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Multi-cohort comprehensive analysis unveiling the clinical value and therapeutic effect of GNAl in glioma

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Oncology Research 2024年第5期32卷 965-981页

作者： ZHEN lIU lIANGWANG YANG ZHENGXING XIE HUI YU TIANYI GU DAOMING SHI NING CAI SHENGHUA ZHUO department of neurosurgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China department of neurosurgery First Affiliated Hospital of Hainan Medical UniversityHaikou570100China department of Cardiothoracic Surgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China department of General Surgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China

Clinical data indicates that glioma patients have poor treatment outcomes and clinical *** role of olfactory signaling pathway-related genes(OSPRGs)in glioma has not been fully *** this study,we aimed to investigate the role and relationship between OSPRGs and *** and multivariate Cox regression analyses were performed to assess the relationship between OSPRGs and the overall survival of glioma based on public cohorts,and the target gene(G Protein Subunit Alpha l,GNAl)was *** association of GNAl expression with clinicopathological characteristics,gene mutation landscape,tumor immune microenvironment(TIME),deoxyribonucleic acid(DNA)methylation,and naris-occlusion controlled genes(NOCGs)was *** was used to evaluate GNAl level in *** analysis was conducted to evaluate the drug sensitivity,immunotherapy response,and functional enrichment of *** was an independent prognostic factor,and patients with low GNAl expression have a poor *** of GNAl was closely associated with clinicopathological characteristics,DNA methylation,and several immune-related *** infiltration analysis indicated that GNAl levels were negatively correlated with immune *** low-expression group showed efficacy with anti-PD-1 *** compounds with significantly different half-maximal inhibitory concentration(IC50)values between the GNAl high and low-expression groups were ***,its expression was associated with several immune cells,immune-related genes,and *** expression of GNAl is closely associated with clinicopathological characteristics,TIME,and the response to therapeutic interventions,highlighting its potential as a prognostic biomarker for glioma.

关键词： Glioma Olfaction GNAl Tumor immune microenvironment Immunotherapy/chemotherapy response

Predicting tremor improvement after MRgFUS thalamotomy in essential tremor from preoperative spontaneous brain activity:A machine learning approach

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Science Bulletin 2024年第19期69卷 3098-3105页

作者： Dong Zhang Yongqin Xiong Haoxuan lu Caohui Duan Jiayu Huang Yan li Xiangbing Bian Dekang Zhang Jiayou Zhou longsheng Pan Xin lou department of Radiology The First Medical CenterChinese PLA General HospitalBeijing 100853China department of neurosurgery The First Medical CenterChinese PLA General HospitalBeijing 100853China

Magnetic resonance-guided focused ultrasound surgery(MRgFUS)thalamotomy is an emerging technique for medication-refractory essential tremor(ET),but with variable *** study used pattern regression analysis to identify brain signatures predictive of tremor ***-four ET patients(mean age=63.06 years,standard deviation(SD)=10.55 years,38 males)underwent unilateral MRg FUS thalamotomy and were scanned for resting-state functional magnetic resonance imaging(rsf MRI).Seventy-four healthy controls(mean age=58.09 years,SD=10.30 years,38 males)were recruited for *** responses at 12 months posttreatment were evaluated by the Clinical Rating Scale for *** fractional amplitude of low-frequency fluctuations(f AlFF)was calculated from rs-f MRI ***-sample t-test was used to generate a disease-specific mask,within which Multivariate Kernel Ridge Regression analyses were *** and actual clinical scores were compared using Pearson's correlation coefficient(r)and normalized mean squared error(***).Permutation test and leave-one-out strategy were applied for results *** identified f AlFF patterns that significantly predicted the hand tremor improvement(r=0.23,P=0.025;***=0.05,P=0.026)and the postural tremor improvement(r=0.28,P=0.025;***=0.06,P=0.023),but not action tremor *** VI of right cerebellum(Cerebelum_6_R),right superior occipital gyrus(Occipital_Sup_R)and lobule X of vermis(Vermis_10)contributed most for hand tremor prediction(normalized weights(NW):2.77%,2.40%,2.34%)while Vermis_10,left supplementary motor area(Supp_Motor_Area_l)and right hippocampus(Hippocampus_R)for postural tremor prediction(NW:2.69%,2.12%,2.05%).The low contributing NW of the individual brain regions suggested that the f AlFF pattern as a whole is an overall predicting *** f AlFF pattern predicts tremor benefits induced by MRg FUS *** *** number:NCT04570046.

