1.The correlation between serum sTREM2 levels and cognitive impairment in patients with cerebral small vessel disease
Hanfang CUI ; Fangyuan DING ; Zhixiu XU ; Qing LI ; Yifan ZHANG ; Sen ZHANG ; Mengke GAO ; Yuhui CHEN ; Xiaowen ZHAO ; Jialu ZHAO ; Chengbiao LU ; Shaomin LI ; Jianhua ZHAO
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(11):976-982
Objective:To explore the correlation between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and cognitive impairment in patients with cerebral small vessel disease (CSVD), and the role of deep medullary vein (DMV) score in this process.Methods:A total of 140 patients with CSVD admitted to the Department of Neurology, the First Affiliated Hospital of Henan Medical University from December 2022 to August 2024 were selected as the research objects. The basic data statistics, head magnetic resonance imaging examination, cognitive function assessment, serum sTREM2 detection and DMV score were performed. All data were analyzed by SPSS 29.0 software and GraphPad Prism 10.0 software packages. Logistic regression model was used to explore the influencing factors of cognitive impairment. Structural equation model was used to analyze the mediating effect of DMV score on the association between serum sTREM2 and cognitive impairment. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum sTREM2 level and DMV score for cognitive impairment in CSVD patients.Results:Serum sTREM2 level ( B=0.017, OR=1.017, 95% CI=1.003-1.031), DMV score ( B=0.375, OR=1.455, 95% CI=1.175-1.802) and years of education ( B=-0.248, OR=0.780, 95% CI=0.635-0.958) were risk factors for cognitive impairment (all P<0.05). sTREM2 not only directly affected cognitive function, but also indirectly affected cognitive function through DMV score. The direct effect (effect size=-0.022) and mediating effect (effect size=-0.007) accounted for 75.9% and 24.1% of the total effect (effect size=-0.029), respectively. The areas under the ROC curve of serum sTREM2 level, DMV score, and their combination for predicting cognitive impairment in CSVD patients were 0.880, 0.891, and 0.910, respectively (all P<0.001). Conclusion:Serum sTREM2 not only directly affects the cognitive function of patients with cerebral small vessel disease, but also indirectly affects cognitive function through DMV score. The combination of serum sTREM2 levels and DMV score has high predictive value for the risk of CSVD-related cognitive impairment.
2.The correlation between serum sTREM2 levels and cognitive impairment in patients with cerebral small vessel disease
Hanfang CUI ; Fangyuan DING ; Zhixiu XU ; Qing LI ; Yifan ZHANG ; Sen ZHANG ; Mengke GAO ; Yuhui CHEN ; Xiaowen ZHAO ; Jialu ZHAO ; Chengbiao LU ; Shaomin LI ; Jianhua ZHAO
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(11):976-982
Objective:To explore the correlation between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and cognitive impairment in patients with cerebral small vessel disease (CSVD), and the role of deep medullary vein (DMV) score in this process.Methods:A total of 140 patients with CSVD admitted to the Department of Neurology, the First Affiliated Hospital of Henan Medical University from December 2022 to August 2024 were selected as the research objects. The basic data statistics, head magnetic resonance imaging examination, cognitive function assessment, serum sTREM2 detection and DMV score were performed. All data were analyzed by SPSS 29.0 software and GraphPad Prism 10.0 software packages. Logistic regression model was used to explore the influencing factors of cognitive impairment. Structural equation model was used to analyze the mediating effect of DMV score on the association between serum sTREM2 and cognitive impairment. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum sTREM2 level and DMV score for cognitive impairment in CSVD patients.Results:Serum sTREM2 level ( B=0.017, OR=1.017, 95% CI=1.003-1.031), DMV score ( B=0.375, OR=1.455, 95% CI=1.175-1.802) and years of education ( B=-0.248, OR=0.780, 95% CI=0.635-0.958) were risk factors for cognitive impairment (all P<0.05). sTREM2 not only directly affected cognitive function, but also indirectly affected cognitive function through DMV score. The direct effect (effect size=-0.022) and mediating effect (effect size=-0.007) accounted for 75.9% and 24.1% of the total effect (effect size=-0.029), respectively. The areas under the ROC curve of serum sTREM2 level, DMV score, and their combination for predicting cognitive impairment in CSVD patients were 0.880, 0.891, and 0.910, respectively (all P<0.001). Conclusion:Serum sTREM2 not only directly affects the cognitive function of patients with cerebral small vessel disease, but also indirectly affects cognitive function through DMV score. The combination of serum sTREM2 levels and DMV score has high predictive value for the risk of CSVD-related cognitive impairment.
