patients consider medical technology, cost, experience, quality of service and convenience before seeking care. OUTCOMES: A total of 18 cross-sectional studies involving 10,348 samples were included. After combining the effect size, the factors affecting the choice of Chinese patients for medical treatment were medical technology and quality (49%), the convenience of medical treatment (37%), medical expenses (23%), hospital service quality (20%) medical insurance policy (16%), and acquaintance relationship (11%). CONCLUSION: The selection of medical treatment for Chinese residents is primarily influenced by medical technology and convenience. The medical insurance policy does not provide sufficient guidance. Furthermore, the tiered medical care system should be optimized to improve the usability of primary care services.


Subject(s)
East Asian People , Hospitals , Humans , Cross-Sectional Studies , Delivery of Health Care , China
4.
Front Surg ; 9: 945857, 2022.
Article in English | MEDLINE | ID: mdl-37152352

ABSTRACT

Objective: The purpose of this study was to analyze the techniques used to resection cervical extra-intraspinal neuromas (also known as cervical dumbbell neuromas) through the enlarged intervertebral foramen. Methods: A total of 34 consecutive patients (19 male, 15 female) with cervical dumbbell neuromas reviewed retrospectively between April 2008 and May 2020. Sixteen tumors were found in the intervertebral foramen of C1-C3, four in C3-C4, and 14 in C4-T1. The approach in all cases was to expose the tumors by intermuscular dissection and to remove them through the enlarged intervertebral foramen without excision of any bony structures. However, to expose tumors at different locations, the incisions shall be made accordingly. In this case series, the incisions were made along the posterior border of the sternocleidomastoid muscle for the C1-C3 tumors and along the anterior border of the muscle for the C3-C4 tumors. Transverse incisions were required for the C4-T1 tumors. Results: Following the mentioned incising approach, all 34 tumors were completely exposed. 31 were completely removed in one stage, and 3 tumors underwent subtotal resection because of brachial plexus nerve adhesion. The vertebral artery and spinal cord were undamaged for all cases. The patients who had total tumor resection showed no sign of recurrence on enhanced magnetic resonance imaging during follow-ups. The status of patients who underwent subtotal resection was stable after radiation therapy. None of the patients developed spinal instability. Conclusions: Cervical dumbbell neuromas can be exposed and removed through the enlarged intervertebral foramen without causing spinal instability or injury to the spinal cord or vertebral artery. This operative approach can retain the integrity of the structures of spine and should be considered the ideal approach for cervical dumbbell neuromas.

5.
Anal Methods ; 13(37): 4307-4313, 2021 09 30.
Article in English | MEDLINE | ID: mdl-34473140

ABSTRACT

The pharmacokinetic variations of a single drug in an antituberculosis regimen are associated with acquired drug resistance and therapy failure. This study aimed to develop a simple and effective method for monitoring the serum levels of isoniazid (INH), rifampicin (RFP), and pyrazinamide (PZA), three antibiotics used in patients with spinal tuberculosis using capillary electrophoresis (CE). A standard solution of INH, RFP, and PZA was prepared and mixed with serum to prepare the standard curve. The detection limit, quantification limit, precision, stability, repeatability, and sample recovery were determined. Then, INH, RFP, and PZA were measured from the leftover serum samples of all patients with spinal tuberculosis who were treated with 2SHRZ/2.5H2R2Z2 combined with surgery in a tertiary hospital in Qinghai from October 2015 to September 2017. A total of 107 patients with spinal tuberculosis treated using the 2SHRZ/2.5H2R2Z2 regimen combined with surgery were included in this study. All three antibiotics had linear standard curves with high correlation coefficients (R2 = 0.9997, 0.9994, and 0.9986). The recovery rates were 98.1% for INH, 96.5% for PZA, and 97.2% for RFP. The results from the serum samples showed that the plasma concentrations of INH (4.989 ± 1.692 µg mL-1) and RFP (9.400 ± 1.711 µg mL-1) reached effective therapeutic concentrations in all patients, but not PZA (33.860 ± 1.830 µg mL-1). The CE method for measuring INH, RFP, and PZA simultaneously in serum samples of patients with spinal tuberculosis is simple, rapid, and sensitive. This method is suitable for the routine monitoring of INH, RFP, and PZA concentrations in the serum of patients with spinal tuberculosis.