关键词： MRgFUS Essential tremor fAlFF Machine learning

Role of JAK-STAT3 signaling pathway during neuronal differentiation of rat bone marrow mesenchymal stem cells

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Neural Regeneration Research 2010年第5期5卷 337-341页

作者： Huaiyong Hao Yongguang Wang Feng Cheng Baosheng Huang Heping Tian Xueliang Dai lixin li department of neurosurgery First Affiliated Hospital of Nanjing Medical University Nanjing 210029 Jiangsu Province China department of Radiology Zaozhuang Shizhong District People's HospitaI Zaozhuang 277100 Shandong Province China department of neurosurgery BenQ Hospital Affiliated to Nanjing Medical University Nanjing 210029 Jiangsu Province China

Recent studies regarding neuronal differentiation of mesenchymal stem cells （MSCs） have primarily focused on induction methods and transplantation in vivo. However, knowledge about the intrinsic regulatory mechanisms underlying neuronal induction of MSCs remains limited and unclear. OBJECTIVE： To elucidate the role of JAK-STAT3 signaling pathway during neuronal differentiation of MSCs using a combination of the JAK-STAT3 signaling inhibitor AG490 and growth factors. DESIGN, TIME AND SETTING： Neural, molecular, biomedical, in vitro experiment was performed at the laboratory of Pharmacology, School of Pharmacy, Nanjing Medical University between March and December 2008 MATERIAlS： An inhibitor of the JAK-STAT3 signaling pathway was purchased from Calbiochem, USA. Antibody kit for total and phosphorylated STAT3 was purchased from Cell Signaling, USA. METHODS： MSCs from passage 3 were assigned to non-induced, growth factor, and AG490 groups. MAIN OUTCOME MEASURE： The number of cells expressing neuron-specific enolase, microtubule-associated protein, and glial fibrillary acidic protein were determined by immunocytochemistry. Total and phosphorylated （Tyr705） expression levels of STAT3 protein were measured by Western blot analysis. RESUlTS： MSCs were transdifferentiated into neuronal- and astrocyte-like phenotypes through the induction of epidermal growth factor, basic fibroblast growth factor, and brain-derived neurotrophic factor. In addition, the JAK-STAT3 signaling pathway was significantly activated during neural differentiation. Expression of phosphorylated （Tyr705） STAT3 was inhibited with AG490 （5 pmol/l） prior to neural induction with epidermal growth factor, basic fibroblast growth factor, and brain-derived neurotrophic factor; proportion of astrocyte-like cells was significantly reduced （P 〈 0.01）, and the proportion of neuronal-like phenotypes was significantly increased （P〈 0.01）. CONClUSION： JAK-STAT3 signaling pathway was shown to regulate neuronal inductio

关键词： JAK-STAT3 signaling pathway, mesenchymal stem cells AG490, neuronal induction neurons astrocytes stem cells neural regeneration

Neuroprotection by cattle encephalon glycoside and ignotin beyond the time window of thrombolysis in ischemic stroke

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Neural Regeneration Research 2021年第2期16卷 312-318页

作者： Jun Zhong Rong-Wei li Ju Wang Ying Wang Hong-Fei Ge Ji-Shu Xian Hua Feng liang Tan department of neurosurgery Southwest HospitalThe Third Military Medical University(Army Medical University)ChongqingChina department of neurosurgery Hanzhong Central HospitalHanzhongShaanxi ProvinceChina department of Oncology Hanzhong Central HospitalHanzhongShaanxi ProvinceChina State Key laboratory of Power Transmission Equipment and System Security and New Technology School of Electrical EngineeringChongqing UniversityChongqingChina

