1.Kinetic characteristics of T cell expansion in patients with B tumor after CAR19 T cell therapy
Lan DAI ; Ren MEI ; Wenhong SHEN ; Ziling ZHU ; Mengjie CAI ; Na′na PING ; Chongsheng QIAN ; Linyan HE ; Xia BAI ; Mingqing ZHU
Chinese Journal of Laboratory Medicine 2024;47(12):1435-1441
Objective:To investigate the proliferation kinetics of T cells in patients with B-cell hematologic malignancies who received CAR19 T cell therapy.Methods:Observational study. Flow cytometry was used to monitor the levels of CAR19+and CAR19-T cell expansion and the dynamic changes of T lymphocyte subsets before and after CAR19 T cell therapy. The 52 patients with B-cell hematologic malignancies (including 12 B-ALL and 40 NHL) who received CAR19 T cell therapy in the First Affiliated Hospital of Soochow University from November 2021 to December 2023 were recruited in this study. Patients were divided into complete response group and incomplete response group according to the efficacy evaluation criteria in the treatment guidelines for B-cell hematologic malignancies. T test or non-parametric rank sum test were used to compare the differences of CAR19+and CAR19-T cell subsets between the two groups.Results:At the peak of CAR19+T cell expansion, there was no statistic difference of CAR19+T cell subsets between the complete response group and the incomplete response group. After 6 months, the percentage of CD4+T cells (CD3+CD4+CD8-) in CAR19-T cells in patients was lower than the pre-treatment level(48.0+27.2,63.1+19.7,<0.01), and the percentages of CD197+CD45RA+and CD197-CD45RA-subsets recovered to the pre-treatment level, while the percentage of CD197-CD45RA+subset(4.2+3.0,21.1+15.6,<0.01) was lower than the pre-treatment level. The percentage of CD8+T cells (CD3+CD4-CD8+) returned to pre-treatment level after 6 months, CD197-CD45RA-subset in CD8+T cells returned to pre-treatment level, while CD197+CD45RA+subset(16.6+8.7,35.1+30.1,<0.01),CD197+CD45RA-subset(18.7+9.1,25.8+19.1,<0.01) were still lower than pre-treatment level.Conclusion:After CAR19 T cell treatment, there was no significant differences in the proportions of CAR19+T cell subsets in patients with different therapeutic effects. After treatment, the proportion of CAR19-CD3+CD4-CD8+cells recovered earlier than CD3+CD4+CD8-cells, and the dynamic changes of each subgroup were different. This therapeutic regimen has a great impact on the subpopulation of CAR19-T cells in vivo, and the reconstruction of such T cells takes a long time.
2.Kinetic characteristics of T cell expansion in patients with B tumor after CAR19 T cell therapy
Lan DAI ; Ren MEI ; Wenhong SHEN ; Ziling ZHU ; Mengjie CAI ; Na′na PING ; Chongsheng QIAN ; Linyan HE ; Xia BAI ; Mingqing ZHU
Chinese Journal of Laboratory Medicine 2024;47(12):1435-1441
Objective:To investigate the proliferation kinetics of T cells in patients with B-cell hematologic malignancies who received CAR19 T cell therapy.Methods:Observational study. Flow cytometry was used to monitor the levels of CAR19+and CAR19-T cell expansion and the dynamic changes of T lymphocyte subsets before and after CAR19 T cell therapy. The 52 patients with B-cell hematologic malignancies (including 12 B-ALL and 40 NHL) who received CAR19 T cell therapy in the First Affiliated Hospital of Soochow University from November 2021 to December 2023 were recruited in this study. Patients were divided into complete response group and incomplete response group according to the efficacy evaluation criteria in the treatment guidelines for B-cell hematologic malignancies. T test or non-parametric rank sum test were used to compare the differences of CAR19+and CAR19-T cell subsets between the two groups.Results:At the peak of CAR19+T cell expansion, there was no statistic difference of CAR19+T cell subsets between the complete response group and the incomplete response group. After 6 months, the percentage of CD4+T cells (CD3+CD4+CD8-) in CAR19-T cells in patients was lower than the pre-treatment level(48.0+27.2,63.1+19.7,<0.01), and the percentages of CD197+CD45RA+and CD197-CD45RA-subsets recovered to the pre-treatment level, while the percentage of CD197-CD45RA+subset(4.2+3.0,21.1+15.6,<0.01) was lower than the pre-treatment level. The percentage of CD8+T cells (CD3+CD4-CD8+) returned to pre-treatment level after 6 months, CD197-CD45RA-subset in CD8+T cells returned to pre-treatment level, while CD197+CD45RA+subset(16.6+8.7,35.1+30.1,<0.01),CD197+CD45RA-subset(18.7+9.1,25.8+19.1,<0.01) were still lower than pre-treatment level.Conclusion:After CAR19 T cell treatment, there was no significant differences in the proportions of CAR19+T cell subsets in patients with different therapeutic effects. After treatment, the proportion of CAR19-CD3+CD4-CD8+cells recovered earlier than CD3+CD4+CD8-cells, and the dynamic changes of each subgroup were different. This therapeutic regimen has a great impact on the subpopulation of CAR19-T cells in vivo, and the reconstruction of such T cells takes a long time.