Subject(s)
Antitubercular Agents , Tuberculosis, Spinal , Antitubercular Agents/therapeutic use , Electrophoresis, Capillary , Humans , Isoniazid , Pyrazinamide , Tuberculosis, Spinal/drug therapy
6.
J Orthop Surg Res ; 16(1): 133, 2021 Feb 12.
Article in English | MEDLINE | ID: mdl-33579305

ABSTRACT

BACKGROUND: Osteoarthritis (OA) is thought to be the most prevalent chronic joint disease, especially in Tibet of China. Here, we aimed to explore the integrative lncRNA and mRNA landscape between the OA patients of Tibet and Han. METHODS: The lncRNA and mRNA expression microarray profiling was performed by SurePrint G3 Human Gene Expression 8x60K v2 Microarray in articular cartilage samples from OA patients of Han nationality and Tibetans, followed by GO, KEGG, and trans-regulation and cis-regulation analysis of lncRNA and mRNA. RESULTS: We found a total of 117 lncRNAs and 297 mRNAs differently expressed in the cartilage tissues of Tibetans (n = 5) comparing with those of Chinese Han (n = 3), in which 49 lncRNAs and 158 mRNAs were upregulated, and 68 lncRNAs and 139 mRNAs were downregulated. GO and KEGG analysis showed that several unreported biological processes and signaling pathways were particularly identified. LncRNA-mRNA co-expression analysis revealed a remarkable lncRNA-mRNA relationship, in which OTOA may play a critical role in the different mechanisms of the OA progression between Tibetans and Chinese Han. CONCLUSION: This study identified different lncRNA/mRNA expression profiling between OA patients of Tibetans and Han, which were involved in many characteristic biological processes and signaling pathways.


Subject(s)
Gene Expression Profiling/methods , Gene Expression/genetics , Genetics, Population , Osteoarthritis/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Tissue Array Analysis/methods , Asian People/genetics , Cartilage, Articular/metabolism , China , Humans , Tibet
7.
Oxid Med Cell Longev ; 2020: 5609637, 2020.
Article in English | MEDLINE | ID: mdl-33110474

ABSTRACT

The underlying molecular mechanisms that the hypoxic microenvironment could aggravate neuronal injury are still not clear. In this study, we hypothesized that the exosomes, exosomal miRNAs, and the mTOR signaling pathway might be involved in hypoxic peritumoral neuronal injury in glioma. Multimodal radiological images, HE, and HIF-1α staining of high-grade glioma (HGG) samples revealed that the peritumoral hypoxic area overlapped with the cytotoxic edema region and directly contacted with normal neurons. In either direct or indirect coculture system, hypoxia could promote normal mouse hippocampal neuronal cell (HT22) injury, and the growth of HT22 cells was suppressed by C6 glioma cells under hypoxic condition. For administrating hypoxia-induced glioma-derived exosomes (HIGDE) that could aggravate oxygen-glucose deprivation (OGD)/reperfusion neuronal injury, we identified that exosomes may be the communication medium between glioma cells and peritumoral neurons, and we furtherly found that exosomal miR-199a-3p mediated the OGD/reperfusion neuronal injury process by suppressing the mTOR signaling pathway. Moreover, the upregulation of miRNA-199a-3p in exosomes from glioma cells was induced by hypoxia-related HIF-1α activation. To sum up, hypoxia-induced glioma-derived exosomal miRNA-199a-3p can be upregulated by the activation of HIF-1α and is able to increase the ischemic injury of peritumoral neurons by inhibiting the mTOR pathway.


