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.Effects of modified radical prostatectomy via an extraperitoneal approach on urinary control and sexual function in patients with prostate cancer
Liyu SHEN ; Hongzhang CHEN ; Wenhong CHEN ; Mingtao LI ; Yuping WU ; Haifeng CHEN
Chinese Journal of Primary Medicine and Pharmacy 2022;29(7):1019-1022
Objective:To investigate the effects of modified radical prostatectomy via an extraperitoneal approach on urinary control and sexual function in patients with prostate cancer.Methods:Fifty-six patients with stable prostate cancer who received treatment in Deqing People's Hospital between March 2015 and March 2018 were included in this study. They were randomly divided into observation and control groups ( n = 28/group). The observation group was subjected to modified radical prostatectomy via an extraperitoneal approach. The control group underwent standard laparoscopic surgery. Clinical efficacy and the effects of modified radical prostatectomy via an extraperitoneal approach on urinary control and sexual function were compared between the two groups. Results:Amount of blood loss and postoperative drainage were (125.39 ± 11.12) mL and (65.39 ± 10.12) mL in the observation group, and (224.79 ± 14.01) mL and (104.79 ± 15.01) mL in the control group. There were no significant differences in amount of blood loss and postoperative drainage between the two groups ( t = 18.83, 15.67, both P < 0.05). At 1, 3 and 6 months after surgery, the percentage of patients who had urinary control recovery in the observation group was 53.57% (15/28), 78.57% (22/28), 98.21% (27/28), respectively, which were significantly higher than those in the control group [21.43% (6/28), 35.71% (10/28), 67.86% (19/28), χ2 = 4.12, 7.21, 5.01, all P < 0.05]. At 1, 3 and 6 months after surgery, the score of erectile function recovery in the observation group was (15.98 ± 0.28) points, (15.99 ± 0.72) points, and (18.91 ± 0.48) points, which were significantly higher than those in the control group [(17.11 ± 0.34) points, (13.11 ± 0.48) points, (13.41 ± 0.39) points, t = 3.01, 12.89, 15.78, all P < 0.05]. Conclusion:Modified radical prostatectomy via an extraperitoneal approach can improve postoperative urinary control and sexual dysfunction.
4.Clinical characteristics of the 2019 novel coronavirus Omicron variant infected cases
Ying LYU ; Wei YUAN ; Dongling SHI ; Yixin LIAO ; Yingchuan LI ; Ming ZHONG ; Feng LI ; Enqiang MAO ; Yinzhong SHEN ; Jinfu XU ; Yuanlin SONG ; Bijie HU ; Wenhong ZHANG ; Yun LING
Chinese Journal of Infectious Diseases 2022;40(5):257-263
Objective:To investigate the clinical characteristics and prognostic factors of 2019 novel coronavirus (2019-nCoV) Omicron variant infected cases.Methods:A total of 987 coronavirus disease 2019 (COVID-19) adult imported cases admitted to Shanghai Public Health Clinical Center, Fudan University from July 1, 2021 to January 6, 2022 were recruited. The cases were divided into Omicron group (193 cases) and non-Omicron group (794 cases) according to the genotype of the virus. The clinical data, imaging examination and laboratory results of two groups were collected and compared. Chi-square test and Mann-Whitney U test were used as statistical methods. Multiple linear regression analysis was used for multiple linear regression analysis. Results:The majority of patients in Omicron group were 18 to 30 years old, accounting for 51.3%(99/193), which was higher than 31.4%(249/794) in non-Omicron group. The difference was statistically significant ( χ2=52.75, P<0.001). The proportion of mild cases in Omicron group was 88.6%(171/193), which was higher than 81.6%(648/794) in non-Omicron group. The difference was statistically significant ( χ2=5.37, P=0.021). Cases with symptoms were more common in Omicron group than those in non-Omicron group (60.1%(116/193) vs 29.1%(231/794)), and the difference was statistically significant ( χ2=65.49, P<0.001), with the main clinical manifestations of sore/itchy throat, fever and cough/expectoration. The proportion of cases with pulmonary computed tomography (CT) imaging manifestations at admission in Omicron group was 13.0%(25/193), which was lower than that in non-Omicron group (215/794, 27.1%). The difference was statistically significant ( χ2=16.83, P<0.001). The proportion of cases with 2019-nCoV IgG positive