3.Clinical prognostic analysis of 124 adult patients with hemophagocytic lymphohistiocytosis: a multicenter retrospective study of the Huaihai Lymphoma Working Group
Ziyuan SHEN ; Chenlu HE ; Qian SUN ; Shuo ZHANG ; Lingling HU ; Qinhua LIU ; Hao ZHANG ; Xin LIU ; Yuqing MIAO ; Weiying GU ; Fei WANG ; Chunling WANG ; Yuye SHI ; Ling WANG ; Jun JIAO ; Jingjing YE ; Linyan XU ; Dongmei YAN ; Zhenyu LI ; Yingliang JIN ; Shuiping HUANG ; Kailin XU ; Wei SANG
Chinese Journal of Hematology 2021;42(10):800-806
Objective:Factors influencing the prognosis of hemophagocytic lymphohistiocytosis (HLH) in adults were analyzed based on multicentric data.Methods:Clinical data of 124 adult patients with HLH diagnosed in eight medical centers in the Huaihai Lymphoma Working Group from March 2014 to July 2020 were collected. The optimal truncation value of continuous variables was obtained based on the Maxstat algorithm, X-Tile software, and restricted cubic spline. Cox proportional risk regression model was used to construct the adult HLH risk prediction model, and the visualization of the model was realized through the histogram. The bootstrap resampling method was used to verify the model, C-index and calibration curve was used to verify the histogram, and the prediction accuracy was checked. Kaplan-Meier analysis was used to calculate the survival rate and draw the survival curve. Furthermore, the differences between groups were tested by log-rank.Results:The median age of the 124 patients was 55 (18-84) years, including 61 (49.19%) males. The most common etiology was infection. Serum ferritin increased in 110 cases (88.71%) , hepatosplenomegaly in 57 cases (45.97%) . Of the 124 patients, 77 (62.10%) died, and the median survival time of the patients was 7.07 months. Univariate results showed that the prognosis of adult HLH was influenced by sex, age, fibrinogen, serum creatinine, alanine aminotransferase, and albumin ( P<0.05) . The results of multivariate analysis showed that gender, platelet, albumin, alanine aminotransferase, and treatment regimens were independent influencing factors for prognosis. Based on the above five risk factors, the prediction model of the histogram was established, and the C-index of the model was 0.739. Finally, the calibration chart showed good consistency between the observed and predicted values of HLH. Conclusion:The prognosis of the adult hemophagocytic syndrome is influenced by many factors. Gender, platelet, albumin, alanine aminotransferase, and treatment regimens are independent risk factors. Therefore, the established histogram provides a visual tool for clinicians to evaluate the prognosis of adult HLH.
4. Maternal breast feeding safety of hepatitis B virus carrying parturient women with hepatitis B surface antigen and hepatitis B e antigen double positive
Hong WANG ; Hongping WANG ; Linyan QIAN ; Lingyan XU
Chinese Journal of Infectious Diseases 2020;38(1):44-48
Objective:
To explore hepatitis B virus (HBV) infection rate of breast feeding to newborn babies of HBV carrying parturient women with hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) double positive.