Subject(s)
Exosomes/metabolism , MicroRNAs/metabolism , TOR Serine-Threonine Kinases/metabolism , Animals , Antagomirs/metabolism , Cell Hypoxia , Cell Proliferation , Cells, Cultured , Female , Glioma/metabolism , Glioma/pathology , Glucose/deficiency , Glucose/pharmacology , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Mice , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , Neurons/cytology , Neurons/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/antagonists & inhibitors , Up-Regulation
8.
World Neurosurg ; 126: e1140-e1146, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30880192

ABSTRACT

BACKGROUND: Clear cell sarcoma (CCS) is a rare malignant soft tissue tumor with poor prognosis owing to metastasis and insensitive response to chemotherapy and radiotherapy. METHODS: We first searched PubMed and Embase using the terms "clear cell sarcoma," "malignant melanoma of soft tissue," "head," and "neck." In the 15 articles selected for literature review, only 27% (4/15) of patients were diagnosed with primary CCS of the head. Pathologically, those tumors arose from either the scalp or the superficial temporal fascia, but none invaded the skull and brain. Next, the search was performed in the same database using the terms "clear cell sarcoma," "malignant melanoma of soft tissue," and "bone," and only 24 articles were selected. RESULTS: In the case reported here, a 36-year-old woman was found to have a palpable mass located at the left temporal-occipital region, and surgical finding confirmed the invasion into the skull and the brain. The diagnosis of primary CCS was made because of the detection of t(12;22)(q13;q12) in >50% of tumor cells by fluorescence in situ hybridization, and metastasis to the lymph nodes and lungs was discovered by postoperative positron emission tomography-computed tomography. CONCLUSIONS: To the best of our knowledge, this is the first case of primary central nervous system CCS. Primary CCS may involve the skull and should be one of the differential diagnoses for intra-extracranial communicating tumors. Further research on biological characteristics and molecular targeted therapy of CCS are needed to improve its poor prognosis.


Subject(s)
Brain Neoplasms/pathology , Sarcoma, Clear Cell/pathology , Skull Neoplasms/pathology , Adult , Brain Neoplasms/diagnosis , Brain Neoplasms/genetics , Female , Humans , Lung Neoplasms/secondary , Lymphatic Metastasis/pathology , Sarcoma, Clear Cell/diagnosis , Sarcoma, Clear Cell/genetics , Skull Neoplasms/diagnosis , Skull Neoplasms/genetics , Translocation, Genetic
9.
Biotechnol Appl Biochem ; 66(3): 309-315, 2019 May.
Article in English | MEDLINE | ID: mdl-30624798

ABSTRACT

Oval cells, a kind of hepatic progenitor cell quiescent at normal condition, activates to proliferate and differentiate into hepatocytes under severe and long-term liver injury, which usually raises severe inflammation. However, how oval cell survives in the inflammatory milieu interne is still unclear. Tumor necrosis factor α (TNFα), mimicking inflammatory hepatic milieu interne, was used to treat oval cell line, WB-F344, to test the protective function of matrilin-2. In this study, our data suggested that matrilin-2 prevented TNFα-induced apoptosis in WB-F344 cells via inhibiting ASK1/MKK7/JNK pathway. In conclusion, we determined that matrilin-2 plays the key role in maintaining the survival of oval cell and guarantees its proliferation under various injury factors.


Subject(s)
Apoptosis/drug effects , JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors , Tumor Necrosis Factor-alpha/pharmacology , Animals , Cell Survival/drug effects , Cells, Cultured , JNK Mitogen-Activated Protein Kinases/metabolism , Matrilin Proteins/metabolism , Rats , Rats, Inbred F344
10.
World Neurosurg ; 118: e105-e114, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29959074

ABSTRACT

OBJECTIVE: Spinal cord intramedullary cavernous malformation (SICM) is kind of rare vascular disease, and the therapeutic strategy is still under debate. The purpose of this article is to analyze outcome of SICM surgical resection and to find the possible factors indicating a better outcome. METHODS: A retrospective analysis of 83 patients with SICM in a single center from 2005 to 2017 was performed. Neurologic status was assessed using the McCormick Scale. Clinical information was collected and analyzed using multivariate logistic regression analysis. RESULTS: Eighty patients with SICM were included, 48% of whom were male (n = 40). The mean age was 39.0 years; 7% of patients (n = 6) had a family history and 4% of patients (n = 3) had multiple lesions; and 41% (n = 34) were found with definite hemorrhage. Before surgery, neurologic status of the patients was 43.4%, 31.3%, 13.3%, and 12.0% in grades I (n = 36), II (n = 26), III (n = 11), and IV (n = 10), respectively. Sixty-three patients received long-term follow-up, of whom 19 improved, 39 remained in stable condition, and 5 deteriorated. Patients with duration of symptoms less than 3 months showed a higher improved outcome rate than those with duration longer than 3 months. CONCLUSIONS: The finding suggests that if total resection of SICM is achievable, surgical therapy could be considered to avoid risks of severe complications followed by lesion bleeding. Early microsurgical resection (usually within 3 months) for patients with SICM can lead to better clinical outcomes.