3.Investigating the Effect of Dihydroartemisinin on Proliferation and Metastasis of Prostate Cancer Cells based on the SPOP/HnRNPK Pathway
Jiantong ZHANG ; Zhenzhuang GAO ; Zhixiu WANG ; Lina SUN
Journal of Kunming Medical University 2025;46(11):26-34
Objective To investigate the effects of dihydroartemisinin(DHA)on the proliferation and metastasis of prostate cancer cells via the speckle-type POZ protein(SPOP)/heterogeneous nuclear ribonucleoprotein K(HnRNPK)pathway.Methods The prostate cancer cell line DU145 was cultured in vitro and treated with different concentrations of DHA.Cells were divided into groups based on DHA concentration:blank group(0 μmol/L),low-concentration group(10 μmol/L),medium-concentration group(50 μmol/L),and high-concentration group(100 μmol/L).Colony formation assay,scratch assay,and Transwell assay were performed to observe changes in proliferation,migration,and invasion of DU145 cells under different DHA treatments.Western blotting was used to detect the expression levels of SPOP,HnRNPK,Vimentin,Neural-cadherin(N-cadherin),Epithelial-cadherin(E-cadherin),and Zonula occludens-1(ZO-1).SPOP expression was knocked down in DU145 cells(SPOP-shNC-DU145,SPOP-sh-DU145),which were then subjected to the aforementioned low,medium,and high DHA concentration interventions for rescue experiments.A xenograft mouse model was established by injecting SPOP-knockdown cells into mice,followed by oral administration of low(2.5 mg/kg),medium(5 mg/kg),and high(10 mg/kg)concentrations of DHA.Results Compared with the blank group,the proliferation,migration,and invasion of DU145 cells in the low-,medium-,and high-concentration groups were significantly inhibited(P<0.05),Intracellular expression levels of HnRNPK,Vimentin,and N-cadherin were decreased(P<0.05),while the expression levels of SPOP,E-cadherin,and ZO-1 were increased(P<0.05).Compared with SPOP-shNC DU145 cells,the inhibitory effects of DHA on SPOP-sh DU145 cells were attenuated,with increased expression levels of HnRNPK,Vimentin,and N-cadherin(P<0.05),and decreased expression levels of E-cadherin and ZO-1(P<0.05).Conclusion DHA may target and induce increased SPOP expression,thereby inhibiting the proliferation and metastasis of DU145 cells.
