1.Expression and clinical significance of TTK and MDM2 in cervical lesion tissue
Mengmeng FAN ; Lili XIONG ; Ruoqi DU ; Doudou XU ; Gailing FU
Journal of China Medical University 2025;54(11):1005-1010
Objective To investigate the expression and roles of serine/threonine and tyrosine kinases(TTK)and mouse dual microbody 2(MDM2)in cervical lesion tissue.Methods Patients(n=180)who underwent gynecological surgery at the First Affiliated Hospital of Henan University of Science and Technology from June 2022 to January 2024 were evaluated,including 50 patients in the cervical cancer group,50 patients in the high-grade lesion group,40 patients in the low-grade lesion group,and 40 patients in the non-cervical lesion(control)group.The mRNA expression and protein levels of TTK and MDM2 in each group were detected and compared by real-time quantitative PCR and immunohistochemistry,respectively.The diagnostic value of the mRNA expression levels of TTK and MDM2 in cer-vical cancer was analyzed using receiver operating characteristic curves.Results The mRNA levels of TTK and MDM2 significantly dif-fered among the four groups(P<0.05);with increases in the lesion grade,the mRNA levels of TTK and MDM2 increased gradually and showed significant differences(P<0.05).Immunohistochemical results showed that TTK was mainly located in the cytoplasm,whereas MDM2 was mainly located in the nucleus,with positive expression rates in cervical cancer tissues of 84.00%and 90.00%,respectively.These values were higher than those in other pathological tissues(P<0.05).The mRNA levels of TTK and MDM2 were significantly cor-related with the degree of differentiation and lymph node metastasis(P<0.05).The receiver operating characteristic curve showed that the areas under the curve of TTK and MDM2 mRNA for diagnosing cervical cancer were 0.803 and 0.798,respectively.Additionally,the area under the curve of the combined diagnosis was 0.912,which was higher than that observed for single detection(Z=2.230,2.553,P<0.05).Conclusion The mRNA expression of TTK and MDM2 and their corresponding protein levels were increased in cervical lesions,demonstrating their potential as biological indicators for the clinical diagnosis of cervical cancer.
2.Expression and clinical significance of TTK and MDM2 in cervical lesion tissue
Mengmeng FAN ; Lili XIONG ; Ruoqi DU ; Doudou XU ; Gailing FU
Journal of China Medical University 2025;54(11):1005-1010
Objective To investigate the expression and roles of serine/threonine and tyrosine kinases(TTK)and mouse dual microbody 2(MDM2)in cervical lesion tissue.Methods Patients(n=180)who underwent gynecological surgery at the First Affiliated Hospital of Henan University of Science and Technology from June 2022 to January 2024 were evaluated,including 50 patients in the cervical cancer group,50 patients in the high-grade lesion group,40 patients in the low-grade lesion group,and 40 patients in the non-cervical lesion(control)group.The mRNA expression and protein levels of TTK and MDM2 in each group were detected and compared by real-time quantitative PCR and immunohistochemistry,respectively.The diagnostic value of the mRNA expression levels of TTK and MDM2 in cer-vical cancer was analyzed using receiver operating characteristic curves.Results The mRNA levels of TTK and MDM2 significantly dif-fered among the four groups(P<0.05);with increases in the lesion grade,the mRNA levels of TTK and MDM2 increased gradually and showed significant differences(P<0.05).Immunohistochemical results showed that TTK was mainly located in the cytoplasm,whereas MDM2 was mainly located in the nucleus,with positive expression rates in cervical cancer tissues of 84.00%and 90.00%,respectively.These values were higher than those in other pathological tissues(P<0.05).The mRNA levels of TTK and MDM2 were significantly cor-related with the degree of differentiation and lymph node metastasis(P<0.05).The receiver operating characteristic curve showed that the areas under the curve of TTK and MDM2 mRNA for diagnosing cervical cancer were 0.803 and 0.798,respectively.Additionally,the area under the curve of the combined diagnosis was 0.912,which was higher than that observed for single detection(Z=2.230,2.553,P<0.05).Conclusion The mRNA expression of TTK and MDM2 and their corresponding protein levels were increased in cervical lesions,demonstrating their potential as biological indicators for the clinical diagnosis of cervical cancer.
