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BACKGROUND:Neuronal necroptosis induced by intracerebral hemorrhage is an important cause of secondary brain injury.Activating transcription factor 4(ATF4)is a member of the transcription activator family,which plays an important role in secondary brain injury after intracerebral hemorrhage.However,the mechanism of ATF4 in neuronal necroptosis after intracerebral hemorrhage remains unclear. OBJECTIVE:To explore the effect of ATF4 silencing(ATF4 small interfering RNA,ATF4 siRNA)on neuronal necroptosis after intracerebral hemorrhage. METHODS:The HT-22 mouse hippocampal neuron cell line and the BV-2 mouse microglial cell line were co-cultured,and hemin was used to mimic an in vitro model of intracerebral hemorrhage.A gradient concentration of hemin was used to treat cells and was set in the interval of 0-100 μmol/L,and the cell viability was evaluated by MTT assay after 24 hours of administration of hemin.The cells were divided into four groups:the blank control group without any intervention;the control group was treated with hemin(50 μmol/L),and the other two groups were treated with negative control small interfering RNA(NC siRNA)and ATF4 small interfering RNA(ATF4 siRNA)48 hours before administration of hemin.After the cells were treated with hemin(50 μmol/L)for 24 hours,PI/Hoechst staining was used to detect neuronal necroptosis.Western blot assay was used to detect the protein expression of ATF4,receptor-interacting protein 3(RIP3),and mixed lineage kinase domain-like protein(MLKL),and double immunofluorescent staining was located in neurons to observe the level of neuronal necroptosis and the regulatory effect of ATF4 on it. RESULTS AND CONCLUSION:(1)50 μmol/L of hemin could induce neuronal necroptosis to a greater extent.(2)The number of PI+/Hoechst+ cells in the control group and NC siRNA group was higher than that in the blank control group(P<0.000 1).The number of PI+/Hoechst+ cells in the ATF4 siRNA group was lower than that in the control group(P<0.000 1).(3)Compared with the control group,the ATF4 siRNA group not only inhibited the expression of ATF4 protein(P<0.001),but also inhibited the expression of RIP3 and MLKL protein(P<0.001).(4)Through double immunofluorescent staining,compared with the control group,the protein expression of RIP3 and MLKL was significantly reduced in the ATF4 siRNA group(P<0.000 1).(5)The results show that the silencing of the ATF4 gene can directly or indirectly inhibit the expression of genes related to neuronal necroptosis after intracerebral hemorrhage,and play a vital role in alleviating secondary brain injury.
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Objective:To investigate the surgical outcome and prognostic factors of para-split laminotomy for removal of lumbar spinal canal tumors.Methods:Retrospectively review the clinical data of 35 patients suffering lumbar spinal canal tumors, who underwent the para-split laminotomy for tumor resection in Department of Neurosurgery, Clinical Medical College of Yangzhou University from October 2016 to August 2019, including 16 males and 19 females, and the age was(40.1±10.6)years. Intraoperative blood loss, operation time, tumor resection, tumor pathological results, perioperative complications were observed. Follow-up situations, including tumor recurrence, bony fusion of laminae and spinal stability. Follow-up using outpatient examination and telephone interview was performed by the end of August 2022. The JOA back pain scoring system was used to evaluate the neurological function of the spinal cord, and paired t-test were performed to compare the overall preoperative and postoperative spinal cord neurological function scores. Linear regression and multiple linear regression were used to analyze the prognostic factors. Measurement data of normal distribution were expressed as mean±standard deviation ( ± s), and the comparison before and after operation was performed by paired t-test. Mearsurement data of skewed distribution were expressed as M( Q1, Q3). Count data were expressed as cases. Results:The tumors of 35 patients were resected completely. The median blood loss was 100(75, 140)mL and the average operative duration was (181.1±42.7) min. The postoperative pathological results were as follows: 24 neurilemmomas, 6 meningiomas, 4 ependymomas and 1 neurofibroma. There were no surgery-related complications occurred. The postoperative follow-up ranged from 36 to 69 months, with no tumor recurrence or spinal instability, and bony fusion of laminae seen in some patients on CT imaging. The overall spinal cord neurological function scores of pre and post operation were(19.5±3.4)versus(25.4±2.2), Paired t-test analysis revealed a significant difference between the overall postoperative spinal cord neurological function scores and the preoperative scores, and the postoperative scores were better than the preoperative scores( P<0.05). Multiple linear regression analysis showed a positive correlation between preoperative JOA scores and postoperative JOA scores, and postoperative JOA scores has negative correlation with tumor volume and the age at the time of operation ( P<0.05). Conclusion:Para-split laminotomy with less damage to the posterior spinal structures can effectively improve the neurological function of the spinal cord and protect the stability of the lumbar spine in patients with lumbar spinal canal tumors, and the better the preoperative neurological function of the spinal cord, the better the prognosis of patients, and the smaller the tumor volume, the better the prognosis.
