1.Correlation of SERPINC1 and SERPINE1 gene polymorphisms with venous thromboembolism in patients with malignant tumors
Zihui ZHU ; Man HE ; Xueping HOU ; Yuying WANG ; Jianan LIN ; Lizhong WANG ; Weihua JIANG
Cancer Research and Clinic 2025;37(1):14-18
Objective:To investigate the correlation of SERPINC1 and SERPINE1 gene polymorphisms with venous thromboembolism (VTE) in patients with malignant tumors.Methods:A retrospective case-control study was conducted. A total of 227 patients with malignant tumors in the Cancer Hospital Affiliated to Xinjiang Medical University from November 2023 to February 2024 were selected, of which 47 cases developed VTE (VTE group) and 180 cases did not develop VTE (non-VTE group). The patients' venous blood was collected, and D-dimer level was analyzed by using fully automatic coagulation analyzer; fluorescence staining was performed by using digoxin staining solution, and SERPINC1 rs2227589 locus and SERPINE1 rs1799762 locus were used as candidate genes, and fluorescence sequencing was performed by using multichannel fluorescence quantitative analyzer, and the frequencies of C, T, 4G and 5G genes were calculated.Results:There were no statistically significant differences in the age, gender, smoking, alcohol consumption, anticoagulant use, diabetes mellitus, hypertension, coronary artery disease, surgical treatment, intravenous cannulae, radiotherapy, chemotherapy, and targeted therapy between the 2 groups (all P > 0.05). The level of D-dimer in the VTE group was higher than that in the non-VTE group [(8.7±6.9) kg/m 2vs. (2.8±1.0) kg/m 2], and the difference was statistically significant ( t = 5.15, P < 0.001). The differences in C and T genotypes and gene frequencies at the SERPINC1 rs2227589 locus between the VTE group and the non-VTE group were not statistically significant (all P > 0.05). The differences in 4G and 5G genotypes and gene frequencies at the SERPINE1 rs1799762 locus between the VTE group and the non-VTE group were statistically significant (all P < 0.05), and 4G allele frequency in the VTE group was higher than that in the non-VTE group (52.13% vs. 39.72%), and the difference was statistically significant ( χ2 = 4.70, P = 0.030). Conclusions:The elevated expression of 4G allele at the SERPINE1 rs1799762 locus in patients with malignant tumors is associated with development of VTE.
2.Correlation of SERPINC1 and SERPINE1 gene polymorphisms with venous thromboembolism in patients with malignant tumors
Zihui ZHU ; Man HE ; Xueping HOU ; Yuying WANG ; Jianan LIN ; Lizhong WANG ; Weihua JIANG
Cancer Research and Clinic 2025;37(1):14-18
Objective:To investigate the correlation of SERPINC1 and SERPINE1 gene polymorphisms with venous thromboembolism (VTE) in patients with malignant tumors.Methods:A retrospective case-control study was conducted. A total of 227 patients with malignant tumors in the Cancer Hospital Affiliated to Xinjiang Medical University from November 2023 to February 2024 were selected, of which 47 cases developed VTE (VTE group) and 180 cases did not develop VTE (non-VTE group). The patients' venous blood was collected, and D-dimer level was analyzed by using fully automatic coagulation analyzer; fluorescence staining was performed by using digoxin staining solution, and SERPINC1 rs2227589 locus and SERPINE1 rs1799762 locus were used as candidate genes, and fluorescence sequencing was performed by using multichannel fluorescence quantitative analyzer, and the frequencies of C, T, 4G and 5G genes were calculated.Results:There were no statistically significant differences in the age, gender, smoking, alcohol consumption, anticoagulant use, diabetes mellitus, hypertension, coronary artery disease, surgical treatment, intravenous cannulae, radiotherapy, chemotherapy, and targeted therapy between the 2 groups (all P > 0.05). The level of D-dimer in the VTE group was higher than that in the non-VTE group [(8.7±6.9) kg/m 2vs. (2.8±1.0) kg/m 2], and the difference was statistically significant ( t = 5.15, P < 0.001). The differences in C and T genotypes and gene frequencies at the SERPINC1 rs2227589 locus between the VTE group and the non-VTE group were not statistically significant (all P > 0.05). The differences in 4G and 5G genotypes and gene frequencies at the SERPINE1 rs1799762 locus between the VTE group and the non-VTE group were statistically significant (all P < 0.05), and 4G allele frequency in the VTE group was higher than that in the non-VTE group (52.13% vs. 39.72%), and the difference was statistically significant ( χ2 = 4.70, P = 0.030). Conclusions:The elevated expression of 4G allele at the SERPINE1 rs1799762 locus in patients with malignant tumors is associated with development of VTE.
