1.High expression of CPNE3 correlates with poor long-term prognosis of gastric cancer by inhibiting cell apoptosis via activating PI3K/AKT signaling
Ting DUAN ; Zhen ZHANG ; Jinran SHI ; Linyu XIAO ; Jingjing YANG ; Lixia YIN ; Xiaofeng ZHANG ; Zhijun GENG ; Guoyu LU
Journal of Southern Medical University 2024;44(1):129-137
Objective To explore the correlation of CPNE3 expression with long-term prognosis of patients with gastric cancer(GC)and the possible mechanism.Methods We retrospectively collected the data of 104 GC patients undergoing radical surgery in our hospital from February,2013 to October,2017.TCGA database and immunohistochemistry were used to analyze CPNE3 expression level in GC tissues and its effects on tumor progression and long-term prognosis of the patients.GO analysis was performed to predict the biological role of CPNE3 in GC.We also conducted cell experiments with MGC803 cells and observed the effects of CPNE3 knockdown,CPNE3 overexpression and LY294002(a PI3K/AKT inhibitor)treatment on cell apoptosis and cellular expressions of apoptotic proteins using flow cytometry and Western blotting.Results TCGA analysis and immunohistochemistry both showed high expressions of CPNE3 in GC(P<0.05).The patients with high CPNE3 expressions had a reduced 5-year survival(P<0.01),and a high CPNE3 expression,CEA level≥5 μg/L,CA19-9 level≥37 kU/L,T3-T4 stage,and N2-N3 stage were all independent risk factors for a lowered 5-year survival rate after surgery.The sensitivity and specificity of CPNE3 for predicting 5-year mortality was 79.59%and 74.55%,respectively(P<0.05).GO analysis predicted that CPNE3 negatively regulated GC cell apoptosis.In MGC803 cells,CPNE3 knockdown significantly increased cell apoptosis,enhanced Bax and Cleaved Caspase-3 expressions and decreased Bcl-2 expression,while CPNE3 overexpression produced the opposite results(P<0.05).The cellular expressions of p-PI3K and p-AKT were significantly decreased following CPNE3 knockdown and increased following CPNE3 overexpression(P<0.05).Treatment with LY294002 obviously attenuated the inhibitory effect of CPNE3 overexpression on apoptosis of MGC803 cells(P<0.05).Conclusion CPNE3 is highly expressed in GC tissues and affects the long-term prognosis of the patients possibly by inhibiting GC cell apoptosis through activation of PI3K/AKT signaling.
2.High expression of CPNE3 correlates with poor long-term prognosis of gastric cancer by inhibiting cell apoptosis via activating PI3K/AKT signaling
Ting DUAN ; Zhen ZHANG ; Jinran SHI ; Linyu XIAO ; Jingjing YANG ; Lixia YIN ; Xiaofeng ZHANG ; Zhijun GENG ; Guoyu LU
Journal of Southern Medical University 2024;44(1):129-137
Objective To explore the correlation of CPNE3 expression with long-term prognosis of patients with gastric cancer(GC)and the possible mechanism.Methods We retrospectively collected the data of 104 GC patients undergoing radical surgery in our hospital from February,2013 to October,2017.TCGA database and immunohistochemistry were used to analyze CPNE3 expression level in GC tissues and its effects on tumor progression and long-term prognosis of the patients.GO analysis was performed to predict the biological role of CPNE3 in GC.We also conducted cell experiments with MGC803 cells and observed the effects of CPNE3 knockdown,CPNE3 overexpression and LY294002(a PI3K/AKT inhibitor)treatment on cell apoptosis and cellular expressions of apoptotic proteins using flow cytometry and Western blotting.Results TCGA analysis and immunohistochemistry both showed high expressions of CPNE3 in GC(P<0.05).The patients with high CPNE3 expressions had a reduced 5-year survival(P<0.01),and a high CPNE3 expression,CEA level≥5 μg/L,CA19-9 level≥37 kU/L,T3-T4 stage,and N2-N3 stage were all independent risk factors for a lowered 5-year survival rate after surgery.The sensitivity and specificity of CPNE3 for predicting 5-year mortality was 79.59%and 74.55%,respectively(P<0.05).GO analysis predicted that CPNE3 negatively regulated GC cell apoptosis.In MGC803 cells,CPNE3 knockdown significantly increased cell apoptosis,enhanced Bax and Cleaved Caspase-3 expressions and decreased Bcl-2 expression,while CPNE3 overexpression produced the opposite results(P<0.05).The cellular expressions of p-PI3K and p-AKT were significantly decreased following CPNE3 knockdown and increased following CPNE3 overexpression(P<0.05).Treatment with LY294002 obviously attenuated the inhibitory effect of CPNE3 overexpression on apoptosis of MGC803 cells(P<0.05).Conclusion CPNE3 is highly expressed in GC tissues and affects the long-term prognosis of the patients possibly by inhibiting GC cell apoptosis through activation of PI3K/AKT signaling.