Subject(s)
Hemangioma, Cavernous, Central Nervous System/diagnostic imaging , Hemangioma, Cavernous, Central Nervous System/surgery , Neurosurgical Procedures/trends , Spinal Cord Neoplasms/diagnostic imaging , Spinal Cord Neoplasms/surgery , Adult , Female , Follow-Up Studies , Humans , Male , Retrospective Studies , Time Factors , Treatment Outcome
11.
Neurosci Lett ; 671: 108-113, 2018 04 03.
Article in English | MEDLINE | ID: mdl-29432779

ABSTRACT

Alpha-lipoic Acid(ALA), an endogenous short-chain fatty acid, has been found inducing a protective effect against ischemia and reperfusion(I/R) injury. Recently, mTOR signaling pathway has been proved to involve in the mechanism of I/R injury. In our previous study, we determined that ALA could protect cerebral endothelial cells against I/R injury via mTOR signaling pathway. However, whether ALA can protect against brain I/R injury in vivo and its mechanisms is uncertain. In this study, we try to explore if the ALA treatment can protect against brain I/R injury and confirm the relationship between ALA and mTOR signaling pathway. ALA was administrated to the animals after dMCAo and reperfusion model established with or without rapamycin pre-treatment. The results showed the infarct size was obviously reduced after ALA treatment in acute stage, neurological functions were also improved distinctly. The mTOR signaling pathway was remarkably blocked after brain I/R injury while it could be activated through ALA treatment. However, rapamycin, can abolish the protective effects induced by ALA treatment in both acute and long-term phase. In conclusion, we demonstrate the protective effects induced by ALA treatment against the brain I/R injury in rats and mTOR signaling pathway is required for the protective effects of ALA against brain I/R injury. The results might contribute to the potential clinical application of ALA and provide a potential therapeutic target on ischemic stroke.


Subject(s)
Brain Ischemia/prevention & control , Neuroprotective Agents/therapeutic use , Reperfusion Injury/prevention & control , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism , Thioctic Acid/therapeutic use , Animals , Brain Ischemia/drug therapy , Brain Ischemia/metabolism , Male , Neuroprotective Agents/pharmacology , Rats , Rats, Sprague-Dawley , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Sirolimus/pharmacology , TOR Serine-Threonine Kinases/antagonists & inhibitors , Thioctic Acid/pharmacology
12.
Biomed Pharmacother ; 92: 879-887, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28601045

ABSTRACT

Multiple cellular, molecular, and biochemical changes contribute to the etiology and treatment outcome of contusion spinal cord injury (SCI). MicroRNAs (miRNAs) aberrant expression have been found after SCI in recent studies. However, little is known about the functional significance of the unique role of miRNAs in SCI. Here, we established a rat SCI model and performed the miRNA microarray to analyze miRNAs expression at different times post-SCI. Microarray data revealed that 14 miRNAs were upregulated and 46 miRNAs were downregulated by 2 times compared with sham rat spinal cords, and miR-494 was one of the miRNAs being most significantly downregulated. Subsequently, we investigated miR-494 function and found that upregulation of miR-494 by agomir-494 improves functional recovery, reduces lesion size and inhibits apoptotic cell in rats following SCI. Moreover, our data showed that miR-494 suppresses phosphatase and tensin homolog (PTEN), a negative regulator of AKT/mTOR pathway, through directly targeting its 3'-UTR in BV-2 cells. Most importantly, we demonstrated that overexpression of miR-494 activates AKT/mTOR signaling pathway via inhibiting PTEN expression in rat SCI model. These findings suggested that miR-494 harbored the protective effect after SCI by modulating PTEN/AKT/mTOR pathway in rats and it is a potential candidate for SCI therapeutics.