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Central nervous system (CNS) tumors pose a substantial risk to human health. Conventional therapeutic modalities, including surgical excision, radiotherapy, and chemotherapy, exhibit inherent limitations and adverse effects. Nonetheless, the emergence of minimally invasive surgical techniques and advanced imaging technology have spurred research interest in the realm of neurology toward developing minimally invasive treatments for neurosurgical tumors. These approaches encompass tumor laser interstitial thermal therapy, tumor treating fields, photodynamic therapy, and other related interventions. Minimally invasive treatments offer notable advantages, such as reduced tissue trauma, expedited recovery, and pronounced therapeutic efficacy, rendering them extensively employed in clinical settings. This comprehensive review aims to elucidate accomplishments in the field of minimally invasive CNS tumor treatments while delineating prospective avenues for future development.
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Glioma has a high malignant degree, high recurrence rate and poor prognosis. We analyzed signal pathway of the Hippo/YAP, PI3K/AKT/mTOR, miRNA, WNT/β-catenin, Notch, Hedgehog, TGF-β and the mechanism of key enzymes in glioma. It is concluded that YAP1 inhibitor may become an effective target for the treatment of glioma in the future.Inhibiting PI3K/AKT/mTOR, Shh, Wnt/β-Catenin and HIF-1α can reduce the migration ability and drug resistance of tumor cells to improve the prognosis of glioma. The analysis shows that Notch1 and Sox2 have a positive feedback regulation mechanism, and Notch4 predicts the malignant degree of glioma. In this way, notch can not only be treated for glioma stem cells in clinic, but also be used as an evaluation index to evaluate the prognosis, and provide an exploratory attempt for the direction of glioma treatment. MiRNA plays an important role in diagnosis, and in the treatment of glioma, it can play a further role with the delivery of nanoparticles and TMZ. It is believed that these studies will help us to have a deeper understanding of glioma, so that we will find new and better treatment schemes to gradually conquer the problem of glioma.
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Spastic hemiplegia after stroke seriously affects the quality of life of patients. Finding a method which can not only improve the movement of hemiplegic limbs, but also relieve spasm has become one of the important subjects in the medical field. In addition to conservative treatments such as traditional Chinese medicine, medicines, and rehabilitation training, surgical treatment has gradually become the main means of clinical treatment with advantages of definite clinical effecacy and rapid recovery. At present, there is no unified standard for clinical surgical methods for spastic hemiplegia after stroke. This article reviews the pathogenesis, surgical methods and clinical efficacies of the disease, and discusses the advantages and disadvantages of different surgical methods so as to provide clinical evidence and help for in-depth understanding of surgical treatments of spastic hemiplegia after stroke and optimizing the treatment plans.
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Objective To investigate the clinical effect of laminoplasty technique with bone grafting in the treatment of multiple segmental intraspinal tumors.Methods Retrospectively review the clinical data of 35 patients suffering multiple segmental intraspinal tumors,who underwent the laminoplasty with bone grafting for intraspinal tumor resection in Department of Neurosurgery,Clinical Medical College of Yangzhou University,from June 2013 to May 2016.Observation indicators:(1) surgical and postoperative recovery situations,including tumor resection,number of lamina reset,tumor pathological results,clinical efficacy evaluation,complications,etc;(2) follow-up situations,including spinal stability evaluation,rate of bone graft fusion,tumor recurrence.Follow-up using outpatient examination and telephone interview was performed by the end of December 2017.Results (1) Surgical and postoperative recovery situations:of the 35 patients,31 achieved total tumor resection,3 subtotal tumor resection and 1 partial tumor resection.There were no spinal dura mater injuries when laminectomy was performed,and 84 laminae were repositioned and implanted.The neurological function of the spinal cord was evaluated based on McCormick scoring system:32 cases were improved and 3 cases were controlled.Incision healing was bad in 2 patients,and cerebrospinal fluid leakage occurred in 1 case,which all recovered after treatment.(2) Follow-up situations:all the 35 patients were followed up for 8 to 36 months,with a median time of 14.2 months.Imaging examination more than 6 months after operation:no spinal instability was found in standing spine X-ray examination;CT scan showed a total of 142 sides in the 84 vertebral plates (168 sides) had achieved bone fusion,the fusion rate was 84.5％,and no titanium nail removal and connecting piece shift was found;MRI showed no tumor recurrence in all patients.Conclusion Use of the laminoplasty technique with bone grafting in the treatment of multiple segmental intraspinal tumors can achieve good clinical efficacy,high fusion rate for resected laminae and satisfactory spinal stability.
