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Objective To detect the changes of cellular immune level in patients with different grades of glioma in perioperative period, and to investigate its relationship with the postoperative intracranial infection. Methods A total of 53 patients with glioma newly diagnosed by pathology who underwent the surgical treatment in the First Hospital of Shanxi Medical University from September 2017 to September 2018 were collected. According to the World Health Organization (WHO) classification criteria, the patients were divided into the low-grade group (grade Ⅰ-Ⅱ, 21 cases) and the high-grade group (grade Ⅲ-Ⅳ, 32 cases). The peripheral blood at the time of 1 day before the operation, 1 day and 7 days after the operation was drawn to detect the T lymphocyte subsets, and then the differences of cell immunity indexes from different grade gliomas were analyzed. The relationship between immune level and postoperative intracranial infection was analyzed. SPSS 22.0 statistical software was used to analyze the data. Results The levels of CD3+, CD4+, CD8+, CD4+CD25+Foxp3+and CD4+/CD8+in the high-grade group at the time of 1 day before the operation were (54.09±4.25)％, (31.93±3.08)％, (34.23±2.48)％, (9.66±1.47)％, 0.93±0.06, respectively; the levels at the time of 1 day after the operation were (48.84±3.69)％, (27.49±2.41)％, (34.99±2.96)％, (11.09±1.70)％, 0.84± 0.05, respectively; the levels at the time of 7 days after the operation were (59.45 ±3.47)％, (33.59 ±2.66)％, (31.99±1.97)％, (7.45±1.48)％, 1.05±0.07, respectively. The levels of CD3+, CD4+, CD8+, CD4+CD25+Foxp3+and CD4+/CD8+in the low-grade group at the time of 1 day before the operation were (62.37±6.57)％, (34.88± 4.43)％, (30.16 ±3.75)％, (6.30 ±1.29)％, 1.16 ±0.11, respectively; the levels at the time of 1 day after the operation were (55.44 ±7.25)％, (29.05 ±4.04)％, (31.66 ±3.13)％, (7.95 ±1.67)％, 0.92 ±0.11, respectively; the levels at the time of 7 days after the operation were (67.73 ±7.18)％, (35.55 ±4.95)％, (28.10 ±3.12)％, (5.50 ± 1.25)％, 1.27±0.12, respectively. The levels of CD3+, CD4+, CD4+/CD8+before and after the operation in the high-grade group were lower than those in the low-grade group (all P< 0.05), while the levels of CD8+and CD4+CD25+Foxp3+were higher than those in the low-grade group (all P<0.05). Compared with the levels at the time of 1 day before the operation, the levels of CD3+, CD4+, CD4+/CD8+at the time of 1 day after the operation of both groups were decreased, while the levels of CD8+and CD4+CD25+Foxp3+were increased (all P< 0.05). The levels of CD3+, CD4+and CD4+/CD8+ at the time of 7 days after the operation in the both groups were increased, while the levels of CD8+ and CD4+ CD25+ Foxp3+ were decreased (all P< 0.05). Among 53 patients, 8 cases had postoperative intracranial infection, and the infection rate was 15.09％. Age, duration of surgery, pathological stage, and intraoperative blood transfusion were the independent affecting factors of postoperative intracranial infection of cerebral glioma (OR= 1.513, P= 0.024; OR= 1.722, P<0.01; OR= 1.365, P= 0.001; OR= 1.262, P< 0.01). Conclusions The peripheral blood cellular immune level of glioma patients is related with the malignancy of glioma. The inhibition degree of the cellular immunity could be relieved after the resection of glioma. The detection of T lymphocyte subsets could be considered as an evaluating index for the malignancy and prognosis in patients with glioma. The clinical detection of cellular immune can play a positive role in predicting and preventing the postoperative intracranial infection in patients with glioma.