at admission was 47.7%(92/193) in Omicron group, which was lower than 61.1%(485/794) in non-Omicron group, and the difference was statistically significant ( χ2=11.51, P<0.001). The hospitalization time of Omicron group was 20.0 (16.0, 23.0) d, which was longer than that of non-Omicron group (14.0 (10.0, 22.0) d), and the difference was statistically significant ( Z=-7.42, P<0.001). Multiple linear regression analysis showed that the time of hospitalization of cases with 2019-nCoV IgG positive at admission was shorter, while that of the cases with fever in Omicron group was longer (both P<0.050). Conclusions:The main clinical characteristics of cases with Omicron variant are fever and upper respiratory symptoms. Their pulmonary CT imaging manifestations are less, and the time of hospitalization is slightly longer. The time of hospitalization and the virus clearance time in Omicron variant infected cases with 2019-nCoV IgG positive at admission and not presented with fever are both shorter.
5.Correlation of soluble thrombomodulin and high sensitive C reactive protein with hypercoagulability in children with primary nephrotic syndrome
Xuan ZHANG ; Bili ZHANG ; Wenhong WANG ; Yan LIU ; Xin WANG ; Yongming SHEN
Chinese Journal of Applied Clinical Pediatrics 2017;32(5):342-345
Objective To explore the correlations of soluble thrombomodulin (sTM) and high sensitive C reactive protein(hs-CRP) levels with the hypercoagulable state and indicators of predicting thrombosis in children with primary nephrotic syndrome(PNS).Methods Sixty-four PNS patients who had primary clinical diagnosis or recurrence after hormone withdrawal for 6 months or more hospitalized in Department of Urology,the Second Children's Hospital of Tianjin from January 2010 to January 2014 were selected as PNS group.Thirty patients with inguinal hernia undergoing elective surgery hospitalized in Department of Surgery,the Second Children's Hospital of Tianjin from January 2010 to January 2014 were selected as control group.All the selected patients were extracted for venous blood samples,and the double-antibody sandwich enzyme-linked immunosorbent assay was used to detect plasma sTM levels,while immunoturbidimetric assay was used to detect plasma hs-CRP levels;the indicators of predicting thrombosis as blood lipid and fibrinogen(Fb) etc.were simultaneously detected.Inspection results were compared and the correlation was analyzed by using statistical methods.Results The level of plasma sTM in children with PNS was significantly higher than that in the control group[(1.63 ±0.68) μg/L vs.(0.30 ±0.24) μg/L],and the difference was statistically significant between the 2 groups (t =12.545,P < 0.05).The level of plasma sTM in PNS group with urine protein negative was significantly lower than that before hormone treatment[(1.05 ± 0.56) μg/L vs.(1.63 ± 0.68) μg/L],and there was a statistically significant difference(t =6.298,P < 0.05).The level of plasma sTM in children with PNS had positive correlation with 24 h urinary protein,low density lipoprotein,apolipoprotein B,lipoprotein a and Fb (r =0.379,0.203,0.184,0.177,0.224,all P < 0.05).The level of plasma hs-CRP in children with PNS was significantly higher than that in the control group [(1.9 ± 1.7) mg/L vs.(0.7 ± 0.6) mg/L],and the difference was statistically significant between the 2 groups (t =3.487,P < 0.05).In PNS group,the level of plasma hs-CRP with urine protein negative was significandy lower than that before hormone treatment[(0.4 ±0.3) mg/L vs.(1.9 ± 1.7) mg/L],and there was a statistically significant difference (t =5.473,P < 0.05).The level of plasma hs-CRP in children with PNS was negatively correlated with plasma albumin (r =-0.194,P < 0.05),but positively correlated with Fb (r =0.257,P < 0.01).Plasma sTM and hs-CRP levels in children with PNS were positively correlated (r =0.395,P < 0.05).Conclusions sTM involves in the formation process of PNS hypercoagulable state possibly through dual influencing by blood coagulation process and blood lipids.sTM may be used as one of the reference indicators for PNS activity and prediction of thrombosis.Plasma hs-CRP reflects the micro-inflammatory state in children with PNS,and involves in the formation of hypercoagulability by effecting blood coagulation process,and should be used as indicators for monitoring the hypercoagulability of active PNS.
