1.Research progress on macrophage polarization in cancer bone metastasis
Xiang LI ; Zhenyu WEN ; Qiping HUANG ; Yi YANG ; Honghan WU ; Qingde WA
Chongqing Medicine 2024;53(24):3793-3799
Bone metastasis is a common complication of many advanced cancers,especially prostate cancer(85%),breast cancer(70%)and lung cancer(40%),which severely affects the quality of life of the pa-tients and increases its death risk.Macrophages are the essential immune cells in the human body that play a crucial role in the tumor microenvironment(TME),including phagocytosis or removal of cell debris,damaged or apoptotic cells.The phenotypic and functional transition of macrophages is a dynamic process.Under vari-ous stimulation conditions in TME,they can be transformed into two major subpopulations:M1 and M2.In TME,M1 macrophages exert anti-tumor effects and contribute to tumor immunity.M2 macrophages display a robust immunosuppressive phenotype,aiding in tumor cell proliferation and thereby promoting the occurrence of bone metastasis.This article reviews the interaction between macrophages and TME,and explores the role of macrophage polarization in bone metastasis of common cancers such as prostate cancer,breast cancer and lung cancer,and the influence in the occurrence and development of tumors.
2.Evaluation of brain glymphatic system function in patients with multiple sclerosis based on diffusion tensor imaging
Lin WU ; Zhi ZHANG ; Xiao LIANG ; Yanyan ZHU ; Honghan GONG ; Fuqing ZHOU
Chinese Journal of Neuromedicine 2022;21(11):1133-1137
Objective:To investigate the changes of glymphatic system function at relapse and remission phases in patients with relapsing remitting multiple sclerosis (RRMS) and their relations with clinical parameters.Methods:Sixteen patients with RRMS at relapsing phase and 25 patients with RRMS at remitting phase, admitted to Department of Neurology, First Affiliated Hospital of Nanchang University from September 2012 to December 2020, were enrolled; and 29 normal controls were recruited at the same period in Physical Examination Center the same hospital. The diffusion tensor imaging data were analyzed retrospectively, and the along perivascular space (ALPS) index was calculated. The differences in clinical data and ALPS index among the 3 groups were compared, and the correlations between ALPS index and clinical parameters in RRMS patients were analyzed.Results:The scores of expanded disability status scale (EDSS) and modified fatigue impact scale (MFIS) in patients at relapsing phase were significantly higher than those in patients at remitting phase ( P<0.05). The ALPS index in bilateral cerebral hemispheres in the control group was significantly higher than that in RRMS patients at relapse and remission phases ( P<0.05). In patients with RRMS at relapse phase, the ALPS index in the left cerebral hemisphere was negatively correlated with disease duration and EDSS scores ( r=-0.536, P=0.032; r=-0.573, P=0.020). Conclusion:Patients with RRMS have glymphatic system dysfunction; this dysfunction may be the potential pathological basis of clinical dysfunction in patients with RRMS at relapsing phase.
3.Study on the Mechanism of Periplaneta americana Extract Reversing Multi-drug Resistance of Human Hepato- cellular Carcinoma HepG 2/ADM Cells
Cailin LI ; Dingyu WU ; Hong LYU ; Honghan ZHANG ; Yanquan WANG ; Mohammerd NAJIB ; Fang PENG
China Pharmacy 2020;31(15):1816-1823
OBJECTIVE:To study the mechanism of Periplaneta americana extract degreasing cream and CⅡ-3(shorted for “degreasing cream ”and“CⅡ-3”)reversing the multi-drug resistance of human HepG 2/ADM cells. METHODS :MTT assay was used to investigate the toxicity effects of different concentrations of sorafenib (positive control ),degreasing cream and C Ⅱ-3 on HepG2/ADM cells ,then IC 20 was calculated. The experiment was divided into sensitivity drug ,drug-resistance group ,sorafenib group,degreasing cream group and C Ⅱ-3 group. HepG 2 cells were included in sensitivity group ,and HepG 2/ADM cells were included