3.Clinical characteristics and management strategies of lymphoma patients with COVID-19
Xueping DANG ; Shuling HOU ; Pan CHEN ; Guiqin WANG ; Yizhuo CHEN
Chinese Journal of Clinical Infectious Diseases 2023;16(4):315-320
Novel coronavirus has brought great threats to the people and challenges to the health systems around the world. Compared with general population, lymphoma patients are more vulnerable to novel coronavirus infection(COVID-19) and have poorer prognosis. So the clinical management of COVID-19 in lymphoma patients in more difficult and the great importance should be attached. This article reviews the clinical characteristics and current management strategies of lymphoma patients with COVID-19, to provide reference for the clinical treatment of lymphoma patients with COVID-19.
4.Comprehensive and deep profiling of the plasma proteome with protein corona on zeolite NaY
Congcong MA ; Yanwei LI ; Jie LI ; Lei SONG ; Liangyu CHEN ; Na ZHAO ; Xueping LI ; Ning CHEN ; Lixia LONG ; Jin ZHAO ; Xin HOU ; Li REN ; Xubo YUAN
Journal of Pharmaceutical Analysis 2023;13(5):503-513
Proteomic characterization of plasma is critical for the development of novel pharmacodynamic bio-markers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the"masking"effect caused by high-abundance proteins.The relative abundance of middle-and low-abundance proteins increased substantially from 2.54%to 54.41%,and the top 20 high-abundance proteins decreased from 83.63%to 25.77%.Notably,our method can quantify approxi-mately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins iden-tified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.
5.BGB-A445, a novel non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical models.
Beibei JIANG ; Tong ZHANG ; Minjuan DENG ; Wei JIN ; Yuan HONG ; Xiaotong CHEN ; Xin CHEN ; Jing WANG ; Hongjia HOU ; Yajuan GAO ; Wenfeng GONG ; Xing WANG ; Haiying LI ; Xiaosui ZHOU ; Yingcai FENG ; Bo ZHANG ; Bin JIANG ; Xueping LU ; Lijie ZHANG ; Yang LI ; Weiwei SONG ; Hanzi SUN ; Zuobai WANG ; Xiaomin SONG ; Zhirong SHEN ; Xuesong LIU ; Kang LI ; Lai WANG ; Ye LIU
Frontiers of Medicine 2023;17(6):1170-1185
OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice
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Animals
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Receptors, Tumor Necrosis Factor/physiology*
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Receptors, OX40
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Membrane Glycoproteins
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Ligands
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Antibodies, Monoclonal/pharmacology*
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Antineoplastic Agents/pharmacology*
6.Exosomes' roles in the pathogenesis of Alzheimer's disease and the diagnostic and therapeutic values
Xueying LIU ; Renjun LYU ; Qingqing YIN ; Xunyao HOU ; Xueping LIU
Chinese Journal of Geriatrics 2022;41(6):734-738
Exosomes are nanoscal-scale vesicles containing a variety of proteins(HSP70, actin, Alix, etc.), lipids, mRNAs and miRNAs.They are commonly found in various tissues and cells of the organism.They are involved in processes such as intercellular communication, immune regulation and cell signaling pathway regulation, and then play an important role.Recent studies have shown that exosome-mediated intercellular signaling plays an important role in the progression of Alzheimer's disease(AD). This paper reviewed the general characteristics of exosomes, clarifies the possible role of exosomes in the pathogenesis of AD, and also discussed the application prospect and the related challenges of exosomes as a new potential option in the future treatment of AD.