4.Correlation between serum VEGF level and white matter hyperintensity and cognitive dysfunction in patients with cerebral small vessel disease
Jin WANG ; Jianhua ZHAO ; Hao LIU ; Junli LIU ; Fangli YANG ; Qiong LI ; Minghua WANG ; Panpan ZHAO ; Fan WANG ; Qing LI ; Zhixiu XU ; Junyan YUE ; Jian ZHANG ; Sibei JI ; Ruiyan CAI ; Shaomin LI
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(4):333-340
Objective:To investigate the relationship between serum vascular endothelial growth factor (VEGF) levels and white matter high signal and non-dementia vascular cognitive dysfunction in patients with cerebral small vascular disease (CSVD).Methods:Total 106 patients with CSVD who were admitted to the Department of Neurology of the First Affiliated Hospital of Xinxiang Medical College from April 2019 to December 2020 were enrolled.They were divided into vascular cognitive impairment no dementia group (VCIND group, n=47) and no vascular cognitive impairment group (N-VCI group, n=59)according to mini-mental assessment scale (MMSE), Montreal cognitive assessment (MoCA) scale and activity of daily living scale (ADL). Serum VEGF levels were detected by enzyme-linked immunosorbent assay (ELISA). The baseline data, serum VEGF levels, MoCA score and Fazekas score were compared between the two groups.The correlation between serum VEGF level and white matter high signal and cognitive function was analyzed.SPSS 19.0 software was used for data processing.The statistical methods were t-test, Chi square test, nonparametric test, Logistic regression analysis, Pearson correlation analysis and Spearman correlation analysis. Results:There were significant differences in serum VEGF level((464.18±114.58)pg/mL, (414.17±45.80)pg/mL, F=22.880), MoCA score((13.07±6.48), (20.17±4.06), F=17.920) and Fazekas score (4(3, 5), 3(1, 3), Z=-4.189)between the two groups (all P<0.05). The level of VEGF( β=0.008, OR=1.008, 95% CI=1.001-1.015, P<0.05) was the influencing factor of cognitive function in patients with CSVD .The level of VEGF was negatively correlated with the total score of MoCA, attention and calculation power, and orientation ability ( r=-0.345, -0.373, -0.445, all P<0.05) and it was positively correlated with the total Fazekas score and the Fazekas score of paraventricular and deep white matter ( r=0.392, 0.495, 0.302, all P<0.05). There was a linear trend between the high signal grade of paraventricular and deep white matter and VCIND (both P<0.05). Conclusion:Serum VEGF level is correlated with cognitive function and white matter hyperintensity in patients with CSVD.The increase of VEGF level may be a factor reflecting cognitive dysfunction.In addition, with the increase of white matter hyperintensity level, the risk of VCIND in CSVD is increased.
5.Molecular genetic and clinical characteristics of MEF2D-BCL9 fusion gene-positive acute B-cell lymphoblastic leukemia
Zhixiu LIU ; Xue CHEN ; Fang WANG ; Xian ZHANG ; Tong WANG ; Ping WU ; Xiaoli MA ; Mingyue LIU ; Yang ZHANG ; Yijun LIU ; Panxiang CAO ; Jiancheng FANG ; Lili YUAN ; Hongxing LIU
Journal of Leukemia & Lymphoma 2022;31(8):480-483
Objective:To investigate the molecular genetic and clinical characteristics of MEF2D-BCL9 fusion gene-positive acute B-cell lymphoblastic leukemia (B-ALL), and to provide the reference for the diagnosis and treatment of the disease.Methods:The medical record and experimental examination data of a 18-year-old female MEF2D-BCL9 fusion gene-positive B-ALL patient were retrospectively analyzed. The clinical manifestations and biological characteristics of MEF2D-BCL9 fusion gene-positive B-ALL were summarized.Results:This 18-year-old female patient was treated in a local hospital in December 2018 and was diagnosed as B-ALL. She achieved complete remission after chemotherapy and recurred at 6 months after the initial onset, and then she was admitted to Hebei Yanda Ludaopei Hospital in the 9 months after the initial onset.MEF2D-BCL9 fusion gene was detected through RNA-sequencing (RNA-seq) and verified by using polymerase chain reaction and Sanger sequencing. Bone marrow cell morphology was similar to mature B cells with vacuoles but without characteristic chromosome karyotype abnormalities. The patient achieved remission after VLD regimen chemotherapy, chimeric antigen receptor T-cell (CAR-T) therapy and bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT). She has maintained complete remission for 2 years at the last follow-up in February 2022.Conclusions:MEF2D-BCL9 fusion gene-positive B-ALL is characterized with high risk, early relapse and poor prognosis. These patients may benefit from CAR-T and allo-HSCT. It further emphasizes the importance of taking MEF2D-BCL9 fusion gene into the detection or identification by using RNA-seq, particularly for those newly diagnosed B-ALL patients in children and adolescents with specific bone marrow morphology.
6.Bioactive natural compounds against human coronaviruses: a review and perspective.