in the latter 4 groups. Sensitivity group and drug-resistance group were treated with routine medium ,and other 3 groups were treated with relevant medicine (IC20 as drug concentration ). The content of ADM in HepG 2/ADM cells was determined by Laser scanning confocal microscopy. The expression of apoptosis-related protein as Bcl- 2 and Cleaved-Caspase- 9 p37 were detected by Western blotting assay. RT-qPCR and immunocytochemistry were adopted to detect mRNA and protein expressions that related to multidrug resistance [P-gp (expression produce of MDR1 gene),LRP,BCRP] and that related to enzyme-mediated multidrug resistance pathway (GST-π and Topo Ⅱ). RESULTS :The IC 20 of degreasing cream ,CⅡ-3 and sorafenib were (2.40±0.16), (200.44±27.52),(18.00±1.82)μg/mL,respectively. Compared with sensitivity group ,the protein expressions of Bcl- 2,P-gp, LRP,BCRP and Topo Ⅱ,the mRNA expressions of MDR 1, LRP,BCRP and GST-π were increased significantly in drug resistance group (P<0.05 or P<0.01). Compared with @qq.com drug-resistance group ,the mRNA and protein expression of MDR1 mRNA and LRP ,BCRP,GST-π were significantly decreased in degreasing cream group and C Ⅱ-3 group(P< 0.05 or P<0.01);the protein expression of Bcl- 2 and the mRNA expression of Topo Ⅱ were significantly decreased (P<0.01), while the protein expression level of Cleaved-Caspase- 9 p37 was significantly increased in C Ⅱ -3 group (P<0.05). CONCLUSIONS:Degreasing cream and C Ⅱ-3 can reverse multidrug resistance of HepG 2/ADM cells by reducing drug efflux , promoting cell apoptosis ,reducing the mRNA and protein expression of multi-drug resistance gene as well as gene in enzyme-mediated multi-drug resistance pathway. The effect of C Ⅱ-3 is better than that of degreasing cream.
4.Alteration of cerebral regional homogeneity within sensorimotor network in patients with cervical spondylotic myelopathy after spinal cord decompression:a resting-state functional MRI study
Yongming TAN ; Fuqing ZHOU ; Zhili LIU ; Lin WU ; Xianjun ZENG ; Honghan GONG ; Laichang HE
Chinese Journal of Radiology 2016;50(7):495-499
Objective To assess the altered regional homogeneity (ReHo) of local intrinsic cerebral activity within sensorimotor network(SMN) in patients with cervical spondylotic myelopathy (CSM) before or after spinal cord decompression using functional MRI (fMRI). Methods Twenty-one CSM patients who would decompress spinal canal, and 21 healthy volunteers (age, gender and level of education matched) were enrolled from June 2013 to April 2014. All the patients underwent rs-fMRI examination before and 3 months after spinal cord decompression. ReHo measurement was performed statistically within a SMN mask. A second-level random-effect 2-tailed Student's t test was applied to compare the ReHo results between pre-and post-operation CSM patients and healthy volunteers. A second-level paired 2-tailed Student's t test was applied to compare the ReHo results between pre-and post-operation CSM patients. Pearson correlation analysis was performed to assess the correlations between the altered ReHo and clinical evaluation. Results Compared with healthy volunteers, pre-operation patients showed significantly lower ReHo in the left postcentral gyrus/precentral gyrus, together with enhanced ReHo in the right superior parietal lobule (GRF correction, P<0.05). Post-operation CSM patients showed significantly lower ReHo in the right superior parietal lobule comparing with healthy volunteers, as well as enhanced ReHo in the left postcentral gyrus/precentral gyrus comparing with pre-operation (GRF correction, P<0.05). Abnormal ReHo areas in CSM patients demonstrated no significant correlation with clinical measurements (P>0.05) between pre-operation and post-operation. Conclusions Myelopathy in cervical cord may affect intrinsic cerebral activity, as patients with CSM show disrupted regional homogeneity within sensorimotor network. The change of ReHo following decompression suggests that central plasticity may influence functional recovery.