3.Feasibility of Using Serum, Plasma, and Platelet 5-hydroxytryptamine as Peripheral Biomarker for the Depression Diagnosis and Response Evaluation to Antidepressants: Animal Experimental Study
Zuanjun SU ; Zhicong CHEN ; Jinming CAO ; Canye LI ; Jingjing DUAN ; Ting ZHOU ; Zhen YANG ; Yuanchi CHENG ; Zhijun XIAO ; Feng XU
Clinical Psychopharmacology and Neuroscience 2024;22(4):594-609
Objective:
Whether peripheral blood 5-hydroxytrptamine (5-HT) levels serve as biomarker for depression diagnosis/response evaluation has not been well determined. This work was explored to address this inconclusive issue.
Methods:
Animals were randomized into normal control group (NC, n = 10) and chronic unpredictable mild stress model group (CUMS-model, n = 20), respectively. Animals in CUMS-model group were subjected to chronic stress, then they were randomly subdivided into CUMS subgroup and CUMS + fluoxetine subgroup (CUMS + FLX). After FLX treatment, blood and tissues were collected. 5-HT and relevant protein expression were measured.
Results:
In mice model, there was a significant increase in serum and a significant reduction in plasma 5-HT levels in CUMS-model group versus NC group, while platelet 5-HT levels change little. After FLX treatment, serum and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup, while plasma 5-HT levels had not much change versus CUMS subgroup. Chronic stress enhanced colon and platelet serotonin transporter (SERT) expression and FLX treatment mitigated SERT expression. In rats’ model, there was a significant increase in serum 5-HT levels while plasma and platelet 5-HT levels showed little change in CUMS group versus NC group. After FLX treatment, serum, plasma and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup versus CUMS subgroup. The profile of relevant proteins expression changed by FLX were like those in mice.
Conclusion
Serum 5-HT levels might serve as a potential biomarker for depression diagnosis, meanwhile serum and platelet 5-HT levels might respond to antidepressant treatment.
4.Feasibility of Using Serum, Plasma, and Platelet 5-hydroxytryptamine as Peripheral Biomarker for the Depression Diagnosis and Response Evaluation to Antidepressants: Animal Experimental Study
Zuanjun SU ; Zhicong CHEN ; Jinming CAO ; Canye LI ; Jingjing DUAN ; Ting ZHOU ; Zhen YANG ; Yuanchi CHENG ; Zhijun XIAO ; Feng XU
Clinical Psychopharmacology and Neuroscience 2024;22(4):594-609
Objective:
Whether peripheral blood 5-hydroxytrptamine (5-HT) levels serve as biomarker for depression diagnosis/response evaluation has not been well determined. This work was explored to address this inconclusive issue.
Methods:
Animals were randomized into normal control group (NC, n = 10) and chronic unpredictable mild stress model group (CUMS-model, n = 20), respectively. Animals in CUMS-model group were subjected to chronic stress, then they were randomly subdivided into CUMS subgroup and CUMS + fluoxetine subgroup (CUMS + FLX). After FLX treatment, blood and tissues were collected. 5-HT and relevant protein expression were measured.
Results:
In mice model, there was a significant increase in serum and a significant reduction in plasma 5-HT levels in CUMS-model group versus NC group, while platelet 5-HT levels change little. After FLX treatment, serum and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup, while plasma 5-HT levels had not much change versus CUMS subgroup. Chronic stress enhanced colon and platelet serotonin transporter (SERT) expression and FLX treatment mitigated SERT expression. In rats’ model, there was a significant increase in serum 5-HT levels while plasma and platelet 5-HT levels showed little change in CUMS group versus NC group. After FLX treatment, serum, plasma and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup versus CUMS subgroup. The profile of relevant proteins expression changed by FLX were like those in mice.