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Objective To explore the differences of curative effect and short-term prognosis to severe traumatic brain injury patients with three different early postoperative nutritional supports.Methods A retrospective study was performed on 60 severe traumatic brain injury patients received in Neurosurgical Intensive Care Unit of Northern Jiangsu People's Hospital from July 2014 to July 2016.A total of 60 cases were randomly divided into the early enteral nutrition support therapy group,the early parenteral nutrition group,and the early compound nutrition group.The clinical indicators such as basic clinical characteristics before treatment,the nutrition data in two weeks,the length of stay in the Neurosurgical Intensive Care Unit,complications and GCS scores between the three groups were observed and analyzed.Results The indicators of early compound nutrition group were fasting blood-glucose (5.74 ± 0.64) mmol/L,prealbumin(203.80 ± 10.45) mg/L,total serum protein(61.99 ± 1.34) g/L,blood hemoglobin (114.53 ± 2.69) g/L,C-reactive protein(0.37 ± 0.06) mg/dl.The length of stay in Neurosurgical Intensive Care Unit was (11.6 ± 0.42) days in the compound nutrition group while those in the early enteral nutrition group was (13.20 ±0.42) days and those in the early parenteral nutrition group was(14.65 ± 0.42) days.The postoperative complications of the compound nutrition group were significantly lower than other two groups.The GCS scores of early compound nutrition group was(11.40 ± 1.60),which was the best in three groups.The differences were statistically significant (P ＜ 0.05).Conclusions Early compound nutrition support has an exact curative effect on postoperative severe traumatic brain injury patients in Neurosurgical Intensive Care Unit.It can obviously improve the nutrition status of patients with less complications,shorter length of stay in Neurosurgical Intensive Care Unit,higher safety and lower degree of coma,worth clinical promotion.
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Objective To investigate the value of bispectral index and intracranial pressure monitoring in evaluation of postoperative consciousness and short-term prognosis in patients with severe traumatic brain injury.Methods A simple random sampling method was used in 30 cases of brain trauma coma patients in the People's Hospital of Northern Jiangsu Province from January 2014 to December 2014.Glasgow coma scale (GCS) were evaluated at intervals of 8 hours,GCS were recorded for 3 days after surgery,The bispectral index value and intracranial pressure value are recorded at the same time.According to GCS,the patients were divided into two groups,group A (3≤GCS≤5) and group B(5 ＜ GCS≤8).The 21-days natural survival rate was counted.The Kaplan-Meier Method and Log-rank test were used to analyze the relationship between Bispectral index and intracranial pressure.Results The bispectral index value of group A was 45.3 ± 3.8,the intracranial pressure value of group A was (18.6 ± 2.8) mmHg,The bispectral index value of group B was 32.2 ± 8.2,the intracranial pressure value of group B was (33.4 ±4.6) mmHg.The 21-days survival rate of group A was 55％,and 21-days survival rate of group B was 30％.The Spearman rank correlation method was used to analyze the values.Bispectral index value was positively correlated with coma degree after operation in patients with severe traumatic brain injury,and was negatively correlated with intracranial pressure value (r =0.532,P ＜ 0.05;r =0.521,P ＜ 0.05).The more severer the patient's craniocerebral injury.,the more severer the condition,the higher the intracranial pressure,the lower the bispectral index value,the worse the prognosis is.Conclusion Combined monitoring of bispectral index and intracranial pressure has high application value in evaluating the coma degree and prognosis of patients with severe craniocerebral injury after operation.
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Intraspinal tumors with kinds of pathological type are common in clinic, whose first option of the treatment is the surgical resection.In recent years, neurosurgeons pay more attention to the postoperative stability of spine biomechanics on the basis of the total resection of the tumors.This paper reviews the approaches in intraspinal tumors resection and the methods of the reconstruction of spinal stability postoperatively which influence the stability of spine biomechanics most.