6.Analysis of clinical characteristics and risk factors of stroke-associated pneumonia in patients with acute cerebral hemorrhage
Haiyan LI ; Bin DAI ; Guangli SHEN ; Wenhong LIU ; Rui FU
Chinese Journal of Geriatrics 2017;36(3):274-277
Objective To explore the clinical characteristics and risk factors of strokeassociated pneumonia (SAP) in patients with acute cerebral hemorrhage.Methods A total of 375 patients with acute cerebral hemorrhage were selected from the department of neurology and neurosurgery during January 2013 to December 2015 in our hospital.According to the incidence of SAP,they were divided into the observation group (complicated with SAP,n =79) and control group (not complicated with SAP,n =296).Clinical data were collected,and clinical characteristics and related risk factors of SAP complicated with acute cerebral hemorrhage were analyzed.Results Among all the 79 SAP patients in observation group,there were 38 cases with gram-negative bacterial infections,25 cases with gram-positive bacterial infections,16 cases with mixed infections.The SAP incidence in patients with massive hemorrhage was higher than that in patients with nonmasive hemorrhage (x2 =11.301,P< 0.01),and was higher in patients with cerebellum,brainstem,ventricle,thalamus and multifoeal hemorrhage than that in patients with basal ganglion and brain lobe hemorrhage(x2 =4.023,P<0.05).The hospitalization days of the observation group was longer than that of the control group [(32.7 ± 16.2) versus (17.3 ± 6.7),t=2.93,P< 0.01].The mortality of the observation group was higher than that of the control group (24.1% versus 3.7%),(x2 =8.720,P< 0.01).Multivariate Logistic regression analysis showed that age≥ 65 (OR =4.87),underlying lung diseases (OR =5.30),bulbar paralysis (OR =7.39),disorder of consciousness (OR=4.11),NIHSS score > 4 (OR =3.96),invasive airway operations (OR=3.78),gastric tube (OR =4.37),H2-receptor blocking agents application (OR =2.09) were independent risk factors for SAP in acute intraerebral hemorrhage patients.Conclusions Gram-negative bacteria are the main pathogens of SAP in patients with acute cerebral hemorrhage.The patients complicated with SAP after acute cerebral hemorrhage have poor prognosis including prolonged hospitalization period and higher mortality.SAP in acute intraerebral hemorrhage patients is closely related to the following factors:age≥65,underlying lung diseases,bulbar paralysis,disorder of consciousness,NIHSS score > 4,invasive airway operations,gastric tube,H2-receptor blocking agents.