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Spinal cord injury (SCI) is a central nervous system(CNS)-related disorder. There is yet no successful treatment for this issue at present. Cell-based therapies have been explored for SCI restoration, including the use of pluripotent human stem cells, and a number of adult-derived stem and mature cells such as mesenchymal stem cells, olfactory ensheathing cells. However, cell transplantation is often hampered by the poor cell survival in the treatment of spinal cord injuries. Alternatively, the therapeutic role of different cells has been used in tissue engineering approaches by engrafting cells with biomaterials. The latter have the advantages of physically mimicking the CNS tissue, while promoting a more permissive environment for cell survival, growth, and differentiation. The roles of both cell transplantation and biomaterial-based therapies as single therapeutic approaches for SCI repair will be discussed in this review.
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Objective To investigate the correlation between Dishevelled protein expression and the proliferation and invasion of glioma cells.Methods 67 cases of brain glioma specimens were collected.The expression of Dishevelled protein was detected with immunohistochemical method.The immunoreactivity score (IRS) of Dishevelled protein,and proliferation index (PⅠ) and invasion index (Ⅱ) were measured and their correlations were analyzed.Results The positive rate of Dishevelled protein in glioma was 65.7 ％ (44/67).IRS,PⅠ and Ⅱ were 4.15±3.13,(30.93±17.92) ％,(20.38±13.36) ％,respectively.Both PⅠ and Ⅱ significantly increased with an increase in the pathological grade of brain glioma (P ＜ 0.001).Furthermore,PⅠ and Ⅱ were significantly higher in the Dishevelled protein-positive group than those in the Dishevelled protein-negative group [(38.27±17.60) ％ vs (16.02±8.92) ％ of PⅠ and (30.03±13.81) ％ vs (10.63±4.41) ％ of Ⅱ,respectively,P ＜ 0.001].PⅠ and Ⅱ of glioma cells were positively correlated with IRS of Dishevelled protein (r =0.940 between PⅠ and IRS,and r =0.953 between Ⅱ and IRS,respectively).Conclusion Dishevelled protein plays an important role in the proliferation and invasion of brain malignant glioma.
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Objective To observe the influence of p53-upregulated modulator of apoptosis (PUMA) on the growth of human brain glioma cell lines U251 (p53 mutant) and SHG-44 (p53 wild type),and to explore its possible mechanism.Methods Construct the adenovirus PUMA (Ad-PUMA) and vector of adenovirus (AdDsRed) which were respectively transfected into glioma cell lines U251 and SHG-44.Cells proliferation rates were measured with cell counting kit-8 (CCK-8).The apoptotic ratios were detected by flow cytometry.The expression of PUMA and apoptosis associated proteins (bcl-2,Bax) were determined with Western blot analysis.Caspase-3,Caspase-8,Caspase-9 activity were measured by Caspase activity assay kit.Results Compared with vector group and blank control group,Ad-PUMA transfected group showed strong cell proliferating inhibition effects [the inhibition rates were (50.89±4.73) ％ and (44.45±5.33) ％ respectively,P ＜0.05] and pro-apoptotic effects [apoptotic rates were (44.89±5.08) ％ and (31.67±7.32) ％,P ＜ 0.05] in different p53 glioma cell lines U251 and SHG-44.Western blot analysis showed that PUMA protein expression increased after Ad-PUMA transfection,accompanied by the reduced expression of the anti-apoptotic protein bcl-2 and the increased expression of pro-apoptotic protein Bax.The activity of Caspase testing results showed that the Caspase-3,Caspase-9 activity increased significantly,while the Caspase-8 activity changed little.Conclusion No matter how p53 phenotype,PUMA can inhibit glioma proliferation,promote apoptosis,and its mechanism may be through the mitochondrial apoptotic pathways,upregulation of Bax and inhibition of bcl-2 expression,which activated Caspase-9.Ad-PUMA is expected to become a new target for gene therapy of gliomas.
