1.Tumor inhibitory effects of 131I-Trastuzumab on human epidermal growth factor receptor 2 overexpressing breast cancer cells and its possible mechanisms
Longjie ZHANG ; Helei HOU ; Guoming WANG ; Zhenzhen HAN ; Xiaochun ZHANG ; Shengli YUAN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2015;35(4):293-297
Objective To explore antitumor effect of 131I-Trastuzumab on human epidermal growth factor receptor(HER) 2 overexpressing breast cancer cells and investigate its possible mechanism.Methods The expression levels of HER2 of three different breast cancer cell lines (BT474,MCF-7,HCC1937) were detected with immunofluorescence.Trastuzumab was labeled with 131I using the Iodogen method and 131I-Trastuzumab was isolated with ultrafiltration membrane,then the labeling efficiency,radiochemical purity and immunoreactivity were measured.The effects of 131I,Trastuzumab and 131I-Trastuzumab on viability of BT474 cells were evaluated with cell counting kit-8 (CCK-8) assay.The levels of total Akt and phosphorylated Akt (p-Akt) were detected with Western blot analysis.One-way analysis of variance (ANOVA),ANOVA for factorial design,Bonferroni correction and Pearson correlation analysis were used for data analysis.Results The expression level of HER2 in BT474 cells was much higher than those in HCC1937 and MCF-7 cells.The labeling efficiency,radiochemical purity and immunoreactivity of 131I-Trastuzumab were (89.71± 2.93)%,(91.80±1.43)% and (58.84±3.35)% respectively.131I (4.625 GBq/L),Trastuzumab(125.0 rmg/L) and 131I-Trastuzumab(4.625 GBq/L) exhibited a dose-dependent cytotoxicity against BT474 cells (r =-0.964,-0.912,-0.618;all P<0.05).The cell viability of 131I-Trastuzumab treated gourp (34.73% ±5.03%) was significantly lower than those of 131I and Trastuzumab treated groups (64.36%± 1.51% and 58.09%±4.14%;t=10.373 and 8.180,both P<0.05),and the cell viability of control group was (100.00±4.54)%.131I-Trastuzumab shown a positive multiplicative interaction between 131I and Trastuzumab (F=9.226,P<0.05;CDI =0.929).Western blot results showed that there was no significant difference of total Akt expression among the control group,131I group,Trastuzumab group and 131I-Trastuzmab group (F=0.208,P>0.05).P-Akt expression in both Trastuzumab group and 131I-Trastuzumab group were much lower than those of control group and 131I group (t=12.524,15.984,7.347,10.807;all P<0.05),while there was no significant difference of p-Akt expression between Trastuzumab group and 131I-Trastuzumab group(t =3.460,P>0.05).Conclusions 131I-Trastuzumab may kill HER2 overexpressing breast cancer cells more effectively than Trastuzumab alone.The underlying mechanism may be attributed to that 131I-Trastuzumab may enhance the radiosensitivity by the inhibitory effect on PI3K/Akt pathway and thus exert synergistic effects with 131I.