Cattle encephalon glycoside and ignotin(CEGI)injection is known as a multi-target neuroprotective drug that contains numerous liposoluble molecules,such as polypeptides,monosialotetrahexosyl ganglioside(GM-1),free amino acids,hypoxanthine and *** has been approved by the Chinese State Food and Drug Administration and widely used in the treatments of various diseases,such as stroke and Alzheimer's ***,the neuroprotective effects of CEGI beyond the time window of thrombolysis(within 4.5 hours)on acute ischemic stroke remain *** study constructed a rat middle cerebral artery occlusion model by suture-occluded method to simulate ischemic *** first daily dose was intraperitoneally injected at 8 hours post-surgery and the CEGI treatments continued for 14 *** of the modified five-point Bederson scale,beam balance test and rotameric test showed the neurological function of ischemic stroke rats treated with 4 m l/kg/d CEGI improved significantly,but the mortality within 14 days did not change *** MRI and 2,3,5-triphenyltetrazolium chloride staining confirmed that the infarct size in the 4 m l/kg/d CEGI-treated rats was significantly reduced compared with ischemic insult *** results of transmission electron microscopy and double immunofluorescence staining showed that the hippocampal neuronal necrosis in the ischemic penumbra decreased whereas the immunopositivity of new neuronal-specific protein doublecortin and the percentage of Ki67/doublecortin positive cells increased in CEGI-treated rats compared with untreated *** results suggest that CEGI has an effective neuroprotective effect on ischemic stroke when administered after the time window of *** study was approved by the Animal Ethics Committee of The Third Military Medical University,China.

关键词： apoptosis brain cattle encephalon glycoside and ignotin central nervous system neurological function plasticity rat regeneration stroke

Increased leakage of brain antigens after traumatic brain injury and effect of immune tolerance induced by cells on traumatic brain injury

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Chinese Medical Journal 2012年第9期125卷 1618-1626页

作者： YAN Hua ZHANG Hong-wei WU Qiao-li ZHANG Guo-bin lIU Kui ZHI Da-shi HU Zhen-bo ZENG Xian-wei department of neurosurgery Tianjin Huanhu Hospital Tianjin 300070 China department of neurosurgery Second Hospital of Tianjin Medical University Tianjin 300070 China department of-neurosurgery Tianjin l eople＇s Hospital Tianjin 300070 China department of Stem Cell Research and Transplantation Center Affiliated Hospital of Weifang Medical College Weifang Shandong 261053 China department of neurosurgery Affiliated Hospital of Weifang Medical College Weifang Shandong 261053 China

Background Although traumatic brain injury can lead to opening the blood-brain barrier and leaking of blood substances （including water） into brain tissue, few studies of brain antigens leaking into the blood and the pathways have been reported. Brain antigens result in damage to brain tissues by stimulating the immune system to produce anti-brain antibodies, but no treatment has been reported to reduce the production of anti-brain antibodies and protect the brain tissue. The aim of the study is to confirm the relationship between immune injury and arachnoid granulations following traumatic brain injury, and provide some new methods to inhibit the immune injury.Methods In part one, methylene blue was injected into the rabbits’ cisterna magna after traumatic brain injury, and concentrations of methylene blue and tumor necrosis factor （TNF）-α in blood were detected to determine the permeability of arachnoid granulations. In part two, umbilical cord mesenchymal stem cells and immature dendritic cells were injected into veins, and concentrations of interleukin 1 （Il-1）, Il-10, interferon （IFN）-γ, transforming growth factor （TGF）-β, anti-brain antibodies （ABAb）, and Il-12 were measured by ElISA on days 1, 3, 7, 14 and 21 after injury, and the numbers of leukocytes in the blood were counted. Twenty-one days after injury, expression of glutamate in brain tissue was determined by immunohistochemical staining, and neuronal degeneration was detected by H＆E staining. Results In part one, blood concentrations of methylene blue and TNF-α in the traumatic brain injury group were higher than in the control group （P 〈0.05）. Concentrations of methylene blue and TNF-α in the trauma cerebrospinal fluid （CSF） injected group were higher than in the control cerebrospinal fluid injected group （P 〈0.05）. In part two, concentrations of Il-1, IFN-γ, ABAb, Il-12, expression of glutamate （Glu）, neuronal degeneration and number of peripheral blood leukocytes were lower in the group with

关键词： traumatic brain injury stem cell antigen dendritic cell immune tolerance

Inhibitory effect of cyclosporin A on the immunological rejection of rats with cerebral hemorrhage following transplantation of nerve growth factors transfected glial cells

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Neural Regeneration Research 2006年第3期1卷 204-208页