Subject(s)
Apoptosis/genetics , MicroRNAs/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Recovery of Function , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , 3' Untranslated Regions/genetics , Animals , Antagomirs/pharmacology , Apoptosis/drug effects , Base Sequence , Disease Models, Animal , Female , Mice , MicroRNAs/genetics , PTEN Phosphohydrolase/metabolism , Rats, Sprague-Dawley , Recovery of Function/drug effects , Spinal Cord/drug effects , Spinal Cord/metabolism , Spinal Cord/pathology , Spinal Cord/physiopathology , Spinal Cord Injuries/genetics , TOR Serine-Threonine Kinases/metabolism , Up-Regulation/drug effects
13.
Int J Mol Sci ; 18(4)2017 Apr 01.
Article in English | MEDLINE | ID: mdl-28368292

ABSTRACT

Recent evidence has suggested that long non-coding RNAs (lncRNAs) may play a significant role in the pathogenesis of several neurological diseases, including spinal cord injury (SCI). However, little is known about the role of lncRNAs in SCI. The aim of the present study was to evaluate the potential functions of lncRNAs in SCI and to identify the underlying mechanisms of action. We firstly analyzed Gene Expression Omnibus (GEO) datasets to investigate aberrantly-expressed lncRNAs which might be involved in the pathogenesis of SCI. The long non-coding RNA X-inactive specific transcript (XIST) was found to be one of the most significantly upregulated lncRNAs in the GEO dataset analysis, and is associated with apoptosis. We, therefore, selected this as a candidate lncRNA and investigated its function. We found that knockdown of lncRNA-XIST by Lv-shRNA had a prominent protective effect on SCI recovery by suppressing apoptosis through reactivation of the PI3K/AKT signaling pathway in rat spinal cord tissue. In particular, our results suggested that lncRNA-XIST may act as a competitive endogenous RNA, effectively becoming a sink for miR-494, leading to derepression of its target gene, phosphatase and tensin homolog deleted on chromosome ten (PTEN). In addition, an inverse relationship between lncRNA-XIST and miR-494 was observed in spinal cord tissues of SCI rats. Further study demonstrated that antagomiR-494 could reverse the protective effects of lncRNA-XIST knockdown on SCI rats through blocking the PTEN/PI3K/AKT signaling pathway. These results suggested that lncRNA-XIST knockdown may play an important role in limiting neuronal apoptosis in rats following SCI, and that the observed protective effects of lncRNA-XIST knockdown might have been mediated by its regulation on the phosphorylation of AKT by competitively binding miR-494. These findings have revealed, for the first time, the importance of the XIST/miR-494/PTEN/AKT signaling axis in the pathogenesis of SCI and suggest that lncRNA-XIST may be a promising molecular target for SCI therapy.


Subject(s)
Apoptosis/genetics , MicroRNAs/genetics , Proto-Oncogene Proteins c-akt/genetics , RNA, Long Noncoding/genetics , Spinal Cord Injuries/genetics , Animals , Blotting, Western , Down-Regulation , Gene Expression Profiling/methods , Immunohistochemistry , Male , Neurons/metabolism , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , RNA Interference , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/genetics , Spinal Cord Injuries/metabolism
14.
Neurosci Lett ; 638: 129-134, 2017 01 18.
Article in English | MEDLINE | ID: mdl-27993707