3.Clinical and immunological characteristics of patients with CMV infection after allogeneic hematopoietic stem cell transplantation
Man CHEN ; Wei ZHAO ; Rong WANG ; Gele TONG ; Minjing FU ; Jing ZHOU ; Ting LI ; Gailing WANG ; Nianju HAN ; Hui WANG
Chinese Journal of Laboratory Medicine 2024;47(12):1442-1449
Objective:To investigate the significance and value of peripheral blood lymphocyte subset characteristics in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for distinguishing cytomegalovirus (CMV) infection.Methods:This retrospective study gathered data from allo-HSCT patients treated at Beijing Ludaopei Hospital between May 2021 and January 2023. This study included 50 patients in the CMV infection group and 47 patients in the non-CMV infection group. Flow cytometry was used to detect peripheral blood lymphocyte subsets 1 month after the allo-HSCT. The absolute lymphocyte count and their subsets were analyzed to assess their predictive significance in the occurrence of CMV infection. Mamn-whiney U test and χ 2 test were used. Indicators with statistical significance in univariate analysis were further subjected to binary logistic regression analysis and receiver operating characteristic (ROC) curves construction. The generation of survival curves for different outcomes was conducted using the Kaplan-Meier method, and the Log-rank test was applied. A two-sided P-value of<0.05 was considered statistically significant. Results:1. Among patients in the CMV infection group, 22% (11/50) were diagnosed with CMV viremia combined with CMV disease. The maximum CMV viral load in peripheral whole blood in these patients was 1 600 (1 400, 5 800) copies/ml, which was significantly higher than that in patients without confirmed CMV disease 970 (670, 2 300) copies/ml, with a statistically significant difference ( Z=-2.281, P=0.029). 2. The overall survival (OS) at the follow-up endpoint was 80% (40/50) in the CMV infection group and 87.2% (41/47) in the non-CMV infection group. There was no statistically significant difference in OS between the two groups at the follow-up endpoint ( χ2=0.231, P=0.630). 3. In the binary logistic regression model, the number of CD34 cells transfused into the patient, the percentage of CD3+CD38+T cells in CD3+T cells, and the percentage of CD4+CD38+T cells in CD4+lymphocytes were identified as important independent risk factors for infection. The ROC curve analysis demonstrated that the area under the curve (AUC) for these independent risk factors of CMV infection was 0.914 (>0.7, P<0.001), with a decision value of 0.702, a sensitivity of 0.857, and a specificity of 0.844. Conclusion:Followingallo-HSCT, the immune subsets in the CMV infection group exhibited a diminished proportion of T cells and CD4+T cells in comparison to the non-CMV infection group. In terms of T cell differentiation, there was an increase in TEM cells and a decrease in Naive T cells. Additionally, the expression level of the activation marker CD38 on T cells exhibited a high degree of predictive value for the occurrence of CMV infection. Understanding the immune characteristics of post-transplant CMV-infected patients is beneficial for the analysis of their immune reconstitution status, providing valuable insights for clinicians in the diagnosis and treatment of CMV infection after transplantation.