7.Visual attention impairment in patients with cerebral small vessel disease: an event-related potential P3 study
Shanjing NIE ; Song XU ; Yan HONG ; Xunyao HOU ; Xueping LIU
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(1):71-76
Objective:To investigate the value of event-related potential (ERP) P3 in the assessment of visual attention impairment in patients with cerebral small vessel disease (CSVD).Methods:Twenty-five patients with CSVD diagnosed in the Shandong Provincial Hospital Affiliated to Shandong First Medical University from July 2019 to December 2020 were selected as the CSVD group, while 25 healthy subjects who underwent physical examination in the same period were selected as the control group.The neuropsychological evaluation of CSVD group and control group was carried out by Montreal cognitive assessment (MoCA), 7-items generalized anxiety disorder (GAD-7) and patient health questionnaire-9 (PHQ-9). Magnetic resonance imaging brain white matter high signal of CSVD group and control group was carried out by Fazekas score.The amplitude and latency of ERP component P3 were measured by visual tristimulation Oddball experimental paradigm.SPSS 23.0 software was used for statistical analysis.The differences of amplitude and latency between the two groups were compared by repeated measurement analysis of variance.Pearson or Spearman correlation analysis were used to explore the correlation between P3 amplitude, latency and related scale scores.Results:(1)In the amplitude of P3, the interaction effect between group and stimulation was significant( F(2, 96)=3.922, P=0.023). The main effect between groups was significant( F(1, 46)=15.976, P<0.01). The main effect of stimulation was significant( F(2, 96)=86.212, P<0.01). Further simple effect analysis showed that compared with the control group((9.82±5.14)μV, (11.12±4.72)μV) the P3 amplitude induced by target stimulation ((6.59±4.22)μV, F(1, 48)=7.363, P=0.009) and novel stimulation ((7.08±3.91)μV, F(1, 48)=13.907, P=0.001) in CSVD group decreased significantly.(2)In the latency of P3, the main effect between groups was significant( F(1, 48)=4.870, P=0.032). The main effect of stimulation was significant( F(2, 96)=86.212, P<0.01). The interaction effect between group and stimulation was significant( F(2, 96)=4.561, P=0.013). The main effect of stimulation was significant( F(2, 96)=16.299, P<0.01). Further simple effect analysis showed that the P3 latency induced by novel stimulation in CSVD group was longer than that in control group( F(1, 48)=17.124, P<0.01). (3)P3 amplitude induced by target stimulation was positively correlated with MoCA score ( r=0.255, P=0.027). The P3 amplitude ( r=-0.502, P<0.01) and P3 latency ( r=-0.265, P=0.022) induced by novel stimulation were negatively correlated with Fazekas score. Conclusion:The speed and ability of patients with CSVD to process visual spatial information are impaired, especially for rare stimulation.ERP examination may be a rapid, objective and sensitive method for the diagnosis of visual attention impairment in patients with CSVD.
8.Recent advance in role of galectin-3 in central neurodegenerative diseases
Zhongyu FAN ; Xunyao HOU ; Xueping LIU ; Qingqing YIN
Chinese Journal of Neuromedicine 2022;21(2):183-188
Galectin-3 (Gal3) is a multipotent protein involved in cell activation, proliferation and migration, which plays an important role in a variety of physiological and pathological processes. Recent studies have shown that Gal3 plays an important role in the pathogenesis of central nervous system degenerative diseases, but its specific mechanism is not clear. This article reviews the research progress on the mechanism and expression of Gal3 in central nervous system degenerative diseases, and discusses the application value of Gal3 as a new therapeutic target in central nervous system degenerative diseases, so as to provide new scientific basis for early prevention and treatment of central nervous system degenerative diseases.
9.Research progress on neurotoxicity related to chimeric antigen receptor T cell immunotherapy
Wei CHEN ; Shuling HOU ; Pan CHEN ; Xueping DANG
Adverse Drug Reactions Journal 2022;24(2):88-91
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common adverse reaction of chimeric antigen receptor T-cell (CAR-T) immunotherapy. Its mechanism is mainly related to the destruction of brain mural cells, increase of cytokine level, the inflammation mediated by natural killer cells, and the activation of endothelial cells. The main clinical manifestations of ICANS are aphasia, tremor, dysgraphia, drowsiness, and epilepsy. In severe cases, asphyxia, coma, or brain edema may occur, and sometimes it is even life-threatening. The factors affecting ICANS include age, peak value of CAR-T amplification, product type, and disease type, etc. American Society for Blood and Marrow Transplantation recommends symptomatic and supportive treatments for mild ICANS and hormonal shock therapy for severe cases.
10.Research progress on neurotoxicity related to chimeric antigen receptor T cell immunotherapy
Wei CHEN ; Shuling HOU ; Pan CHEN ; Xueping DANG
Adverse Drug Reactions Journal 2022;24(2):88-91
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common adverse reaction of chimeric antigen receptor T-cell (CAR-T) immunotherapy. Its mechanism is mainly related to the destruction of brain mural cells, increase of cytokine level, the inflammation mediated by natural killer cells, and the activation of endothelial cells. The main clinical manifestations of ICANS are aphasia, tremor, dysgraphia, drowsiness, and epilepsy. In severe cases, asphyxia, coma, or brain edema may occur, and sometimes it is even life-threatening. The factors affecting ICANS include age, peak value of CAR-T amplification, product type, and disease type, etc. American Society for Blood and Marrow Transplantation recommends symptomatic and supportive treatments for mild ICANS and hormonal shock therapy for severe cases.

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