1.The Changes of Endothelial-dependent Vasodilatation and Cyclophilin A Expression at Different Phases of Atherosclerosis in Experimental Rats
Chongxiao SHENG ; Honghua LI ; Kang LIU ; Haisong FENG
Chinese Circulation Journal 2015;(6):576-579
Objective: To observe the changes of endothelial-dependent vasodilatation and cyclophilin A (CyPA) expression at different phases of atherosclerosis in experimental rats. Methods: A total of 30 male Wistar rats were divided into 4 groups: Control group, the rats received normal diet, and 3 atherosclerosis groups, the rats received high cholesterol diet for different period of time and a single dose intraperitoneal injection of Vitamin D3 at 600,000 IU/kg, as Atherosclerosis at 8 weeks (AS 8W) group, AS 12W group and AS 15W group, n=8 in each AS group. The rats were sacriifced at the same time to isolate aorta abdominalis. The expression of CyPA at the wall of aorta abdominalis was detected by HE staining and immunohistochemistry. In addition, the aorta abdominalises was cut into 5 mm rings to observe its response to acethylcholine in exvivo organ bath. Results: With prolonged modeling time, the rats at different groups presented normal vessel structure, endothelial cell damage, vessel smooth muscle cell proliferation, atherosclerosis plaque formation and calciifed plaque formation for differentpathological characteristics. The endothelial-dependent vasodilatation was decreased and the maximum vasodilatation percentage in Control group, AS 8W group, AS 12W group and AS 15W group were at (93.46 ± 2.80) %, (82.58 ± 3.25) %, (61.19 ± 3.72)% and (41.28 ± 2.68)% respectively,P<0.05 between each group. The CyPA expression in endothelial cell and vessel smooth muscle cell were increased accordingly in 4 groups by OD value as (0.25 ± 0.06), (0.34 ± 0.09), (0.53 ± 0.09) and (0.68 ± 0.13) respectively,P<0.05 between each group. Conclusion: The CyPA expression increased and the endothelial-dependent vasodilatation decreased with the progress of atherosclerosis accordingly in experimental rats. The expression level of CyPA is related to atherosclerosis degree and it is one of the initial factors for atherosclerosis in rats.
2.Expression of CyclinD1 protein in cerebral glioma in the evaluation of prognosis
Wei SHI ; Bin BAI ; Fangru WANG ; Chongxiao LIU ; Ying SONG
Chinese Journal of Tissue Engineering Research 2005;9(14):218-219
BACKGROUND: Research has showed that the abnormal expression of some proteins closely relates to the occurrence and development of cerebral glioma. However, the relationship between the abnormal expression of CyelinD1protein and the occurrence, development and prognosis of glioma is still uncertain which needs further study.OBJECTIVE: To study the expression of CyclinD1 protein in cerebral glioma and relationship between it and the impact of tumor DESIGN: Control study based on pathological specimens.SETTING: Neurosurgery department of a university hospital.PARTICIPANTS: Totally 48 glioma specimens of different malignaut degree were collected from the patients who accepted surgery treatment in Neurosurgery Department of Second Hospital of Xi' an Jiaotong University during January 1990 and December 1995. Twelve normal cerebral specimens were from the non-tumor patients who were conducted intracranial pressure reducing in Neurosurgery Department of Second Hospital of Xi' an Jiaotong University during January 1990 and December 1995.METHODS: S-P immunohistochemical technique was used to detect the abnormal expression of Cyclin D1 protein. Simultaneously, the dyeing results and clinical characters of patients were associated in order to conduct comparison.RESULTS: The positive expression rate of CyclinD1 protein in human cerebral glioma was 54. 12% while in normal cerebral tissue it was about 8.33%. There was significant difference between them(x2 =8. 148 1,P = 0. 004 3 ) . And the positive expression rate in cerebral glioma of low malignancy was 37.04% while in specimens of high malignancy it was 76.19%, there was significant difference (x2 = 7. 294 0, P = 0. 006 9). The positive expression rate of CyclinD1 protein in specimens of patients with long survival period and short survival period after surgery was 70. 37% and 33.33% respectively with significant difference between them (x2 = 6. 5268,P =0.010 6).CONCLUSION: CyclinD1 is closely related to the occurrence and development of human cerebral glioma. It has provided experimental evidence for the prevention to the occurrence of glioma and the estimation of its prognosis by studying the abnormal proliferation of glioma cells targeted on CyclinD1.