Yanfang XIAN ; Juan ZHANG ; Zhaoxiang BIAN ; Hua ZHOU ; Zhenbiao ZHANG ; Zhixiu LIN ; Hongxi XU
Acta Pharmaceutica Sinica B 2020;10(7):1163-1174
Coronaviruses (CoVs), a family of enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, unusually large RNA genome, and unique replication capability. CoVs are known to cause various potentially lethal human respiratory infectious diseases, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the very recent coronavirus disease 2019 (COVID-19) outbreak. Unfortunately, neither drug nor vaccine has yet been approved to date to prevent and treat these diseases caused by CoVs. Therefore, effective prevention and treatment medications against human coronavirus are in urgent need. In the past decades, many natural compounds have been reported to possess multiple biological activities, including antiviral properties. In this article, we provided a comprehensive review on the natural compounds that interfere with the life cycles of SARS and MERS, and discussed their potential use for the treatment of COVID-19.
7. Correlation between serum HBV DNA level and HBsAg titer in HBeAg-positive pregnant women and impact of genomic variability of hepatitis B virus pre S/S regions on their correlations
Xin ZHANG ; Ling YAN ; Ying LU ; Kaiping WEI ; Zhixiu LIU ; Yiwei XIAO ; Feng DING ; Hui ZHUANG ; Jie LI
Chinese Journal of Hepatology 2018;26(8):579-584
Objective:
To analyze the correlation between serum HBV DNA level and HBsAg titer in hepatitis B e antigen positive pregnant women without antiviral therapy, and investigate the impact of genomic variability of preS/S regions on their correlations.
Methods:
Prenatal serum samples from 882 pregnant women with chronic HBV infection who were positive for HBsAg, HBeAg and HBV DNA and were not on antiviral therapy were included in the analysis. The Abbott i2000 and m2000 systems were used to qualitatively or quantitatively detect HBsAg, HBeAg and HBV DNA levels, respectively. HBV genotyping was performed using a type-specific primer nested polymerase chain reaction (nPCR). In addition, serum samples of pregnant women with HBV DNA levels correlated with HBsAg titer and HBV DNA levels higher than HBsAg titers were used to perform preS/S region amplification by nPCR method. PCR products were directly sequenced and mutation sites were analyzed by MEGA6.0 stasticial software. Mann-Whitney
8.Expression difference of FKBP51 in colorectal cancer and normal tissues and its relationship with clinicopathological features
Zhixiu XIA ; Changliang WANG ; Yanshuo HAN ; Chunsheng CHEN ; Guohua ZHANG ; Yong FENG
Journal of Chinese Physician 2017;19(3):362-366
Objective To explore the difference of the expression level of FK506 Binding Protein 51 (FKBP51) in colorectal adenocarcinoma and normal colorectal tissues,and the correlation between FKBP51 expression level and clinicopathological characteristics,and to clarify whether FKBP51 is involved in the occurrence and development of colorectal cancer.Methods By immunohistochemical staining [streptavidin-peroxidase (SP) method] and Western blotting methods tested 31 cases of colorectal cancer tumor tissues and normal colorectal tissues far from tumor 5 cm,and explored the expression level difference of FKBP51.Combined with clinical data of patients,results were analyzed by statistical method x2 test of four case table data.Results The high expression rate of FKBP51 in tumor tissues was 74.19% (23/31 cases),while the high expression rate of FKBP51 in normal tissue was 9.68% (3/31 cases).The difference was significant.The expression level of FKBP51 in patients with colorectal carcinoma had no obvious correlation with gender (P =0.771),age (P =0.474),tumor location (P =0.213),degree of differentiation (P =0.318),lymph node metastasis (P =0.124),distant metastasis (P =0.318) and clinical stage (P =0.171);and the tumor size (P =0.049),depth of invasion related (P =0.031),the difference was statistically significant.Conclusions The expression of FKBP51 in colorectal cancer was strong,while weak expression in normal colorectal tissues.With the increase of tumor infiltration and deepening,the expression of FKBP51 became stronger,which indicated that FKBP51 participated in the genesis and development of colorectal cancer,and it might become a new target for individual therapy of colorectal cancer.