ABSTRACT

Spinal cord ischemia-reperfusion (I/R) injury is a severe clinical condition, while the mechanism is still not clarified and the therapeutic approach is limited. Ischemia post-conditioning (PC) has been found to have the protective effects against I/R injury in brain. Recently p53 has been reported to take part in the regulation and protection of I/R injury. We hypothesize that PC has the protective effects in primary cultured spinal cord neurons against ischemia-reperfusion injury, and MDM2-p53 signaling pathway may involve in its protective mechanism. In this study, we used an OGD (oxygen and glucose deprivation)-reperfusion model in primary cultured spinal cord neurons to simulate the I/R injury of spinal cord in vitro, and PC was conducted by 3 cycles of 15min restoration of glucose and oxygen with 15min OGD, followed by 6h fully restoration as reperfusion. Lentiviral vectors were used to knock down MDM2 or over-express p53 genes in primary cultured spinal cord neurons. The results showed that 3 cycles of 15min PC generated the most significant protective effects in primary cultured spinal cord neurons against OGD-reperfusion injury. The levels of MDM2 were decreased while p53, Bax, and cleaved Caspase 3 were increased under OGD-reperfusion condition. PC could significantly reverse the down-regulation of MDM2 and up-regulation of p53, Bax, and cleaved Caspase 3 by OGD-reperfusion injury. Moreover, MDM2 knockdown or p53 over-expression could induce the cleaved Caspase 3 expression and blocked the protective effects of PC in primary cultured spinal cord neurons against OGD-reperfusion injury. In conclusion, our work demonstrated that MDM2-p53 pathway plays a pivotal role in the protective effect of PC against OGD-reperfusion injury and PC may be a feasible therapy strategy in the treatment for spinal cord I/R injury.


Subject(s)
Glucose/deficiency , Ischemic Postconditioning , Oxygen/metabolism , Reperfusion Injury/prevention & control , Spinal Cord Ischemia/prevention & control , Spinal Cord/pathology , Tumor Suppressor Protein p53/metabolism , Animals , Apoptosis , Cell Hypoxia , Cells, Cultured , Primary Cell Culture , Proto-Oncogene Proteins c-mdm2/metabolism , Rats, Sprague-Dawley , Reperfusion Injury/pathology , Signal Transduction , Spinal Cord Ischemia/pathology
15.
World Neurosurg ; 90: 414-419, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26960287

ABSTRACT

OBJECTIVE: Hemangiopericytoma (HPC) is a rare mesenchymal tumor that tends to affect the central nervous system and is associated with distant metastasis and a high recurrence rate. The purpose of this study was to analyze the prognostic factors in patients with primary HPC who received surgical treatment. METHODS: This retrospective study reviewed all adult patients with primary HPC of the central nervous system treated from 2001 to 2009 at our institution. Clinical information, adjuvant radiation, and expression levels of Ki-67 and p53 were correlated with patient outcomes. RESULTS: The final analysis included 103 patients. The mean follow-up period was 75.9 months ± 36.5 (range, 1-165 months). There was a significant difference in progression-free survival (PFS) (P < 0.001) and overall survival (P = 0.014) between patients who underwent gross total resection versus subtotal resection. Expression of p53 was found in 48.5% of patients and showed utility as an independent unfavorable prognostic factor for PFS (P = 0.006). Multivariate analysis revealed that only extent of tumor resection (P = 0.004) and p53 expression (P = 0.024) were independent prognostic factors for PFS. Adjuvant radiation was found to extend PFS only in the p53-negative expression group (P = 0.044). CONCLUSIONS: Gross total resection significantly improves the outcome of patients with primary HPCs, whereas adjuvant radiation contributes significantly to PFS only in patients with negative p53 expression and in patients with incomplete resections. Extent of resection and p53 expression may serve as prognostic markers for the outcome of patients with primary HPC.


Subject(s)
Central Nervous System Neoplasms/diagnosis , Central Nervous System Neoplasms/surgery , Hemangiopericytoma/diagnosis , Hemangiopericytoma/surgery , Adolescent , Adult , Aged , Biomarkers, Tumor/metabolism , Central Nervous System Neoplasms/pathology , Central Nervous System Neoplasms/radiotherapy , Female , Follow-Up Studies , Hemangiopericytoma/pathology , Hemangiopericytoma/radiotherapy , Humans , Immunohistochemistry , Ki-67 Antigen/metabolism , Male , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local/diagnosis , Prognosis , Radiotherapy, Adjuvant , Retrospective Studies , Survival Analysis , Treatment Outcome , Tumor Suppressor Protein p53/metabolism , Young Adult
16.
Acta Neurochir (Wien) ; 158(1): 101-7, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26577638