5.Application of fractional anisotropy entropy in cervical spondylotic myelopathy
Qin WU ; Fuqing ZHOU ; Yongming TAN ; Laichang HE ; Honghan GONG ; Xianjun ZENG
Chinese Journal of Radiology 2016;50(8):571-575
Objective To quantitative analyze the injury degree of cervical cord in cervical spondylotic myelopathy (CSM) patients using fractional anisotropy (FA) entropy of diffusion tensor imaging (DTI).Methods Twenty-four CSM patients and well-match healthy volunteers underwent cervical cord DTI scanning.FA value was measured at each segment of spinal cord (including grey matter and white matter) of spinal cord level and intervertebral disc level.Further Shannon entropy of FA value was calculated in each segment to observe the disorder degree of cervical cord structure in CSM patients.After the analysis of homogeneity of variance,two samples t test analysis was used to identify FC's differences of FA and Shannon entropy of FA value between the two groups.Result In CSM group,the average FA value of whole cervical cord was 0.644 ± 0.056,while it was 0.672 ± 0.035 in the healthy control group.There was significant difference of FA values between the two groups (t=-2.049,P=0.046).The FA entropy of CSM patients' cervical cord was 0.687±0.043,while it was 0.854±0.027 in the healthy control group.The FA entropy of CSM patients' cervical cord was lower than that of control group.There was significant difference of FA entropy between the two groups (t=-12.100,P<0.001).The significant difference between the two groups was only found at C6 level for each level's FA value.The FA entropy of CSM patients' cervical cord was significantly lower than that of control group for every level.Conclusion This decreased FA entropy of cervical cord in CSM patients indicates that FA entropy can be used to detect the disorder of cervical cord structure in CSM patients.
6."The ""small-world"" property of default mode network in relapsing-remitting multiple sclerosis:a graph theory resting-state functional network analysis"
Ying ZHUANG ; Fuqing ZHOU ; Honghan GONG ; Weichang TAN ; Qin WU ; Hui WAN
Chinese Journal of Behavioral Medicine and Brain Science 2014;23(5):408-412
Objective To investigate the small-world property of default mode network in relapsingremitting multiple sclerosis (RRMS) compared with the (matched) healthy control subjects,using a graph theory for resting-state functional network analysis.Methods Twenty four patients with RRMS and 24 age-,and sexmatched healthy controls were exanined with resting-state functional MRI (R-fMRI) and 3D-T1WI on Trio 3.0 Tesla.The R-fMRI data were preprocessed,then 20 regions of interest (ROIs) was defined and extracted from the default mode network.The functional connectivity between a pair of regions was defined as the Pearson's correlation coefficient in the time courses.Graph theoretical analysis was implemented and compared with the property of binary functional network.Further,the relationships were examined between the topological property of functional networks and the clinical parameters.Results In this study,functional network in the default mode network was conducted,and the small-world characteristics were observed in both RRMS and healthy control group.In the range of densities (Dmin:0.01∶0.48 ;Dmin =0.42),compared with healthy control group,RRMS groups had a slightly smaller normalized clustering coefficient (P>0.05),a slightly larger normalized path length (P>0.05),and a slightly decrease small-world index (P>0.05).The left posterior cingulated cortex showed a significantly larger clustering coefficient in RRMS group (P=0.031) on the network threshold at Dmin.The area under a curve (AUC) for clustering coefficient measure curves of the left posterior cingulated cortex (density range of 0.42:0.01:0.48) between two groups were compared.The AUC result was similar to the Dmin result (P=0.031).Negative correlation was observed between the clustering coefficient of left posterior cingulated cortex and the Paced Auditory Serial Addition Test (PASAT) in both the Dmin(P=0.023) and the AUC (P=0.020).Conclusion The default mode network has small-world property in RRMS group.The significantly increased clustering coefficience is observed in the left posterior cingulated cortex,which may be a side effect.
7.Diagnostic performance of stress perfusion cardiovascular magnetic resonance for detection of coronary artery disease:a Meta-analysis
Jing ZHAO ; Pan XU ; Honghan GONG ; Lin WU
Journal of Practical Radiology 2014;(4):593-599
Objective To evaluate the value of stress perfusion cardiovascular magnetic resonance in the diagnosis of coronary ar-tery disease.Methods Relevant literatures about stress perfusion cardiovascular magnetic resonance in the diagnosis of coronary ar-tery disease were searched.According to the recommended contents of the Cochrane Collaboration,we set inclusion criteria and screen literatures.Using software STATA 12.0 and Meta-disc 1.4,we analyzed the data ,including the heterogeneity,publication bias,subgroup analysis,Meta-regression,clinical application,pooled sensitivity(SEN),specificity(SPE),positive likelihood ratio (PLR),negative likelihood ratio(NLR),diagnostic odds ratio(DOR)and 95%confidence interval(95%CI),we drew the summary receiver operating characteristic curve(SROC)and calculated the area under the curve(AUC).Results Twenty-nine literatures were included,the pooled SEN,SPE,PLR,NLR,DOR and 95%CI were 0.90(0.89~0.92)、0.78(0.75~0.80)、4.03(3.32~4.91)、0.14 (0.11~0.18)、32.54(22.25~47.60)respectively.The AUC of SROC was 0.907 8.Conclusion The current evidence indicates that stress perfusion cardiovascular magnetic resonance has a high diagnostic accuracy for detection coronary artery disease.However, the relatively high false positive rate was found due to the medium specificity.