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Objective To explore differences of drug resistance of temozolomide(TMZ) on different CD133 immune prototype of glioma cells and study on the changes of their sensitivity to TMZ through increased PUMA. Methods CD133+-U87MG cells sorted by CD133 magnetic beads were cultured in serum-free stem cell medium respectively. The cells were infected with recombinant adenovirus, Ad-PUMA, diluted in cell culture medium with or without TMZ intervention.The inhibitory rate of cell proliferation was detected by MTT assay and 50 ％ inhibition concentration of TMZ was calculated. Apoptosis rates of CD133+-U87MG cells were assessed by flow cytometry (FCM) before and after intervention of exogenous PUMA and TMZ.Results The TMZ IC50 values of CD133+glioma cells were higher than that of CD133- glioma cells. There were significant differences in apoptosis rate between CD133+ glioma cell and CD133- glioma cell (all P＜0.05).Conclusion AdPUMA joint TMZ can promote glioma stem cells apoptosis, thus improve the sensitivity to chemotherapy of glioma.
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ObjectiveTo explore the function of intraoperative monitoring by brainstem auditory evoked potential and free electromyography during the operation of large acoustic neuroma for improving the operation more accurately and safely. MethodsThe intraoperative monitoring of affected cranial nerve and brainstem function respectively by brainstem auditory evoked potential and free electromyography was performed in 26 patients with large acoustic neuroma. According to the monitoring result the strategy and method of surgery was adjusted. Facial nerve function was assessed using the House-Brackmann facial nerve grading system immediately after two weeks of surgery.Results23 cases (88 ％) achieved total resection,3 cases(12 ％)achieved subtotal resection. The facial nerve was preserved anatomically in 25 patients.According to the House-Brackmann facial nerve grading system,21 cases (80 ％) got preserve of facial nerve function in grade Ⅰ - Ⅱ, 3 cases(12 ％)got preserve of facial nerve function in grade ]Ⅲ-Ⅳ and 1 cases (4 ％) got preserve of facial nerve function in grade Ⅴ after two weeks of surgery.ConclusionIntraoperative physiological monitoring may increase the anatomical and functional preservation rate of affected cranial nerve and also may improve the operation more accurately and safely.
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Objective To investigate the inhibitive effects of Ad-PUMA combined with temozolomide on human glioblastoma cells growth in vivo experiments. Methods The nude mouse model with human glioblastoma cells subcutaneous transplantation was established. The mice were randomly divided into 4 groups to receive subcutaneous injection at the 14th day separately with: Normal saline 100 μl (control, n=8), Ad-PUMA 2×108 pfu/100 μl (PUMA group, n=8), 10 mg/kg TMZ (TMZ group, n=8) and 2×108 pfu/100 μl Ad-PUMA + 10 mg/kg TMZ (combined group, n=8). Mice were killed after 20 days treatment.Tumor volume, inhibition rates and apoptotic index (AI) were measured, meanwhile, apoptotic tumor cells were detected by TUNEL technology respectively. The expression of MGMT mRNA and MGMT protein were revealed by the methods of RT-PCR and Western blot. Results According to the order: control group, AdPUMA group, TMZ group, combined group, tumor volumes were (3.68±0.09), (2.63±0.13), (2.13±0.07),(0.97±0.02) cm3 respectively (P＜0.05); the inhibitive rates were 0, 28.5 %, 42.1%, 73.6 % respectively and AI were (2.0±1.2) %, (11.4±2.6) %, (7.6±3.2) %, (20.6±8.6) % (P＜0.05). The results of Western blot and RT-PCR showed that MGMT mRNA and MGMT protein levels in TMZ group were higher than other groups (all P＜0.01). Conclusion Ad-PUMA combined with TMZ greatly enhances the sensitivity of human glioblastoma cells to TMZ and could effectively inhibit the proliferation and promote the apeptosis of glioblastoma cells, its mechanism was probably related Ad-PUMA promote apoptosis and inhibit MGMT expression.