3.Glutamate enhances the expression of vascular endothelial growth factor in cultured SD rat astrocytes
Chongxiao LIU ; Yong LIU ; Wei SHI ; Xinlin CHEN ; Xinli XIAO ; Lingyu ZHAO ; Yumei TIAN ; Junfeng ZHANG
Journal of Pharmaceutical Analysis 2009;21(3):198-201
Objective To study the effect of glutamate on the expression of vascular endothelial growth factor (VEGF) mRNA and protein in cultured rat astrocytes. Methods Cultured rat astrocytes were randomly divided into 6 groups: control group (C), glutamate group (G), QA group (Q), DCG-IV group (D), L-AP4 group (L) and glutanmte-FMCPG gronp (G+M). Cells were cultured under nomoxic condition (95% air, 5% CO2). RT-PCR and ELISA methods were used to detect the expression of VEGF mRNA and protein in cultured astrocytes, respectively. G+ M group was preincubated with lmM MCPG for 30 min prior to the stimulation with glutamate. There were 7 time points at 0,4,8,12,16,24 and 48 h in each group except G+M group. Results The expression of VEGF mRNA and protein did not differ significantly among D group, L group and C group. Different from that in C group, the expression of VEGF mRNA and protein could be enhanced both in a dose-dependent and time-dependent manner in G group and Q group. Meanwhile, the enhanced expression of VEGF mRNA and protein in G group was completely suppressed by MCPG after 24 h. Conclusion Glutamate can increase the expression of VEGF mRNA and protein in cultured astrocytes, which may be due to the activation of group I metabotropic glutamate receptors in astrocytes.
4.Application of navigation assisted neurosurgery operation system in clinical practice teaching of clinical medicine specialty
Zhenyu GUO ; Chongxiao LIU ; Ren ZHOU ; Gang WANG ; Wei SHI ; Yahong ZHANG
Chinese Journal of Medical Education Research 2016;15(11):1175-1179
Objective To explore the effect of navigation assisted surgery system in the medical teaching in the department of neurosurgery. Method From May 4 of 2015 to June 3 of 2015, 51 medical undergraduates of clinical medicine in the Second Affiliated Hospital of Xi'an Jiaotong University were ran-domly divided into experiment group (navigation assisted surgical technique system teaching, n=25) and traditional group (traditional teaching, n=26). Practical effect of the different modes was evaluated by ques-tionnaire and examination results. Data were analyzed by SPSS 20.0. Enumeration data were compared between groups using chi square test or t test. Result After the teaching, the theoretical results of the experimental group and the control group were (83.05 ± 6.03) and (74.32 ± 7.12), and the difference was statistically significant (t=4.96, P=0.005). Clinical skills scores were (89.43 ± 5.12) and (81.11 ± 8.02), and the difference was statistically significant (t=2.91, P=0.029). The questionnaire showed that the experimental group students'!satisfaction degree to their own teaching method was better than that of control group (P<0.05). Conclusion Compared with the traditional teaching, the navigation assisted neurosurgical operation has obvious advantages. It can improve students'!enthusiasm for learning the professional knowledge and skills in neurosurgery, stimulate students'!learning interest and improve students'!test scores.
5.Increased risk of metabolic disease in offspring rats due to maternal high fat diet
Fang FANG ; Yuanwen CHEN ; Ning LIN ; Xiaoyu WAN ; Chongxiao LIU ; Yan DONG
Journal of Clinical Pediatrics 2013;(7):655-659
Objectives To examine the association of the maternal high-fat (HF) diet with increased susceptibility to obe-sity and the development of metabolic diseases in their offspring, and observe difference in the effect of maternal vs. acquired high fat diet on metabolic state in their offspring. Methods A total of 15 SD female rats were divided into HF diet group (group H, n=9) and control diet group (group C, n=6). After fed on different diet for seven weeks, they were mated at the age of ten weeks and became pregnant. Their offspring were then divided to groups CH and HH fed HF diet and groups CC and HC fed control diet. At the age of 3 and 8 weeks, the metabolic markers and the liver pathohistological evidences of their offspring were obtained. Results The body weight, area under curve (AUC) of glucose tolerance, cholesterol and triglyceride were all higher in group H than those in group C (P<0.05) before pregnancy. The offspring of group H had a higher body weight than the offspring of group C at the age of 3 weeks (P=0.002), and no difference in AUC was found between two groups (P>0.05). At the age of 8 weeks, there was no difference in fasting glucose and insulin levels among the four offspring groups. The AUC and body weight were higher in group H than in group C (main effect of maternal diet, P=0.024, P=0.013). The AUCs were also higher in groups CH and HH than groups CC and HC respectively (main effect of acquired diet, P=0.041). The levels of total cholesterol, triglycerides and LDL at the age of 8 weeks were all higher in HH and CH groups than those in HC and CC groups (main effect of acquired diet, P=0.008, 0.007, 0.000, respectively). Their histological analysis at 8 weeks showed different degrees of fatty liver in HH, HC and CH groups, and normal liver in CC group. Conclusions Maternal HF diet may result in increased body weight, fatty liver and impaired glucose tolerance in their adult offspring, and thus increase the risk of developing metabolic diseases at their later age. .