7.Analysis of distribution characteristics of clinical isolates of nontuberculous mycobacteria in a general hospital
Yaojie SHEN ; Wei LIU ; Jialin JIN ; Xiaofei JIANG ; Xuelian ZHANG ; Wenhong ZHANG
Chinese Journal of Infectious Diseases 2017;35(10):580-584
Objective To investigate the current prevalence of nontuberculous mycobacteria (NTM) in Shanghai,and to study the distribution characteristics of NTM clinical isolates,which may help to improve the diagnostic level of NTM and provide guidance for effective prevention and treatment of NTM infection.Methods Culture-positive isolates of clinical mycobacteria were collected from 2008 to 2013 in Huashan Hospital affiliated to Fudan University.All isolates were heat inactivated,and the genomic DNA was extracted and the species were identified by comprehensive comparative analysis of 16S rDNA,hsp65 and rpoB target genes sequencing.Results From January 2008 to December 2013,the overall mycobacterial culture-positive rate was 4.1 % (411/10 015).After excluding the repeated isolates,a total of 253 culture-positive mycobacteria isolates were collected for the species identification.By genes sequencing analysis,140 isolates were identified as mycobacterium tuberculosis complex (MTBc),102 NTM and 11 Nocardias,accounting for 55.3%,40.3% and 4.4%,respectively.Positive rate of NTM isolates had an increasing trend from 25.0% in 2008 to 42.7% in 2013,reaching a highest rate of 54.9% in 2012.In further analysis of 102 NTM isolates,16 species were identified.Among them,28 were M.abscesses,18 strains of M.marinum,17 strains of M.avium-intracellulare complex and 10 strains of M.fortuitum,accounted for 27.5%,17.6%,16.7% and 9.8%,respectively.Conclusions Both of the isolation number and isolation rate of NTM in the general hospital are increasing.NTM related cases are also increasing in recent years,which mainly caused by M.abscess,M.marinum,M.aviumintracellulare complex and M.fortuitum.
8.Evaluation on allergic rhinitis treated by sphenopalatine ganglion stimulation with acupuncture:a systematic review
Lihe CHEN ; Lu ZHANG ; Wenhong MAO ; Jianwu SHEN ; Bo LI ; Zhixian XU ; Mengmeng GUO ; Kejian WANG ; Lijuan ZHANG ; Feng XU
International Journal of Traditional Chinese Medicine 2016;38(3):254-260
Objective The advantages of the treating allergic rhinitis (AR) by sphenopalatine ganglion stimulation with acupuncture were evaluated.Methods Databases including CBMDisk, CNKI, WanFang, VIP, Cochrane Library, PubMed, ProQuest, ChiCTR, ISRCTN, ClinicalTrials.gov and CENTRAL were searched from the beginning of database established to Jan 2015. All issues from Jan 2004 to Jan 2015 published onjournals Chinese Acupuncture & Moxibustion,Shanghai Journal of Acupuncture and Moxibustion, Acupuncture Research,Journal of Clinical Acupuncture and Moxibustion,Chinese Journal of Integrated Traditional and Western Medicine and Chinese Journal of Otorhinolaryngology in Integrative Medicine were searched by hand at meantime. All data were extracted based on the inclusive and exclusive criteria which was pre-designed, the Revman5.3 was applied for meta-analysis, and the studies qualities were analyzed by grade score.Results 118 articles were collected, 7 studies that involving 1 230 patients met the inclusive criteria. The result indicated that the sphenopalatine ganglion stimulation with acupuncture as the main treatment of AR showed the better total response rate compared to conventional drugs, theOR(95%CI) was 3.22(1.81 - 5.75); however the change of total symptom score had no statistical significant difference, the MD(95%CI) was 0.69 (-0.56 - 1.93), the change of IgE had no statistical significant difference,theSMD(95%CI) was -0.07 (-0.97 - 0.83).Conclusion The main treatment on AR by sphenopalatine ganglion stimulation with acupuncture may has better efficacy than western medicine. But due to the methodological biases existed in most studies, future high-quality RCTs were needed to be included into Meta-analysis to test today’s study conclusion.