Methods:
A prospective cohort study was conducted to include HBsAg and HBeAg double-positive HBV carrying parturient women and their babies born from February 2016 to May 2018 at the Women′s Hospital, Zhejiang University School of Medicine, and 323 parturient women and 323 babies were enrolled. The babies were divided into breast feeding group and artificial feeding group. Chemiluminescence immunoassay and polymerase chain reaction-fluorescent probe method were used to detect the positive rates of serum HBV markers and HBV DNA levels in the newborns <24 h and seven-month-old age, respectively. The statistical method was performed using
5. Rapamycin in the treatment of renal diseases associated with tuberous sclerosis complex
Shuo DUN ; Liping ZOU ; Mengna ZHANG ; Yangyang WANG ; Wen HE ; Huimin CHEN ; Linyan HU ; Xiaoqiao CHEN ; Qian LU ; Lingyu PANG ; Liying LIU ; Lina TANG ; Bin WANG
Chinese Journal of Pediatrics 2019;57(11):852-856
Objective:
To investigate the efficacy and safety of rapamycin in children with tuberous sclerosis complex (TSC) associated renal disease.
Methods:
A prospective self-control study was conducted. The clinical data of 92 children diagnosed with tuberous sclerosis complex associated kidney disease at the People′s Liberation Army General Hospital from January 2011 to January 2019 were collected. The long-term rapamycin treatment for all patients initiated at 1 mg/(m2·d), which was gradually adjusted to reach a blood concentration of 5-10 μg/L. The changes of the maximum diameter of renal lesions in children after rapamycin treatment were observed and analyzed with Wilcoxon test.
Results:
Ninety-two children, including 52 males and 40 females, who met the criteria were analyzed. Sixty patients had only renal angiomyolipoma(RAML), while 24 patients had only multiple renal cysts(MRC), and 8 patients had both lesions. The age of TSC diagnosis was 16.0 (7.0, 42.0) months, and the age of initial treatment with rapamycin was 63.5 (21.0, 103.0) months. The follow-up lasted for 12.0 (4.0, 23.0) months. Sequencing of TSC1 and TSC2 genes was performed in 54 children with TSC, including 3 patients (6%) with mutations in TSC1 gene and 51 patients (94%) with mutations in TSC2 gene. The maximum RAML diameter before treatment was 7.0 (4.0, 9.0) mm. The best effect reached at 3 months of treatment, with the diameter of 4.0 (0,7.0) mm. The maximum diameters at 6 months, 1 year and 1-2 years were 5.0 (0,9.8) mm, 5.0 (1.5, 8.5) mm, 5.5 (3.0, 9.0) mm, respectively, and were significantly different from the baseline (
6.Rapamycin in the treatment of renal diseases associated with tuberous sclerosis complex
Shuo DUN ; Liping ZOU ; Mengna ZHANG ; Yangyang WANG ; Wen HE ; Huimin CHEN ; Linyan HU ; Xiaoqiao CHEN ; Qian LU ; Lingyu PANG ; Liying LIU ; Lina TANG ; Bin WANG
Chinese Journal of Pediatrics 2019;57(11):852-856
To investigate the efficacy and safety of rapamycin in children with tuberous sclerosis complex (TSC) associated renal disease. Methods A prospective self?control study was conducted. The clinical data of 92 children diagnosed with tuberous sclerosis complex associated kidney disease at the People's Liberation Army General Hospital from January 2011 to January 2019 were collected. The long?term rapamycin treatment for all patients initiated at 1 mg/(m2·d), which was gradually adjusted to reach a blood concentration of 5-10 μg/L. The changes of the maximum diameter of renal lesions in children after rapamycin treatment were observed and analyzed with Wilcoxon test. Results Ninety?two children, including 52 males and 40 females, who met the criteria were analyzed. Sixty patients had only renal angiomyolipoma(RAML), while 24 patients had only multiple renal cysts(MRC), and 8 patients had both lesions. The age of TSC diagnosis was 16.0 (7.0, 42.0) months, and the age of initial treatment with rapamycin was 63.5 (21.0, 103.0) months. The follow?up lasted for 12.0 (4.0, 23.0) months. Sequencing of TSC1 and TSC2 genes was performed in 54 children with TSC, including 3 patients (6%) with mutations in TSC1 gene and 51 patients (94%) with mutations in TSC2 gene. The maximum RAML diameter before treatment was 7.0 (4.0, 9.0) mm. The best effect