4.Clinical and immunological characteristics of patients with CMV infection after allogeneic hematopoietic stem cell transplantation
Man CHEN ; Wei ZHAO ; Rong WANG ; Gele TONG ; Minjing FU ; Jing ZHOU ; Ting LI ; Gailing WANG ; Nianju HAN ; Hui WANG
Chinese Journal of Laboratory Medicine 2024;47(12):1442-1449
Objective:To investigate the significance and value of peripheral blood lymphocyte subset characteristics in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for distinguishing cytomegalovirus (CMV) infection.Methods:This retrospective study gathered data from allo-HSCT patients treated at Beijing Ludaopei Hospital between May 2021 and January 2023. This study included 50 patients in the CMV infection group and 47 patients in the non-CMV infection group. Flow cytometry was used to detect peripheral blood lymphocyte subsets 1 month after the allo-HSCT. The absolute lymphocyte count and their subsets were analyzed to assess their predictive significance in the occurrence of CMV infection. Mamn-whiney U test and χ 2 test were used. Indicators with statistical significance in univariate analysis were further subjected to binary logistic regression analysis and receiver operating characteristic (ROC) curves construction. The generation of survival curves for different outcomes was conducted using the Kaplan-Meier method, and the Log-rank test was applied. A two-sided P-value of<0.05 was considered statistically significant. Results:1. Among patients in the CMV infection group, 22% (11/50) were diagnosed with CMV viremia combined with CMV disease. The maximum CMV viral load in peripheral whole blood in these patients was 1 600 (1 400, 5 800) copies/ml, which was significantly higher than that in patients without confirmed CMV disease 970 (670, 2 300) copies/ml, with a statistically significant difference ( Z=-2.281, P=0.029). 2. The overall survival (OS) at the follow-up endpoint was 80% (40/50) in the CMV infection group and 87.2% (41/47) in the non-CMV infection group. There was no statistically significant difference in OS between the two groups at the follow-up endpoint ( χ2=0.231, P=0.630). 3. In the binary logistic regression model, the number of CD34 cells transfused into the patient, the percentage of CD3+CD38+T cells in CD3+T cells, and the percentage of CD4+CD38+T cells in CD4+lymphocytes were identified as important independent risk factors for infection. The ROC curve analysis demonstrated that the area under the curve (AUC) for these independent risk factors of CMV infection was 0.914 (>0.7, P<0.001), with a decision value of 0.702, a sensitivity of 0.857, and a specificity of 0.844. Conclusion:Followingallo-HSCT, the immune subsets in the CMV infection group exhibited a diminished proportion of T cells and CD4+T cells in comparison to the non-CMV infection group. In terms of T cell differentiation, there was an increase in TEM cells and a decrease in Naive T cells. Additionally, the expression level of the activation marker CD38 on T cells exhibited a high degree of predictive value for the occurrence of CMV infection. Understanding the immune characteristics of post-transplant CMV-infected patients is beneficial for the analysis of their immune reconstitution status, providing valuable insights for clinicians in the diagnosis and treatment of CMV infection after transplantation.
5.Study on the relationship between serum cytokines levels after chimeric antigen receptor (CAR)-T cell immunotherapy and the prognosis of bridged allogeneic hematopoietic stem cell transplantation in acute B lymphoblastic leukemia patients
Xiaoqi OU ; Man CHEN ; Wei ZHAO ; Gailing ZHANG ; Minjing FU ; Dongchu WANG ; Liyuan QIU ; Rong WANG ; Nenggang JIANG ; Jiwen FAN ; Xian ZHANG ; Yi LI ; Hui WANG
Chinese Journal of Laboratory Medicine 2023;46(5):493-500