ABSTRACT

BACKGROUND: Myxopapillary ependymoma (MPE) is a rare subtype of ependymoma that develops almost exclusively within the spinal cord. Despite its benign biological nature, MPE has a propensity to recur locally or distantly. Although variables influencing the prognosis, such as age, the extent of surgery and radiotherapy, have been widely discussed, no definitive standard has been established. Compared to other spinal tumors, many fewer histological markers have been elucidated to assist the determination of the prognosis. METHODS: Twenty-seven patients who underwent resection of MPE were enrolled. We determined their demographic features, imaging characteristics, clinical presentations and outcomes, surgical procedures and histological properties by chart review, telephone contact, reviewing of surgical notes, pre-/postoperative imaging and immunohistological staining. RESULTS: GTR (gross total resection) was achieved in 18 patients (66.7 %) and STR (subtotal resection) in 9 (33.3 %). Although GTR rendered a better disease control rate, the difference was not significant. Pediatric patients suffered from a greater risk of recurrence as well as a shorter period to disease relapse. In the majority of cases, we observed the overexpression of platelet-derived growth factor receptor α (PDGFRα), matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-14 (MMP14). Epidermal growth factor receptor (EGFR) was observed in the tumors of 7 of 23 nonrecurrent patients, but not in any recurrent tumors. CONCLUSIONS: The results of the present study indicate that the extent of resection and age are major factors related to tumor recurrence. Therefore, gross total resection is recommended whenever possible unless following neurological dysfunction is predictable. Moreover, pediatric patients need considerable attention after surgery, particularly in the early stages. PDGFRα, MMP2 and MMP14 may be new diagnostic and therapeutic targets and EGFR a potential predictor of improved prognosis for MPE.


Subject(s)
Ependymoma/surgery , Neoplasm Recurrence, Local/pathology , Spinal Cord Neoplasms/surgery , Adolescent , Adult , Child , Ependymoma/blood , ErbB Receptors/metabolism , Female , Humans , Male , Middle Aged , Retrospective Studies , Spinal Cord Neoplasms/blood , Treatment Outcome , Young Adult
17.
Onco Targets Ther ; 8: 1119-27, 2015.
Article in English | MEDLINE | ID: mdl-26056476

ABSTRACT

"Glioblastoma multiforme" (GBM) is the frequent form of malignant glioma. Immature colon carcinoma transcript-1 (ICT1) is essential for cell vitality and mitochondrial function and has been recognized in several human cancers. In the study reported here, we attempted to evaluate the functional role of ICT1 in GBM cells. Lentivirus-mediated RNA interference (RNAi) was applied to silence ICT1 expression in human GBM cell lines U251 and U87. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony-formation assays. Cell-cycle progression was determined by flow cytometry with propidium iodide staining. The results revealed that lentivirus-mediated short hairpin RNA (shRNA) can specifically suppress the expression of ICT1 in U251 and U87 cells. Functional investigations proved for the first time, as far as we are aware, that ICT1 knockdown significantly inhibited the proliferation of both cell lines. Moreover, the cell cycle of U251 cells was arrested at Gap 2 (G2)/mitotic (M) phase after ICT1 knockdown, with a concomitant accumulation of cells in the Sub-Gap 1 (G1) phase. This study highlights the crucial role of ICT1 in promoting GBM cell proliferation, and provides a foundation for further study into the clinical potential of lentivirus-mediated silencing of ICT1 for GBM therapy.

