1.Silencing of activating transcription factor 4 inhibits neuronal necroptosis after intracerebral hemorrhage in vitro
Dengfeng FENG ; Min WEI ; Hengzhu ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(13):2030-2035
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.
2.Anatomical study and clinical application of neuroendoscopy assisted contralateral cervical 7 nerve transfer via prespinal route in central upper limb spastic paralysis
Zhengcun YAN ; Jiaxiang GU ; Hongjun LIU ; Wenmiao LUO ; Xiaodong WANG ; Xingdong WANG ; Min WEI ; Yongxiang WANG ; Hengzhu ZHANG
Chinese Journal of Neuromedicine 2024;23(9):911-917
Objective:To simulate the neuroendoscopy assisted contralateral cervical 7 (C 7) nerve transfer via prespinal route and measure its relevant anatomical landmarks to explore the clinical feasibility and efficacy of this surgical approach for central upper limb spastic paralysis. Methods:(1) Six fresh cadaver specimens of the head and neck were obtained. Linear incisions of approximately 5 cm were made above the midpoint of the bilateral clavicles to simulate neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route. With the superior margin of midpoint of the clavicle as central point, distance to the distal bifurcation of the C 7 nerve, distances to the superior or inferior trunks of the proximal brachial plexus nerves, and distances to the exit of the intervertebral foramina of the C 6, C 7, and C 8 nerves were measured. (2) One patient with upper limb spastic paralysis after intracerebral hemorrhage accepted neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route; the clinical data and efficacy of the patient were retrospectively analyzed. Results:(1) The C 7 nerve, the upper trunk of brachial plexus formed by the C 5 and C 6 nerves and the lower trunk of brachial plexus formed by the C 8 and T 1 nerves could be exposed after neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route. The distance between the superior margin of midpoint of the clavicle and the distal bifurcation of the C 7 nerve is (2.20±0.11) cm, and its distance to the superior trunk of the proximal brachial plexus is (2.62±0.10) cm, and its distance to the inforior trunk of the proximal brachial plexus nerve is (2.72±0.11) cm. The distance between the superior margin of midpoint of the clavicle and the proximal C 7 nerve (at the exit of the intervertebral foramen) is (7.22±0.15) cm, its distance to the proximal C 6 nerve (at the exit of the intervertebral foramen) is (7.84±0.12) cm, and its distance to the proximal C 8 nerve (at the exit of the intervertebral foramen) is (6.96±0.12) cm. (2) The patient with central upper limb spastic paralysis accepted neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route successfully, with surgical time lasting for 2 h and bleeding amount of 20 mL. After surgery, the incision healed well, and the patient experienced pain and numbness in the healthy side of the upper limb with subsided symptoms one month after surgery. The spasticity symptoms of the affected upper limb obviously improved after surgery with decreased muscle tone. Follow-up after discharge was performed for 14 months, and the muscle strength of the affected upper limb recovered to level 1 +. Conclusion:Neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route can expose the proximal and distal C 7 nerves, with minimal invasion; this clinical study has preliminarily confirmed the safety and effectiveness of this transfer via prespinal route in central upper limb spastic paralysis.
3.Clinical effects and mid-term follow-up analysis of para-split laminotomy for lumbar spinal canal tumors
Hao PENG ; Hengzhu ZHANG ; Xiaodong WANG ; Zhengcun YAN ; Can TANG ; Xingdong WANG ; Min WEI ; Lei SHE
International Journal of Surgery 2023;50(4):259-264
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.
4.Current Situation and Research Progress of Minimally Invasive Treatment on Central Nervous System Tumors
Cancer Research on Prevention and Treatment 2023;50(11):1045-1050
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.
5.Research progress in the regulation mechanism of key signal pathways affecting the prognosis of glioma
International Journal of Surgery 2022;49(1):57-62,F4
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.
6.Recent advance in surgical treatment of spastic hemiplegia after cerebral stroke
Chinese Journal of Neuromedicine 2021;20(12):1275-1280
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.
7.Efficacy of laminoplasty and bone graft in the treatment of multilevel intraspinal tumor
Xiaodong WANG ; Hengzhu ZHANG ; Zhengcun YAN ; Lei SHE ; Xingdong WANG ; Shuwen SUN
International Journal of Surgery 2018;45(10):680-683,封4
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.
8.The choice and curative effect analysis of early postoperative nutritional support for severe traumatic brain injury patients
Can TANG ; Lun DONG ; Hengzhu ZHANG ; Min WEI ; Xingdong WANG
International Journal of Surgery 2017;44(1):11-15
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.
9.Combined monitoring of intracranial pressure and bispectral index in patients with severe craniocerebral trauma after operation
Lun DONG ; Can TANG ; Hengzhu ZHANG ; Lang CHEN ; Min WEI ; Xingdong WANG
International Journal of Surgery 2017;44(7):464-467,封4
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.
10.Approaches in intraspinal tumors resection and the reconstruction of spinal stability postoperatively
Xingdong WANG ; Hengzhu ZHANG ; Xiaodong WANG
International Journal of Surgery 2015;42(11):763-767
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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