Conclusion
Serum 5-HT levels might serve as a potential biomarker for depression diagnosis, meanwhile serum and platelet 5-HT levels might respond to antidepressant treatment.
5.Feasibility of Using Serum, Plasma, and Platelet 5-hydroxytryptamine as Peripheral Biomarker for the Depression Diagnosis and Response Evaluation to Antidepressants: Animal Experimental Study
Zuanjun SU ; Zhicong CHEN ; Jinming CAO ; Canye LI ; Jingjing DUAN ; Ting ZHOU ; Zhen YANG ; Yuanchi CHENG ; Zhijun XIAO ; Feng XU
Clinical Psychopharmacology and Neuroscience 2024;22(4):594-609
Objective:
Whether peripheral blood 5-hydroxytrptamine (5-HT) levels serve as biomarker for depression diagnosis/response evaluation has not been well determined. This work was explored to address this inconclusive issue.
Methods:
Animals were randomized into normal control group (NC, n = 10) and chronic unpredictable mild stress model group (CUMS-model, n = 20), respectively. Animals in CUMS-model group were subjected to chronic stress, then they were randomly subdivided into CUMS subgroup and CUMS + fluoxetine subgroup (CUMS + FLX). After FLX treatment, blood and tissues were collected. 5-HT and relevant protein expression were measured.
Results:
In mice model, there was a significant increase in serum and a significant reduction in plasma 5-HT levels in CUMS-model group versus NC group, while platelet 5-HT levels change little. After FLX treatment, serum and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup, while plasma 5-HT levels had not much change versus CUMS subgroup. Chronic stress enhanced colon and platelet serotonin transporter (SERT) expression and FLX treatment mitigated SERT expression. In rats’ model, there was a significant increase in serum 5-HT levels while plasma and platelet 5-HT levels showed little change in CUMS group versus NC group. After FLX treatment, serum, plasma and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup versus CUMS subgroup. The profile of relevant proteins expression changed by FLX were like those in mice.
Conclusion
Serum 5-HT levels might serve as a potential biomarker for depression diagnosis, meanwhile serum and platelet 5-HT levels might respond to antidepressant treatment.
6.Feasibility of Using Serum, Plasma, and Platelet 5-hydroxytryptamine as Peripheral Biomarker for the Depression Diagnosis and Response Evaluation to Antidepressants: Animal Experimental Study
Zuanjun SU ; Zhicong CHEN ; Jinming CAO ; Canye LI ; Jingjing DUAN ; Ting ZHOU ; Zhen YANG ; Yuanchi CHENG ; Zhijun XIAO ; Feng XU
Clinical Psychopharmacology and Neuroscience 2024;22(4):594-609
Objective:
Whether peripheral blood 5-hydroxytrptamine (5-HT) levels serve as biomarker for depression diagnosis/response evaluation has not been well determined. This work was explored to address this inconclusive issue.
Methods:
Animals were randomized into normal control group (NC, n = 10) and chronic unpredictable mild stress model group (CUMS-model, n = 20), respectively. Animals in CUMS-model group were subjected to chronic stress, then they were randomly subdivided into CUMS subgroup and CUMS + fluoxetine subgroup (CUMS + FLX). After FLX treatment, blood and tissues were collected. 5-HT and relevant protein expression were measured.
Results:
In mice model, there was a significant increase in serum and a significant reduction in plasma 5-HT levels in CUMS-model group versus NC group, while platelet 5-HT levels change little. After FLX treatment, serum and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup, while plasma 5-HT levels had not much change versus CUMS subgroup. Chronic stress enhanced colon and platelet serotonin transporter (SERT) expression and FLX treatment mitigated SERT expression. In rats’ model, there was a significant increase in serum 5-HT levels while plasma and platelet 5-HT levels showed little change in CUMS group versus NC group. After FLX treatment, serum, plasma and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup versus CUMS subgroup. The profile of relevant proteins expression changed by FLX were like those in mice.
Conclusion
Serum 5-HT levels might serve as a potential biomarker for depression diagnosis, meanwhile serum and platelet 5-HT levels might respond to antidepressant treatment.