作者： Rufei Dai Chao Yan lei Wang Jun Cai Xiaoming li Ning liu Fengyi Zhu department of neurosurgery Second Affiliated Hospital of Xuzhou Medical College Xuzhou 221006 Jiangsu Province China department of neurosurgery First Affiliated Hospital of Nanjing Medical University Nanjing 210029 Jiangsu Province China

BACKGROUND： At present, it has been confirmed that immunological rejection exists in the cell transplantation in brain tissue, the effects of immunosuppressant on the immunological rejection and the survival of grafts in brain cell transplantation are worthy being investigated further. OBJECTIVE： To observe the immunological rejection after transgeneic cell transplantation in treating cerebra hemorrhage in rats, and investigate the interventional effect of cyclosprin. DESIGN ： A randomized controlled study SETTINGS： Second Affiliated Hospital of Xuzhou Medical College; First Affiliated Hospital of Nanjing Medica University. MATERIAlS： Thirty-five healthy clean-degree SD rats of 6-8 weeks old were used, weighing 200-250 g, either male or female; The FACSort flow cytometer （American BD Company） and NYD-1000 image analytical system were used, The rat-anti-rat CD4 monoclonal antibody, rat-anti-rat CD8 monoclonal antibody, and rat-anti-rat MHC Ⅱ antigen monoclonal antibody were purchased from Santa Cruz Company; SP and DAB kits were purchased from Beijing Zhongshan Bio-engineering Company. XSP-8C2 light microscope was the product of Shanghai Zousun Optical Instrument, Co.,ltd, and KYKY-3800B electron microscope was the product of China KYKY Technology Development Co.,ltd. METHODS ： The experiments were carried out in the animal experimental center of Nanjing Medical University from April to July in 2003. ① Model establishment： The rats were anesthetized, and then the coordinates of left internal capsule were identified, and the needle was withdrawn after 120 μl blood was injected into the internal capsule. Adenoviruses were taken as the carriers, after the astrocytes were successfully transfected by nerve growth factor（NGF） gene, 0.2 ml cell suspension was injected into the sites of cerebral hemorrhage. Thirty successfully established rat models were randomly divided into cyclosporin A group （n=18） and control group, the rats were treated with intraperitoneal injection o

关键词： Inhibitory effect of cyclosporin A on the immunological rejection of rats with cerebral hemorrhage following transplantation of MHC

IN SITU PCR AND IMMUNOHISTOCHEMICAl STUDIES ON p16 GENE IN PITUITARY ADENOMAS

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Chinese Journal of Cancer Research 2000年第1期12卷 10-15页

作者：易静陈玉英熊文浩李骁雄沈建康 department of Biophysics and Cell Biology Shanghai Second Medical University Shanghai China department of neurosurgery Ren Ji Hospital Shanghai Second Medical University Shanghai China department of neurosurgery Rui Jin Hospita Shanghai Second Medical University Shanghai China

Objective: To examine the occurrence of p16 gene deletion and to analyze p16 expression on paraffin-embedded human pituitary adenoma specimens. Efforts were made to optimize the technical conditions forin situ PCR. Methods:In situ PCR techniques and inimuno-histochemistry were used. Results: Immunohistochemically, p16-positive tumor cells were observed in all cases with various proportions. The majority of the stromal cells and part of tumor cells was devoid of p16 immunostaining, but signal ofin situ PCR for p16 gene, exon 2, was displayed in these cells. Conclusion: The results implied that p16 gene might not be deleted in these pituitary adenomas. It also indicated thatin situ PCR, both direct and indirect methods, proved feasible and informative to the aim of DNA detection. It is critical to overcome non-specific amplification in directin situ PCR by means of higher annealing temperature, fewer cycle, lower magnesium concentration and stringent washing. A target DNA-deleted sample as the negative control is extremely necessary. For the indirect method, the way to improve the sensitivity is to loosen the conditions for amplification and washing, so that more amplification products are subject to hybridization, and signal detection is facilitated.