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Objective To study the impact of super early tracheotomy in the prognosis of patients with primary massive cerebral hemorrhage (＞50 mL).Methods A retrospective analysis was conducted on the clinical data of 100 patients with primary massive cerebral hemorrhage who underwent the comprehensive treatment of craniotomy operation plus tracheotomy from January 2010 to December 2013.The patients underwent tracheotomy before brain operation were classified as super early tracheotomy (SET) group,and the patients accepted tracheotomy within 3 days or 4-7 days after brain operation were classified,respectively,as early tracheotomy (ET) group or late tracheotomy (LT) group.Clinical variables such as age,gender,Glasgow coma scale (GCS) scores,postoperative re-bleeding rate,tracheal cannula indwelling time,hospitalization time,improvement rate and mortality were analyzed contrastively among the 3 groups.Results There was no statistical difference in primary clinical characteristics among 3 groups (P＞0.05).The postoperative re-bleeding rate of ET group (14.28％) was higher than one of SET group (5.55％) and LT group (10.34％).The tracheal cannula indwelling mean time of SET group was significantly shorter than one of ET group and LT group (P＜0.05).Significant differences existed among the 3 groups in the mean hospitalization time (SET group＜ET group＜LT group,P＜0.05).There was no significant difference in the improvement rate between SET group and ET group,however,the improvement rate of LT group was significantly lower than one of the other two groups (P＜0.05).No statistical difference in the mortality existed among 3 groups (P＞0.05).Conclusion It is effective and feasible to perform SET to reduce the postoperative re-bleeding rate,shorten the hospitalization time,improve the prognosis of the patients with primary massive cerebral hemorrhage.
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Glioma is an important cause of death in adults and children among the most common neural malignancies,with high morbidity and mortality in primary brain tumors.Despite advances in radiation and chemotherapy following surgical resection of the tumor,the median survival time of glioma remains poor.The effects of miR-21expression on tumor growth and invasion via regulating the pathways in human glioma cells,which regulate the expression of some small molecule.This review is mainly focused on the discovery of the correlation between microRNA-21 (miR-21) and glioma and the important role in the resistance of cancer cells to radiation and chemotherapeutic agents.
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Objective To construct a lentiviral vector containing mir-7-3 gene and study the function of mir-7-3 gene and its role in glioma gene therapy.Methods The plasmid Lenti-GFP-mir-7-3 and packaging plasmids pRsv-REV,pMDlg-pRRE and pMD2G were co-transfected into the human embryonic kidney epithelial cell line 293T cells,and then,recombinant lentiviral FIV-CMV-GFP-mir-7-3 carried mir-7-3 gene and GFP gene was obtained; fluorescence expression of 293T cells was observed under fluorescence microscope.The supematant was collected,concentrated and identified,and then,it was used to transfect into the U251 glioma cells (positive transfection group); and blank control group (cells transfected with empty vector) and negative control group (parental cells) were also employed.Real time-PCR was used to examine the relative contents of mir-7-3 in U251 cells; Westem blotting was employed to detect the epidermal growth factor (EGFR) and serine/threonine kinase (AKT2) protein expressions; cell cycle was analyzed by flow cytometry and cell proliferative activities were measured by MTT method.Results Recombinant lentiviral FIV-CMV-GFP-mir-7-3 carried mir-7-3 gene and GFP gene was successfully constructed in 293T cells; electrophores showed that the sequence of RT-PCR product was consistent with the data ofmir-7-3 by DNA sequence analysis,indicating that the mir-7-3 gene was successfully cloned; strong green fluorwscence was observed by fluorwscent microscopy.The supernatant of lentivirus-transfected 293T cells was effectively infected into U251 cells and the relative content of mir-7-3 could be observed in the transfected U251 cells.As compared with those in the parental cells and the cells transfected with empty vector,the protein expressions of EGFR and AKT2 in the transfected group decreased significantly,reaching 38％ and 42％,respectively (P＜0.05).As compared with those in the parental cells and the cells transfected with empty vector,the cells at G0/G1 phase increased,the S phase fiaction was lower and the survival rates dramatically dropped in the mir-7-3 transfected cells 3,4,5 and 6 d after implanation.Conclusions The lentiviral vector containing mir-7-3 gene was constructed successfully.Mir-7-3 could specifically suppress EGFR and AKT2 expressions,induce gene silencing,inhibit cell growth,indicating that this way should be a new strategy in glioma gene therapy.
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Objective To construct a lentiviral vector containing mir-7-3 gene and green fluorescent protein (GFP) gene,and to detect the expression of mir-7-3 gene in U251 cells.Methods The fragments containing all the mir-7-3 gene were amplified by RT-PCR and were cloned into the lentivirus vectors labeled with GFP,which was transfected together with the packaging plasmids into 293T cells by CaC12.The supernatant was collected,concentrated,identified,and was transfected to U251 cells of gliomas.Fluorescent microscopy was used to observe the fluorescence in the 293T cell,and real time RT-PCR was used to examine the relative contents of mir-7-3 in U251 cells.Results Electrophores was shown that the sequence of the RT-PCR product was consistent with the data of mir-7-3 by DNA sequence analysis,indicating that the mir-7-3 gene was successfully cloned,and strong green fluorescence was observed by fluorescent microscopy.The supernatant of lentivirus-transfected 293T cells effectively infected U251 cells and the relative content of mir-7-3 was observed in the transfected U251 cells.Conclusion It is concluded that the lentiviral vector containing mir-7-3 gene was constructed successfully,which provides a basis for further study of mir-7-3 function.