6.Effects of maternal high-fat diet on liver fatty acid metabolism-related gene expression in the early life of rat offspring
Tingting YE ; Yanhong HUANG ; Fang FANG ; Chongxiao LIU ; Yuanwen CHEN ; Yan DONG
Journal of Clinical Pediatrics 2015;(2):170-173
Objective To study the impact of maternal high-fat diet during pregnancy and lactation on hepatic steatosis in the early life of offspring rats and its possible mechanism. Methods Female Sprague-Dawley rats were fed either a high fat diet (HF) or control (C) diet for 8 weeks before mating and throughout gestation and ifrst 3 weeks of lactation. The expressions of hepatic fatty acid catabolism related genes, including peroxisome proliferator-activated receptor alpha (PPARα), acyl-CoA syn-thease long-chain family member3 (ACSL3), carnitine palmitoyltransferase-1α(CPT-1α) and 3-hydroxyacyl CoA dehydrogenase (Ehhadh) were determined in offspring liver tissue. The liver pathology was examined in offspring rats at 3 weeks of age. Results Pathohistological ifndings at 3 weeks of age showed that there were diffuse vacuolar degeneration in cytoplasm of hepatocytes and spot necrosis in hepatic lobular in the HF offspring liver. The mRNA expressions of PPARαand Ehhadh genes were markedly increased in the HF offspring as compared to the control group (P<0.05). The mRNA expression of CPT-1αgene was also higher in the HF offspring than that in control group (P=0.19). The level of ACSL3 gene expression, however, was markedly decreased (P<0.05). Conclusions Maternal high fat diet during pregnancy and lactation could result in an increased expression of genes related to hepatic fatty acidβ-oxidation, including PPARα, CPT1αand Ehhadh, but the liver steatosis cannot be reversed in the early life of offspring.
7.Clinicopathological characteristics of ovarian seromucinous borderline tumor
Yanyan DONG ; Yunxiao LIU ; Chongxiao QU
Cancer Research and Clinic 2018;30(9):603-606
Objective To explore the clinicopathological characteristics,immunohistochemical phenotype and differential diagnosis of ovarian seromucinous borderline tumor.Methods Fifteen cases of ovarian seromucinous borderline tumor in Shanxi Provincial People's Hospital from January 2013 to May 2017 were collected.The surgical specimens were observed after HE and immunohistochemical staining,the patients were followed-up,and the relevant literature was reviewed.Results The age of 15 cases of ovarian seromucinous borderline tumor ranged from 26 to 56 years(mean 37 years).Eight cases occurred in the right,5 cases occurred in the left,only 2 cases were bilateral tumors.The complaint of most patients was abdominal distention,3 cases was ascites.The maximum diameter of these tumors ranged from 4 to 13 cm(mean 9.3 cm).Grossly,15 cases mainly showed cystic performance,varying amounts of papillae inside wall of the cysts.Small region of 2 cases were solid.Microscopically,9 tumors were composed of endocervical-like mucinous epithelium,4 tumors were endocervical-like mucinous epithelium and serous epithelium.2 cases were accompanied with endometriosis.Tumor cells mainly expressed estrogen receptor(ER),progesterone receptor(PR),paired box gene protein 8(PAX-8),cytokeratin 7(CK7),these markers were immunophenotypes of Mullerian tumors.Followed up for 3 to 24 months(mean 16.7 months),2 cases showed bilateral tumors,1 case was peritoneal implantation.No tumor recurrence was found in the remaining 12 cases.Conclusions Different from mucinous borderline tumor,ovarian seromucinous borderline tumor possesses relative special clinicopathological features,morphological and immunohistochemical phenotypes,with better prognosis.Combination of immunohistochemical markers ER,PR,PAX-8,CK7,CK20,Vimentin,CDX-2 and WT-1 can make an accurate diagnosis of this tumor.
8.Parathyroid Hormone-Related Protein Promotes the Proliferation of Patient-Derived Glioblastoma Stem Cells via Activating cAMP/PKA Signaling Pathway
Zhenyu GUO ; Tingqin HUANG ; Yingfei LIU ; Chongxiao LIU
International Journal of Stem Cells 2023;16(3):315-325
Background and Objectives:
Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its hetero-geneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM.
Methods:
and Results: Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP.