关键词： In situ PCR Immunohistochemistry p16 gene Pituitary adenoma

Changes and significance of serum ubiquitin carboxyl-terminal hydrolase l1 and glial fibrillary acidic protein in patients with glioma

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World Journal of Clinical Cases 2023年第14期11卷 3158-3166页

作者： Qing-Hua Zhu Jing-Kun Wu Gao-lei Hou department of neurosurgery Affiliated Hospital of Hebei Engineering UniversityHandan 056002Hebei ProvinceChina

BACKGROUND Brain gliomas are malignant tumors with high postoperative recurrence *** prediction of prognosis using specific indicators is of great *** To assess changes in ubiquitin carboxy-terminal hydrolase l1(UCH-l1)and glial fibrillary acidic protein(GFAP)levels in patients with glioma pre-and *** Between June 2018 and June 2021,91 patients with gliomas who underwent surgery at our hospital were enrolled in the glioma *** healthy volunteers were included in the control *** UCH-l1 and GFAP levels were measured in peripheral blood collected from patients with glioma before and 3 d after ***-l1 and GFAP levels in patients with glioma with different clinicopathological characteristics were compared before and after *** patients were followed-up until February *** glioma recurrence was recorded to determine the serum UCH-l1 and GFAP levels,which could assist in predicting postoperative glioma *** UCH-l1 and GFAP levels in patients with glioma decreased significantly 3 d after surgery compared to those before therapy(Pl1 and GFAP levels in the glioma group were significantly higher than those in the control group before and after surgery(Plly significant differences in preoperative serum UCH-l1 and GFAP levels among patients with glioma according to sex,age,pathological type,tumor location,or number of lesions(P>0.05).Serum UCH-l1 and GFAP levels were significantly lower in the patients with WHO grade I-II tumors than in those with gradeⅢ-IV tumors(Pl1 and GFAP levels were lower in the patients with tumor diameter≤5 cm than in those with diameter>5 cm,in which the differences were statistically significant(Plioma recurred in 22 *** preoperative and 3-d postoperative serum UCH-l1 and GFAP levels were significantly higher in the recurrence group than these in the non-recurrence group(P<

关键词： Glioma Ubiquitin carboxy-terminal hydrolase l1 Glial fibrillary acidic protein Surgery Prognosis Clinical significance

Abnormal expressions of proliferating cell nuclear antigen and P27 protein in brain glioma

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Neural Regeneration Research 2007年第10期2卷 591-594页

作者： Yong feng Hu Wei Shi Chong xiao liu Jian jun Sun Rui zhi Wang Zhen yu Guo department of neurosurgery Mianxian Country HospitalMianxian724200Shanxi ProvinceChina department of neurosurgery the Second Affiliated Hospital of Medical CollegeXi＇an Jiaotong UniversityXi＇an 710004Shanxi Provincechina

Both proliferating cell nuclear antigen and P27 protein are important factors to regulate cell cycle. While, the combination of them can provide exactly objective markers to evaluate prognosis of patients with brain glioma needs to be further studied based on pathological level. OBJECTIVE： To observe the expressions of proliferating cell nuclear antigen and P27 protein in both injured and normal brain glioma tissues and analyze the effect of them on onset and development of brain glioma. DESIGN： Case contrast observation. SETTING： department of neurosurgery, the Second Affiliated Hospital of Xi＇an Jiaotong University. PARTICIPANTS： A total of 63 patients with brain glioma were selected from department of neurosurgery, the Second Affiliated Hospital of Xi＇an Jiaotong University from July 1996 to June 2000. There were 38 males and 25 females and their ages ranged from 23 to 71 years. Based on pathological classification and grading standards of brain glioma, patients were divided into grade I - II （n=30） and grade III- IV （n = 33）. All cases received one operation but no radiotherapy and chemiotherapy before operation. Sample tissues were collected from tumor parenchyma. Non-neoplastic brain tissues were collected from another 12 non-tumor subjects who received craniocerebral trauma infra-decompression and regarded as the control group. There were l0 males and 2 females and their ages ranged from 16 to 54 years. The experiment had got confirmed consent from local ethic committee and the collection was provided confirmed consent from patients and their relatives. All samples were restained with HE staining so as to diagnose as the brain glioma. While, all patients with brain glioma received radiotherapy after operation and their survival periods were followed up. METHODS： Primary lesion wax of brain glioma was cut into serial sections and stained with S-P immunohistochemical staining. Brown substance which was observed in tumor nucleus was regarded as the positive expr

关键词： brain glioma proliferating cell nuclear antigen P27 protein pathological grade prognosis