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Objective: To explore the effect of single-nostril transsphenoidal approach on pituitary adenoma. Methods: We retrospectively analyzed 46 cases of pituitary tumors treated with single-nostril transsphenoidal approach and the effects and complications of surgery.Dunng the surgery,a nasal speculum was inserted through right nostril slowly towards the anterior wall of sphenoid sinus.A nasal mucosa incision of about 1.5cm was made in the right nasal cavity at the level of the middle nasal turbinate.With a fracture of the bony septum,a space was developed between the bilateral nasal mucosa and bony septum to the sphenoid sinus.Then,the face of the sphenoid sinus was exposed.The remainder of the bony septum,the anterior sphenoid sinus wall,and the sphenoid mucosa were removed.The antenor sphenoidotomy should be less than 1.5cm wide.After confirming the tumor by dural puncture,a cross incision of dura was made and the tumor was removed.The saddle was usually Collapsed and visible after total tumor removal.When the tumor was resected,sevaral gelatin sponges were stuffed into the Surgical cavity to stop bleeding. Results: Thirty-four cases had total resection and 12 cases had subtotal resection.No deaths or disability occurred.Hormone levels in almost all patients were improved.Seventeen cases had a sign of diabetes insipidus.Electrolyte disturbance occuwed in 5 cases.NO postoperative cerebrospinal fluid rhinorrhea was observed. Conclusion: Single-nostril transsphenoidal approach has many advantages in treating pituitary adenomas such as simplified approach,brief technology and high security.
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Objective To explore the clinical application of keyhole craniotomy microsurgery in neurosurgery. Methods Corresponding keyhole approach operation was employed in 13 cases of sellar region tumor, 6 cases of meningoma, 5 cases of hypertensive cerebral hemorrhage, 2 cases of glioma of corpus callosum, 2 cases of acoustic neuroma, 1 case of metastatic cerebral tumor, 1 case of epidural hematoma and 1 case of C 2 intravertebral tumor. Results Among the 25 cases, total resection was accomplished in 19 cases and subtotal resection, 6 cases. Lesions were all thoroughly cleared away in 5 cases of cerebral hemorrhage and 1 case of epidural hematoma. One case of acoustic neuroma died of re-bleeding in the lesion on the 3rd postoperative day. Subcutaneous dropsy took place in 2 cases and transient diabetes insipidus occurred in 3 cases. Conclusions Keyhole craniotomy microsurgery has the advantages of minimal exposure, micro-invasion, fewer complications and faster recovery.
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Objective To explore the posibility of removing the jugular tubercle precisely and design a new far-lateral supraeondylar keyhole approach based on keyhole idea.Methods Eight cadaveric heads fixed by 10% formalin and perfused intracranial vessels with colored silicone were used in this study.Before the operation,navigation data of these cadaveric heads were established and circumscriptions of jugular tuber- cle were outlined in the navigation system in order to aid drilling it in operation.A 7cm longitudinal“S”shaped skin incision as we reported was performed.After inverting suboccipital muscles and exposing the far lateral of the occipital bone,occipital condyle,jugular tubercle,hemilamina of C_1,vertebral artery and pos- terolateral portion of foramen magnum,a 3cm retro-condylar bone window was made.Under the microscope, anatomic structures were observed and important structures were measured after jugular tubercle removal assis- ted by neuro-navigation.Results The 7cm longitudinal“S”shaped skin incision with its superior border 2cm behind the middle point of mastoid and inferior margin at the level of C_2 can fully meet the needs of the far-lateral supracondylar keyhole approach;jugular tubercle can be drilled satisfactorily with the help of neuro- navigation;inferior segment of basilar artery[long(15.65?1.34)mm]and anterior inferior cerebellar artery [long(20.36?4.18)mm] can be exposed.Conchlsion Owing to the area of middle clivus is increasingly exposed after removal of jugular tubercle,it is feasible to perform the far-lateral supracondylar keyhole ap- proach on the operations of vertebral-basilar artery aneurysm,anterior inferior cerebellar artery aneurysm and tumor located inferior and middle clivi or jugular foramen.