9.The tuberculosis prevalence and risk factors among silicotic patients
Xitian HUANG ; Xuefeng LIU ; Qiaoling RUAN ; Lingyun SHAO ; Wei LIU ; Limin CAI ; Qiao LING ; Yaojie SHEN ; Qingluan YANG ; Feng SUN ; Yuhang LING ; Yan GAO ; Wenhong. ZHANG
Chinese Journal of Infectious Diseases 2015;(5):276-280
Objective To investigate the prevalence of tuberculosis among silicosis patients and silica exposure patients,and to analysis the risk factors of tuberculosis among these population.Methods A total of 1 227 silica exposure patients from Wenling,Zhejiang were enrolled in this field study.Basic demographic information was collected and chest X-ray was taken for each patient.Sputum was collected for Mycobacterium tuberculosis culture and strain identification. In univariate analysis,t test was performed for continuous variables andχ2 test for categorical variables.In multivariate analysis,the odds ratio (OR )was calculated along with a 95 % confidence interval (CI )by binary Logistic regression. Results A total of 1 204 silica exposure patients had full basic information and 99.8% were male patients with mean age of (59.4 ± 6.8 )years.The patients in phase 0 + to phase Ⅲ were 172 (14.3%),255 (21 .2%),160 (13.3%)and 617 (51 .2%),respectively.The tuberculosis prevalence rate was about 7.3% among these population.The risk factors for tuberculosis including phase Ⅱ silicosis (OR =2.96, 95 %CI :1 .05 -8.32,P =0.04)and phase Ⅲ silicosis (OR=3.88,95 %CI :1 .58-9.56,P <0.01),and contacting with tuberculosis patients (OR=4.14,95 %CI :1 .91 -8.98,P <0.01).Patients complicated with tuberculosis lacked specific symptoms,but fever and weight loss were more frequent.Conclusion Tuberculosis is highly prevalent in silicotic patients,especially in patients with phase Ⅱ/Ⅲ silicosis and in patients with tuberculosis contact history.
10.The association of genetic polymorphisms of N-acetyltransferase 2 gene with hepatotoxicity and efficacy in Chinese Han patients with tuberculosis
Tingting SHEN ; Qin ZHANG ; Wenhong ZHANG ; Jing WU ; Jiazhen CHEN ; Fangxing QIAN ; Shu CHEN
Chinese Journal of Infectious Diseases 2015;(6):327-330
Objective To investigate the association of the polymorphism of the N-acetyltransferase 2 (NAT2 )gene with isoniazid-induced hepatotoxicity and anti-tuberculous treatment efficacy in Chinese Han patients with tuberculosis(TB).Methods A total of 108 TB patients who received initial anti-TB treatment were followed up prospectively.A polymerase chain reaction direct sequencing approach was used to detect genetic polymorphisms of the NAT2 gene.Associations between NAT2 genotype and isoniazid-induced hepatitis/early treatment were analyzed.Chi-square test was used for statistical analysis. Results Among the 108 TB patients, intermediate-acetylators (IA ) was the most frequent NAT2 genotype with the proportion of 54.63%(59/108).The proportion of rapid-acetylators(RA)was 33.33%(36/108),slow-acetylators (SA)was 10.19%(11/108)and super-rapid acetylators was 1 .85 % (2/108). Among the 20 patients who developed drug-induced hepatitis,2 were RA,5 were SA and 13 were IA. Regarding NAT2 genotype,RA patients had a lower incidence of hepatotoxicity (OR =0.176,95 %CI :0.038-0.809,P =0.014)and SA patients were more likely to developed drug-induced hepatic injury (OR=4.556,95 %CI :1 .231 -16.854,P =0.044 ).Statistical analysis revealed that the frequency of variant diplotypes,NAT2*4/*6A (OR=7.741 ,95 %CI :2.653-22.586,P <0.01 )and NAT2 *6A/*6A (OR=15 .353,95 %CI :1 .506 -156.552,P =0.020)were significantly increased in TB patients with hepatotoxicity.NAT2 *4/*4 was less likely to developed hepatic injury (OR =0.176,95 %CI :0.038-0.809,P =0.014).Among the 58 culture-positive patients,12(31 .03%)were persistent culture positive after 2 months standard therapy.Early treatment failure was observed with significantly higher incidence rate in RA than other genotypes (OR = 7.200, 95 % CI :1 .794-28.900, P = 0.008). Conclusions In Chinese Han TB patients,IA is the most frequent NAT2 genotype.The SA status of NAT2 is a risk factor of isoniazid-induced hepatotoxicity.The diplotype of NAT2 *6A has clearly high risk of isoniazid-induced hepatotoxicity.In contrast,NAT2 * 4/* 4 is protective diplotype.RA is associated with early treatment failure in culture-positive patients.

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