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ObjectiveTo study the methods of how to protect facial nerve function following complete resection of acoustic neurinomas and the value of the techniques of F wave assisted electrophysiological monitoring intraoperatively.Methods Retrospectivelysummarizing theresultsof combining three electrophysiological monitoring techniques such as nasal muscle F wave recording,online EMG and triggered EMG to monitor 46 cases of microoperations for acoustic neurinomas intraoperatively during the period of Feb.2004 to Dec. 2008. Correlating every intraoperative monitoring index with their follow-up results of facial nerve function 1 day and 6 months after their operations.The tendency of the two continuous monitoring techniques between nasal F wave recording and online EMG of facial muscles has also been studied in this paper. Results Among 46 cases of acoustic neurinomas, 45(97.83 %) tumors have been totally resected, and 1 (2.17 %) tumor subtotally resected,lcase (2.17 %)died after operation,and 2ases occurred the leakage of cerebrospinal fluid(CSF) which have been cured through conservative treatment. The whole anatomic protection rate of facial nerve is 97.83 %,and their functional protection rates 6 months after operation are:HB Ⅰ - Ⅱ,75.56 %;Ⅲ-Ⅳ,22.22 % and Ⅴ-Ⅵ,2.22 %.The completely accordant rate between the intraoperative findings of nasal F wave recording and online EMG is 52.17 %, partially accordant rate is 45.65 %, and totally opposite rate is 2.17 % (x2 趋势= 6.113, P ＜0.05). The intraoperative monitoring indexes in nasal muscle F wave recording are correlated well with the facial nerve function in the 6th month' s follow-up (κ=0.429, P ＜0.001).In triggered EMG monitoring after tumors being resected,the stimulus threshold ratio and maximum amplitude ratio of facial nerve between leaving brain stem part and inner acoustic porus part are also correlated well with the facial nerve function 6 months after operation(κ=0.576, P ＜0.001; κ=0.595, P ＜0.001). ConclusionNasal muscle F wa recording cooperated well with online EMG and triggered EMG intraoperatively and correlates well with the postoperative facial nerve function, so they should be routinely applied together intraoperatively.
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With the advent of the cancer stem cell hypothesis,the field of cancer research has experienced a revolution in how we think of and approach cancer. The discovery of "tumor-initiating cell" has offered an explanation for several long-standing conundrums on why tumors behave the way they do to treatment. Despite the great amount of research that has been done in order to understand the molecular aspects of tumors,the prognosis of tumors remains dismal. The slow progress in extending the survival of patients with malignant tumors is very likely due to poor understanding of the cell of origin in these tumors.This review article discusses the progress in our understanding of tumor-initiating cell as the cell of origin in cancers. We review the different proposed mechanisms of how tumor-initiating cell may originate,the molecular mechanisms of cancer initiation and progression, and finally the clinical implications of this research.
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Objective To investigate the role of endoplasmic reticulum stress ( ERS) in human brain gliomas cell(SHG-44) apoptosis induced by proteasome inhibitor MG-132. Methods Human glioma cells were passage cultured. Glioma cells were treated by MG-132 with varying concentration(5, 10, 15 and 50 μmol/L) for 24 h. Compared with cells prior to the treatment (control group), cell viability was detected by MTT assay and the expression of ERS associated proteins GRP78 and apoptosis associated proteins Caspsse-12 was examined by PCR and Western-blotting. Results After MG-132 treatment for 24 h, SHG-44 cell viability was decreased significantly (39 %) (P <0.05), and continued to show a significant decline with the increasing concentration of MG-132 (P <0.05). RT-PCR results showed that the expression of ERS associated proteins GRP78 in SHG-44 cells were significantly increased after 5, 10, 15 and 50 μmol/L MG-132 treatment, and the expression of Caspase-12 was significantly increased after 5 μmol/L MG-132 treatment, slightly increased after 10 and 15 μmol/L treatment compared with that after 5 μmol/L treatment and reached the peak after 50 μmol/L treatment. Western-blotting results of GRP78 in SHG-44 cells were same as results of RT-PCR. Conclusion ERS may be involved in the apoptosis of gliomas cells induced by proteasome inhibitor MG-132.