7.Relationship between serum miR-130a,AngⅡ levels and the degree of coronary artery lesions in patients with acute coronary syndrome
Tianbao FENG ; Hongying LIU ; Yuan FANG ; Yang ZHANG ; Zhijun WEN ; Zhen LI
International Journal of Laboratory Medicine 2023;44(24):3001-3005
Objective To investigate the relationship between serum levels of microRNA-130a(miR-130a),angiotensin Ⅱ(AngⅡ)and the degree of coronary artery lesions in patients with acute coronary syn-drome(ACS).Methods A total of 160 ACS patients admitted to the hospital from January 2021 to February 2023 were selected as the ACS group.According to total Gensini score,ACS patients were divided into mild group(57 cases),moderate group(54 cases)and severe group(49 cases).At the same time,160 healthy peo-ple were selected as the control group.The clinical data of all subjects were collected.The serum levels of miR-130a and AngⅡ were detected by real-time fluorescence quantitative PCR and enzyme-linked immunosor-bent assay,respectively.The clinical data and serum levels of miR-130a and AngⅡ were compared between control group and ACS group.The serum levels of miR-130a and AngⅡ were compared between ACS patients with different degrees of disease.Pearson correlation analysis was used to analyze the correlation between ser-um miR-130a level and AngⅡ in ACS patients.Multivariate Logistic regression was used to analyze the risk factors of ACS.Receiver operating characteristic curve was used to analyze the diagnostic value of serum miR-130a and AngⅡ levels for moderate and severe ACS.Results Compared with the control group,the ACS group had significantly higher proportions of patients with a history of hypertension and diabetes and signifi-cantly higher serum levels of miR-130a and AngⅡ(P<0.05).The serum levels of miR-130a and AngⅡ were increased sequentially in the mild group,moderate group and severe group(P<0.05).Serum miR-130a level was positively correlated with AngⅡ level in ACS patients(P<0.05).Hypertension,diabetes history and ele-vated serum levels of miR-130a and AngⅡ were independent risk factors for ACS(P<0.05).The area under the curve(AUC)of serum miR-130a,AngⅡ and their combination in the diagnosis of moderate ACS were 0.728,0.823 and 0.885,respectively,and the AUC of the combination of miR-130a and AngⅡ was higher than that of miR-130a,AngⅡ(P<0.05).The AUC of serum miR-130a,AngⅡ and their combination in the diagnosis of severe ACS were 0.731,0.730 and 0.825,respectively.The AUC of the combination of miR-130a and AngⅡ was higher than that of miR-130a and AngⅡ(P<0.05).Conclusion ACS patients serum miR-130-a,AngⅡ level is higher,and the serum miR-130a,AngⅡ levels are associated with the ACS degree of cor-onary artery lesions,the combination of the both degree of coronary artery lesions with high diagnostic value.
8.FJX1 overexpression is associated with poor prognosis and promotes gastric cancer proliferation via the PI3K/AKT signaling pathway.
Hao ZHANG ; Zhen ZHANG ; Qiusheng WANG ; Lian WANG ; Zi YANG ; Zhijun GENG ; Yueyue WANG ; Jing LI ; Lugen ZUO
Journal of Southern Medical University 2023;43(6):975-984
OBJECTIVE:
To investigate the expression of four-jointed box kinase 1 (FJX1) in gastric cancer (GC), its correlation with survival outcomes of the patients, and its role in GC progression.
METHODS:
The expression level of FJX1 in GC tissues and normal gastric mucosal tissues and its correlation with the survival outcomes of GC patients were analyzed using TCGA and GEO database GC cohort. Immunohistochemistry was used to detect FJX1 expression level in clinical specimens of GC tissue, and its correlations with the patients' clinicopathological parameters and prognosis were analyzed. Bioinformatic analysis was performed to identify the potential pathways of FJX1 in GC. The effects of FJX1 overexpression or FJX1 silencing on GC cell proliferation and expressions of proliferation-related proteins, PI3K, AKT, p-PI3K, and p-AKT were evaluated using CCK-8 assay and Western blotting. The effect of FJX1 overexpression on GC cell tumorigenicity was evaluated in nude mice.