Objective:To investigate the relationship between the levels of serum cytokines and chemokines and the prognosis of patients with acute B-ALL after receiving chimeric antigen receptor (CAR)-T cell immunotherapy and acute graft-versus-host disease (aGVHD) in patients after bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:According to the case-control principle, Forty-two patients with B-ALL who received CD19-CAR-T cell immunotherapy bridged to allo-HSCT at Heibei Yanda Ludaopei Hospital from September 18, 2019 to May 9, 2022 were enrolled. Mann-Whitney U test was used to compare the changes of aGVHD-related cytokines and chemokine levels between CAR-T cell immunotherapy and bridging transplantation in different patients at the same time. Their plasma levels of cytokines and chemokines related to aGVHD were monitored at the day before CAR-T therapy and after CAR-T treatment at day 4, 7,14,21,28. The receiver operating characteristic curve was drawn to evaluate the predictive value of cytokines and chemokines in predicting the occurrence and the death of aGVHD patients. Kaplan-Meier method and Log-rank tests were used for Overall survival (OS) analysis. Results:Twenty-four of total 42 patients had aGVHD, of which 11 patients died and 31 patients survived. There was no significant difference in cytokines and chemokines between the aGVHD group and the non-aGVHD group on the day before CAR-T cell treatment. According to statistical analysis, the serum Elafin levels of aGVHD group was higher than that of non-aGVHD group at the 21st day [4 482 (2 811, 6 061) ng/L vs 2 466 (1 948, 3 375) ng/L, Z=3.145, P=0.001] and the 28st day [4 391 (2 808, 5594) ng/L vs 2 463 (1 658, 2 830) ng/L, Z=2.038, P=0.048] separately. At the 14th day, serum cytokines and chemokines levels between the two group were as follows,MIP-1 α [21.02 (12.36, 30.35) ng/L vs 5.56 (3.64, 10.79) ng/L], sCD25 [422.47 (257.99, 1 233.78) IU/ml vs 216.11 (133.75,457.39) IU/ml], Elafin [4 101 (2 393, 5 006) ng/L vs 2 155 (1 781, 3 033) ng/L], IL-6 [119.08 (23.97, 183.43) ng/L vs 8.39 (2.91, 17.42) ng/L] and IL-8 [13.56 (12.50, 24.52) ng/L vs 2.83 (1.73,6.87) ng/L] were at higher levels ( Z=2.653, P=0.007; Z=2.176, P=0. 030; Z=2.058, P=0.041; Z=3.329, P<0.001; Z=3.162, P=0.001). The KM survival curve showed that the cumulative survival rates of patients with higher serum levels of MIP-1α, sCD25, Elafin, IL-6 and IL-8 were lower than those with low levels at day 14, and the difference was statistically significant (χ 2=12.353, 4.890, 6.551, 10.563, 20.755, P<0.05). Conclusion:The outcomes of patients treated with CAR-T cell therapy bridged to allo-HSCT was correlated with serum MIP-1α, sCD25, Elafin, IL-6 and IL-8 levels after receiving CAR-T therapy. High concentrations of MIP-1α, sCD25, Elafin, IL-6 and IL-8 suggest poor prognosis and can be used as biomarkers to suggest appropriate clinical selection of therapy.
6.Significance of multicolor flow cytometry in the detection of minimal residual disease in monitoring CD19-CAR-T cell bridging allo-HSCT treatment of B-ALL patients
Man CHEN ; Wei ZHAO ; Minjing FU ; Aixian WANG ; Gailing ZHANG ; Liyuan QIU ; Rong WANG ; Yanli ZHAO ; Xuan ZHANG ; Hui WANG
Chinese Journal of Laboratory Medicine 2022;45(8):813-819
Objective:To investigate the significance of multicolor flow cytometry (MFC) monitoring of minimal residual disease (MRD) in the course of allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CD19-chimeric antigen receptor(CAR)-T cell immunotherapy for patients with refractory, relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL).Methods:37 patients with r/r B-ALL admitted to Hebei Yanda Lu Daopei Hospital from January to July 2019, aged 15 (6, 19) years old, including 24 males and 13 females, were treated with CD19-CAR-T cell immunotherapy bridging allo-HSCT. MFC with cytoplasmic CD79a antibody to set up B-cell gates was used to monitor patients′ bone marrow (BM), cerebrospinal fluid (CSF), and tissue samples on day 0 (prior to the CAR-T cell immunotherapy), day 15, day 28 post CAR-T cell immunotherapy, and post transplantation.The MRD values of these samples were analyzed to evaluate the residual tumor cells and metastasis. The killing effect of the CAR-T cells was evaluated by the recovery of CD19+B cells before transplantation and the period between the timepoint when CD19+B cells was recovered and the timepoint when CAR-T cells were infused. Peripheral blood CAR-T cells were counted at different time points. Statistic analysis was performed by Kaplan-Meie assay and Log-rank test to analyze the difference of univariate cumulative survival.Results:(1)Among the 37 patients, 8 died and 29 survived. 