reached at 3 months of treatment, with the diameter of 4.0 (0, 7.0) mm. The maximum diameters at 6 months, 1 year and 1-2 years were 5.0 (0,9.8) mm, 5.0 (1.5, 8.5) mm, 5.5 (3.0, 9.0) mm, respectively, and were significantly different from the baseline (Z=-2.404,-2.350,-2.750, P=0.016,0.019,0.006, respectively). The maximum diameter after 2-3 years, and≥3 years were 5.0 (3.9,7.0) mm and 6.0 (1.0, 11.0) mm, without significant difference from the baseline (Z=-0.856,-0.102, P=0.393, 0.919, respectively).The maximum diameters of MRC after 3 months, 6 months, 1 year,1-2 years, 2-3 years, and≥3 years were 11.0 (5.0, 14.0) mm,3.0 (0.0,11.0) mm,5.0 (0,21.0) mm,0 (0,14.0) mm,0 (0,10.0) mm, and 0 (0, 18.3) mm, respectively, but were not significantly different rom the baseline (7.0 (5.0, 15.7) mm) (Z=-0.944,-1.214,-1.035,-1.896,-1.603,-1.214, P=0.345, 0.225, 0.301, 0.058, 0.109, 0.225, respectively). Twenty?nine patients (32%) had oral ulcers during the entire treatment period, and no serious adverse reactions were observed. Conclusions Rapamycin could decrease the diameter of TSC?related RAML, but could not inhibit the growth of cysts. It is well tolerated in the treatment of renal diseases associated with tuberous sclerosis complex.
7.Design of a portable SSVEP signal acquisition system
Yabin DONG ; Lei WANG ; Linlin WANG ; Qian LI ; Linyan CHAI ; Yan WANG
International Journal of Biomedical Engineering 2019;42(3):222-226
Objective To design a portable electroencephalography(EEG) acquisition system to acquire and analysis steady-state visual potentials (SSVEP). Methods The microprocessor MSP432P401 series MCU was used to control the high-performance integrated analog front end ADS1299 to realize the acquisition, amplification and analog-to-digital (AD) conversion of EEG signals. The digital EEG signal is sent to the host computer for processing by WIFI. Spontaneous EEG signals and steady-state visually evoked EEG signals from 3 healthy subjects were collected to verify system performance. Results The collected signal had a clear α-wave rhythm of closed-eye spontaneous EEG signals. The power spectrum density shows that the steady-state visually induced EEG signal frequency and harmonic frequency peak at the corresponding stimulation frequency, indicating that the system works normally and the performance is good. Conclusions The designed portable EEG acquisition system can accurately collect the spontaneous and induced EEG signals of the human body, which provides technical support for the clinical application of SSVEP technology.
8.Aberrant Resting-State Functional Connectivity in the Default Mode Network in Pediatric Bipolar Disorder Patients with and without Psychotic Symptoms.
Yuan ZHONG ; Chun WANG ; Weijia GAO ; Qian XIAO ; Dali LU ; Qing JIAO ; Linyan SU ; Guangming LU
Neuroscience Bulletin 2019;35(4):581-590
Mood disorders/psychosis have been associated with dysfunctions in the default mode network (DMN). However, the relative contributions of DMN regions to state and trait disturbances in pediatric bipolar disorder (PBD) remain unclear. The aim of this study was to investigate the possible mechanisms of PBD through brain imaging and explore the influence of psychotic symptoms on functional alterations in PBD patients. Twenty-nine psychotic and 26 non-psychotic PBD patients, as well as 19 age- and sex-matched healthy controls underwent a resting-state functional MRI scan and the data were analyzed by independent component analysis. The DMN component from the fMRI data was extracted for each participant. Spearman's rank correlation analysis was performed between aberrant connectivity and clinical measurements. The results demonstrated that psychotic PBD was characterized by aberrant DMN connectivity in the anterior cingulate cortex/medial prefrontal cortex, bilateral caudate nucleus, bilateral angular gyri, and left middle temporal gyrus, while non-psychotic PBD was not, suggesting further impairment with the development of psychosis. In summary, we demonstrated unique impairment in DMN functional connectivity in the psychotic PBD group. These specific neuroanatomical abnormalities may shed light on the underlying pathophysiology and presentation of PBD.