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Objective To explore the value of F wave recording in evaluating facial nerve function and its pathological changes in the pressure-induced rat models of acoustic neurinoma. Methods 58 rats in different groups were conducted F wave recording and biotinylated dextran amine(BDA) retrograde tracing for their right facial nerve one week after establishing models. Their latencies, amplitudes and F/M rates were analyzed first. 72 hours after BDA was injected into right whisker muscle, the rats were infused with 4% polyoxymethylene, then pontines and facial nerves in the CPA cistern were obtained. Pontiues were cut into frozen sections for histochemical staining with avidin-horseradish peroxidase (HRP)-DAB and Nissl 's counterstaining, calculating the positive BDA neurons ratio(BDA+-N%)in facial nuclear. Facial nerves were cut and stained with toluidine blue for light-micrescope inspection, and/or stained for transmission electron microscope observation. Correlating F/M with BDA+-N% and the facial nerve pathological findings. Results F/M are 97.66 % and 97.48 % in normal and pseudo-operation group, respectively, when stimulus are 1.4 mA; while 77.13 %, 48.91% and 11.54 % in from small to large tumor model groups because F waves were delayed in latencies or increasinglylost (P <0.001). Similarly, BDA+-N% are 98.37 % and 97.96 % in the above two control groups, while 77.28 %, 48.28 % and 11.55 % in from small to large tumor model groups (P < 0.001). Thus F/M are positively correlated with their BDA+-N% in all groups (r =0.996,P <0.001). Facial nerve examinations under light and electron microscope show increasing pathological changes along with increasing "tumor" size. Conclusion The findings of F wave recording in facial nerve may reflect its functional status and pathological changes. Therefore, F wave detection may help electrophysiological monitoring during acoustic neurinoma resection and facial nerve function evaluation after surgery.
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Objective To explore the expression of CD133 and nestin in human glioma cell of patients with neuroglioeytoma and to see whether CD133 and nestin expression associate with the differentiation and pathologic grading.Methods The expression of CD133 and nesfin was detected by immunohistochemistry staining in 65 cases of human glioma and 19 specimens of normal brain tissues.Results The rate of the CD133 positive ceUs was 18.46%in human glioma and 0 in the control group(P＜0.01),and that of nesfin was 23.79%and 5.16%respectively.The positive cell rates of CD133 or nestin varied accordingly to different pathological grades.There were significant difference between grade Ⅰ and grade Ⅲ or grade Ⅳ (P＜0.01).There were difference between grade Ⅱ and grade Ⅲor grade Ⅳ (P＜0.01).The same significance were also found between grade Ⅲ and grade Ⅳ(P＜0.01).The higher pathological grades had higher positive cell rates.There was a significant corl~lation between the rate of CD133 positive cells and that of nestin in experimental group (r=0.408,P＜0.01).Conclusion Detecting CD133 and nestin in the human glioma can be used in diagnosing,judging the malignancy degree and the prognosis.
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Objective To investigate the effect of berberine on growth and apoptosis of human cervical cancer cell line HeLa and its possible mechanism.Methods The effect of berberine on growth of HeLa cells was studied by MTT assay.Apoptosis of HeLa cells exposed to berberine was observed by flow cytometry and DNA gel electrophoresis.The expression of Bax and Bcl-2 was studied by Western blotting analysis.Results Berberine markedly inhibited the proliferation of HeLa cells in a time-and dose-dependent manner.After incubation of HeLa cells with 20 and 40 mg/L berberine for 48 h,DNA Ladder can be observed.A typical "sub-G1 peak" was checked by flow cytometry.There was a very low rate of natural apoptosis(1.9?0.6)%,while in 5 mg/L berberine group,the apoptosis rate was(2.3?0.8)%.After exposing HeLa cells for 48 h to 20 and 40 mg/L berberine,the apoptosis rate reached(16.7?2.8)%(P