18.
Cell Tissue Bank ; 16(2): 271-81, 2015 Jun.
Article in English | MEDLINE | ID: mdl-24929994

ABSTRACT

Cerebral glioma is the most common brain tumor as well as one of the top ten malignant tumors in human beings. In spite of the great progress on chemotherapy and radiotherapy as well as the surgery strategies during the past decades, the mortality and morbidity are still high. One of the major challenges is to explore the pathogenesis and invasion of glioma at various "omics" levels (such as proteomics or genomics) and the clinical implications of biomarkers for diagnosis, prognosis or treatment of glioma patients. Establishment of a standardized tissue bank with high quality biospecimens annotated with clinical information is pivotal to the solution of these questions as well as the drug development process and translational research on glioma. Therefore, based on previous experience of tissue banks, standardized protocols for sample collection and storage were developed. We also developed two systems for glioma patient and sample management, a local database for medical records and a local image database for medical images. For future set-up of a regional biobank network in Shanghai, we also founded a centralized database for medical records. Hence we established a standardized glioma tissue bank with sufficient clinical data and medical images in Huashan Hospital. By September, 2013, tissues samples from 1,326 cases were collected. Histological diagnosis revealed that 73 % were astrocytic tumors, 17 % were oligodendroglial tumors, 2 % were oligoastrocytic tumors, 4 % were ependymal tumors and 4 % were other central nervous system neoplasms.


Subject(s)
Biological Specimen Banks/standards , Biomedical Research/standards , Glioma/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , China , Databases, Factual/standards , Female , Glioma/surgery , Humans , Infant , Male , Middle Aged , Specimen Handling , Translational Research, Biomedical/standards , Young Adult
19.
Clin Neurol Neurosurg ; 126: 156-61, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25259876

ABSTRACT

Gangliocytomas occurring in the sellar region are extremely rare. We examined a cohort of these tumors to examine their clinical presentations and prognoses. Between January 2000 and December 2012, 23 patients were diagnosed with sellar region gangliocytomas in Huashan Hospital. These patients were retrospectively reviewed for medical histories, endocrinological examinations, preoperative magnetic resonance imaging (MRI), pathological findings and follow-ups. Endocrinological tests revealed elevated prolactin (PRL) levels in 10 cases (43.5%) and elevated growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels in 9 cases (39.1%). Scattered ganglion cells admixed with adenomatous components were observed in 16 cases (69.6%). In the remaining 7 cases (30.4%), only fragments with ganglion cells dispersed in the fibrillar matrix without adenohypophyseal components were detected. Immunohistochemistry revealed PRL-positive adenomas in 6 cases (26.1%) and GH-positive adenomas in 8 cases (34.8%). The average follow-up period was 4.2 years (range: 1-12.7 years). Gross total resection was achieved in 20 cases (87.0%). One patient recurred five years after tumor resection (4.3%). One patient died of acute myocardial infarction six years after operation. Gangliocytomas located in the sellar region may represent a unique immunopathological entity. The surgical results and prognoses of the gangliocytomas were comparable with those of pituitary adenomas.


Subject(s)
Ganglioneuroma/pathology , Pituitary Neoplasms/pathology , Sella Turcica/pathology , Adolescent , Adult , Aged , Child , Cohort Studies , Female , Ganglioneuroma/surgery , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Pituitary Neoplasms/surgery , Young Adult
20.
Zhonghua Yi Xue Za Zhi ; 94(19): 1455-8, 2014 May 20.
Article in Chinese | MEDLINE | ID: mdl-25143162

ABSTRACT

OBJECTIVE: To explore the prognostic factors of intramedullary high grade astrocytomas. METHODS: Retrospective analyses were conducted for 21 surgical patients with high grade astrocytoma in spinal cord during 2008 to 2012 at our hospital. Their preoperative and postoperative profiles were recorded and evaluated by modified McCormick classification scheme. RESULTS: Their median age was 32.5 years. There were anaplastic astrocytoma (n = 14) and glioblastoma (n = 7). The prognoses of high grade astrocytomas were correlated with pathology grade and MIB-1 index. No statistic significance existed in age, gender, McCormick score, extent of resection, radiotherapy or chemotherapy. CONCLUSION: Intramedullary high grade astrocytoma has a low incidence, but its outcome is poor. Once definitely diagnosed, operation is recommended as early as possible. Frozen pathology should be performed to determine the extent of resection. After operation, chemotherapy and radiotherapy are also suggested.


Subject(s)
Astrocytoma , Spinal Cord Neoplasms , Adolescent , Adult , Aged , Astrocytoma/diagnosis , Astrocytoma/pathology , Astrocytoma/surgery , Child , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Spinal Cord Neoplasms/diagnosis , Spinal Cord Neoplasms/pathology , Spinal Cord Neoplasms/surgery , Young Adult
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