9.Binary cardiac rehabilitation in patients with acute myocardial infarction and the measurement of 6-minute Walk Test
Xiaoru CHE ; Linyan QIAN ; Jie PANG ; Juebao LI ; Hui WANG ; Yunlan DAI ; Zhanhong QIAN ; Yaju QIU ; Jing WANG ; Xuelie HU ; Xianda CHE
Chinese Journal of Emergency Medicine 2018;27(6):657-662
Objective To study the effects of binary cardiac rehabilitation (CR) composed of hospital-based and home-based CR in patients after acute myocardial infarction (AMI) evaluated by six-minute walking distance (6MWD). Methods A total of 38 post-MI patients were divided into two groups, namely conventional CR group (n=20) and binary CR group (n=18). In the first seven days, CR training was carried out in all 38 patients in our hospital, and then 20 patients were kept at CR training in the hospital (hospital-based CR group), whereas the remaining 18 patients (binary CR group) got tele-monitored walking training at home for eight weeks (binary model). Before discharge from hospital based CR or after 8 weeks CR at home, all patients received Cardiopulmonary Exercise Testing and Six-minute Walk Test, and the data of patients' body mass index (BMI),thyroid function, serum lipid metabolism and echocardiography were collected before and after CR. Results After CR, BMI and low density lipoprotein (LDL) decrease in both groups compared with those before CR[hospital-based group: BMI, (25.99±3.36)kg/m2 vs. (23.04±3.72) kg/m2,P<0.05; LDL, (3.40±1.38) mg/dl vs. (2.04±0.73)mg/ dl,P<0.01; binary group: BMI, (24.84±2.70) kg/m2 vs. (22.88±2.56) kg/m2,P<0.05; LDL, (3.40±1.01) mg/dl vs. (92.11±0.37) mg/dl,P<0.01]. After 8 weeks CR at home or hospital based CR until discharge, the anaerobic threshold (AT), maximum rate of oxygen consumption (VO2max),metabolic equivalent (MET) and 6MWD improved significantly in both groups compared with those at 7 days after CR in hospital [Hospital-based group: AT, (12.37±1.53) mL/(kg. min) vs. (14.77±1.57) mL/(kg. min); VO2max (17.87± 1.66 mL/(kg. min) vs. (20.73±2.14) mL/(kg. min); MET (5.02±0.36) vs. (6.09±0.53); 6MWD (500±53.36) m vs. (582.5±57.6) m,P<0.01; Binary group: AT, (12.56±1.11) mL/(kg·min) vs. (14.30±1.23) mL/(kg. min); V02max, (17.28±1.38) mL/(kg. min) vs. (20.02±1.37) mL/(kg. min); MET, (5.07±0.47)vs (5.94±0.46); 6MWD,(511.4±50.96) m vs. (590.3±56.1)m,P<0.01]. There was no significant difference in CR effects observed between two groups (P>0.05). Conclusions In post-MI patients,a binary model of CR training improved physical capacity and was a similarly effective form of CR as a entirely hospital-based approach. A home-based tele-monitored program facilitated patients' adherence to CR. The 6 minute walk experiment is economical and good evaluation on the CR effect of binary cardiac rehabilitation.
10. Intervention study of compassion fatigue of oncology nurses in Balint group activities
Linyan YAO ; Minli XIANG ; Zhihong YE ; Ying QIAN ; Qin LU ; Linjuan YAN ; Liya JIANG ; Hongbo ZHONG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2017;35(12):910-913
Objective:
To explore the effectiveness of Balint group on compassion fatigue among oncology nurses.
Methods:
From January to December 2016, 35 oncology nurses from one general hospital were enrolled. 18 cases were allocated in the observation group and 17 cases in the control group by computer randomization. Nurses in the observation group were received a total of 8 times Balint Group activities, with 2 times a month and 1.5 hours each time, which is aiming to discuss difficult cases encountered in the clinic to help nurses have a deeper experience and a better understanding of the emotions and behaviors, fantasies and needs between nurse-patient interaction. Nurses in the control group without intervention. All the Participants were requested to complete the survey of the Professional Quality of Life (ProQOL) , the Jefferson Scale of Empathy-Health Professionals (JSE-HP) , and the General Health Questionnaire (GHQ) at pre and post intervention.
Results:
Before intervention, two group of nurses in age, working years, marriage, and education were not statistically significant (

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