9.An Ethical Ponder on Preservation and Utilization of Zoic Medication under "The Belt and Road Initiative"
Yanwan ZHANG ; Xiaoping CHEN ; Bin LONG ; Zhixiu TAN
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(6):1006-1011
With the accelerated pace of the world population aging,it has provided great opportunities for the rapid development of traditional Chinese medicine (TCM) with natural medicine as its main component.However,the lack of legal status of TCM has long been a great influence on Chinese medicine.There is a big difference in the degree of recognition of TCM among people along the way.If people are still able to accept herbal medicine,they are very exclusive of zoic medication.Although zoic medication is an important part of TCM,zoic medication and animal rights appeal have a sharp contradiction.The question is how to solve the dilemma between the protection and utilization of zoic medication,utility and lofty.This article analyzed the understanding difference and consensus of zoic medication from the ethics perspective under both Chinese and western culture.It clarified the understanding and practice of zoic medication in TCM.It also illustrated the rational protection and sustainable using of zoic medication in TCM.
10.Clinical significance of the expression levels of ERCC1, BRCA1 and TS in advanced colorectal cancer
Zhixiu XIA ; Changliang WANG ; Jinchun CONG ; Guohua ZHANG ; Yong FENG
Chinese Journal of Postgraduates of Medicine 2017;40(8):697-703
Objective To explore the relationship between the expression levels of excision repair cross complementation group 1(ERCC1), breast cancer susceptibility gene 1(BRCA1), thymidylate synthase (TS) mRNA and clinicopathological features, prognosis in advanced colorectal cancer, and the correlation between the expression levels of ERCC1 and BRCA1. Methods The expression levels of ERCC1, BRCA1 and TS mRNA of postoperative paraffin embedded tissue were tested by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) in 49 advanced colorectal cancer cases. The results were analyzed by χ2 test of the correlation between the expression levels and clinicopathological characteristics. Patients were followed up by clinic or telephone. The prognosis was analyzed by small sample Kaplan-Meier survival analysis and Log-rank time series analysis, and P<0.05 was statistically significant. Results The expression level of ERCC1 mRNA in patients with colorectal carcinoma had no obvious correlation with the clinical and pathological characteristics such as gender, age, tumor location, lymph node metastasis, distant metastasis, CEA and differentiation degree (P>0.05). The expression level of BRCA1 mRNA had no significant correlation with the above clinical and pathological features (P>0.05) except distant metastasis (P=0.030) and differentiation degree (P=0.002). The expression level of TS mRNA had no significant correlation with the above clinical and pathological features (P>0.05) except distant metastasis (P=0.003). The expression level of ERCC1 and BRCA1 mRNA obviously correlated (P=0.002). The 1 year overall survival rate was 95.92%(47/49);the 2 year overall survival rate was 83.67%(41/49);and the 3 year overall survival rate was 73.47%(36/49). Overall survival and progression-free survival time in ERCC1 mRNA low expression group (47.8, 41.0 months) was higher than that in ERCC1 mRNA low expression group (27.3, 20.0 months) respectively (P=0.001, P=0.001). Overall survival and progression-free survival time in BRCA1 mRNA low expression group (43.7, 42.7 months) was higher than that in BRCA1 mRNA high expression group (29.3, 25.1 months) respectively (P=0.009, 0.006). Overall survival time in TS mRNA low expression group (39.8 months) was higher than that in BRCA1 mRNA high expression group (25.2 months). Conclusions The expression level of ERCC1 mRNA is not correlated with its clinical and pathological characteristics, but with its biological characteristics. BRCA1 and TS levels are correlated with invasion and metastasis. Low levels of ERCC1 and BRCA1 expression have a better prognostic effect on platinum based first-line chemotherapy for advanced colorectal cancer, and they are correlated. Low level of TS also has longer disease-free survival. Three joint detection could be used as a prognostic factor for colorectal cancer chemotherapy.

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