2.Prediction of mortality using Chinese version of epidemiology-based mortality score in status epilepticus (EMSE)
Yan JIANG ; Ying ZHANG ; Zhenzhen KANG ; Lin YANG ; Liping ZHANG ; Qun HOU
Chinese Journal of Emergency Medicine 2017;26(9):1059-1064
Objective To study the value of epidemiology-based mortality score,a novel scoring system,in in-hospital adult patients with status epilepticus (SE) for predicting mortality,and to compare it with the status epilepticus severity score (STESS).Methods The clinical and electroencephalography data of 54 adult patients with SE admitted from June 2013 to June 2016 were derived from a prospective SE database of Zhejiang Provincial Hospital of Traditional Chinese Medicine.The outcome was defined as inhospital death or survival at discharge.When the receiver-operating characteristic (ROC) curves were made,the area under ROC (AUC) and the optimal cutoff value were calculated.Fisher's linear discriminant function analysis was conducted with the outcome as dependent variable and the scores as independent variables.Results Among 54 patients with SE recruited into the study,13 (24.10 %) died in the hospital.The ROC curve for prediction of in-hospital death based on the STESS had a AUC of 0.705with an optimal cutoff value for discrimination (best match for both sensitivity (0.77) and specificity (0.56) to be ≥ 3 points.The AUC based on the EMSE was 0.800 with an optimal cutoff value for discrimination (best match for both sensitivity (0.92) and specificity (0.61) to be ≥ 79 points.Three elements added in combination with EMSE system (etiology-age-comorbidity,EMSE-EAC) predicted inhospital mortality with the best match for both sensitivity (1.00) and specificity (0.56) as the optimal cutoff point was ≥32 points,and the AUC was 0.814.Four elements added in combination with EMSE system (etiology-age-comorbidity-EEG,EMSE-EACE) predicted in-hospital mortality with the best match for both sensitivity (0.77) and specificity (0.98) as the optimal cutoff point was ≥71 points with an AUC of 0.925.The AUC of EMSE-EACE was larger than that of both STESS and EMSE (Both P < 0.01).Discriminant equations were found by Fisher linear discriminant analysis.The rates of accuracy of the equation for predicting patients' prognosis were 44.44% (STESS),62.96% (EMSE),70.37% (EMSE-EAC) and 81.48% (EMSE-EACE) respectively,suggesting that the equations of EMSE,EMSE-EAC and EMSE-EACE have superior stability.Conclusions The EMSE is an effective clinical scoring system that focuses on individual mortality.EMSE-EACE is superior over both STESS and EMSE in the prediction of inhospital death.
3.Exploratory research on the probable shared molecular mechanism and transcription factors between chronic periodontitis and chronic obstructive pulmonary disease.
Chen ZHANG ; Zhenzhen HOU ; Yingrui ZONG
West China Journal of Stomatology 2023;41(5):533-540
OBJECTIVES:
To investigate possible cross-talk genes, associated pathways, and transcription factors between chronic periodontitis (CP) and chronic obstructive pulmonary disease (COPD).
METHODS:
The gene expression profiles of CP (GSE10334 and GSE16134) and COPD (GSE76925) were downloaded from the GEO database. Differential expression and functional clustering analyses were performed. The protein‑protein interaction (PPI) network was constructed. The core cross-talk genes were filtered using four topological analysis algorithms and modular segmentation. Then, functional clustering analysis was performed again.
RESULTS:
GSE10334 detected 164 differentially expressed genes (DEGs) (119 upregulated and 45 downregulated). GSE16134 identified 208 DEGs (154 upregulated and 54 downregulated). GSE76925 identified 1 408 DEGs (557 upregulated and 851 downregulated). The PPI network included 21 nodes and 20 edges. The final screening included seven cross-talk genes: CD79A, FCRLA, CD19, IRF4, CD27, SELL, and CXCL13. Relevant pathways included primary immunodeficiency, the B-cell receptor signaling pathway, and cytokine-cytokine receptor interaction.
CONCLUSIONS
This study indicates the probability of shared pathophysiology between CP and COPD, and their cross-talk genes, associated pathways, and transcription factors may offer novel concepts for future mechanistic investigations.
Humans
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Chronic Periodontitis/genetics*
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Gene Regulatory Networks
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Gene Expression Profiling
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Protein Interaction Maps/genetics*
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Pulmonary Disease, Chronic Obstructive/genetics*
4.Distribution characteristics of Mycobacterium tuberculosis and streptomycin and ethambutol resistance patterns by high⁃resolution melt analysis
Tengfei Guo ; Zhenzhen Wang ; Yi Hou ; Zhanqin Zhao ; Xiangyang Zu ; Tao Jiang ; Yun Xue
Acta Universitatis Medicinalis Anhui 2023;58(7):1227-1232
Objective :
To study the resistance pattern of streptomycin and ethambutol in Mycobacterium tuberculosis in Luoyang area , guide clinical medication and supplement epidemiological data on local drug⁃resistant tuberculosis .