5 patients relapsed after transplantation, of which 4 relapsed patients died and 1 survived. (2)MFC MRD negative remission rate of the death group was lower than that of the survival group at the following time points: post-CAR-T therapy and prior to transplantation (5/8 vs. 28/29, χ 2=7.540, P=0.006); day 15 of the CAR-T cell reinfusion (3/8 vs. 24/29, χ 2=6.512, P=0.011); day 28 of the reinfusion (3/8 vs. 276/29, χ 2=10.065, P=0.002). The probability of extramedullary MFC MRD positive tumor infiltration in the death group was higher than that in the survival group(7/8 vs. 14/29, χ 2=3.931, P=0.047). After CAR-T cell immunotherapy, the recovery period of CD19-positive cells in the death group, or the time for CAR-T cells to kill CD19-positive cells, was shorter than that in the survival group [42.00 days(30.00,49.00) vs. 55.00 days(41.50,73.50), Z=0.022, P=0.020]. Conclusion:The positive results of MRD by MFC at the following timepoints may predict unfavorable outcomes, such as post-CAR-T therapy and prior to transplantation, day 15 and 28 of the CAR-T cell immunotherapy, which may provide some guidance for clinical management.
7.Clinical study of gemcitabine combined with radiotherapy in the treatment of elderly patients with advanced cervical cancer
Chinese Journal of Biochemical Pharmaceutics 2014;(2):128-129,132
Objective To investigate the clinical efifcacy and adverse reactions of gemcitabine combined with radiotherapy in the treatment of elderly patients with advanced cervical cancer. Methods 80 elderly patients with advanced cervical cancer in the First Affiliated Hospital of Henan University of Science and Technology from June 2009 to Febrary 2012 were selected and randomly divided into control group(n=40) and observation group(n=40). Control group was given radiotherapy, while observation group was given gemcitabine combined with radiotherapy. The clinical efifcacy, incidences of adverse reactions and quality of life between two groups were compared. Results The total effective rates in 6 weeks after treatment were signiifcantly better than 1 week in both two groups(P<0.05), but there was no difference between two groups. The quality-of-life scores in observation group were signiifcantly higher than control group(P<0.05), but the incidence of adverse reactions in observation group was also signiifcantly higher than control group(P<0.05). Conclusion Gemcitabine combined with radiotherapy in the treatment of elderly patients with advanced cervical cancer has better clinical efifcacy and patients could enjoy a better quality of life, but it has a higher incidence of adverse reactions, so this combination therapy should depend on the speciifc situation of patients.
8.Therapeutic Effect of Jade Maid Decoction for Experimental Periodontitis in Rabbits
Yi LI ; Yanhui LIU ; Gailing WANG ; Ludi FU
Journal of Guangzhou University of Traditional Chinese Medicine 2000;0(04):-
Objective To observe the therapeutic effect of Jade Maid Decoction(JMD),a Chinese herbal prescription for nourishing yin and clearing stomach-heat,on experimental periodontitis.Methods Twenty-four New Zealand rabbits were randomized into the model group,JMD group(oral use of JMD 23 g?kg-1?d-1),external application group(periodontal injection of minocycline hydrochloride ointment 50mg),and the combination group(oral use of JMD and periodontal injection of minocycline hydrochloride ointment).Experimental periodontitis was induced by ligation method.The treatment lasted 6 weeks.Gingival bleeding on probing(BOP) and probing pocket depth(PPD) were detected each week after medication,and pathological examination of the mandible was used to confirm the therapeutic effect after treatment.Results Gingival BOP was reduced to various degrees at different time in the three medication groups,and the effect was obvious in the combination group;PPD was also decreased to various degrees,and the difference of PPD between the three medication groups and the model group was significant after treatment for 4 weeks(P

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