RESULTS:
GC tissues showed significantly higher expressions of FJX1 mRNA and protein compared with normal gastric mucosa tissues (P < 0.05). The high expression of FJX1 was associated with poor prognosis of GC patients (P < 0.05) and served as an independent risk factor for poor survival outcomes in GC (P < 0.05). FJX1 was expressed mainly in the cytoplasm of GC cells in positive correlation with Ki67 expression (R=0.34, P < 0.05), and was correlated with CA199 levels, depth of tumor infiltration and lymph node metastasis of GC (P < 0.05). In the cell experiment, FJX1 level was shown to regulate the expressions of Ki67 and PCNA and GC cell proliferation (P < 0.05). Gene set enrichment analysis indicated that the PI3K/AKT pathway potentially mediated the effect of FJX1, which regulated the expressions of PI3K and AKT and their phosphorylated proteins. In nude mice, FJX1 overexpression in GC cells significantly promoted the growth of the transplanted tumors (P < 0.05).
CONCLUSION
FJX1 is highly expressed in GC tissues and is correlated with poor prognosis of GC patients. FJX1 overexpression promotes GC cell proliferation through the PI3K/AKT signaling pathway, and may serve as a potential prognostic biomarker and therapeutic target for GC.
Animals
;
Mice
;
Cell Proliferation
;
Ki-67 Antigen
;
Mice, Nude
;
Phosphatidylinositol 3-Kinases
;
Proto-Oncogene Proteins c-akt
;
Signal Transduction
;
Stomach Neoplasms/pathology*
;
Humans
;
Intercellular Signaling Peptides and Proteins/genetics*
9.Evaluation of the residual risk of HIV transmission through blood transfusion after nucleic acid testing in blood centers in China
Yanhong WAN ; Zhijun ZHEN ; Ying LI ; Yanqin HE ; Feng YAN ; Dongmin ZHANG ; Shouguang XU ; Nan WU ; Kejin LI ; Youhua SHEN ; Lin BAO ; Xiaoli CAO ; Xia DU ; Jianling ZHONG ; Weiping FENG ; Peng WANG ; Ying LI ; Dong GUO ; Yang LIU ; Li LI ; Xinyan FAN ; Junbing ZHOU ; Xiaotong SUN ; Lijun ZHOU ; Liping NENG ; Bing JU ; Fang WANG ; Yan QIU
Chinese Journal of Experimental and Clinical Virology 2023;37(4):361-366
Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.
10.Research on the present situation of detection strategies for infectious markers related to transfusion transimission in China
Wei TAN ; Shengyan YING ; Ning CHENG ; Yujun LI ; Xiaoli CHEN ; Fang WANG ; Yang ZHANG ; Xiaojie LIU ; Lin BAO ; Yong DUAN ; Chen MA ; Chunlan LIU ; Dengfeng WANG ; Zhijun ZHEN ; Li LI ; Jian ZHANG ; Ranran LU ; Peng WANG ; Mingxia LI ; Xinli JIN ; Xiaobo CAI ; Mei YU ; Jianling ZHONG ; Lili ZHU ; Jianping LI
Chinese Journal of Experimental and Clinical Virology 2023;37(4):383-388
Objective:To analyze the detection strategy and basic detection situation of markers of infectious diseases transmitted by transfusion in blood testing laboratories of blood stations in China.Methods:Based on the data of practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021, the data on the testing strategies and the basic detection information of the markers for the transmission of infectious diseases through transfusion in the member laboratories of the practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021 were collected, and the situation of the selection for testing markers, testing strategy and the testing method and other relevant aspects were sorted out and analyzed by charts.Results:The selection of the testing markers was consistent, but HTLV testing item was added in some member laboratories. The detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously was adopted in 47 member blood stations; 3) NAT method was dominated by mini pool-NAT in member laboratories. The number of members adopting mini-pools of 8 (MP8)-NAT decreased from 17 in 2017 to 14 in 2021, while the number of members adopting mini-pools of 6 (MP6)-NAT increased from 13 in 2017 to 22 in 2021; Roche NAT system accounted for the largest proportion.Conclusions:In order to ensure blood safety and avoid missing detection, the blood stations still adopt the detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously; Meanwhile, in order to increase the NAT positive rate, the proportion of mini pool-NAT mainly decreased year by year despite its dominating role, while the proportion of individual donation-NAT increased year by year; NAT method is transiting from mini-pools of 8 (MP8) to mini-pools of 6 (MP6); The proportion of imported NAT system used in NAT laboratory is relatively large.

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