Methods :
The positive results of high⁃resolution melting curve (HRM) in 2 941 cases in Luoyang area were analyzed to assess the risk factors associated with streptomycin and ethambutol resistance .
Results :
Of the 2 941 HRM⁃positive patients , 18 . 4% were resistant to streptomycin and 8. 0% were ethambutol . Both streptomycin and ethambutol and resistance rates were higher in men than those in women ( 19. 0% vs 16. 9% , P = 0. 129 ; 8. 0% vs 7. 9% , P = 0. 987) . The resistance rates to streptomycin and ethambutol were higher in urban than those in rural areas (21 . 3% vs 16. 6% , P = 0. 002 ; 9. 8% vs 6. 9% , P = 0. 004) . The resistance rate was much higher in previously treated patients than those newly diagnosed for MTB infection (25 . 8% vs 17. 3% , P < 0. 001 ; 12. 1% vs 7. 4% , P = 0. 002) . The resistance rates to streptomycin were higher in the < 51 years than those in the > 50 years group (21 . 1% vs 16. 1% , P < 0. 001) . According to age , the highest resistance rates to streptomycin and ethambutol occurred in the age range of 31 - 35 years and 56 - 60 years in men , respectively , while in the age range of 21 - 25 years and 56 - 60 years in women , respectively . In multivariate models , prior treatment history , age less than 51 years , and urban area were positively associated with streptomycin and ethambutol resistance after adjusting for smear results and year testing .
Conclusion
Men , prior treatment history , age less than 51 years , and urban residents are key monitoring targets for streptomycin and ethambutol resistant tuberculosis .
5.The coronary flow reserve in patients with coronary slow flow and diagnostic value of myocardial work indices for coronary slow flow
Qiaoyan WU ; Zhenzhen DING ; Huiping HOU ; Mengzhang WU ; Yongshi WANG ; Weipeng ZHAO ; Limin LUO
Chinese Journal of Clinical Medicine 2024;31(5):765-771
Objective To explore the coronary flow reserve (CFR) in patients with coronary slow flow (CSF) and the diagnostic value of non-invasive myocardial work indices derived from echocardiography for CSF. Methods A retrospective study was conducted on 65 patients who underwent coronary angiography at the Zhongshan Hospital (Xiamen Branch), Fudan University due to angina pectoris, coronary artery risk factors, or electrocardiographic abnormalities from August 2020 to November 2023. Patients were divided into two groups based on the corrected TIMI frame count (cTFC): the CSF group (n=35) and the normal coronary blood flow velocity group (control group, n=30). Both groups underwent an adenosine triphosphate (ATP) drug load test to measure their coronary flow reserve (CFR). Conventional indices and myocardial work indices via echocardiography and two-dimensional speckle-tracking imaging (2D-STI) were acquired: left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), E/e' ratio, global longitudinal strain (GLS), global constructive work (GCW), global wasted work (GWW), global work index (GWI), and global work efficiency (GWE). Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of myocardial work indices for CSF. Results There was no significant difference in CFR values between the two groups, but the proportion of CSF group with CFR less than 2 was higher than that of the control group (P=0.023). Compared with the control group, the CSF group showed significantly lower levels of GLS, GWI, and GCW (P<0.05). ROC curve analysis revealed that the GLS diagnostic threshold for CSF was −19.5%, with a sensitivity of 64.7%, specificity of 78.6%, and AUC of 0.793. Among the myocardial work indices, the AUC of GWI was the highest (0.825), with a sensitivity of 88.2% and specificity of 75.0%. Conclusions Some CSF patients retain coronary microcirculatory blood flow reserve function, but the proportion of patients with reduced CFR function is increasing. The left ventricular myocardial work indices can identify early myocardial work abnormalities and monitor myocardial ischemic damage in CSF patients.