Conclusions
Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.
9.Features of mammographic mass edge in digital X-ray three dimensional tomography and their correlations with pathological parameters in breast cancer
Caixian YANG ; Hongguang ZHAO ; Hui LIU ; Chongxiao QU
Cancer Research and Clinic 2019;31(1):16-21
Objective To analyze the diagnostic value of features of mammographic mass edge in digital three dimensional tomography, and to discuss the correlations between the mammographic mass edge features and pathological features and molecular biological indicators, in order to provide evidence for early and accurate diagnosis and treatment of breast cancer and prognosis evaluation. Methods A retrospective analysis was made in 392 cases of breast cancer confirmed by operation and pathology in the People ' s Hospital of Shanxi Province from August 2017 to June 2018. These patients were examined by digital breast tomography (DBT) and full-field digital mammography (FFDM) before operation. Postoperative specimens were stained by immunohistochemical SP method to measure the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67. The correlation between the mammographic mass edge features and pathological features and molecular biological indicators were analyzed by usingχ2 test and Fisher exact probability method. Results In 392 patients, 352 cases (89.80%) were invasive ductal carcinoma, 6 cases (1.53%) were ductal carcinoma in situ with microinvasion, 7 cases (1.79%) were invasive lobular carcinoma, 17 cases (4.34%) were papillary carcinoma, 8 cases (2.04%) were mucinous carcinoma, 1 case (0.26%) was medullary carcinoma, and 1 case (0.26%) was metaplastic carcinoma. DBT were significantly better than FFDM in the detection rate [93.6% (367/392) vs. 77.8% (305/392)] and the diagnostic coincidence rate [88.2%(345/392) vs. 76.8%(278/392)] for breast cancer and judging the marginal features of tumor. The DBT imaging features of mucinous carcinomas were mostly regular in shape and clear in margin. The DBT imaging features of invasive ductal carcinomas were marginal burr sign or burr with lobulation sign. Immunohistochemical detection displayed the positive expression rates of ER and PR were highest, the positive expression rates of HER2 and Ki-67 were the lowest in marginal burr masses;the positive expression rates of ER and PR were high, the positive expression rates of HER2 and Ki-67 were low in marginal lobulated masses; the positive expression rate of HER2 was highest in borderline masses or partial borderline masses; the positive expression rates of HER2 and Ki-67 were highest in clear margin masses. Conclusions Breast DBT can reduce or eliminate the tissue overlap in FFDM examination, and improve the detection rate, the diagnostic coincidence rate and the specificity of breast cancer. It can also indirectly provide evidence for preoperative judgment of biological behavior of tumors, guide clinical treatment and assess the prognosis through the morphological and marginal features of breast masses. Breast DBT is worthy of a wide clinical application in breast examination.
10.The development of an OxyHb animal model in mice and the study on OxyHb-induced apoptosis of mouse brain cells in vivo
wei SHI ; Ruizhi WANG ; Liyong HUANG ; Jianjun SUN ; Fangru WANG ; Chongxiao LIU ; Le ZHOU ; Zhenyu GUO ; Hzhang JOHN
Journal of Pharmaceutical Analysis 2008;20(2):109-112,137
Objective On the basis of developing a new animal model for oxyhemoglobin (OxyHb) injection into subarachnoid space in mice, this research was to explore the temporal dependence and spatial distribution of OxyHb- induced apoptosis in the mouse brain cells in vivo and the mechanism of neurocyte injury induced by OxyHb. Methods The animal model for OxyHb injection into subarachnoid space in mice was developed. Mice were divided randomly into the experimental group (n=40) and the control group (n= 35). The control group received saline injection (50 μL ) and the experimental group received OxyHb injection (50 μL ), both into the subarachnoid space. The mice of the two groups were subdivided according to different postoperative time (3 h, 6 h, 12 h, 24 h and 48 h). The apoptosis or necrosis of cells was distinguished with microscopy (HE staining), transmission electron microscopy and TUNEL method. Results The distribution of apoptosis was mainly in the ipsilateral neocortex and bilateral hippocampal gyrus. The apoptotic mouse brain cells showed morphological changes in the experimental group by HE staining and transmission electron microscopy. The count of TUNEL-positive cells showed substantial increase in the experimental group, and there was a significant difference between the control and experimental groups, and the number of OxyHb- induced apoptotic cells decreased with time. Conclusion OxyHb in subarachnoid space in mice can induce apoptasis, but not necrosis of mouse brain cells in viro. The apoptotic brain cells show the pattern of temporal dependence and spatial distribution. It is suggested that the early treatment should be the method of first choice for treating the hemorrhagic brain injury.