8.Alteration of the cerebral inter-hemispheric resting-state functional connectivity in amyotrophic lateral sclerosis:a voxel-mirrored homotopic connectivity MRI study
Fuqing ZHOU ; Honghan GONG ; Lin WU ; Jian JIANG ; Ying ZHUANG ; Fangjun LI ; Rensi XU
Chinese Journal of Radiology 2014;(5):375-380
Objective To investigate the difference of cerebral inter-hemispheric functional connectivity between the patients with amyotrophic lateral sclerosis ( ALS) and healthy controls ( HC) by a newly developed voxel-mirrored homotopic connectivity ( VMHC) method based on resting-state functional MRI ( rs-fMRI) , as well as its correlation to the structural imaging indices and clinical neurological scales .Methods Twenty patients with ALS ( ALS group ) and 20 age-, and sex-matched healthy controls ( HC group) were examined by rs-fMRI and diffusion tensor imaging ( DTI ) on 3.0 T MR imaging system ( Siemens Trio Tim ).The rs-fMRI data preprocessing were performed using data processing assistant for rs-fMRI ( DPARSF) based on Matlab 2009a, and the rs-fMRI data analysis toolkit ( REST) with an automated VMHC approach was utilized to calculate and compare the VMHC correlation coefficients between the ALS group and the HC group[P<0.05, corrected with false discovery rate (FDR)].Region of interest (ROIs) were prescribed on the regions which showed abnormal VMHC coefficients in ALS group , then the mean time series of the ROIs were extracted to examine the difference of the seed ( ROIs)-based functional connectivity between the ALS and HC groups.At last, linear correlations were performed to assess the relationships among the VMHC coefficients and clinical measures including the revised amyotrophic lateral sclerosis functional rating scale ( ALSFRS-r) score, disease duration , the rate of disease progression and fractional anisotropy ( FA) values of the corpus callosum ( CC).Results Compared with HC group , the patients with ALS showed lower VMHC coefficients in the precentral gyrus ( M1 ) , postcentral gyrus ( PCG ) , inferior parietal lobule (IPL), cuneus/precuneus (Cu/Pcu), and anterior cingulate gyrus (ACC).Higher VMHC coefficients were found in the supplementary motor area , superior frontal gyrus , and middle occipital gyrus (P<0.05,FDR corrected).Significant functional connectivity alterations were detected in motor cortex and frontal/temporal/occipital lobe between the ALS and HC groups using seed ( ROIs )-based functional connectivity based on the regions which showed abnormal VMHC coefficients in ALS group ( P <0.05, AlphaSim corrected, clusters≥228 voxels).Significant positive correlation was detected between the VMHC coefficients (0.311 ±0.108) of M1 and FA values (0.394 ±0.016) of CC III region (r=0.530, P=0.016), between the VMHC coefficients (0.767 ±0.043) of ACC and FA values (0.360 ±0.105) of CC I region (r=0.513, P=0.021), respectively.Significant positive correlation was observed between VMHC coefficients (0.311 ±0.108) of M1 and the ALSFRS-r score (35.4 ±2.5) in ALS patients(r=0.447, P=0.048).There was not significant correlation observed between the VMHC coefficients and disease duration , or the ratio of disease prognosis (P>0.05).Conclusions Abnormal VMHC coefficients were detected in ALS patients.The decreased VMHC in ACC and M1 are associated with the reduced micro-structure integrity of CC, meanwhile, and they may be related to disease severity.

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